Tainano Nanobiotechnology Glossary

A

acetyl CoA Small, water-soluble metabolite comprising an acetyl group linked to coenzyme A (CoA); formed during oxidation of pyruvate, fatty acids, and amino acids. Its acetyl group is transferred to citrate in the citric acid cycle. (Figure 16-10)

Figure 16-10. The structure of acetyl CoA. This compound is an important intermediate in the aerobic oxidation of pyruvate, fatty acids, and many amino acids. It also contributes acetyl groups in many biosynthetic pathways.

acetylcholine (ACh) Neurotransmitter that functions at vertebrate neuromuscular junctions and at various neuron-neuron synapses in the brain and peripheral nervous system.
acid A compound that can donate a proton (H+). The carboxyl and phosphate groups are the primary acidic groups in biological molecules.
actin Abundant structural protein in eukaryotic cells that interacts with many other proteins. The monomeric globular form (G actin) polymerizes to form actin filaments (F actin). In muscle cells, F actin interacts with myosin during contraction. See also microfilaments.
action potential Rapid, transient, all-or-none electrical activity that is propagated in the plasma membrane of excitable cells such as neurons and muscle cells. Action potentials, or nerve impulses, allow long-distance signaling in the nervous system. (Figure 21-14)

Figure 21-14. Unidirectional conduction of an action potential due to transient inactivation of voltage-gated Na⁺ channels. At time 0, an action potential (purple) is at the 2-mm position on the axon. The membrane depolarization spreads passively in both directions along the axon (Figure 21-11). Because the Na⁺ channels at the 1-mm position are still inactivated (green), they cannot yet be reopened by the small depolarization caused by passive spread. Each region of the membrane is refractory (inactive) for a few milliseconds after an action potential has passed. Thus, the depolarization at the 2-mm site at time 0 triggers action potentials downstream only; at 1 ms an action potential is passing the 3-mm position, and at 2 ms, an action potential is passing the 4-mm position.

activation energy The input of energy required to (overcome the barrier to) initiate a chemical reaction. By reducing the activation energy, an enzyme increases the rate of a reaction. (Figure 2-27)

Figure 2-27. Hypothetical energy changes in the conversion of a reactant ¡X say, glyceraldehyde 3-phosphate (G3P) ¡X to a product ¡X say, dihydroxyacetone phosphate (DHAP) ¡X in the presence and absence of a catalyst. The trough in each curve represents a stable intermediate in the reaction, as depicted in Figure 2-28. The total activation energy (£GG^‡) is the difference between the free energy of the reactants and that represented by the highest crest along the pathway. A catalyst accelerates the rate of a reaction by reducing the free energy of the transition state, so that the activation energy of the catalyzed reaction, £GG^‡_cat, is less than that of the uncatalyzed reaction, £GG^‡_uncat. Catalysts do not alter the free energy of reactants or products or affect their equilibrium concentrations.

Figure 2-28. The conversion of glyceraldehyde 3-phosphate (G3P) to dihydroxyacetone phosphate (DHAP) involves an intermediate. Two groups, a base B⁻ and an acid HA, are parts of triosephosphate isomerase, the enzyme that catalyzes this reaction. To form the intermediate, B⁻ abstracts a proton (blue) from carbon 2 of G3P; HA adds a proton (red) to the aldehyde oxygen on carbon 1. To convert the intermediate to DHAP, BH donates its proton to carbon 1 (regenerating the original B⁻) and A⁻ abstracts a proton from the ¡XOH on carbon 2 (regenerating HA). The curved arrows denote the movements of pairs of electrons that accompany the making and breaking of these bonds. [See D. Straus et al., 1985, Proc. Nat'l. Acad. Sci. 82:2272.]

active site Region of an enzyme molecule where the substrate binds and undergoes a catalyzed reaction.
active transport Energy-requiring movement of an ion or small molecule across a membrane against its concentration gradient or electrochemical gradient. Energy is provided by the coupled hydrolysis of ATP or the cotransport of another molecule down its electrochemical gradient.
adenosine triphosphate See ATP.
adenylyl cyclase Membrane-bound enzyme that catalyzes formation of cyclic AMP (cAMP) from ATP; also called adenylate cyclase. Binding of certain ligands to their cell-surface receptors leads to activation of adenylyl cyclase and a rise in intracellular cAMP. (Figure 20-15)

Figure 20-15. Schematic diagram of mammalian adenylyl cyclases. The membrane-bound enzyme contains two similar catalytic domains on the cytosolic face of the membrane and two integral membrane domains, each of which is thought to contain six transmembrane £\ helices. The six adenylyl cyclase isoforms present in mammals are activated or inhibited by transducing G proteins following hormone binding to an appropriate receptor. One isoform found mainly in the brain also is activated by Ca²⁺ ions complexed to the protein calmodulin. [See W. -J. Tang and A. G. Gilman, 1992, Cell 70:869.]

aerobic Referring to a cell, organism, or metabolic process that utilizes O2 or that can grow in the presence of O2.
aerobic oxidation Oxygen-requiring metabolism of sugars and fatty acids to CO2 and H2O coupled to the synthesis of ATP.
allele One of two or more alternative forms of a gene located at the corresponding site (locus) on homologous chromosomes.
allosteric transition Change in the tertiary and/or quaternary structure of a protein induced by binding of a small molecule to a specific regulatory site, causing a change in the protein's activity. Allosteric regulation is particularly prevalent in multisubunit enzymes.
alpha (£\) helix Common secondary structure of proteins in which the linear sequence of amino acids is folded into a right-handed spiral stabilized by hydrogen bonds between carboxyl and amide groups in the backbone. (Figure 3-6)

Figure 3-6. Model of the £\ helix. The polypeptide backbone is folded into a spiral that is held in place by hydrogen bonds (black dots) between backbone oxygen atoms and hydrogen atoms. Note that all the hydrogen bonds have the same polarity. The outer surface of the helix is covered by the side-chain R groups.

amino acid An organic compound containing at least one amino group and one carboxyl group. In the 20 different amino acids that compose proteins, an amino group and carboxyl group are linked to a central carbon atom, the £\ carbon, to which a variable side chain is bound. (Figure 3-2)

Figure 3-2. The structures of the 20 common amino acids grouped into three categories: hydrophilic, hydrophobic, and special amino acids. The side chain determines the characteristic properties of each amino acid. Shown are the zwitterion forms, which exist at the pH of the cytosol. In parentheses are the three-letter and one-letter abbreviations for each amino acid.

aminoacyl-tRNA Activated form of an amino acid, used in protein synthesis, consisting of an amino acid linked via a highenergy ester bond to the 3¡¬-hydroxyl group of a tRNA molecule. (Figure 4-29)

Figure 4-29. Aminoacylation of tRNA. Amino acids are covalently linked to tRNAs by aminoacyl-tRNA synthetases. Each of these enzymes recognizes one kind of amino acid and all the cognate tRNAs that recognize codons for that amino acid. The two-step aminoacylation reaction requires energy from the hydrolysis of ATP. The equilibrium of the overall reaction favors the indicated products because the pyrophosphate (PP_i) released in step 1 is converted to inorganic phosphate (P_i) by a pyrophosphatase. The 3¡¬ end of all tRNAs, to which the amino acid attaches, has the sequence CCA. Class I synthetases (purple) attach the amino acid to the 2¡¬ hydroxyl of the terminal adenylate in tRNA; class II synthetases (green) attach the amino acid to the 3¡¬ hydroxyl. (Ad = adenine; Cyt = cytosine.)

amphipathic Referring to a molecule or structure that has both a hydrophobic and a hydrophilic part.
anabolism Cellular processes whereby energy is used to synthesize complex molecules from simpler ones. See also catabolism.
anaerobic Referring to a cell, organism, or metabolic process that functions in the absence of O2.
anaphase Mitotic stage during which the sister chromatids (or paired homologs in meiosis I) separate and move apart (segregate) toward the spindle poles. (Figure 19-34)

Figure 19-34. The stages of mitosis and cytokinesis in an animal cell. (Morphological types of chromosomes are distinguished by color.) (a) Interphase: The G₂ stage of inter-phase immediately precedes the beginning of mitosis and follows chromosomal DNA replication during the S phase. The chromosomes, each containing a sister chromatid, are still dispersed and not visible as distinct structures. During interphase, the centrioles also are replicated, forming small daughter centrioles. (b) Early prophase: The centrosomes, each with a daughter centriole, begin moving toward opposite poles of the cell. The chromosomes can be seen as long threads, and the nuclear membrane begins to disaggregate into small vesicles. (c) Middle and late prophase: Chromosome condensation is completed; each visible chromosome structure is composed of two chromatids held together at their centromeres. The microtubular spindle fibers begin to radiate from the regions just adjacent to the centrosomes, which are moving closer to their poles. Some spindle fibers reach from pole to pole; most go to chromatids and attach at kinetochores. (d) Metaphase: The chromosomes move toward the equator of the cell, where they become aligned in the equatorial plane. The sister chromatids have not yet separated. This is the phase in which morphological studies of chromosomes are usually carried out. (e) Anaphase: The two sister chromatids separate into independent chromosomes. Each contains a centromere that is linked by a spindle fiber to one pole, to which it moves. Simultaneously, the cell elongates, as do the pole-to-pole spindles. Cytokinesis begins as the cleavage furrow starts to form. (f) Telophase: New nuclear membranes form around the daughter nuclei; the chromosomes uncoil and become less distinct; and the nucleolus becomes visible again. Cytokinesis is nearly complete, and the spindle disappears as the microtubules and other fibers depolymerize. Throughout mitosis the ¡§daughter¡¨ centriole at each pole grows, so that by telophase each of the emerging daughter cells has two full-length centrioles. Upon the completion of cytokinesis, each daughter cell enters the G₁ phase of the cell cycle and proceeds again around the cycle.

antibody A protein that interacts with a particular site (epitope) on an antigen and facilitates clearance of that antigen by various mechanisms. See also immunoglobulin. (Figure 3-21)

Figure 3-21. Structure of an antibody molecule, which consists of two identical heavy chains (blue and orange) and two identical light chains (yellow and green). The Y-shaped molecule contains two identical Fab domains, forming the arms, and one Fc domain, forming the stem. In the native molecule, each heavy chain is a continuous polypeptide, with a hinge region connecting the two halves shown in this figure. Antigen molecules (white) bind to the complementarity-determining regions (CDRs), which are highly variable regions located at the ends of each arm. Antibodies contain carbohydrate moieties (red) and thus are glycoproteins. [From A. Levine, 1992, Viruses, W. H. Freeman, p. 53.]

anticodon Sequence of three nucleotides in a tRNA that is complementary to a codon in an mRNA. During protein synthesis, base pairing between a codon and anticodon aligns the tRNA carrying the corresponding amino acid for addition to the growing peptide chain.
antigen Any material (usually foreign) that elicits production of and is specifically bound by an antibody.
antiport A type of cotransport in which a membrane protein (antiporter) transports two different molecules or ions across a cell membrane in opposite directions. See also symport.
antisense RNA An RNA, with sequence complementary to a specific RNA transcript or mRNA, whose binding prevents processing of the transcript or translation of the mRNA. (Figure 11-46)

Figure 11-46. Antisense control of translation of transposase mRNA encoded by IS 10m a bacterial mobile element. The 5¡¬ end of transposase mRNA (red), produced from the lower strand beginning at P_IN, is complementary to the 5¡¬ end of antisense RNA (black), produced from the top strand beginning at P_OUT. Because P_OUT is a much stronger promoter than P_IN, more antisense RNA than transposase mRNA is produced, so that nearly all of the transposase mRNA hybridizes to the more abundant antisense RNA. Since the AUG start codon (green highlight) and the ribosome-binding Shine-Delgarno sequence (yellow highlight) are in the hybridized region, initiation of translation of transposase mRNA is blocked. Very rarely, translation of a transposase mRNA is initiated before hybridization to an antisense RNA, leading to a low rate of IS10 transposition.

apoptosis Regulated process leading to cell death via a series of well-defined morphological changes; also called programmed cell death. (Figure 23-45)

Figure 23-45. Ultrastructural features of cell death by apoptosis. (a) Schematic drawings illustrating the progression of morphologic changes observed in apoptotic cells. Early in apoptosis, dense chromosome condensation occurs along the nuclear periphery. The cell body also shrinks although most organelles remain intact. Later both the nucleus and cytoplasm fragment, forming apoptotic bodies. These are phagocytosed by surrounding cells. (b) Photomicrographs comparing a normal cell (top) and apoptotic cell (bottom). Clearly visible in the latter are dense spheres of compacted chromatin as the nucleus begins to fragment. [Part (a) adapted from J. Kuby, 1997, Immunology, 3d ed., W. H. Freeman & Co., p. 53. Part (b) from M. J. Arends and A. H. Wyllie, 1991, Inter. Rev. Exp. Pathol. 32:223.]

archaea Class of prokaryotes that constitutes one of the three distinct evolutionary lineages of modern-day organisms; also called archaebacteria and archaeans. These prokaryotes are in some respects more similar to eukaryotes than to the so-called true bacteria (eubacteria). (Figure 1-5)

Figure 1-5. The three kingdoms of organisms are related through common sequences of their ribosomal RNAs. Their lineage depicts a view of how all life on earth, from simple bacteria to complex mammals, evolved from a common, single-celled progenitor.

association constant (K_a) See equilibrium constant.
aster Star-shaped structure composed of microtubules (called astral fibers) that radiates outward from a centrosome during mitosis. (Figure 19-34)

Figure 2-6. Stereoisomers of the amino acid alanine. The asymmetric £\ carbon is black. Although the chemical properties of such optical isomers are identical, their biological activities are distinct.

ATP (adenosine 5¡¬-triphosphate) A nucleotide that is the most important molecule for capturing and transferring free energy in cells. Hydrolysis of each of the two high-energy phosphoanhydride bonds in ATP is accompanied by a large free-energy change (£GG) of −7 kcal/mole. (Figure 2-24)

Figure 2-24. In adenosine triphosphate (ATP), two high-energy phosphoanhydride bonds (red) link the three phosphate groups.

ATP synthase Multimeric protein complex bound to inner mitochondrial membranes, thylakoid membranes of chloroplasts, and the bacterial plasma membrane that catalyzes synthesis of ATP during oxidative phosphorylation and photosynthesis; also called F0F1 complex. (Figure 16-28)

Figure 16-28. Model of the structure of ATP synthase (the F₀F₁ ATPase complex) in the bacterial plasma membrane. The F₀ portion is built of three integral membrane proteins: a, b, and 9 ¡V 12 copies of c arranged in a ring in the plane of the membrane. The proton channel lies at the interface between the a subunit and c ring. The F₁ portion contains three copies each of subunits £\ and £] that form a hexamer resting atop the single rod-shaped £^ subunit, which is inserted into the c ring of F₀. The £` subunit is attached to the £^ and probably also contacts the c subunits, and the £_ subunit links the F₁ complex to the b subunit of F₀. ATP synthases in the inner mitochondrial membrane and chloroplast thylakoid membranes have a similar structure, although the number of c units may vary and some additional subunits may be present, depending on species. [Adapted from Y. Zhou et al., 1997, Proc. Nat'l. Acad. Sci. USA 94:10583; T. Elston et al., 1998, Nature 391:510; and J. Abrahams et al., 1994, Nature 370:621.]

ATPase One of a large group of enzymes that catalyze hydrolysis of ATP to yield ADP and inorganic phosphate with release of free energy.
autonomously replicating sequence (ARS) Sequence that permits a DNA molecule to replicate in yeast; a yeast DNA replication origin. (Figure 9-40)

Figure 9-40. Experimental demonstration of functional chromosomal elements in experiments with yeast cells that lack an enzyme necessary for leucine synthesis (leu ⁻ cells). In these experiments, plasmids containing the LEU gene from normal yeast cells are constructed and introduced into leu ⁻ cells by transfection. If the plasmid is maintained in the leu ⁻ cells, they are transformed to LEU ⁺ by the LEU gene on the plasmid and can form colonies on medium lacking leucine. (a) Sequences that allow autonomous replication (ARS) of a plasmid were identified because their insertion into a plasmid vector containing a cloned LEU gene resulted in a high frequency of transformation to LEU ⁺. However, even plasmids with ARS exhibit poor segregation during mitosis, and therefore do not appear in each of the daughter cells. (b) When randomly broken pieces of genomic yeast DNA are inserted into plasmids containing ARS and LEU, some of the transfected cells produce large colonies, indicating that a high rate of mitotic segregation among their plasmids is facilitating the continuous growth of daughter cells. The DNA recovered from plasmids in these large colonies contains yeast centromere (CEN) sequences. (c) When leu ⁻ yeast cells are transfected with linearized plasmids containing LEU, ARS, and CEN, no colonies grow. Addition of telomere (TEL) sequences to the ends of the linear DNA gives the linearized plasmids the ability to replicate as new chromosomes that behave very much like a normal chromosome in both mitosis and meiosis. [See A. W. Murray and J. W. Szostak, 1983, Nature 305:89; L. Clarke and J. Carbon, 1985, Ann. Rev. Genetics 19:29.]

autoradiography Technique for visualizing radioactive molecules in a sample (e.g., a tissue section or electrophoretic gel) by exposing a photographic film or emulsion to the sample. The exposed film is called an autoradiogram or autoradiograph. (Figure 3-45)

Figure 3-45. Autoradiography. (a) A radiation-sensitive photographic emulsion containing silver salts (AgBr) is placed over tritium-labeled cells attached to a glass slide (for the light microscope) or to a carbon-coated grid (for the electron microscope). The cell regions containing the labeled molecules emit radioactive particles, along the tracks of which silver is deposited. When the photographic emulsion is developed, the silver deposits appear as dark grains under the light microscope and as curly filaments in the electron microscope. (b) When cells are incubated with [³H]thymidine for a short period, any DNA synthesized during this labeling period incorporates the labeled precursor and can be localized by autoradiography. The root cells of a lily, shown here, were pulse-labeled; a sample was then taken 8 hours later. During the pulse period, the silver grains lie over both chromatids of the chromosomes. [Part (a) adapted from E. D. P. DeRobertis and E. M. F. DeRobertis, 1979, Cell and Molecular Biology, Saunders, p. 62; part (b) courtesy of J. H. Taylor.]

autosome Any chromosome other than a sex chromosome.
auxotroph A mutant cell or microorganism that grows only when the medium contains a specific nutrient or metabolite that is not required by the wild type.
axon Long process extending from the cell body of a neuron that is capable of conducting an electric impulse (action potential) generated at the junction with the cell body (called the axon hillock) toward its distal, branching end (called the axon terminal). (Figure 21-1)

Figure 21-1. Structure of typical mammalian neurons. Arrows indicate the direction of conduction of action potentials in axons (red). (a) Multipolar interneurons. Each has profusely branched dendrites, which receive signals at synapses with several hundred other neurons, and a single long axon that branches laterally and at its terminus. (b) A motor neuron that innervates a muscle cell. Typically, motor neurons have a single long axon extending from the cell body to the effector cell. In mammalian motor neurons an insulating sheath of myelin usually covers all parts of the axon except at the nodes of Ranvier and the axon terminals. (c) A sensory neuron in which the axon branches just after it leaves the cell body. The peripheral branch carries the nerve impulse from the receptor cell to the cell body, which is located in the dorsal root ganglion near the spinal cord; the central branch carries the impulse from the cell body to the spinal cord or brain. Both branches are structurally and functionally axons, except at their terminal portions, even though the peripheral branch conducts impulses toward, rather than away from, the cell body.

axoneme Bundle of microtubules and associated proteins present in cilia and flagella and responsible for their movement. (Figure 19-28)

Figure 19-28. Structure of ciliary and flagellar axonemes. (a) Cross-sectional diagram of a typical flagellum showing its major structures. The dynein arms and radial spokes with attached heads occur only at intervals along the longitudinal axis. The central microtubules, C1 and C2, are distinguished by fibers bound only to C1. (b) Micrograph of a transverse section through an isolated demembranated cilium. The two central singlet microtubules are surrounded by nine outer doublets, each composed of an A and a B subfiber. [Part (b) courtesy of L. Tilney; see U. W. Goodenough and J. E. Heuser, 1985, J. Cell Biol. 100:2008.]

B

bacteriophage (phage) Any virus that infects bacterial cells. Some bacteriophage are widely used as cloning vectors.
basal body Structure at the base of cilia and flagella from which microtubules forming the axoneme radiate; structurally similar to a centriole.
basal lamina (pl. basal laminae) A thin sheetlike network of extracellular-matrix components that underlies most animal epi-thelial layers and other organized groups of cells (e.g., muscle), separating them from connective tissue.
base A compound, usually containing nitrogen, that can accept a proton (H+). Commonly used to denote the purines and pyrimidines in DNA and RNA.
base pair Association of two complementary nucleotides in a DNA or RNA molecule stabilized by hydrogen bonding between their base components. Adenine pairs with thymine or uracil (A¡PT, A¡PU) and guanine pairs with cytosine (G¡PC). (Figure 4-4b)
benign Referring to a tumor containing cells that closely resemble normal cells. Benign tumors stay in the tissue where they originate. See also malignant.
beta (£]) sheet A planar secondary structure of proteins that is created by hydrogen bonding between the backbone atoms in two different polypeptide chains or segments of a single folded chain. (Figure 3-8)

Figure 3-8. £] SHEETS. (a) A simple two-stranded £] sheet with antiparallel £] strands. A sheet is stabilized by hydrogen bonds (black dots) between the £] strands. The planarity of the peptide bond forces a £] sheet to be pleated; hence, this structure is also called a £] pleated sheet, or simply a pleated sheet. (b) Side view of a £] sheet showing how the R groups protrude above and below the plane of the sheet. (c) Model of binding site in class I MHC (major histocompatibility complex) molecules, which are involved in graft rejection. A sheet comprising eight antiparallel £] strands (green) forms the bottom of the binding cleft, which is lined by a pair of £\ helices (blue). A disulfide bond is shown as two connected yellow spheres. The MHC binding cleft is large enough to bind a peptide 8¡V10 residues long. [Part (b) adapted from C. Branden and J. Tooze, 1991, Introduction to Protein Structure, Garland.]

bilayer See phospholipid bilayer.
biomembrane Permeability barrier, surrounding cells or organelles, that consists of a phospholipid bilayer, associated membrane proteins, and in some cases cholesterol and glycolipids.
blastula An early embryonic form produced by cleavage of a fertilized ovum and usually consisting of a single layer of cells surrounding a fluid-filled spherical cavity.
buffer A solution of the acid (HA) and base (A−) form of a compound that undergoes little change in pH when small quantities of strong acid or base are added.

C

cadherin Protein belonging to a family of Ca2-dependent cell-adhesion molecules that play roles in tissue differentiation and structure.
calmodulin A small cytosolic protein that binds four Ca2+ ions; the Ca2+-calmodulin complex binds to and activates many enzymes. (Figure 20-40)

Figure 20-40. Release of Ca²⁺ stores mediated by ryanodine receptors (RYRs) in skeletal muscle. Voltagesensing dihydropyridine receptors in the plasma membrane contact ryanodine receptors located in the membrane of the sarcoplasmic reticulum. In response to a change in voltage, the dihydropyridine receptors undergo a conformational change; this produces a conformational change in the associated RYRs, opening them so that Ca²⁺ ions can exit into the cytosol. [Adapted from M. J. Berridge, 1993, Nature 361:315.]

Calvin cycle The major metabolic pathway that fixes CO2 into carbohydrates during photosynthesis; also called carbon fixation. It is indirectly dependent on light but can occur both in the dark and light. (Figure 16-49)

Figure 16-49. The pathway of carbon during photosynthesis. (Top) Six molecules of CO₂ are converted into two molecules of glyceraldehyde 3-phosphate. These reactions, which constitute the Calvin cycle, occur in the stroma of the chloroplast. Via the phosphate-triosephosphate antiporter, some glyceraldehyde 3-phosphate is transported to the cytosol in exchange for phosphate. (Bottom) In the cytosol, an exergonic series of reactions converts glyceraldehyde 3-phosphate to fructose 1,6-bisphosphate and, ultimately, to the disaccharide sucrose. Some glyceraldehyde 3-phosphate (not shown here) is also converted to amino acids and fats, compounds essential to plant growth.

cAMP-dependent protein kinase (cAPK) Type of cytosolic enzyme that is activated by cAMP and functions to regulate the activity of numerous cellular proteins; also called protein kinase A. Generally is activated in response to a rise in cAMP level resulting from stimulation of G protein¡Vcoupled receptors. (Figures 3-24 and 20-47)

Figure 3-24. The mechanism of phosphorylation by cAMP-dependent protein kinase (cAPK), which catalyzes transfer of a phosphate group from ATP to a serine side chain in a target peptide sequence. Step 1: Initially, both substrates bind to the active site (see Figure 3-23). Electrons of the phosphate group are delocalized by interactions with lysine residues and Mg²⁺. Asp166 abstracts a proton from the hydroxyl group of the serine in the bound target peptide. Step 2: A new bond then forms between the serine side-chain oxygen and £^ phosphate, yielding a pentavalent transition-state intermediate. Step 3: The phosphoester bond between the £] and £^ phosphates is broken to form a phosphorylated serine side chain and ADP.

Figure 20-47. Schematic diagram of the regulatory feedback loop that controls the activity of G_s protein ¡V coupled receptors by cyclical phosphorylation and dephosphorylation. All receptors of this type are phosphorylated by cAMP-dependent protein kinase (cAPK). Additional residues are phosphorylated by receptor-specific kinases such as BARK, whose substrate is the £]-adrenergic receptor.

capsid The outer proteinaceous coat of a virus, formed by multiple copies of one or more protein subunits and enclosing the viral nucleic acid.
carbohydrate General term for certain polyhydroxyaldehydes, polyhydroxyketones, or compounds derived from these usually having the formula (CH2O)n. Primary type of compound used for storing and supplying energy in animal cells.
carbon fixation See Calvin cycle.
carcinogen Any chemical or physical agent that can cause cancer when cells or organisms are exposed to it.
carcinoma A malignant tumor derived from epithelial cells.
catabolism Cellular processes whereby complex molecules are degraded to simpler ones and energy is released. See also anabolism.
catalyst A substance that increases the rate of a chemical reaction without undergoing a permanent change in its structure. Enzymes are protein catalysts.
catecholamines Group of compounds derived from tyrosine that function as neurotransmitters; include epinephrine, norepinephrine, and dopamine. (Figure 21-28)

Figure 21-28. Structures of several small molecules that function as neurotransmitters. Except for acetylcholine, all of these are amino acids (glycine and glutamate) or derived from the indicated amino acids. The three transmitters synthesized from tyrosine, which contain the catechol moiety (blue highlight), are referred to as catecholamines

cDNA (complementary DNA) DNA molecule copied from an mRNA molecule by reverse transcriptase and therefore lacking the introns present in genomic DNA. Sequencing of a cDNA permits the amino acid sequence of the encoded protein to be deduced; expression of cDNAs in recombinant cells can be used to produce large quantities of their encoded proteins in vitro.
cell cycle Ordered sequence of events in which a cell duplicates its chromosomes and divides into two. Most eukaryotic cell cycles can be commonly divided into four phases: G1 before DNA synthesis occurs; S when DNA replication occurs; G2 after DNA synthesis; and M when cell division occurs, yielding two daughter cells. Under certain conditions, cells exit the cell cycle during G1 and remain in the G0 state as nongrowing, nondividing (quiescent) cells. Appropriate stimulation of such cells induces them to return to G1 and resume growth and division. (Figure 13-1)

Figure 13-1. The fate of a single parental chromosome throughout the eukaryotic cell cycle. Although chromosomes condense only during mitosis, they are shown in condensed form to emphasize the number of chromosomes at different cell-cycle stages. The nuclear envelope is not depicted. Following mitosis (M), daughter cells contain 2n chromosomes in diploid organisms and 1n chromosomes in haploid organisms including yeasts maintained in the haploid state. In proliferating cells, G₁ is the period between ¡§birth¡¨ of a cell following mitosis and the initiation of DNA synthesis, which marks the beginning of the S phase. At the end of the S phase, cells enter G₂ containing twice the number of chromosomes as G₁ cells (4n in diploid organisms). The end of G₂ is marked by the onset of mitosis, during which numerous events leading to cell division occur. The G₁, S, and G₂ phases are collectively referred to as interphase, the period between one mitosis and the next. Most nonproliferating cells in vertebrates leave the cell cycle in G₁, entering the G₀ state. See also Figure 1-10.

cell division Separation of a cell into two daughter cells. In higher eukaryotes, it involves division of the nucleus (mitosis) and of the cytoplasm (cytokinesis); mitosis often is used to refer to both nuclear and cytoplasmic division.
cell fusion Production of a hybrid cell containing two or more nuclei by various techniques that stimulate the fusion of the plasma membranes of two cells at the point of contact and intermingling of their cytoplasms. See also hybridoma.
cell junctions Specialized regions on the cell surface through which cells are joined to each other or to the extracellular matrix. (Figure 15-23)

Figure 15-23. Schematic diagram of epithelial cells lining the small intestine and the principal types of cell junctions that connect them. As in all epithelia, the basal surface of the cells rests on the basal lamina, a fibrous network of collagen and proteoglycans that supports the epithelial cell layer. The apical surface faces the intestinal lumen. Tight junctions, lying just under the microvilli, prevent diffusion of substances between the intestinal lumen and the blood via the extracellular space between cells. Gap junctions allow movement of small molecules and ions between the cytosol of adjacent cells. The remaining three types of junctions, adherens junctions, spot desmosomes, and hemidesmosomes are critical to cell-cell and cell-matrix adhesion.

cell line A population of cultured cells, of plant or animal origin, that has undergone a change allowing the cells to grow indefinitely, in contrast to a cell strain. Cell lines can result from chemical or viral transformation and are said to be immortal.
cell strain A population of cultured cells, of plant or animal origin, that has a finite life span, in contrast to a cell line. (Figure 6-5)

Figure 6-5. Stages in the establishment of a cell culture. (a) When an initial explant is made of human cells, some cells die and others (mainly fibroblasts) start to grow; overall the growth rate increases (phase I). If the remaining cells are continually diluted, the cell strain grows at a constant rate for about 50 cell generations (phase II), after which the growth rate falls rapidly. During the ensuing period of increasing cell death (phase III), all the cells in the culture eventually die. (b) In a culture prepared from mouse or other rodent embryo cells, there is initial cell death coupled with the emergence of healthy growing cells. As these are diluted and allowed to continue growth, they soon begin to lose growth potential and most cells die (the culture goes into crisis). Very rare cells do not die but continue growing until their progeny overgrow the culture. These cells constitute a cell line, which will grow forever if it is appropriately diluted and fed with nutrients: the cells are immortal.

cell wall A specialized, rigid extracellular matrix that lies next to the plasma membrane, protecting a cell and maintaining its shape. It is prominent in most fungi, plants, and prokaryotes, but is not present in most multicellular animals. (Figures 22-29 and 22-32)

Figure 22-29. Schematic representation of the cell wall of an onion. Cellulose and hemicellulose are arranged into at least three layers in a matrix of pectin polymers. The size of the polymers and their separations are drawn to scale. To simplify the diagram, most of the hemicellulose cross-links are not shown. [Adapted from M. McCann and K. R. Roberts, 1991, in C. Lloyd, ed., The Cytoskeletal Basis of Plant Growth and Form, p. 126.]

Figure 22-32. The structure of the secondary cell wall, built up of a series of layers of cellulose. In each layer, the cellulose fibrils run more or less in the same direction, but the direction varies in different layers. As plant cells grow, they deposit new layers of cellulose adjacent to the plasma membrane. Thus the oldest layers are in the primary wall (the outer wall) and in the middle lamella (the pectin-rich part of the cell wall laid down between two daughter cells as they cleave during cell division). Younger regions of the wall ¡X collectively the secondary cell wall ¡X are laid down as successive layers, adjacent to the plasma membrane. The cytoplasms of adjacent cells are usually connected by plasmodesmata that run through the layers of the cell walls.

cell-adhesion molecules (CAMs) Integral membrane proteins that mediate cell-cell binding. The five major classes are the integrins, cadherins, selectins, immunoglobulin (Ig) superfamily, and mucins. (Figure 22-1)

Figure 22-1. Schematic overview of the types of molecules that bind cells to each other and to the extracellular matrix. Cell-adhesion molecules (CAMs) are integral membrane proteins. Some interact with similar molecules on other cells and, via intracellular attachment proteins, form anchors for cytoskeletal proteins. Other CAMs form connections with components of the extracellular matrix and also, via attachment proteins, with cytoskeletal proteins. Multiadhesive proteins bind to cell-surface receptor proteins and to other matrix components. Proteoglycans, consisting of a core protein, to which glycosamino glycan chains are attached, also participate in adhesion of cells to one another and to the protein components of the matrix. Together, these interactions allow cells to adhere to one another, interconnect the cytoskeletons of adjacent cells, and give tissues their strength and resistance to shear forces.

cellulose A structural polysaccharide made of glucose units linked together by £](1n4) glycosidic bonds. It forms long microfibrils, which are the major component of plant cell walls. (Figure 22-31)

Figure 22-31. The structure of cellulose in the plant cell wall. (a) Cellulose is a linear polymer consisting of 2000 ¡V 20,000 glucose residues linked together by £](1¡÷4) glycosidic bonds. Because the £](1¡÷4) linkages cause alternating glucose residues to be rotated by 180¢X, a pair of residues constitute a repeating unit, the cellobiose monomer; these monomers polymerize into straight glucan chains. The chains pack together to form rodlike microfibrils, which are stabilized by hydrogen bonds between the chains. Each glucan chain is polar because its two ends are distinct, and all the chains in a microfibril have the same polarity. (b) A rotary shadowed platinum replica of a rapidly frozen, deep-etched onion cell wall shows the arrangement of cellulose fibers and thinner cross-links presumably composed of hemicellulose or pectin. The scale bar is 200 nm. [Part (b) from: M. C. McCann, B. Wells, and K. Roberts, 1990, Journal of Cell Science 96:327; courtesy of Keith Roberts.]

central nervous system (CNS) The part of the vertebrate nervous system comprising the brain and spinal cord; the main information-processing organ.
centriole Either of two cylindrical structures within the centrosome of animal cells and containing nine sets of triplet microtubules; structurally similar to a basal body. (Figure 19-5b)
centromere Constricted portion of a mitotic chromosome where sister chromatids are attached and from which kinetochore fibers extend toward a spindle pole; required for proper chromosome segregation during mitosis and meiosis.
centrosome (cell center) Organelle located near the nucleus of animal cells that is the primary microtubule-organizing center (MTOC) and contains a pair of centrioles. It divides during mitosis, forming the spindle poles.
chaperone Collective term for two types of proteins that prevent misfolding of a target protein (molecular chaperones) or actively facilitate its proper folding (chaperonins). (Figure 3-15)

Figure 3-15. Chaperone-mediated protein folding. (a) Many proteins 1 fold into their proper three-dimensional structure with the assistance of Hsp70, a molecular chaperone that transiently binds to a nascent polypeptide as it emerges from a ribosome. Proper folding of some proteins 2 also depends on the chaperonin TCiP, a large barrel-shaped complex of Hsp60 units. (b) GroEL, the bacterial homolog of TCiP, is a barrel-shaped complex of 14 identical 60,000-MW subunits arranged in two stacked rings. In the absence of ATP or presence of ADP, GroEL exists in a ¡§tight¡¨ conformational state (left) that binds partially folded or misfolded proteins. Binding of ATP shifts GroEL to a more open, ¡§relaxed¡¨ state (right), which releases the folded protein. [Part (b) from A. Roseman et al., 1996, Cell 87:241. Courtesy of Helen Saibil.]

checkpoint Any of several points in the eukaryotic cell cycle at which progression of a cell to the next stage can be halted until conditions are suitable. (Figure 13-34)

Figure 13-34. Stages at which checkpoint controls can arrest passage through the cell cycle. DNA damage due to irradiation or chemical modification prevents G₁ cells from entering the S phase and G₂ cells from entering mitosis. Unreplicated DNA prevents entry into mitosis. Defects in assembly of the mitotic spindle or the attachment of kinetochores to spindle microtubules prevent activation of the APC polyubiquitination system that leads to degradation of the anaphase inhibitor. Consequently, cells do not enter anaphase until all kinetochores are bound to spindle microtubules. [Adapted from A. Murray and T. Hunt, 1993, The Cell Cycle: An Introduction,W. H. Freeman and Company.]

chemical equilibrium The state of a chemical reaction in which the concentration of all products and reactants is constant and the rates of the forward and reverse reactions are equal.
chemiosmosis Process whereby an electrochemical proton gradient (pH plus electric potential) across a membrane is used to drive an energy-requiring process such as ATP synthesis or transport of molecules across a membrane against their concentration gradient; also called chemiosmotic coupling. (Figure 16-1)

Figure 16-1. Chemiosmotic coupling. This process can occur only in sealed, closed, membrane-limited compartments that are impermeable to H⁺. In photosynthesis, energy absorbed from light is used to move protons across the membrane, generating a transmembrane proton concentration gradient and a voltage gradient, collectively called the proton-motive force. In mitochondria and aerobic bacteria, energy liberated by the oxidation of carbon compounds is used to move protons across the membrane, again generating a proton-motive force. However generated, a proton-motive force can be used to power ATP synthesis 1 ,transport of metabolites across the membrane against their concentration gradient 2 , and rotation of bacterial flagella 3 .

chimera An animal or tissue composed of elements derived from genetically distinct individuals; also a protein molecule containing segments derived from different proteins.
chlorophylls A group of light-absorbing porphyrin pigments that are critical in photosynthesis. (Figure 16-35)

Figure 16-35. The structure of chlorophyll a, the principal pigment that traps light energy. Chlorophyll b differs from chlorophyll a by having a CHO group in place of the CH₃ group (green). In the porphyrin ring, a highly conjugated system, electrons are delocalized among three of the four central rings and the atoms that interconnect them in the molecule (yellow). In chlorophyll, a Mg²⁺ ion, rather than an Fe³⁺ ion, is in the center of the porphyrin ring and an additional five-membered ring (blue) is present; otherwise, its structure is similar to that of heme found in molecules such as hemoglobin and cytochromes (see Figure 16-21). The hydrocarbon phytol ¡§tail¡¨ facilitates the binding of chlorophyll to hydrophobic regions of chlorophyllbinding proteins.

Figure 16-21. Heme prosthetic groups of respiratory-chain cytochromes in mitochondria. Note the differences in substituents on the porphyrin rings. Hemes accept and release one electron at a time.

chloroplast A specialized organelle in plant cells that is surrounded by a double membrane and contains internal chlorophyll-containing membranes (thylakoids) where the light-absorbing reactions of photosynthesis occur. (Figure 16-34)

Figure 16-34. The structure of a leaf and chloroplast. The chloroplast is bounded by a double membrane: the outer membrane contains proteins that render it permeable to small molecules (MW < 6000); the inner membrane forms the permeability barrier of the organelle. Photosynthesis occurs on the thylakoid membrane, which forms a series of flattened vesicles (thylakoids) enclosing a single interconnected luminal space. The green color of plants is due to the green color of chlorophyll, all of which is localized to the thylakoid membrane. A granum is a stack of adjacent thylakoids. The stroma is the space within the inner membrane surrounding the thylakoids. See also Figure 5-46.

Figure 5-46. Electron micrograph of a chloroplast in a section of a plant cell. The internal membrane vesicles (thylakoids) are fused into stacks (grana), which reside in a matrix (the stroma). All the chlorophyll in the cell is contained in the thylakoid membranes. [Courtesy of Biophoto Associates/M. C. Ledbetter/Brookhaven National Laboratory.]

cholesterol An amphipathic lipid containing the four-ring steroid structure with a hydroxyl group on one ring; a major component of many eukaryotic membranes and precursor of steroid hormones. (Figure 5-29)

Figure 5-29. (a) The general structure of a steroid. All steroids contain the same four hydrocarbon rings, conventionally labeled A, B, C, and D, with the carbons numbered as shown. (b) The structure of cholesterol. The major portion of the molecule is hydrophobic (yellow), but the hydroxyl group is hydrophilic (green).

chromatid One copy of a duplicated chromosome, formed during the S phase of the cell cycle, that is still joined at the centromere to the other copy; also called sister chromatid. During mitosis, the two chromatids separate, each becoming a chromosome of one of the two daughter cells.
chromatin Complex of DNA, histones, and nonhistone proteins from which eukaryotic chromosomes are formed. Condensation of chromatin during mitosis yields the visible metaphase chromosomes. (Figure 9-29)

Figure 9-29. Electron micrographs of extracted chromatin in extended and condensed forms. (a) Chromatin isolated in low ionic strength buffer has an extended ¡§beads-on-a-string¡¨ appearance. The ¡§beads¡¨ are nucleosomes (10-nm diameter) and the ¡§string¡¨ is connecting DNA. (b) Chromatin isolated in buffer with a physiologic ionic strength (0.15 M KCl) appears as a condensed fiber 30 nm in diameter. [Part (a) courtesy of S. McKnight and O. Miller, Jr.; part (b) courtesy of B. Hamkalo and J. B. Rattner.]

chromatography, liquid Group of biochemical techniques for separating mixtures of molecules based on their mass (gel-filtration chromatography), charge (ion-exchange chromatography), or ability to bind specifically to other molecules (affinity chromatography). Commonly used technique for separating and purifying proteins. (Figure 3-43)

Figure 3-43. Three commonly used liquid chromatographic techniques. (a) Gel filtration chromatography separates proteins that differ in size. A mixture of proteins is carefully layered on the top of a glass cylinder packed with porous beads. Smaller proteins travel through the column more slowly than larger proteins. Thus different proteins have different elution volumes and can be collected in separate liquid fractions from the bottom. (b) Ion-exchange chromatography separates proteins that differ in net charge in columns packed with special beads that carry either a positive charge (shown here) or a negative charge. Proteins having the same net charge as the beads are repelled and flow through the column, whereas proteins having the opposite charge bind to the beads. Bound proteins, in this case negatively charged, are eluted by passing a salt gradient (usually of NaCl or KCl) through the column. As the ions bind to the beads, they desorb the protein. (c) In antibody-affinity chromatography, a specific antibody is covalently attached to beads packed in a column. Only protein with high affinity for the antibody is retained by the column; all the nonbinding proteins flow through. The bound protein is eluted with an acidic solution, which disrupts the antigen-antibody complexes.

chromosome In eukaryotes, the structural unit of the genetic material consisting of a single, linear double-stranded DNA molecule and associated proteins. During mitosis, chromosomes condense into compact structures visible in the light microscope. In prokaryotes, a single, circular double-stranded DNA molecule constitutes the bulk of the genetic material. See also karyotype.
cilium (pl. cilia) Membrane-enclosed motile structure extending from the surface of eukaryotic cells. Cilia usually occur in groups and beat rhythmically to move a cell (e.g., single-celled organism) or to move small particles or fluid along the surface (e.g., trachea cells). See also axoneme and flagellum.
cis-acting Referring to a regulatory sequence in DNA (e.g., enhancer, promoter) that can control a gene only on the same chromosome. In bacteria, cis-acting elements are adjacent or proximal to the gene(s) they control, whereas in eukaryotes they may also be far away. See also trans-acting.
cisterna (pl. cisternae) Flattened membrane-bounded compartment, as found in the Golgi complex and endoplasmic reticulum.
cistron A genetic unit that encodes a single polypeptide.
citric acid cycle A set of nine coupled reactions occurring in the matrix of the mitochondrion in which acetyl groups derived from food molecules are oxidized, generating CO2 and reduced intermediates used to produce ATP; also called Krebs cycle and tricarboxylic acid cycle (TCA). (Figure 16-12)

Figure 16-12. The citric acid cycle, in which acetyl groups transferred from acetyl CoA are oxidized to CO₂. In reaction 1, a two-carbon acetyl residue from acetyl CoA condenses with the four-carbon molecule oxaloacetate to form the six-carbon molecule citrate. In the remaining reactions (2¡V9), each molecule of citrate is eventually converted back to oxaloacetate, losing two CO₂ molecules in the process. In four of the reactions, four pairs of electrons are removed from the carbon atoms: three pairs are transferred to three molecules of NAD⁺ to form three NADH and three H⁺; one pair is transferred to the acceptor FAD to form FADH₂. The two carbon atoms added from acetyl CoA are highlighted in blue. Note that they are not lost in the turn of the cycle in which they enter. Because fumarate is a symmetric molecule, these two carbon atoms will be equally distributed among the four in oxaloacetate; one will be lost as CO₂ during the next turn of the cycle and the other in subsequent turns.

clathrin A fibrous protein that with the aid of assembly proteins polymerizes into a lattice-like network at specific regions on the cytosolic side of a membrane, thereby forming a clathrin-coated pit, which buds off to form a vesicle. (Figures 17-53 and 17-54)

Figure 17-53. Structure of a clathrin-coated vesicle. (a) A typical clathrin-coated vesicle comprises a membrane-bounded vesicle (tan) about 40 nm in diameter surrounded by a fibrous network of 12 pentagons and 8 hexagons. The fibrous coat is constructed of 36 clathrin triskelions, one of which is shown here in red. One clathrin triskelion is centered on each of the 36 vertices of the coat. Coated vesicles having other sizes and shapes are believed to be constructed similarly: each vesicle contains 12 pentagons but a variable number of hexagons. (b) Detail of a clathrin triskelion. Each of the three clathrin heavy chains has aspecific bent structure. A clathrin light chain is attached to each heavy chain near the center; a globular domain is at each distal (outer) tip. Although it is not obvious in (a) or (b), each triskelion has an intrinsic curvature; when triskelions polymerize, they form a curved (not flat) structure. (c) An intermediate in the assembly of a clathrin coat, containing 10 of the final 36 triskelions, illustrates the intrinsic curvature and the packing of the clathrin triskelions. [Part (a) see B. M. F. Pearse, 1987, EMBO J. 6:2507; part (b) see B. Pishvaee and G. Payne, 1998, Cell 95:443.]

Figure 17-54. Model for the formation of a clathrin-coated pit and the selective incorporation of integral membrane proteins into clathrin-coated vesicles. The cytosolic domains of certain membrane proteins bind specifically to assembly particles that, in turn, bind to clathrin as it polymerizes spontaneously over a region of membrane. Proteins that do not bind to assembly particles are excluded from these vesicles. Dynamin then polymerizes over the neck of the pit; regulated by dynamin-catalyzed hydrolysis of GTP, the neck pinches off, forming a clathrin-coated vesicle. Not depicted here is binding of ARF-GTP to the membrane, which is thought to initiate the process of vesicle budding as in COP I vesicles (see Figure 17-58). [Adapted from K. Takel et al., 1995, Nature 374:186.]

Figure 17-58. Model for formation of COP I¡Vcoated vesicles. Budding is initiated when molecules of ARF protein exchange their bound GDP for GTP, a reaction catalyzed by an enzyme in the Golgi membrane. After ARF-GTP binds to ARF receptors on Golgi cisternae, coatomers bind to the cytosolic face of the Golgi cisterna and polymerize into a fibrous coat that induces vesicle budding. Because they can bind to coatomer, certain integral membrane proteins are incorporated into the vesicles. These include a V-SNARE, which functions in targeting vesicles to appropriate acceptor membranes. Soluble proteins in the lumen are selected for entry into these vesicles by binding to specific membrane receptor proteins. Fatty acyl CoA is essential for the final separation of the transport vesicle from the donor membrane, but how it functions is not known. Finally, hydrolysis of GTP bound to the ARF proteins causes depolymerization of the coat and release of coatomers and ARF-GDP. [Adapted from J. E. Rothman, 1994, Nature 372:55, and J. E. Rothman and F. Wieland, 1996, Science 272:227.]

clone A population of identical cells or DNA molecules descended from a single progenitor. Also viruses or organisms that are genetically identical and descended from a single progenitor.
cloning vector An autonomously replicating genetic element used to carry a cDNA or fragment of genomic DNA into a host cell for the purpose of gene cloning. Commonly used vectors are bacterial plasmids and modified bacteriophage genomes. (Figures 7-3 and 7-12)

Figure 7-3. General procedure for cloning a DNA fragment in a plasmid vector. Although not indicated by color, the plasmid contains a replication origin and ampicillin-resistance gene. Uptake of plasmids by E. coli cells is stimulated by high concentrations of CaCl₂. Even in the presence of CaCl₂, transformation occurs with a quite low frequency, and only a few cells are transformed by incorporation of a single plasmid molecule. Cells that are not transformed die on ampicillin-containing medium. Once incorporated into a host cell, a plasmid can replicate independently of the host-cell chromosome. As a transformed cell multiplies into a colony, at least one plasmid segregates to each daughter cell.

Figure 7-12. Construction of a genomic library of human DNA in a bacteriophage £f vector. The nonessential regions in the right half of the £f genome (dotted areas in Figure 7-10b) usually are deleted to maximize the size of the exogenous DNA fragment that can be inserted. Then the £f DNA is treated to remove the central replaceable region. In this example, the replaceable region is cut out with BamHI, and the total DNA from human cells is partially digested with Sau3A. These two restriction enzymes produce fragments with complementary sticky ends (red lines). The £f vector arms and ≈20-kb genomic fragments are mixed, ligated, and packaged in vitro to produce recombinant £f phage virions, which are plated on a lawn of E. coli cells. In the diagrams of DNA regions, light and dark shades of the same color indicate complementary strands.

Figure 7-10. The bacteriophage genome. (a) Electron micrograph of bacteriophage £f virion. The genome is contained within the head. (b) Simplified map of the £f phage genome. Genes encoding proteins required for assembly of the head and tail map at the left end; those encoding additional proteins required for the lytic cycle map at the right end. Some regions of the genome can be replaced by exogenous DNA (diagonal lines) or deleted (dotted area) without affecting the ability of £f phage to infect host cells and assemble new virions, permitting insertion of up to ≈25 kb of exogenous DNA between the J and N genes. There are about 60 genes on the £f genome. Only a few individual genes are shown in this diagram. Small numbers indicate positions in kilobases (kb). [Photograph courtesy of R. Duda and R. Hendrix.]

codon Sequence of three nucleotides in DNA or mRNA that specifies a particular amino acid during protein synthesis; also called triplet. Of the 64 possible codons, three are stop codons, which do not specify amino acids. (Table 4-2)

coenzyme Small organic molecule that associates with an enzyme and participates in the reaction catalyzed by the enzyme; also called cofactor. Some coenzymes form a transient covalent bond to the substrate; others function as carriers of electrons, acyl groups, or other activated groups. Generally, a coenzyme is bound less firmly to a protein than a prosthetic group.
coenzyme A (CoA) See acetyl CoA.
coiled-coil Stable rodlike quaternary protein structure formed by two or three £\ helices interacting with each other along their length; commonly found in fibrous proteins and certain transcription factors. (Figure 3-9a)

collagen A triple-helical protein that forms fibrils of great tensile strength; a major component of the extracellular matrix and connective tissues. The numerous collagen subtypes differ in their tissue distribution and the extracellular components and cell-surface proteins with which they associate.
complementary Referring to two nucleic acid sequences or strands that can form a perfect base-paired double helix with each other; also describing regions on two interacting molecules (e.g., an enzyme and its substrate) that fit together in a lock-and-key fashion.
complementary DNA (cDNA) See cDNA.
complementation In genetics, the restoration of a wild-type function (e.g., ability to grow on galactose) in diploid heterozygotes generated from haploids, each of which carries a mutation in a different gene whose encoded protein is required for the same biochemical pathway. If two mutants with the same mutant phenotype (e.g., inability to grow on galactose) can complement each other, then their mutations are in different genes. (Figure 8-11)

Figure 8-11. Complementation analysis in S. cerevisiae. (a) Pathway used by yeast cells to metabolize galactose to glucose, which then enters the glycolytic pathway. Yeast cells must produce all four enzymes (red) in order to grow on galactose. GAL1=galactokinase; GAL7=galactose 1-phosphate uridyl transferase; GAL10=UDP-galactose 4-epimerase; GAL5=phosphoglucomutase. (b) Complementation tests can be performed with yeast by mating haploid a and £\ cells to produce diploid cells (see Figure 10-54). This example shows the results that would be obtained in complementation tests of Gal⁻ strains carrying different mutations (indicated by vertical colored lines) in the GAL1 and GAL10 genes, which encode two different enzymes required for galactose metabolism. Both of these genes are located on yeast chromosome II.

Figure 10-54. Life cycle of S. cerevisiae. Two haploid cells that differ in mating type, called a and £\, can mate to form a diploid a/£\ cell, which multiplies by budding. Under starvation conditions, diploid cells undergo meiosis, forming haploid ascospores. Rupture of an ascus releases four haploid spores, which can germinate into haploid cells. Once each generation a haploid cell is converted to the opposite mating type.

conformation The precise shape of a protein or other macromolecule in three dimensions resulting from the spatial location of the atoms in the molecule. A small change in the conformations of some proteins affects their activity considerably.
consensus sequence The nucleotides or amino acids most commonly found at each position in the sequences of related DNAs, RNAs, or proteins. See also homology.
constitutive Referring to cellular production of a molecule at a constant rate, which is not regulated by internal or external stimuli.
constitutive mutant (1) A mutant in which a protein is produced at a constant level, as if continuously induced; (2) a bacterial regulatory mutant in which an operon is transcribed in the absence of inducer; (3) a mutant in which a regulated enzyme is in a continuously active form.
cooperativity Property exhibited by some proteins with multiple ligand-binding sites whereby binding of one ligand molecule increases (positive cooperativity) or decreases (negative cooperativity) the binding affinity of successive ligand molecules.
cosmid A type of vector used to clone large DNA fragments. (Figure 7-16)

Figure 7-16. General procedure for cloning DNA fragments in cosmid vectors. This procedure has the high efficiency associated with £f phage cloning and permits cloning of restriction fragments up to ≈45 kb long. In this example, four different types of recombinant cosmid virions could be generated, each carrying one of the genomic fragments indicated by different colors. Plating of the recombinant virions on E. coli cells would yield four different types of colonies, but only one is depicted. Note that the lengths of vector DNA and genomic fragments are not to scale. See text for further discussion.

cotransport Protein-mediated transport of an ion or small molecule across a membrane against a concentration gradient driven by coupling to movement of a second molecule down its concentration gradient. See also antiport and symport.
covalent bond Stable chemical force that holds the atoms in molecules together by sharing of one or more pairs of electrons. Such a bond has a strength of 50 ¡V 200 kcal/mol. (Table 2-1)

Table 2-1. The Energy Required to Break Some Important Covalent Bonds Found in Biological Molecules*



Type of Bond	Energy (kcal/mol)	Type of Bond	Energy (kcal/mol)


SINGLE BOND		DOUBLE BOND
O¡XH	110	C=O	170
H¡XH	104	C=N	147
P¡XO	100	C=C	146
C¡XH	99	P=O	120
C¡XO	84
C¡XC	83	TRIPLE BOND
S¡XH	81	C¡ÝO	195
C¡XN	70
C¡XS	62
N¡XO	53
S¡XS	51
. Note that double and triple bonds are stronger than single bonds.*

crossing over Exchange of genetic material between maternal and paternal chromatids during meiosis to produce recombined chromosomes. (Figure 8-18) See also recombination.

Figure 8-18. Recombination during meiosis. (a) Crossing over occurs between chromatids of homologous chromosomes aligned in parallel (synapsis) during metaphase preceding the first meiotic division. (b) The longer the distance between two genes on a chromatid, the more likely they are to be separated by crossing over.

cyclic AMP (cAMP) A second messenger, produced in response to hormonal stimulation of certain G protein ¡V coupled receptors, that activates cAMP-dependent protein kinases. (Figure 20-4)

Figure 20-4. Structural formulas of four common intracellular second messengers. Their abbreviations are indicated. The calcium ion (Ca²⁺) and several membrane-bound inositol phospholipids (phosphoinositides) also act as second messengers but are not shown (see Figure 20-38).

Figure 20-38. Several second messengers are derived from phosphatidylinositol (PI). (a) Pathway for synthesis of DAG and IP₃, two important second messengers. Each membrane-bound PI kinase places a phosphate on a specific hydroxyl group on the inositol ring, producing the phosphoinositides PIP and PIP₂. Cleavage of PIP₂ by phospholipase C (PLC) yields DAG and IP₃. (b) Formation of other phosphoinositides (yellow) and inositol phosphates (blue). These reactions are catalyzed by various kinases and PLC. The pathway shown in (a) is highlighted in red. See text for discussion. [See A. Toker and L. C. Cantley, 1997, Nature 387:673-676 and C. L. Carpenter and L. C. Cantley, 1996, Curr. Opin. Cell Biol. 8:153-158.]

cyclin Any of several related proteins whose concentrations rise and fall during the course of the eukaryotic cell cycle. Cyclins form complexes with cyclin-dependent kinases, thereby activating and determining the substrate specificity of these enzymes.
cyclin-dependent kinase (Cdk) A protein kinase that is catalytically active only when bound to a cyclin. Various Cdk-cyclin complexes trigger progression through different stages of the eukaryotic cell cycle by phosphorylating specific target proteins. (Figure 13-29)

Figure 13-29. Activity of mammalian Cdkcyclin complexes through the course of the cell cycle in G₀ cells induced to divide by treatment with growth factors. The width of the colored bands is approximately proportional to the protein kinase activity of the indicated complexes. Cyclin D refers to all three D-type cyclins.

cytochromes A group of colored, heme-containing proteins that transfer electrons during cellular respiration and photosynthesis. (Figure 16-21)

Figure 16-21. Heme prosthetic groups of respiratory-chain cytochromes in mitochondria. Note the differences in substituents on the porphyrin rings. Hemes accept and release one electron at a time.

cytokine Any of numerous secreted, small proteins (e.g., interferons, interleukins) that bind to cell-surface receptors on certain cells to trigger their differentiation or proliferation.
cytokinesis The last stage of mitosis, where the two daughter cells separate, each with a nucleus and cytoplasmic organelles.
cytoplasm Viscous contents of a cell that are contained within the plasma membrane but, in eukaryotic cells, outside the nucleus.
cytoskeleton Network of fibrous elements, consisting primarily of microtubules, actin microfilaments, and intermediate filaments, found in the cytoplasm of eukaryotic cells. The cytoskeleton provides structural support for the cell and permits directed movement of organelles, chromosomes, and the cell itself.
cytosol Unstructured aqueous phase of the cytoplasm excluding organelles, membranes, and insoluble cytoskeletal components.
cytosolic face The face of a cell membrane directed toward the cytoplasm. (Figure 5-31)

Figure 5-31. Faces of cellular membranes. For organelles enclosed in two phospholipid membranes (e.g., the nucleus, chloroplast, mitochondrion), the exoplasmic faces (red) border the space between the inner and outer membranes. Chloroplasts also contain a stack of internal thylakoid membranes; the exoplasmic face of these membranes line the thylakoid lumen.

D

dalton Unit of molecular mass approximately equal to the mass of a hydrogen atom (1.66 ¡Ñ 10−24 g).
degenerate In reference to the genetic code, having more than one codon specifying a particular amino acid.
denaturation Drastic alteration in the conformation of a protein or nucleic acid due to disruption of various noncovalent bonds caused by heating or exposure to certain chemicals; usually results in loss of biological function.
dendrite Process extending from the cell body of a neuron that is relatively short and typically branched and receives signals from axons of other neurons. (Figure 21-1)

deoxyribonucleic acid See DNA.
depolarization Change in the potential that normally exists across the plasma membrane of a cell at rest, resulting in a less negative membrane potential.
desmosomes Specialized regions of the plasma membrane, consisting of dense protein plaques connected to intermediate filaments, that mediate adhesion between adjacent cells (especially epithelial cells) and between cells and the extracellular matrix. (Figure 22-6)

Figure 22-6. Desmosomes. (a) Schematic model showing components of a desmosome between epithelial cells and attachments to the sides of keratin intermediate filaments, which crisscross the interior of cells. The transmembrane linker proteins, desmoglein and desmocollin, belong to the cadherin family. (b) Electron micrograph of a thin section of a desmosome connecting two cultured differentiated human keratinocytes. Bundles of intermediate filaments radiate from the two darkly staining cytoplasmic plaques that line the inner surface of the adjacent plasma membranes. See text for discussion. [Part (a) see B. M. Gumbiner, 1993, Neuron 11:551; D. R. Garrod, 1993, Curr. Opin. Cell Biol. 5:30; Part (b) courtesy of R. van Buskirk.]

determination In embryogenesis, a change in a cell that commits the cell to a particular developmental pathway.
development Overall process involving growth and differentiation by which a fertilized egg gives rise to an adult plant or animal, including the formation of individual cell types, tissues, and organs.
diacylglycerol (DAG) Intracellular signaling molecule produced by cleavage of phosphoinositides in response to stimulation of certain cell-surface receptors; functions as a membrane-bound second messenger in inositol-lipid signaling pathways. (Figures 20-4 and 20-37)

Figure 20-37. Intracellular transduction of an extracellular signal via a cascade of sequential reactions produces a large amplification of the signal. In this example, binding of a single epinephrine molecule to one receptor molecule induces synthesis of a large number of cAMP molecules. These in turn activate multiple enzyme molecules, each of which produces multiple product molecules (e.g., active phosphorylated proteins). The more steps in such a cascade, the greater the signal amplification possible.

differentiation Process usually involving changes in gene expression by which a precursor cell becomes a distinct specialized cell type.
diploid Referring to an organism or cell having two full sets of homologous chromosomes and hence two copies (alleles) of each gene or genetic locus. Somatic cells contain the diploid number of chromosomes (2n) characteristic of a species. See also haploid.
disaccharide A small carbohydrate (sugar) composed of two monosaccharides covalently joined by a glycosidic bond. Common examples are lactose (milk sugar) and sucrose, a major photosynthetic product in higher plants.
dissociation constant (KD) See equilibrium constant.
disulfide bond ( ¡V S ¡V S ¡V ) A common covalent linkage between the sulfhydryl groups on two cysteine residues in different proteins or in different parts of the same protein; generally found only in extracellular proteins or protein domains.
DNA (deoxyribonucleic acid) Long linear polymer, composed of four kinds of deoxyribose nucleotides, that is the carrier of genetic information. In its native state, DNA is a double helix of two antiparallel strands held together by hydrogen bonds between complementary purine and pyramidine bases. (Figure 4-6)

Figure 4-6. Models of various DNA structures that are known to exist. The sugar-phosphate backbone of each chain is on the outside in all structures (one red and one blue) with the bases (silver) oriented inward. Side views are shown at the top, and views along the helical axis at the bot-tom. (a) The B form of DNA, the usual form in cells, is characterized by a helical turn every 10 base pairs (3.4 nm); adjacent stacked base pairs are 0.34 nm apart. The major and minor grooves are also visible. (b) The more compact A form of DNA has 11 base pairs per turn and exhibits a large tilt of the base pairs with respect to the helix axis. In addition, the A form has a central hole (bottom). This helical form is adopted by RNA-DNA and RNA-RNA helices. (c) Z DNA is a left-handed helix and has a zig-zag (hence ¡§Z¡¨) appearance. (d) A triple-helical structure can occur in stretches of DNA where all purines (A, G) in one strand are matched by all pyrimidines (T, C) in the other strand. Such stretches can accommodate a third polypyrimidine strand (yellow). [Courtesy of C. Kielkopf and P. B. Dervan.]

DNA cloning Recombinant DNA technique in which specific cDNAs or fragments of genomic DNA are inserted into a cloning vector, which then is incorporated into cultured host cells (e.g., E. coli cells) and maintained during growth of the host cells; also called gene cloning. (Figures 7-3 and 7-15)

Figure 7-15. Preparation of a bacteriophage £f cDNA library. A mixture of mRNAs, isolated as shown in Figure 7-14, is used to produce cDNAs corresponding to all the cellular mRNAs (steps 1 ¡V 3 ). These single-stranded cDNAs (light green) are then converted into double-stranded cDNAs, which are treated with EcoRI methylase to prevent subsequent digestion by EcoRI (steps 4 ¡V 6 ). The protected double-stranded cDNAs are ligated to a synthetic double-stranded EcoRI-site linker at both ends and then cleaved with the corresponding restriction enzyme, yielding cDNAs with sticky ends (red letters); these are incorporated into £f phage cloning vectors, and the resulting recombinant £f virions are plated on a lawn of E. coli cells (steps 7 ¡V 9 ). See text for further discussion.

DNA library Collection of cloned DNA molecules consisting of fragments of the entire genome (genomic library) or of DNA copies of all the mRNAs produced by a cell type (cDNA library) inserted into a suitable cloning vector.
DNA polymerase An enzyme that copies one strand of DNA (the template strand) to make the complementary strand, forming a new double-stranded DNA molecule. All DNA polymerases add deoxyribonucleotides one at a time in the 5¡¬n3¡¬ direction to a short pre-existing primer strand of DNA or RNA.
domain Region of a protein with a distinct tertiary structure (e.g., globular or rodlike) and characteristic activity; homologous domains may occur in different proteins.
dominant In genetics, referring to that allele of a gene expressed in the phenotype of a heterozygote; the nonexpressed allele is recessive. Also referring to the phenotype associated with a dominant allele. (See Figure 8-1)

Figure 8-1. For a recessive mutation to give rise to a mutant phenotype in a diploid organism, both alleles must carry the mutation. However, one copy of a dominant mutant allele leads to a mutant phenotype. Recessive mutations result in a loss of function, whereas dominant mutations often, but not always, result in a gain of function.

dorsal Relating to the back of an animal or the upper surface of a structure (e.g., leaf, wing).
double helix, DNA The most common three-dimensional structure for cellular DNA in which the two polynucleotide strands are anti-parallel and wound around each other with complementary bases hydrogen-bonded. (Figure 4-4a)
downstream For a gene, the direction RNA polymerase moves during transcription, which is toward the end of the template DNA strand with a 3¡¬ hydroxyl group. By convention, the +1 position of a gene is the first transcribed nucleotide; nucleotides downstream from the +1 position are designated +2, +3, etc. Also, events that occur later in a cascade of steps. See also upstream.
dynein Member of a family of ATP-powered motor proteins that move toward the (−) end of microtubules by sequentially breaking and forming new bonds with microtubule proteins. Dyneins can transport vesicles and are responsible for the movement of cilia and flagella. (Figure 19-32)

Figure 19-32. Structure of axonemal dynein. (a) Electron micrograph of freeze-etched outer-arm dynein from Tetrahymena cilia reveal three globular ¡§blossoms¡¨ connected by stems to a common base. (b) An artist's interpretation of the electron micrographs shows the arrangement of globular domains and short stalks. (c) Model showing the attachment of the outer dynein arm to the A tubule of one doublet and the cross-bridges to the B tubule of an adjacent doublet. The attachment to the A tubule is stable. In the presence of ATP, the successive formation and breakage of cross-bridges to the adjacent B tubule leads to movement of one doublet relative to the other. [Part (a) from U. W. Goodenough and J. E. Heuser, 1984, J. Mol. Biol. 18:1083.]

E

ectoderm Outermost of the three primary cell layers of the animal embryo; gives rise to epidermal tissues, the nervous system, and external sense organs. See also endoderm and mesoderm. (Figure 23-5)

Figure 23-5. Early embryogenesis of the frog Xenopus laevis. The unfertilized egg is divided into two broad hemispheres, giving it an intrinsic asymmetry. The site of sperm entry defines the ventral side of the embryo and leads to rotation of the cortical cytoplasm. Fertilization leads to rapid cell divisions and formation of the early blastula (not shown), a hollow ball of 32 cells called blastomeres. Signals from the vegetal pole induce the formation of mesodermal cells in the marginal zone (blue) separating the vegetal and animal caps in the midblastula stage. During gastrulation, mesodermal cells fold into the embryo. Signals from the invaginating mesoderm induce the development of both the underlying endoderm and neural tissue from the overlying ectoderm. The anterioposterior axis is determined by the mesoderm; cells that invaginate first induce anterior structures. Subsequent interactions between different cell populations play an important role in organogenesis. [Adapted from E. M. De Robertis et al., Sci. Am. 263(1):46.]

electron carrier Any molecule or atom that accepts electrons from donor molecules and transfers them to acceptor molecules. Most are prosthetic groups (e.g., heme, copper, iron-sulfur clusters) associated with membrane-bound proteins.
electron transport Flow of electrons via a series of electron carriers from reduced electron donors (e.g., NADH) to O2 in the inner mitochondrial membrane, or from H2O to NADP in the thylakoid membrane of plant chloroplasts. (Figure 16-17)

Figure 16-17. Stepwise flow of electrons through the electron transport chain from NADH, succinate, and FADH₂ to O₂ (blue arrows). Each of the four large multiprotein complexes in the chain is located in the inner mitochondrial membrane and contains several specific electron carriers. Coenzyme Q (CoQ) and cytochrome c transport electrons between the complexes. As shown by the redox scale, electrons pass in sequence from carriers with a lower reduction potential to those with a higher (more positive) potential. The free-energy scale shows the corresponding reduction in free energy as a pair of electrons moves through the chain. The energy released as electrons flow through three of the complexes is sufficient to power the pumping of H⁺ ions across the membrane, establishing a proton-motive force.

electrophoresis Any of several techniques for separating macromolecules based on their migration in a gel or other medium subjected to a strong electric field. (Figure 3-41)

Figure 3-41. SDS-polyacrylamide gel electrophoresis, a common technique for separating proteins at good resolution. The protein mixture first is treated with SDS, a negatively charged detergent that binds to proteins. This binding dissociates multimeric proteins and forces all polypeptide chains into dena-tured conformations with nearly identical charge:mass ratios. During electrophoresis, the SDS-protein complexes migrate through the polyacrylamide gel. Small proteins are able to move through the pores more easily, and faster, than larger proteins. Thus the proteins separate into bands according to their size as they migrate through the gel. The separated protein bands are visualized by staining with a dye.

electrophoretogram An autoradiogram of a gel in which molecules have been separated by gel electrophoresis. (Figure 7-23b)

Figure 7-23. Visualization of restriction fragments separated by gel electrophoresis. (a) Several different plasmid clones were digested with EcoRI, and the digested DNA was subjected to agarose gel electrophoresis to separate the cloned fragments from the plasmid vector DNA. Each EcoRI-cut plasmid was layered on a separate well. HindIII fragments produced by digestion of adenovirus 2 were layered in the left and right wells of the gel as size markers (M). The gel was treated with ethidium and then observed under ultraviolet light. The plasmid vector can be seen as a common band in all five clones. (b) Autoradiogram of ³²P-labeled fragments separated by polyacrylamide gel electrophoresis. Lengths of fragments are indicated at the left in base pairs. [Courtesy of Carol Eng.]

elongation factor One of a group of nonribosomal proteins required for continued translation of mRNA following initiation. (Figure 4-39)

Figure 4-39. The elongation cycle in protein synthesis visualized for E. coli ribosomes. The models of the E. coli ribosome associated with tRNAs in various states are based on cryoelectron microscopy studies and cross-linking experiments (see Figure 4-34). (a) Elongation begins on the 70S initiation complex with Met-tRNA_i^Met (green) in the P site, assembled as depicted for the eukaryotic system in Figure 4-37. Both ribosomal subunits are shown in blue. (b) A ternary complex consisting of elongation factor EF-Tu bound to GTP (orange and red) plus the correct aminoacyl-tRNA (purple) to decode the second codon then enters the ribosome. (c) Hydrolysis of EF-Tu ¡V GTP to EF-Tu ¡V GDP and P_i brings aa₂-tRNA₂^aa to the A site (purple). (d, e) After binding of EF-G ¡V GTP (dark blue), the peptidyl synthesis and translocation steps occur: Met-tRNA_i^Met (now yellow and moving out of the P site) donates its methionine to the aa₂-tRNA₂^aa (now green and in the P site), producing aa₂-tRNA₂^aa ¡V Met. Hydrolysis of the bound EF-G ¡V GTP furnishes energy for translocation, and the products are released. (f) tRNA_i^Met (now brown) moves completely to the E site and is ejected; a new ternary complex containing aa₃-tRNA₃^aa arrives and the cycle can continue (c ¡÷ d ¡÷ e ¡÷ f). [Adapted from R. K. Agrawal et al., Cell, in press.]

embryogenesis Early development of an individual from a fertilized egg (zygote). Following cleavage of the zygote, the major axes are established during the blastula stage; in the subsequent gastrula stage, the early embryo invaginates and acquires three cell layers. (Figure 23-5)

endocytosis Uptake of extracellular materials by invagination of the plasma membrane to form a small membrane-bounded vesicle (early endosome). (Figure 17-46)

Figure 17-46. Fate of an LDL particle and its receptor after endocytosis. The same pathway is followed by other ligands, such as insulin and other protein hormones, that are internalized by receptor-mediated endocytosis and degraded in the lysosome. After an LDL particle binds to an LDL receptor on the plasma membrane, the receptor-ligand complex is internalized in a clathrin-coated pit that pinches off to become a coated vesicle. The clathrin coat then depolymerizes to triskelions, resulting in an early endosome. This endosome fuses with a sorting vesicle, known as a late endosome, where the low pH (≈5) causes the LDL particles to dissociate from the LDL receptors. A receptor-rich region buds off to form a separate vesicle that recycles the LDL receptors back to the plasma membrane. A vesicle containing an LDL particle may fuse with another late endosome but ultimately fuses with a lysosome to form a larger lysosome. There, the apo-B protein of the LDL particle is degraded to amino acids and the cholesterol esters are hydrolyzed to fatty acids and cholesterol. Abundant imported cholesterol inhibits synthesis by the cell of both cholesterol and LDL receptor protein.

endoderm Innermost of the three primary cell layers of the animal embryo; gives rise to the gut and most of the respiratory tract. See ectoderm and mesoderm. (Figure 23-5)

endoplasmic reticulum (ER) Network of interconnected membranous structures within the cytoplasm of eukaryotic cells. The rough ER, which is associated with ribosomes, functions in the synthesis and processing of secretory and membrane proteins; the smooth ER, which lacks ribosomes, functions in lipid synthesis. (Figure 5-47)

Figure 5-47. Electron micrograph of a section of a rat hepatocyte showing the rough and smooth endoplasmic reticula (ERs). Note the extensive rough endoplasmic reticulum associated with numerous ribosomes (small black dots). The smooth ER lacks ribosomes. Also visible are two mitochondria (M), two peroxisomes (P), and accumulations of glycogen, a polysaccharide that is the primary glucose-storage molecule in animals. [Courtesy of P. Lazarow.]

endosome, late A sorting vesicle with an acidic internal pH in which bound ligands dissociate from their membrane-bound receptor proteins. Late endosomes participate in sorting of lysosomal enzymes and in recycling of receptors endocytosed from the plasma membrane.
endothelium Layer of highly flattened cells that forms the lining of all blood vessels and regulates exchange of materials between the bloodstream and surrounding tissues; it usually is underlain by a basal lamina.
endothermic Referring to a chemical reaction that absorbs heat (i.e., has a positive change in enthalpy).
enhancer A regulatory sequence in eukaryotic DNA (rarely in prokaryotic DNA) that may be located at a great distance from the gene it controls. Binding of specific proteins to an enhancer modulates the rate of transcription of the associated gene. (Figure 10-34)

Figure 10-34. General pattern of cis-acting control elements that regulate gene expression in yeast and multicellular organisms (invertebrates, vertebrates, and plants). (a) Genes of multicellular organisms contain both promoter-proximal elements and enhancers as well as a TATA box or other promoter element. The latter positions RNA polymerase II to initiate transcription at the start site and influences the rate of transcription. Enhancers may be either upstream or downstream and as far away as 50 kb from the transcription start site. In some cases, promoter-proximal elements occur downstream from the start site as well. (b) Most yeast genes contain only one regulatory region, called an upstream activating sequence (UAS), and a TATA box, which is ≈90 base pairs upstream from the start site.

enthalpy (H) Heat; in a chemical reaction, the enthalpy of the reactants or products is equal to their total bond energies.
entropy (S) A measure of the degree of disorder or randomness in a system; the higher the entropy, the greater the disorder.
enzyme A biological macromolecule that acts as a catalyst. Most enzymes are proteins, but certain RNAs, called ribozymes, also have catalytic activity.
epinephrine A catecholamine secreted by the adrenal gland and some neurons in response to stress; also called adrenaline. It functions as both a hormone and neurotransmitter, mediating ¡§fight or flight¡¨ responses including increased blood glucose levels and heart rate. (Figure 21-28)

epithelium Coherent sheet comprising one or more layers of cells that covers an external body surface or lines an internal cavity. (Figure 6-4)

Figure 6-4. Principal types of epithelium. The apical and basal surfaces of epithelial cells exhibit distinctive characteristics. (a) Simple squamous epithelia, composed of thin cells, line the blood vessels and many body cavities. (b) Simple columnar epithelia consist of elongated cells, including mucus-secreting cells (in the lining of the stomach and cervical tract) and absorptive cells (in the lining of the small intestine). (c) Transitional epithelia, composed of several layers of cells with different shapes, line certain cavities subject to expansion and contraction (e.g., the urinary bladder). (d) Stratified squamous (nonkeratinized) epithelia line surfaces such as the mouth and vagina; these linings resist abrasion and generally do not participate in the absorption or secretion of materials into or out of the cavity.

epitope The part of an antigen molecule that binds to an antibody; also called antigenic determinant.
equilibrium constant (K) Ratio of forward and reverse rate constants for a reaction. For a binding reaction, A + B 1 2 AB, it equals the association constant, Ka; the higher the Ka, the tighter the binding between A and B. The reciprocal of the Ka is the dissociation constant, KD; the higher the KD, the weaker the binding between A and B.
eubacteria Class of prokaryotes that constitutes one of the three distinct evolutionary lineages of modern-day organisms; also called the true bacteria or simply bacteria. Phylogenetically distinct from archaea and eukaryotes. (Figure 1-5)

euchromatin Less condensed portions of chromatin, including most transcribed regions, present in interphase chromosomes. See also heterochromatin.
eukaryotes Class of organisms, composed of one or more cells containing a membrane-enclosed nucleus and organelles, that constitutes one of the three distinct evolutionary lineages of modern-day organisms; also called eukarya. Includes all organisms except viruses and prokaryotes.
exocytosis Release of intracellular molecules (e.g., hormones, matrix proteins) contained within a membrane-bounded vesicle by fusion of the vesicle with the plasma membrane of a cell. This is the process whereby most molecules are secreted from eukaryotic cells.
exon Segments of a eukaryotic gene (or of its primary transcript) that reaches the cytoplasm as part of a mature mRNA, rRNA, or tRNA molecule. See also intron.
exoplasmic face The face of a cell membrane directed away from the cytoplasm. The exoplasmic face of the plasma membrane faces the cell exterior, whereas the exoplasmic face of organelles (e.g., mitochondria, chloroplasts, and the endoplasmic reticulum) face their lumen. (Figure 5-31)

exothermic Referring to a chemical reaction that releases heat (i.e., has a negative change in enthalpy).
expression See gene expression.
expression cloning Recombinant DNA techniques for isolating a cDNA or genomic DNA segment based on functional properties of the encoded protein and without prior purification of the protein. Also refers to techniques for producing high levels of a full-length protein once its cDNA or gene has been cloned.
expression vector A modified plasmid or virus that carries a gene or cDNA into a suitable host cell and there directs synthesis of the encoded protein. Some expression vectors are designed for screening DNA libraries for a gene of interest (Figures 7-21 and 20-9); others, for producing large amounts of a protein from its cloned gene (Figures 7-36 and 7-37).

Figure 7-21. Use of £f expression cloning to identify a cloned DNA based on binding of the encoded protein to a specific antibody. The £fgt11 vector was engineered to express the E. coli protein £]-galactosidase at high levels. The only EcoRI recognition site (red) in this vector lies near the 3¡¬ end of the £]-galactosidase gene. If a cDNA (green), or protein-coding fragment of genomic DNA, is inserted into this EcoRI site in the correct orientation and proper reading frame, it will be expressed as a fusion protein in which most of the £]-galactosidase sequence is at the N-terminal end and the protein sequence encoded by the inserted DNA is at the C-terminal end. Plaques resulting from infection with recombinant £fgtll contain high concentrations of such fusion proteins. These proteins can be transferred and bound to a replica filter, which then is incubated with a monoclonal primary antibody (blue) that recognizes the protein of interest. Rinsing the filter washes away antibody molecules that are not bound to the specific fusion protein attached to the filter. Bound antibody usually is detected by incubating the filter with a second radiolabeled antibody (dark red) that binds to the primary antibody. Any signals that appear on the autoradiogram are used to locate plaques on the master plate containing the gene of interest. [Adapted from J. D. Watson et al., 1992, Recombinant DNA,2d ed., Scientific American Books.]

Figure 20-9. Identification and isolation of a cDNA encoding a desired cell-surface receptor by plasmid expression cloning. All mRNA is extracted from cells that normally express the receptor and reverse-transcribed into double-stranded cDNA. (a) The entire population of cDNAs is inserted into plasmid expression vectors in between a strong promoter and a terminator of transcription. The plasmids are transfected into bacterial cells that do not normally express the receptor of interest. The resulting cDNA library is divided into pools, each containing about 1000 different cDNAs. (b) Plasmids in each pool are transfected into a population of cultured cells (e.g., COS cells) that lack the receptor of interest. Only transfected cells that contain the cDNA encoding the desired receptor synthesize it; other transfected cells produce irrelevant proteins. To detect the few cells producing the desired receptor, a radiolabeled ligand specific for the receptor is added to the culture dishes containing the transfected cells; the cells are fixed and subjected to autoradiography. Positive cells synthesizing the specific receptor will be covered with many grains. Alternatively, transfected cells can be treated with a fluorescent-labeled ligand and passed through a fluorescence-activated cell sorter (see Figure 5-21). Cells expressing the receptor will bind the fluorescent label and be separated from those that do not. Plasmid cDNA pools giving rise to a positive signal are maintained in bacteria and subdivided into smaller pools, each of which is rescreened by transfection into cultured cells. After several cycles of screening and subdividing positive cDNA pools, a pure cDNA clone encoding the desired receptor is obtained. [See A. Aruffo and B. Seed, 1987, Proc. Nat'l. Acad. Sci. USA 84:8573; A. D'Andrea, H. F. Lodish, and G. Wong, 1989, Cell 57:277.]

Figure 7-36. A simple E. coli expression vector utilizing the lac promoter. (a) The expression vector plasmid contains a fragment of the E. coli chromosome containing the lac promoter and the neighboring lacZ gene. In the presence of the lactose analog IPTG, RNA polymerase normally transcribes the lacZ gene, producing lacZ mRNA, which is translated into the encoded protein, £]-galactosidase. (b) The lacZ gene can be cut out of the expression vector with restriction enzymes and replaced by the G-CSF cDNA. When the resulting plasmid is transformed into E. coli cells, addition of IPTG and subsequent transcription from the lac promoter produces G-CSF mRNA, which is translated into G-CSF protein.

Figure 7-37. Two-step expression vector system based on bacteriophage T7 RNA polymerase and T7 late promoter. The chromosome of a specially engineered E. coli cell contains a copy of the T7 RNA polymerase gene under the transcriptional control of the lac promoter. When transcription from the lac promoter is induced by addition of IPTG, the T7 RNA polymerase gene is transcribed, and the mRNA is translated into the enzyme. The T7 RNA polymerase molecules produced then initiate transcription at a very high rate from the T7 late promoter on the expression vector. Multiple copies of the expression vector are present in such cells, although only one copy is diagrammed here. The large quantity of mRNA transcribed from the cDNA cloned next to the T7 late promoter is translated into abundant protein product.

extracellular matrix A usually insoluble network consisting of polysaccharides, fibrous proteins, and adhesive proteins that are secreted by animal cells. It provides structural support in tissues and can affect the development and biochemical functions of cells.
extrinsic protein See peripheral membrane protein.

F

F₀F₁ complex See ATP synthase.
facilitated transport Protein-aided transport of an ion or molecule across a cell membrane down its concentration gradient at a rate greater than that obtained by passive diffusion; also called facilitated diffusion. Such transport exhibits ligand specificity and saturation kinetics. The glucose transporter GLUT1 is a wellstudied example of a protein that mediates facilitated diffusion. (Figure 15-7)

Figure 15-7. Model of the mechanism of uniport transport by GLUT1, which is believed to shuttle between two conformational states. In one conformation ( 1 , 2 , and 5 ), the glucose-binding site faces outward; in the other ( 3 , 4 ), the binding site faces inward. Binding of glucose to the outward-facing binding site ( 1 ¡÷ 2 ) triggers a conformational change in the transporter ( 2 ¡÷ 3 ), moving the bound glucose through the protein such that it is now bound to the inward-facing binding site. Glucose can then be released to the inside of the cell ( 3 ¡÷ 4 ). Finally, the transporter undergoes the reverse conformational change ( 4 ¡÷ 5 ), inactivating the inward-facing glucose binding site and regenerating the outward-facing one. If the concentration of glucose is higher inside the cell than outside, the cycle will work in reverse ( 4 ¡÷ 1 ), catalyzing net movement of glucose from inside to out.

FAD (flavin adenine dinucleotide) A coenzyme that participates in oxidation reactions by accepting two electrons from a donor molecule and two H+ from the solution. The reduced form, FADH2, transfers electrons to carriers that function in oxidative phosphorylation. (Figure 16-8)

Figure 16-8. Structure of FAD and its reduction to FADH₂. The coenzyme flavin adenine dinucleotide (FAD) can accept one or two hydrogen atoms. The addition of one electron together with a proton (i.e., a hydrogen atom) generates a semiquinone intermediate. The semiquinone is a free radical because it contains an unpaired electron (denoted by a blue dot), which is delocalized by resonance to all the flavin ring atoms. The addition of a second electron and proton (i.e., a second hydrogen atom) generates the reduced form, FADH₂. Flavin mononucleotide (FMN) is a related coenzyme that contains only the flavin ¡V ribitol phosphate part of FAD (highlighted in blue).

fatty acid Any hydrocarbon chain that has a carboxyl group at one end; a major source of energy during metabolism and precursors for synthesis of phospholipids. (Figure 2-18)

Figure 2-18. The effect of a double bond. Shown are space-filling models and chemical structures of the ionized form of palmitic acid, a saturated fatty acid, and oleic acid, an unsaturated one. In saturated fatty acids, the hydrocarbon chain is linear; the cis double bond in oleate creates a kink in the hydrocarbon chain. [After L. Stryer, 1994, Biochemistry, 4th ed., W. H. Freeman and Company, p. 265.]

fertilization Fusion of a female and male gamete (both haploid) to form a diploid zygote, which develops into a new individual.
fibroblast A common type of connective-tissue cell that secretes collagen and other components of the extracellular matrix. It migrates and proliferates during wound healing and in tissue culture.
fibronectin An extracellular multiadhesive protein that binds to other matrix components, fibrin, and cell-surface receptors of the integrin family. It functions to attach cells to the extracellular matrix and is important in wound healing. (Figure 22-22)

Figure 22-22. Structure of fibronectin chains. Only one of the two chains present in the dimeric fibronectin molecule is shown; both chains have very similar sequences. Each chain contains about 2446 amino acids and is composed of three types of repeating amino acid sequences. Circulating fibronectin lacks one or both of the type III repeats designated EDA and EDB owing to alternative mRNA splicing. At least five different sequences may occur in the IIICS region as the result of alternative splicing. Each chain contains six domains (tan ovals) containing specific binding sites for heparan sulfate, fibrin (a major constituent of blood clots), denatured forms of collagen, and cell-surface integrins. Binding to integrins is dependent on an Arg-Gly-Asp (RGD) sequence. Heparan sulfate and fibrin have binding sites in a shared domain, and each has another binding site in its own, unshared domain; these sites differ in their affinity for the ligand. [Adapted from G. Paolella, M. Barone, and F. Baralle, 1993, in M. Zern and L. Reid, eds., Extracellular Matrix, Marcel Dekker, pp. 3 ¡V 24.]

flagellum (pl. flagella) Long locomotory structure, extending from the surface of a eukaryotic cell, whose whiplike bending propels the cell forward or backward. Usually there is only one flagellum per cell (as in sperm cells). Bacterial flagella are smaller and much simpler structures. See also axoneme and cilium.
fluorescein See fluorescent staining.
fluorescent staining General technique for visualizing cellular components by treating cells with a fluorescent-labeled agent that binds specifically to a component of interest and then observing the cells by fluorescence microscopy. For instance, an antibody specific for a protein of interest can be chemically linked to a fluorescent dye such as fluorescein, which emits green light, or rhodamine, which emits red light. Various fluorescent dyes that bind specifically to DNA are used to detect chromosomes or specific chromosomal regions.
footprinting Technique for identifying protein-binding regions of DNA or RNA. A radiolabeled nucleic acid sample is digested with a nuclease in the presence and absence of a specific binding protein. Because regions of DNA or RNA with bound protein are protected from digestion, the patterns of fragment bands separated by gel electrophoresis obtained from protected and unprotected samples differ, permitting identification of the protein-binding regions. (Figure 10-6)

Figure 10-6. DNase I footprinting, a common technique for identifying protein-binding sites in DNA. (Top) A DNA fragment is labeled at one end with ³²P (red dot) as in the Maxam-Gilbert sequencing method (see Figure 7-25). Portions of the sample then are digested with DNase I in the presence and absence of a protein that binds to a specific sequence in the fragment. DNase I randomly hydrolyzes the phosphodiester bonds of DNA between the 3¡¬ oxygen on the deoxyribose of one nucleotide and the 5¡¬ phosphate of the next nucleotide. A low concentration of DNase I is used so that on average each DNA molecule is cleaved just once (vertical arrows). In the absence of a DNA-binding protein, the sample is cleaved at all possible positions between the labeled and unlabeled ends of the original fragment. The two samples of DNA then are separated from protein, denatured to separate the strands, and electrophoresed. The resulting gel is analyzed by autoradiography, which detects only labeled strands and reveals fragments extending from the labeled end to the site of cleavage by DNase I. (Bottom) Diagram of hypothetical autoradiogram of the gel for the minus protein sample above reveals bands corresponding to all possible fragments produced by DNase I cleavage (−lane). In the sample digested in the presence of a DNA-binding protein, two bands are missing (+lane); these correspond to the DNA region protected from digestion by bound protein and are referred to as the footprint of that protein. This protected region can be precisely aligned with the DNA sequence if sequencing reactions are performed on the original end-labeled DNA and the products electrophoresed on the same gel. In this example, the products of four Maxam-Gilbert sequencing reactions are shown.

free energy (G) A measure of the potential energy of a system, which is a function of the enthalpy (H) and entropy (S).
free-energy change (£GG) The difference in the free energy of the product molecules and of the starting molecules (reactants) in a chemical reaction. A large negative value of £GG indicates that a reaction has a strong tendency to occur; that is, at chemical equilibrium the concentration of products will be much greater than the concentration of reactants.

G

G protein Any of numerous heterotrimeric GTP-binding proteins that function in intracellular signaling pathways; usually activated by ligand binding to a coupled seven-spanning receptor on the cell surface. See also GTPase superfamily. (Table 20-5)

Table 20-5. Properties of Mammalian G Proteins Linked to GPCRs



G_£\ Subclass*	Effect	Associated Effector Protein	2nd Messenger


G_s	¡ô	Adenylyl cyclase	cAMP
	¡ô	Ca²⁺ channel	Ca²⁺
	¡õ	Na⁺ channel	Change in membrane potential
G_i	¡õ	Adenylyl cyclase	cAMP
	¡ô	K⁺ channel	Change in membrane potential
	¡õ	Ca²⁺ channel	Ca²⁺
G_q	¡ô	Phospholipase C	IP₃, DAG
G_o	¡ô	Phospholipase C	IP₃, DAG
	¡õ	Ca²⁺ channel	Ca²⁺
G_t	¡ô	cGMP phosphodiesterase	cGMP
G_b£^	¡ô	Phospholipase C	IP₃, DAG
	¡õ	Adenylyl cyclase	cAMP
. A given G_£\ may be associated with more than one effector protein. To date, only one major G_s£\ has been identified, but multiple G_q£\ and G_i£\ proteins have been described. In some cases (not indicated in this table) effector proteins are regulated by coincident binding to G_a and G_b£^. KEY: ¡ô = stimulation; ¡õ = inhibition. IP₃ = inositol 1,4,5-trisphosphate; DAG = 1,2-diacylglycerol. SOURCE: See A. C. Dolphin, 1987, Trends Neurosci.* 10:53; L. Birnbaumer, 1992, Cell 71:1069.

G protein¡Vcoupled receptor (GPCR) Member of an important class of cell-surface receptors that have seven transmembrane £\ helices and are directly coupled to a trimeric G protein. (Figure 20-16)

Figure 20-16. Activation of adenylyl cyclase following binding of an appropriate hormone (e.g., epinephrine, glucagon) to a G_s protein ¡V coupled receptor. Following ligand binding to the receptor, the G_s protein relays the hormone signal to the effector protein, in this case adenylyl cyclase. G_s cycles between an inactive form with bound GDP and an active form with bound GTP. Dissociation of the active form yields the G_s£\ ¡P GTP complex, which directly activates adenylyl cyclase. Activation is short-lived because GTP is rapidly hydrolyzed (step 5 ). This terminates the hormone signal and leads to reassembly of the inactive G_s ¡P GDP form, returning the system to the resting state. Binding of another hormone molecule causes repetition of the cycle. Both the G_£^ and G_s£\ subunits are linked to the membrane by covalent attachment to lipids. Binding of the activated receptor to G_s£\ promotes dissociation of GDP and its replacement with GTP.

G₀, G₁, G₂phase See cell cycle.
gamete Specialized haploid cell (in animals either a sperm or an egg) produced by meiosis of germ cells; in sexual reproduction, union of a sperm and an egg initiates the development of a new individual.
ganglion (pl. ganglia) Collection of neuron cell bodies located outside of the central nervous system.
ganglioside Any glycolipid containing one or more N-acetylneuraminic acid (sialic acid) residues in its structure. Gangliosides are found in the plasma membrane of eukaryotic cells and confer a net negative charge on most animal cells.
gap junction Protein-lined channel between adjacent cells that allows passage of ions and small molecules between the cells. (Figure 22-8)

Figure 22-8. Structure of gap junctions. (a) In this model, a gap junction is a cluster of channels between two plasma membranes that are separated by a gap of about 2 ¡V 3 nm. (b) Both membranes contain connexon hemichannels, cylinders of six dumbbell-shaped connexin subunits. (c) Each connexin subunit has four transmembrane £\ helices. Two connexons join in the gap between the cells to form a gap-junction channel, 1.5 ¡V 2.0 nm in diameter, that connects the cytoplasm of the two cells.

gastrula An early embryonic form subsequent to the blastula characterized by invagination of the cells to form a rudimentary gut cavity and development of three cell layers.
gene Physical and functional unit of heredity, which carries information from one generation to the next. In molecular terms, it is the entire DNA sequence ¡X including exons, introns, and noncoding transcription-control regions ¡X necessary for production of a functional protein or RNA. See also cistron and transcription unit.
gene cloning See DNA cloning.
gene control All of the mechanisms involved in regulating gene expression. Most common is regulation of transcription, although mechanisms influencing the processing, stabilization, and translation of mRNAs help control expression of some genes.
gene conversion Phenomenon in which one allele of a gene is converted to another during meiotic recombination.
gene expression Overall process by which the information encoded in a gene is converted into an observable phenotype (most commonly production of a protein).
genetic code The set of rules whereby nucleotide triplets (codons) in DNA or RNA specify amino acids in proteins. (See Table 4-2)

Table 4-2. The Genetic Code (RNA to Amino Acids)*

genome Total genetic information carried by a cell or organism.
genomic DNA All the DNA sequences composing the genome of a cell or organism. See also cDNA.
genomics Comparative analysis of the complete genomic sequences from different organisms; used to assess evolutionary relations between species and to predict the number and general types of proteins produced by an organism.
genotype Entire genetic constitution of an individual cell or organism; also, the alleles at one or more specific loci.
germ cell Any precursor cell that can give rise to gametes. See also somatic cell.
germ line Lineage of germ cells, which give rise to gametes and thus participate in formation of the next generation of organisms; also the genetic material transmitted from one generation to the next through the gametes.
glial cells Nonexcitable supportive cells in the nervous system; also called neuroglial cells. Include astrocytes and oligodendrocytes in the vertebrate central nervous system and Schwann cells in the peripheral nervous system.
glucagon A peptide hormone produced in the £\ cells of the pancreas that triggers the conversion of glycogen to glucose by the liver; acts with insulin to control blood glucose levels. (Figure 20-45)

Figure 20-45. Activation of protein kinase B by the Ras-independent insulin signaling pathway. The insulin receptor is a dimeric RTK. Step 1: Insulin binding to the receptor leads to a conformational change that induces autophosphorylation, similar to activation of other RTKs (see Figure 20-21). After IRS1 binds to a phosphotyrosine residue through a PTB domain, the activated kinase in the receptor's cytosolic domain phosphorylates IRS1. One subunit of PI-3 kinase binds to the receptor-bound IRS1 via its SH2 domain, and the other subunit then phosphorylates PI 4,5-bisphosphate and PI 4-phosphate to PI 3,4,5- trisphosphate and PI 3,4-biphosphate, respectively. Step 2 : The phosphoinositides bind the PH domain of protein kinase B (PKB), thereby recruiting it to the membrane. Two membrane-bound kinases, in turn, phosphorylate membrane-associated PKB and activate it. Step 3: Activated PKB is released from the membrane and promotes glucose uptake by the GLUT4 transporter and glycogen synthesis. The former effect results from translocation of the GLUT4 glucose transporter from intracellular vesicles to the plasma membrane. The latter effect occurs by PKB-catalyzed phosphorylation of glycogen synthase kinase 3 (GSK3), converting it from its active to inactive form. As a result, GSK3-mediated inhibition of glycogen synthase is relieved, promoting glycogen synthesis. [See from J. Downward, 1998, Curr. Opin. Cell Biol. 10:262.]

glucose Six-carbon monosaccharide (sugar) that is the primary metabolic fuel in most cells. The large glucose polymers, glycogen and starch, are used to store energy in animal cells and plant cells, respectively.
glycocalyx Carbohydrate-rich layer covering the outer surface of the plasma membrane of eukaryotic cells; composed of membrane glycolipids, the oligosaccharide side chains of integral membrane proteins, and absorbed peripheral membrane proteins.
glycogen A very long, branched polysaccharide, composed exclusively of glucose units, that is the primary storage carbohydrate in animal cells. It is found primarily in liver and muscle cells.
glycogenolysis Breakdown of glycogen to glucose 6-phosphate; stimulated by a rise in cAMP following epinephrine stimulation of cells and, in muscle, by a rise in Ca²⁺ following neuronal stimulation. (Figure 20-43)

Figure 20-43. Multiple regulation of effector proteins mediated by G protein ¡V coupled receptors. Different isoforms of an effector protein (E), such as adenylyl cyclase or phospholipase C, have different binding affinities for the G_£\ ¡P GTP complex and G_£]£^, leading to stimulation or inhibition by various G subunits. See text for details

glycolipid Any lipid to which a short carbohydrate chain is covalently linked; commonly found in the plasma membrane.
glycolysis Metabolic pathway whereby sugars are degraded anaerobically to lactate or pyruvate in the cytosol with the production of ATP; also called Embden-Meyerhof pathway. (Figure 16-3)

Figure 16-3. The glycolytic pathway by which glucose is degraded to pyruvic acid. Reactions in which ATP and ADP are involved are highlighted in blue; the reaction involving NAD and NADH is highlighted in yellow. Note that all the intermediates between glucose and pyruvate are phosphorylated compounds.

glycoprotein Any protein to which one or more oligosaccharide chains are covalently linked. Most secreted proteins and many membrane proteins are glycoproteins.
glycosaminoglycan (GAG) A long, linear, highly charged polymer of a repeating disaccharide in which one member of the pair usually is a sugar acid (uronic acid) and the other is an amino sugar and many residues are sulfated. Generally are covalently bound to core proteins forming proteoglycans, which are major components of the extracellular matrix. (Figure 22-24)

Figure 22-24. Structures of various glycosaminoglycans, the polysaccharide components of proteoglycans. Each of the four classes of glycosaminoglycans is formed by polymerization of a specific disaccharide and subsequent modifications including addition of sulfate groups and inversion (epimerization) of the carboxyl group on carbon 5 of D-glucuronic acid to yield L-iduronic acid. Heparan sulfate, which is ubiquitous, and its derivative heparin, found mostly in mast cells, are actually complex mixtures resulting from the degree of sulfation. Hyaluron is unsulfated. The number (n) of disaccharides typically found in each glycosaminoglycan chain is given.

glycosidic bond The covalent linkage between two monosaccharide residues formed by a condensation reaction in which one carbon, usually carbon #1, of one sugar reacts with a hydroxyl group on a second sugar with the loss of a water molecule. (Figure 2-10)

Figure 2-10. The formation of glycosidic linkages generate the disaccharides lactose and sucrose. The lactose linkage is £](1 ¡÷ 4); the sucrose linkage is £\(1 ¡÷ 2). In any glycosidic linkage, carbon 1 of one sugar molecule (in either the £\ or £] conformation) is linked to a hydroxyl oxygen on another sugar molecule.

glycosyl transferase An enzyme that forms a glycosidic bond between a sugar residue (monosaccharide) and an amino acid side chain of a protein or a residue in an existing carbohydrate chain.
Golgi complex Stacks of membranous structures in eukaryotic cells that function in processing and sorting of proteins and lipids destined for other cellular compartments or for secretion; also called Golgi apparatus. (Figure 5-49)

Figure 5-49. Three-dimensional model of the Golgi complex built by analyzing micrographs of serial sections through a secretory cell. Transfer vesicles that have budded off from the rough ER fuse with the cis membranes of the Golgi complex. In pancreatic acinar cells, the secretory vesicles that form by budding off of sacs on the trans membranes store secretory proteins, such as chymotrypsinogen, in concentrated form. Other vesicles, detailed in Chapter 17, move material from one part of the Golgi to another. [After a model by J. Kephart.]

growing fork Site in double-stranded DNA at which the template strands are separated and addition of deoxyribonucleotides to each newly formed chain occurs; also called replication fork. (Figure 12-9)

Figure 12-9. At a growing fork, one strand is synthesized from multiple primers. (a) The overall structure of a growing fork. Synthesis of the leading strand, catalyzed by DNA polymerase III, occurs by sequential addition of deoxyribonucleotides in the same direction as movement of the growing fork. (b) Steps in the discontinuous synthesis of the lagging strand. This process requires multiple primers, two DNA polymerases, and ligase, which joins the 3¡¬-hydroxyl end of one (Okazaki) fragment to the 5¡¬-phosphate end of the adjacent fragment. (c) DNA ligation. During this reaction, ligase transiently attaches covalently to the 5¡¬ phosphate of one DNA strand, thus activating the phosphate group. E. coli DNA ligase uses NAD⁺as cofactor, generating NMN and AMP, whereas bacteriophage T4 ligase, commonly used in DNA cloning, uses ATP, generating PP_i and AMP.

growth factor An extracellular polypeptide molecule that binds to a cell-surface receptor triggering an intracellular signaling pathway leading to proliferation, differentiation, or other cellular response.
GTP (guanosine 5¡¬-triphosphate) A nucleotide that is a precursor in RNA synthesis and also plays a special role in protein synthesis, signal-transduction pathways, and microtubule assembly.
GTPase superfamily Group of GTP-binding proteins that cycle between an inactive state with bound GDP and an active state with bound GTP. These proteins ¡X including G proteins, Ras proteins, and certain polypeptide elongation factors ¡X function as intracellular switch proteins. (Figure 20-22)

Figure 20-22. Cycling of the Ras protein between the inactive form with bound GDP and the active form with bound GTP occurs in four steps. By mechanisms discussed later, binding of certain growth factors to their receptors induces formation of the active Ras ¡P GTP complex. Step 1: Guanine nucleotide ¡V exchange factor (GEF) facilitates dissociation of GDP from Ras. Step 2: GTP then binds spontaneously, and GEF dissociates yielding the active Ras ¡P GTP form. Steps 3and 4: Hydrolysis of the bound GTP to regenerate the inactive Ras ¡P GDP form is accelerated a hundredfold by GTPase-activating protein (GAP). Unlike G_£\, cycling of Ras thus requires two proteins, GEF and GAP; otherwise, G_£\ and Ras exhibit many common features.

H

haploid Referring to an organism or cell having only one member of each pair of homologous chromosomes and hence only one copy (allele) of each gene or genetic locus. Gametes and bacterial cells are haploid. See also diploid.
HeLa cell Line of human epithelial cells, derived from a human cervical carcinoma, that grows readily in culture and is widely used in research.
helicase Any enzyme that moves along a DNA duplex using the energy released by ATP hydrolysis to separate (unwind) the two strands. Required for the replication and transcription of DNA.
helix-loop-helix A conserved structural motif found in many monomeric Ca²⁺-binding proteins and dimeric eukaryotic transcription factors. (Figure 3-9b)

helix-turn-helix A DNA-binding motif found in most bacterial DNA-binding proteins.
heterochromatin Regions of chromatin that remain highly condensed and transcriptionally inactive during interphase.
heteroduplex A double-stranded DNA molecule containing one or more mispaired bases.
heterokaryon Cell with more than one functional nucleus produced by the fusion of two or more different cells.
heterozygous Referring to a diploid cell or organism having two different alleles of a particular gene.
hexose A six-carbon monosaccharide.
high-energy bond Covalent bond that releases a large amount of energy when hydrolyzed under the usual intracellular conditions. Examples include the phosphoanhydride bonds in ATP, thioester bond in acetyl CoA, and various phosphate ester bonds. (Table 2-7)

Table 2-7. Values of £GG¢X¡¬ for the Hydrolysis of Various Biologically Important Phosphate Compounds*

histones A family of small, highly conserved basic proteins, found in the chromatin of all eukaryotic cells, that associate with DNA in the nucleosome.
Holliday structure Intermediate structure in recombination between homologous chromosomes. (Figures 12-29 and 12-30)

Figure 12-29. Holliday model of genetic recombination. Genetically distinct homologous chromosomes (i.e., double-stranded DNA molecules) are indicated by red and blue; alleles are indicated by capital and lowercase letters (A, a). Complementary DNA strands are distinguished by darker and lighter shades and by the presence or absence of prime signs (A, A¡¬; a, a¡¬). Resolution of the crossed-strand Holliday structure could occur by two different pathways. Steps 4 and 5a or 6 , 7a , and 8a would yield spliced products that exhibit recombination from AC/ac to Ac/aC, with heteroduplex DNA containing the B locus in between. Although step 5b or steps 7b and 8b also resolve the connected strands of the Holliday structure, the resulting patched products are not recombinants, since all markers surrounding the crossover site, that is, to the left of A and to the right of C, are derived from the same initial chromosome. However, these molecules are heteroduplex for the B segment, and as each of these DNA molecules is duplicated, half the progeny will have the B genetic marker and half will have b. [Steps 1 ¡V 5, see R. Holliday, 1964, Genet. Res. 5:282; steps 6, 7a, 7b, 8a, and 8b see D. Dressler and H. Potter, 1982, Ann. Rev. Biochem. 51:727; also see M. Meselson and C. M. Radding, 1975, Proc. Nat'l Acad. Sci. USA 72:358; and N. Sigal and B. Alberts, 1972, J. Mol. Biol. 71:769.]

Figure 12-30. Electron micrographs of plasmid DNA in the process of recombination. (a) Circular plasmid DNA in crossed-strand Holliday structure. (b) More highly magnified view reveals single-stranded ring in center of isomeric Holliday structure that results from rotation about the crossover point. [See H. Potter and D. Dressler, 1978, Cold Spring Harbor Symp. Quant. Biol. 43:969; courtesy of D. Dressler.]

homeobox Conserved DNA sequence that encodes a DNAbinding domain (homeodomain) in a class of transcription factors encoded by certain homeotic genes.
homeodomain A conserved DNA-binding motif found in many developmentally important transcription factors. See also homeobox.
homeosis Transformation of one body part into another arising from mutation in or misexpression of certain developmentally critical genes.
homeotic gene A gene in which mutations cause cells in one region of the body to act as though they were located in another, giving rise to conversions of one cell, tissue, or body region into another.
homologous chromosome One of the two copies of each morphologic type of chromosome present in a diploid cell; also called homologue. Each homologue is derived from a different parent.
homologue See homologous chromosome.
homology Similarity in the sequence of a protein or nucleic acid or in the structure of an organ that reflects a common evolutionary origin. Molecules or sequences that exhibit homology are referred to as homologs. In contrast, analogy is a similarity in structure or function that does not reflect a common evolutionary origin.
homozygous Referring to a diploid cell or organism having two identical alleles of a particular gene.
hormone General term for any extracellular substance that induces specific responses in target cells. Hormones coordinate the growth, differentiation, and metabolic activities of various cells, tissues, and organs in multicellular organisms.
Hox complex Clusters of homologous selector genes, which help determine the body plan in animals.
hyaluronan A large, highly hydrated polysaccharide that is a major component of the extracellular matrix; also called hyaluronic acid and hyaluronate. It imparts stiffness and resilience as well as a lubricating quality to many types of connective tissue.
hybridization Association of two complementary nucleic acid strands to form double-stranded molecules, which can contain two DNA strands, two RNA strands, or one DNA and one RNA strand. Used experimentally in various ways to detect specific DNA or RNA sequences.
hybridoma A clone of hybrid cells that are immortal and produce monoclonal antibodies; formed by fusion of normal antibody-producing B lymphocytes with myeloma cells. (Figure 6-10)

Figure 6-10. Procedure for producing a monoclonal antibody to protein X. Immortal myeloma cells that lack HGPRT, an enzyme of the purine-salvage pathway (see Figure 6-9), are fused with normal antibody-producing spleen cells from an animal that was immunized with protein X. The spleen cells can make HGPRT. When plated in HAT medium, the unfused cells do not grow: the mutant myeloma cells because they cannot make purines via the salvage pathway, and the spleen cells because they have a limited life span in culture. Thus only fused cells, formed from a myeloma cell and a spleen cell, survive on HAT medium, proliferating into clones called hybridomas. Each hybridoma produces a single antibody. Once a hybridoma that produces a desired antibody is identified, the clone can be cultured to yield large amounts of that antibody.

hydrogen bond A noncovalent bond between an electronegative atom (commonly oxygen or nitrogen) and a hydrogen atom covalently bonded to another electronegative atom. Particularly important in stabilizing the three-dimensional structure of proteins and formation of base pairs in nucleic acids.
hydrolysis Reaction in which a covalent bond is cleaved with addition of an H from water to one product of the cleavage and of an OH from water to the other.
hydrophilic Interacting effectively with water. See also polar.
hydrophobic Not interacting effectively with water; in general, poorly soluble or insoluble in water. See also nonpolar.
hydrophobic bond The force that drives nonpolar molecules or parts of molecules to associate with each other in aqueous solution. A type of noncovalent bond that is particularly important in stabilization of the phospholipid bilayer.
hypertonic Referring to an external solution whose solute concentration is high enough to cause water to move out of cells due to osmosis.
hypotonic Referring to an external solution whose solute concentration is low enough to cause water to move into cells due to osmosis.

I

immunoglobulin (Ig) Any protein that functions as an antibody. The five major classes of vertebrate immunoglobulins (IgA, IgD, IgE, IgG, and IgM) differ in their specific functions in the immune response.
in vitro Denoting a reaction or process taking place in an isolated cell-free extract; sometimes used to distinguish cells growing in culture from those in an organism.
in vivo In an intact cell or organism.
induction In embryogenesis, a change in the developmental fate of one cell or tissue caused by direct interaction with another cell or tissue or with an extracellular signaling molecule; in metabolism, an increase in the synthesis of an enzyme or series of enzymes mediated by a specific molecule (inducer).
initiation factor One of a group of proteins that promote the proper association of ribosomes and mRNA and are required for initiation of protein synthesis. (Figure 4-37)

Figure 4-37. Eukaryotic initiation of protein synthesis. Establishment of the initiation complex must follow a precise sequence of events, and the large and small ribosomal subunits must be kept apart until late in the process. Two eukaryotic factors, eIF3 (a large multimeric protein with about eight subunits) and eIF6 fulfill this role. A 43S preinitiation complex is formed when a ternary complex of eIF2 bound to GTP and Met-tRNA_i^Met associates with the small (40S) ribosomal subunit, which is complexed with two other factors, eIF3 and eIF1A, that stabilize binding of the ternary complex. (The inactive eIF2-GDP fails to bind Met-tRNA_i^Met; it also can be phosphorylated, thereby inhibiting protein initiation.) The 5' cap (m⁷G) of the mRNA to be translated is guided to the preinitiation complex by a subunit of the multiprotein eIF4 complex, which also unwinds any secondary structure at the 5' end of the mRNA. Subsequent scanning by the small ribosomal subunit, assisted by eIF3 and eIF4G, positions the initiator tRNA at the AUG start codon, yielding the 40S initiation complex and releasing eIF1A, eIF3, and eIF4. With the Met-tRNA_i^Met properly positioned at the start codon, another factor, eIF5, assists union of the 40S complex with the 60S subunit. Hydrolysis of GTP in eIF2-GTP provides the energy for this step. Factors eIF5 and eIF2-GDP are then released, yielding the final 80S initiation complex, with Met-tRNA_i^Met at the P site. The complex can now accept the second aminoacyl-tRNA (see Figure 4-40).

Figure 4-40. Termination of translation. When a ribosome bearing a nascent protein chain reaches a stop codon (UAA, UGA, UAG), release factors (RFs) enter the ribosomal complex, probably at or near the A site. In bacteria, RF1 or RF2 first recognizes a stop codon. RF3-GTP then catalyzes cleavage of the peptide chain from the tRNA and release of the two ribosomal subunits, reactions that require hydrolysis of GTP.

initiator A eukaryotic promoter sequence for RNA polymerase II that specifies transcription initiation within the sequence.
insulin A protein hormone produced in the £] cells of the pancreas that stimulates uptake of glucose into muscle and fat cells and with glucagon helps to regulate blood glucose levels (Figure 20-45). Insulin also functions as a growth factor for many cells.

integral membrane protein Any membrane-bound protein all or part of which interacts with the hydrophobic core of the phospholipid bilayer and can be removed from the membrane only by extraction with detergent; also called intrinsic membrane protein. (Figure 3-32)

Figure 3-32. Schematic diagram of typical membrane proteins in a biological membrane. The phospholipid bilayer, the basic structure of all cellular membranes, consists of two leaflets of phospholipid molecules whose fatty acyl tails form the hydrophobic interior of the bilayer; their polar, hydrophilic head groups line both surfaces. Most integral proteins span the bilayer as shown; a few are tethered to one leaflet by a covalently attached lipid anchor group. Peripheral proteins are primarily associated with the membrane by specific protein-protein interactions. Oligosaccharides bind mainly to membrane proteins; however, some bind to lipids, forming glycolipids.

integrins A large family of heterodimeric transmembrane proteins that promote adhesion of cells to the extracellular matrix or to the surface of other cells.
interferons (IFNs) Small group of cytokines that bind to cell- surface receptors on target cells inducing changes in gene expression leading to an antiviral state or other cellular responses important in the immune response.
intermediate filaments Cytoskeletal fibers (10 nm in diameter) formed by polymerization of several classes of cell-specific subunit proteins including keratins, lamins, and vimentin. They constitute the major structural proteins of skin and hair; form the scaffold that holds Z disks and myofibrils in place in muscle; and generally function as important structural components of many animal cells and tissues.
interphase Long period of the cell cycle, including the G1, S, and G2 phases, between one M (mitotic) phase and the next. (Figure 13-1)

Figure 1-10. Cell division. A parental cell in G₁ has two copies of each chromosome (2n), one maternal (red) and one paternal (blue). Chromosomes are replicated during the S phase, giving a 4n chromosomal complement. At the midpoint of mitosis (metaphase), the replicated chromosomes are aligned and held in position by the mitotic apparatus. The two identical chromatids composing each replicated chromosome then move to opposite ends of the cell, the nuclear membrane re-forms around each set of chromosomes, and finally cytokinesis splits the cell into two genetically identical daughter cells.

intrinsic protein See integral membrane protein.
intron Part of a primary transcript (or the DNA encoding it) that is removed by splicing during RNA processing and is not included in the mature, functional mRNA, rRNA, or tRNA; also called intervening sequence.
ion channel Any transmembrane protein complex that forms a water-filled channel across the phospholipid bilayer allowing selective ion transport down its electrochemical gradient. See also ion pump.
ion pump Any transmembrane ATPase that couples hydrolysis of ATP to the transport of a specific ion across the phospholipid bilayer against its electrochemical gradient. (Table 15-2)

Table 15-2. Comparison of Major Classes of ATP-Powered Ion and Small-Molecule Pumps



P Class	F Class	V Class	ABC Class


Substances Transported

H⁺, Na⁺, K⁺, Ca²⁺	H⁺ only	H⁺ only	Ions and various small molecules
Structural and Functional Features

Large catalytic £\ subunits (often two) become phosphorylated during solute transport; smaller £] subunits may regulate transport.	Multiple transmembrane and cytosolic subunits generally function to synthesize ATP on £] cytosolic subunits powered by movement of H⁺ down an electrochemical gradient.	Multiple transmembrane and cytosolic subunits generally use energy released by ATP hydrolysis to pump H⁺ ions from cytosol to organelle lumens, acidifying them.	Two transmembrane domains form the pathway for solute; two cytosolic ATP-binding domains couple ATP hydrolysis to solute movement. Domains may be in one or separate subunits.
Location of Specific Pumps

Plasma membrane of plants, fungi, bacteria (H⁺ pump)	Bacterial plasma membranes	Vacuolar membranes in plants, yeast, other fungi	Bacterial plasma membranes (amino acid, sugar, and peptide transporters)
Plasma membrane of higher eukaryotes (Na⁺/K⁺ pump)	Inner mitochondrial membrane	Endosomal and lysosomal membrane in animal cells	Mammalian endoplasmic reticulum (transporters of peptides associated with antigen presentation by MHC proteins)
Apical plasma membrane of mammalian stomach cells (H⁺/K⁺ pump)	Thylakoid membrane of chloroplast	Plasma membrane of certain acid-secreting animal cells (e.g., osteoclasts and some kidney tubule cells)
Plasma membrane of all eukaryotic cells (Ca²⁺ pump)			Mammalian plasma membranes (transporters of small molecules, phospholipids, small lipidlike drugs)
Sarcoplasmic reticulum membrane in muscle cells (Ca²⁺ pump)

ionic bond A noncovalent bond between a positively charged ion (cation) and negatively charged ion (anion).
isoelectric focusing Technique for separating molecules by gel electrophoresis in a pH gradient subjected to an electric field. A protein migrates to the pH at which its overall net charge is zero.
isoelectric point (pI) The pH of a solution at which a dissolved protein or other potentially charged molecule has a net charge of zero and therefore does not move in an electric field.
isoform One of several forms of the same protein whose amino acid sequences differ slightly but whose general activity is identical.
isotonic Referring to a solution whose solute concentration is such that it causes no net movement of water in or out of cells.

K

karyotype Number, sizes, and shapes of the entire set of metaphase chromosomes of a eukaryotic cell. (Figure 9-33)

Figure 9-33. Karyotypes of the Reeves muntjac (a) and the Indian muntjac (b), two species of small deer that are quite similar but do not interbreed. Despite the difference in the number of chromosomes in these animals, the two genomes contain about the same total amount of DNA. (The chromosomes from both deer are shown at the same magnification.) A karyotype is obtained by treating a metaphase cell with a DNA-staining reagent and then ¡§squashing¡¨ the cell on a microscope slide. The homologous chromosomes identified in photographs of the specimen are cut out and remounted in pairs. Each number indicates a homologous pair, and the entire set constitutes the karyotype. [Part (a) (left) courtesy of K. W. Fink/Photo Researchers, Inc.; part (b) (left) courtesy of J. P. Ferrero/Jacana/Photo Researchers, Inc.; both karyotype photographs courtesy of R. Church.]

kinase An enzyme that transfers the terminal (£^) phosphate group from ATP to a substrate. Protein kinases, which phosphorylate specific serine, threonine, or tyrosine residues in target proteins, play a critical role in regulating the activity of many cellular proteins. See also phosphatases.
kinesin Member of a family of motor proteins that use energy released by ATP hydrolysis to move toward the (+) end of a microtubule, transporting vesicles or particles in the process. (Figure 19-24)

Figure 19-24. Model of kinesin-catalyzed anterograde transport. (a) Kinesin-motored transport of vesicles along immobile microtubules. The kinesin molecules, attached to unidentified receptors on the vesicle surface, transport the vesicles from the (−) to the (+) end of a stationary microtubule. (b) Kinesin- catalyzed movement of microtubules. The kinesin molecules bound to the glass surface move toward the (+) end of the microtubule. Because the kinesin molecules are immobilized onto the coverslip, the sliding force is transmitted to the microtubule, which then moves in the direction of its (−) end. ATP is required for movement in both cases. [Adapted from R. D. Vale et al., 1985, Cell 40:559; T. Schroer et al., 1988, J. Cell Biol. 107:1785.]

kinetochore A three-layer protein structure located at or near the centromere of each mitotic chromosome from which microtubules (kinetochore fibers) extend toward the spindle poles of the cell; plays an active role in movement of chromosomes toward the poles during anaphase.
K_m A parameter that describes the affinity of an enzyme for its substrate and equals the substrate concentration that yields the half-maximal reaction rate; also called the Michaelis constant. A similar parameter describes the affinity of a transport protein for the transported molecule or the affinity of a receptor for its ligand. (Figure 3-26)

Figure 3-26. Dependence of the velocity of an enzyme-catalyzed reaction on substrate concentration. (a) The rates of a hypothetical reaction S ¡÷ P at two different concentrations of enzyme [E] as a function of substrate concentration [S]. The [S] that yields a half-maximal reaction rate is the Michaelis constant K_m, a measure of the affinity of E for S. Doubling the concentration of enzyme causes a proportional increase in the reaction rate, so that the maximal velocity V_max is doubled; the K_m, however, is unaltered. (b) The rates of the reactions catalyzed by an enzyme with substrate S, for which the enzyme has a high affinity, and with substrate S¡¬, for which the enzyme has a low affinity. Note that the V_max is the same with both substrates but that K_m is higher for S¡¬, the low-affinity substrate.

knockin, gene Technique in which the coding sequences of one gene are replaced by those of another.
knockout, gene Technique for selectively inactivating a gene by replacing it with a mutant allele in an otherwise normal organism.
Krebs cycle See citric acid cycle.

L

label A fluorescent chemical group or radioactive atom incorporated into a molecule in order to spatially locate the molecule or follow it through a reaction or purification scheme. As a verb, to add such a group or atom to a cell or molecule.
lagging strand Newly synthesized DNA strand formed at the growing fork as short, discontinuous segments, called Okazaki fragments, which are later joined by DNA ligase. Although overall lagging-strand synthesis occurs in the 3¡¬¡÷5¡¬ direction, each Okazaki fragment is synthesized in the 5¡¬¡÷3¡¬ direction. See also leading strand. (Figure 12-9)

laminin A component of the extracellular matrix that is found in all basal laminae and has binding sites for cell-surface receptors, collagen, and heparan sulfate proteoglycans. (Figure 22-19)

Figure 22-19. Structure of laminin, a large heterotrimeric multiadhesive matrix protein found in all basal laminae. The cross-shaped molecule contains globular domains and a coiled-coil region in which the three chains are covalently linked via several disulfide bonds. Different regions of laminin bind to cell-surface receptors and various matrix components. [Adapted from G. R. Martin and R. Timpl, 1987, Ann. Rev. Cell Biol. 3:57; and K. Yamada, 1991, J. Biol. Chem. 266:12809.]

lamins A group of intermediate filament proteins that form the fibrous network (nuclear lamina) on the inner surface of the nuclear envelope. (Figure 13-15)

Figure 13-15. The nuclear lamina and its depolymerization. (a) Electron micrograph of the nuclear lamina. A nuclear membrane from a hand-dissected Xenopus oocyte was fixed to an electron microscope grid and then extracted with a nonionic detergent to remove the lipid membranes and nonpolymerized proteins. Note the regular meshlike network of fibers. (b) Schematic diagram of the nuclear lamina associated with the inner membrane of the double-membrane nuclear envelope of an interphase cell. The nuclear lamina (red) consists of two orthogonal sets of 10-nmdiameter filaments built of lamins A, B, and C. Individual lamin filaments are formed by end-to-end polymerization of lamin tetramers, which consist of two lamin dimers. The red circles represent the globular N-terminal domains. Phosphorylation of specific serine residues near the ends of the coiled-coil rodlike central section of lamin dimers causes the filaments and tetramers to depolymerize, leading to breakdown of the nuclear envelope. [Part (a) from U. Aebi et al., 1986, Nature 323:560; courtesy of U. Aebi. Part (b) adapted from A. Murray and T. Hunt, 1993,The Cell Cycle: An Introduction,W. H. Freeman and Company.]

leading strand Newly synthesized DNA strand formed by continuous synthesis in the 5¡¬n3¡¬ direction at the growing fork. The direction of leading-strand synthesis is the same as movement of the growing fork. See also lagging strand. (Figure 12-9)

lectin Any protein that binds tightly to specific sugars. Lectins can be used in affinity chromatography to purify glycoproteins or as reagents to detect them in situ.
leucine zipper Common structural motif in some dimeric eukaryotic transcription factors characterized by a C-terminal coiled-coil dimerization domain and N-terminal DNA-binding domain. (Figure 10-43)

Figure 10-43. Two views of the interaction of yeast Gcn4, a homodimeric leucine-zipper protein, with DNA. The extended £\-helical regions of the monomers grip the DNA at adjacent major grooves. The coiled-coil dimerization domain in Gcn4 contains precisely spaced leucine residues. Some DNA-binding proteins with this same general motif contain other hydrophobic amino acids in these positions; hence, this structural motif is generally called a basic zipper. [From T. E. Ellenberger et al., 1992, Cell 71:1223.]

leukemia Cancer of white blood cells and their precursors.
library See DNA library.
ligand Any molecule, other than an enzyme substrate, that binds tightly and specifically to a macromolecule, usually a protein, forming a macromolecule-ligand complex.
ligase An enzyme that links together the 3¡¬ end of one nucleic acid strand with the 5¡¬ end of another, forming a continuous strand.
linkage In genetics, the tendency of two different loci on the same chromosome to be inherited together. The closer two loci are, the greater their linkage and the lower the frequency of recombination between them.
lipid Any organic molecule that is insoluble in water but is soluble in nonpolar organic solvents. Lipids contain covalently linked fatty acids and are found in fat droplets and, as phospholipids, in biomembranes.
lipophilic See hydrophobic.
liposome Spherical phospholipid bilayer structure with an aqueous interior that forms in vitro from phospholipids and may contain protein. (Figure 15-4)

Figure 15-4. Liposomes containing a single type of transport protein can be used to investigate properties of the transport process. Here, all the integral proteins of the erythrocyte membrane are solubilized by a nonionic detergent, such as octylglucoside. The glucose transport protein, a uniporter, can be purified by chromatography on a column containing a specific monoclonal antibody and then incorporated into liposomes made of pure phospholipids.

locus In genetics, the specific site of a gene on a chromosome. All the alleles of a particular gene occupy the same locus.
lymphocytes Two classes of white blood cells that can recognize foreign molecules (antigens) and mediate immune responses. B lymphocytes are responsible for production of antibodies; T lymphocytes are responsible for destroying virus- and bacteria-infected cells, foreign cells, and cancer cells.
lysogenic cycle Series of events in which a bacterial virus (bacteriophage) enters a host cell and its DNA is incorporated into the host-cell genome in such a way that the virus (the prophage) lays dormant. The association of a prophage with the host-cell genome is called lysogeny. By various mechanisms, the prophage can be activated so that it enters the lytic cycle. (Figure 6-19.)

Figure 6-19. £f bacteriophage undergoes either lytic replication or lysogeny following infection of E. coli. The linear double-stranded DNA is converted to a circular form immediately after infection. (Left) If the nutritional state of the host cell is favorable, most infected cells undergo lytic replication, similar to lytic replication of cells by bacteriophage T4 (see Figure 6-16). (Right) If the nutritional state of the host cell cannot support production of large numbers of progeny phages, lysogeny is established. In this case, viral genes required for the lytic cycle are repressed, and host-cell enzymes synthesize viral proteins that integrate the viral DNA into a specific sequence in the host-cell chromosome where no host-cell genes are disrupted. The prophage DNA then is replicated along with the host-cell chromosome as the lysogenized cell (called a lysogen) grows and divides. Repression of the viral genes required for lytic replication is maintained in progeny cells. At infrequent intervals, the prophage in a lysogen is induced, or activated, leading to expression of viral proteins that precisely remove the prophage DNA from the host-cell chromosome and to derepression of the genes required for the lytic cycle. As a result, a normal cycle of lytic replication ensues.

lysogeny See lysogenic cycle.
lysosome Small organelle having an internal pH of 4¡V5 and containing hydrolytic enzymes.
lytic cycle Series of events in which a virus enters and replicates within a host cell to produce new viral particles eventually causing lysis of the cell. See also lysogenic cycle. (Figure 6-17)

Figure 6-17. The steps in the lytic replication cycle of an enveloped virus are illustrated for rabies virus, which has a single-stranded RNA genome. The structural components of this virus are depicted at the top. Note that the nucleocapsid of this virus is helical rather than icosahedral. After a virion adsorbs to a specific host membrane protein (step 1), the cell engulfs it in an endosome (step 2). A protein in the endosome membrane pumps protons from the cytosol into the endosome interior. The resulting decrease in endosomal pH induces a conformational change in the viral glycoprotein, leading to fusion of the viral envelope with the endosomal lipid bilayer membrane and release of the nucleocapsid into the cytosol (steps 3 and 4). Viral RNA polymerase uses ribonucleoside triphosphates in the cytosol to replicate the viral RNA genome (step 5) and synthesize viral mRNAs (step 6). One of the viral mRNAs encodes the viral transmembrane glycoprotein (blue), which is inserted into the lumen of the endoplasmic reticulum (ER) as it is synthesized on ER-bound ribosomes (step 7). Carbohydrate is added to the large folded domain inside the ER lumen and is modified as the membrane and the associated glycoprotein pass through the Golgi apparatus (step 8). Vesicles with mature glycoprotein fuse with the plasma membrane, depositing viral glycoprotein on the cell surface with the large folded domain outside the cell, the transmembrane £\ helix spanning the plasma membrane, and the small cytoplasmic domain within the cell (step 9). Meanwhile, other viral mRNAs are translated on host-cell ribosomes into nucleocapsid protein, matrix protein, and viral RNA polymerase (step 10). These proteins are assembled with replicated viral genomic RNA (dark red) into progeny nucleocapsids (step 11), which then associate with the viral transmembrane glycoprotein in the plasma membrane (step 12). As additional copies of the matrix protein on a single nucleocapsid associate with the cytoplasmic domain of additional copies of the viral transmembrane glycoprotein, the plasma membrane is folded around the nucleocapsid, forming a ¡§bud¡¨ that eventually is released (step 13).

M

M (mitotic) phaseSee cell cycle.
macromolecule Any large, usually polymeric molecule (e.g., a protein, nucleic acid, polysaccharide) with a molecular mass greater than a few thousand daltons.
malignant Referring to a tumor or tumor cells that can invade surrounding normal tissue and/or undergo metastasis. See also benign.
MAP kinase Protein kinase that is activated in response to cell stimulation by many different growth factors and that mediates cellular responses by phosphorylating specific target proteins.
mapping Various techniques for determining the relative order of genes on a chromosome (genetic map), the absolute position of genes (physical map), or the relative position of restriction sites (restriction map).
meiosis In eukaryotes, a special type of cell division that occurs during maturation of germ cells; comprises two successive nuclear and cellular divisions with only one round of DNA replication resulting in production of four genetically nonequivalent haploid cells (gametes) from an initial diploid cell. (Figure 8-2)

Figure 8-2. Meiosis. A premeiotic germ cell has two copies of each chromosome (2n), one maternal and one paternal. Chromosomes are replicated during the S phase, giving a 4n chromosomal complement. During the first meiotic division, each replicated chromosome (actually two sister chromatids) aligns at the cell equator, paired with its homologous partner; this pairing off, referred to as synapsis, permits genetic recombination (discussed later). One homolog (both sister chromatids) of each morphologic type goes into one daughter cell, and the other homolog goes into the other cell. The resulting 2n cells undergo a second division without intervening DNA replication. During this second meiotic division, the sister chromatids of each morphologic type separate and these now independent chromosomes are randomly apportioned to the daughter cells. Thus, each diploid cell that undergoes meiosis produces four haploid cells, whereas each diploid cell that undergoes mitosis produces two diploid cells (see Figure 1-10).

membrane See biomembrane.
membrane potential Voltage difference across a membrane due to the slight excess of positive ions (cations) on one side and negative ions (anions) on the other.
mesenchyme Embryonic mesoderm tissue in animals from which are formed the connective tissues, blood vessels, and lymphatic vessels.
mesoderm The middle of the three primary cell layers of the animal embryo, lying between the ectoderm and endoderm; gives rise to the notochord, connective tissue, muscle, blood, and other tissues.
messenger RNA See mRNA.
metabolism The sum of the chemical processes that occur in living cells; includes anabolism and catabolism.
metaphase Mitotic stage at which chromosomes are fully condensed and attached to the mitotic spindle at its equator but have not yet started to segregate toward the opposite spindle poles. (Figure 19-34)

metastasis Spread of tumor cells from their site of origin and establishment of areas of secondary growth.
Michaelis constant See Km.
microfilaments Cytoskeletal fibers (7 nm in diameter) that are formed by polymerization of monomeric globular (G) actin; also called actin filaments. Microfilaments play an important role in muscle contraction, cytokinesis, cell movement, and other cellular functions and structures. (Figure 18-2)

Figure 18-2. Structures of monomeric G-actin and F-actin filament. (a) Model of a £]-actin monomer from a nonmuscle cell shows it to be a platelike molecule (measuring 5.5 ¡Ñ 5.5 ¡Ñ 3.5 nm) divided by a central cleft into two approximately equal-sized lobes and four subdomains, numbered I ¡V IV. ATP (red) binds at the bottom of the cleft and contacts both lobes (the yellow ball represents Mg²⁺). The N- and C-termini lie in subdomain I. (b) In the electron microscope, negatively stained actin filaments appear as long, flexible, and twisted strands of beaded subunits. Because of the twist, the filament appears alternately thinner (7 nm diameter) and thicker (9 nm diameter) (arrows). (c) In one model of the arrangement of subunits in an actin filament, the subunits lie in a tight helix along the filament, as indicated by the arrow. One repeating unit consists of 28 subunits (13 turns of the helix), covering a distance of 72 nm. Only 14 subunits are shown in the figure. The ATP-binding cleft is oriented in the same direction (top) in all actin subunits in the filament. As discussed later, this end of a filament is designated the (−) end; the opposite end is the (+) end. [Part (a) adapted from C. E. Schutt et al., 1993, Nature 365:810, courtesy of M. Rozycki; part (b) courtesy of R. Craig; part (c) see M. F. Schmid et al., 1994, J. Cell Biol. 124:341, courtesy of M. Schmid.]

microtubule-associated protein (MAP) Any protein, including motor proteins, that binds to microtubules in a constant ratio and determines the unique properties of different types of microtubules.
microtubules Cytoskeletal fibers (24 nm in diameter) that are formed by polymerization of £\,£]-tubulin monomers and exhibit structural and functional polarity. They are important components of cilia, flagella, the mitotic spindle, and other cellular structures. (Figure 19-2)

Figure 19-2. Microtubule structure. (a) Ribbon diagram of the dimeric tubulin subunit, showing the £\-tubulin and £]-tubulin monomers and their bound nonexchangeable GTP (red) and exchangeable GDP (blue) nucleotides. An anticancer drug, taxotere (green), was used in the structural studies to stabilize the dimer structure. (b) The organization of tubulin subunits in a microtubule. The subunits are aligned end to end into a protofilament (magenta highlight). The side-by-side packing of protofilaments forms the wall of the microtubule. In this model, the protofilaments are slightly staggered so that £\-tubulin in one protofilament is in contact with £\-tubulin in the neighboring protofilaments. In an alternative model, the protofilaments are staggered by one-half subunit, forming a checkerboard pattern. In either structure, the microtubule displays a structural polarity in that addition of subunits occurs preferentially at one end, designated the (+) end. [Part (a) modified from E. Nogales, S. G. Wolf, and K. H. Downing, 1998, Nature391:199; courtesy of E. Nogales. Part (b) adapted from Y. H. Song and E. Mandelkow, 1993, Proc. Nat'l. Acad. Sci. USA 90:1671.]

microvillus (pl. microvilli) Small, membrane-covered projection on the surface of an animal cell containing a core of actin filaments. Numerous microvilli are present on the absorptive surface of intestinal epithelial cells, increasing the surface area for transport of nutrients. (Figure 18-10)

Figure 18-10. Micrograph of intestinal cell showing microvilli. At the core of each 2-£gm-long microvillus, a bundle of actin filaments, cross-linked by fimbrin and villin, stabilizes the fingerlike structure. The plasma membrane surrounding a microvillus is attached to the sides of the bundle by evenly spaced membrane-microfilament linkages consisting of myosin I. Each bundle continues into the cell as a 0.5-£gm-long rootlet. The rootlets are cross-braced by connecting fibers composed of an intestinal isoform of spectrin, and the bases of the rootlets form attachment sites for keratin filaments. These numerous connections anchor the rootlets in a meshwork of filaments and thereby support the upright orientation of the microvilli. [Courtesy of N. Hirokawa.]

mitochondrion (pl. mitochondria) Large organelle that is surrounded by two phospholipid bilayer membranes, contains DNA, and carries out oxidative phosphorylation, thereby producing most of the ATP in eukaryotic cells. (Figures 5-45 and 16-7)

Figure 5-45. Electron micrograph of a mitochondrion in a section from bat pancreas. This organelle is bounded by a double membrane. The inner membrane, which surrounds the matrix space, has many infoldings, called cristae. [From D. W. Fawcett, 1981, The Cell,2d ed., Saunders, p. 421.]

Figure 16-7. A three-dimensional diagram of a mitochondrion cut longitudinally. The F₀F₁ complexes (small red spheres), which synthesize ATP, are intramembrane particles that protrude from the inner membrane into the matrix. The matrix contains the mitochondrial DNA (blue strand), ribosomes (small blue spheres), and granules (large yellow spheres).

mitogen Any extracellular substance, such as a growth factor, that promotes cell proliferation.
mitosis In eukaryotic cells, the process whereby the nucleus is divided to produce two genetically equivalent daughter nuclei with the diploid number of chromosomes. See also cytokinesis and meiosis. (Figure 19-34)

mitotic apparatus A specialized temporary structure, present in eukaryotic cells only during mitosis, that captures the chromosomes and then pushes and pulls them to opposite sides of the dividing cell. Consists of a central bilaterally symmetric bundle of microtubules with the overall shape of a football (the mitotic spindle) and two star-shaped tufts of microtubules (the asters), one at each pole of the spindle. (Figure 19-36)

Figure 19-36. (a) High-voltage electron micrograph of the mitotic apparatus in a metaphase mammalian cell. To visualize the spindle microtubules more clearly, biotin-tagged anti-tubulin antibodies were added to make microtubules more massive. The large cylindrical objects are chromosomes. (b) Diagram showing the three sets of microtubules (MTs) in the mitotic apparatus. Centered around the poles are astral microtubules, kinetochore microtubules, which are connected to chromosomes (blue), and polar microtubules. The (+) ends of these microtubules all point away from the centrosome at each pole. [Part (a) courtesy of J. R. McIntosh.]

mitotic spindle See mitotic apparatus.
mobile DNA element Any DNA sequence that is not present in the same chromosomal location in all individuals of a species.
monoclonal antibody Antibody produced by the progeny of a single B cell and thus a homogeneous protein exhibiting a single antigen specificity. Experimentally, it is produced by use of a hybridoma. (Figure 6-10)

monomer Any small molecule that can be linked with others of the same type to form a polymer. Examples include amino acids, nucleotides, and monosaccharides.
monomeric For proteins, consisting of a single polypeptide chain.
monosaccharide Any simple sugar with the formula (CH2O)n where n = 3 ¡V 7.
morphogen A molecule that specifies cell identity during development as a function of its concentration.
motif In proteins, a structural unit exhibiting a particular three-dimensional architecture that is found in a variety of proteins and usually is associated with a particular function. (Figure 3-9)

Figure 3-9. Secondary-structure motifs. (a) The coiled-coil motif (left) is characterized by two or more helices wound around one another. In some DNA-binding proteins, like c-Jun, a two-stranded coiled coil is responsible for dimerization (right). Each helix in a coiled coil has a repeated heptad sequence. with a leucine or other hydrophobic residue (red) at positions 1 and 4, forming a hydrophobic stripe along the helix surface. The helices pair by binding along their hydrophobic stripes, as seen in both models displayed here, in which the hydro- phobic side chains are shown in red. (b) The helix-loop-helix motif occurs in many calcium-binding proteins. Oxygen-containing R groups of residues in the loop form a ring around a Ca²⁺ ion. The 14-aa loop sequence (right) is rich in invariant hydrophilic residues. (c) The zincfinger motif is present in many proteins that bind nucleic acids. A Zn²⁺ ion is held between a pair of £] strands (green) and a single £\ helix (blue) by a pair of cysteine and histidine residues. In the 25-aa sequence of this motif the invariant cysteines usually occur at positions 3 and 6, and the invariant histidines at positions 20 and 24. [Part (a) courtesy of V. Malashkevich and S. Choe.]
motor protein Any member of a special class of enzymes that use energy from ATP hydrolysis to walk or slide along a microfilament (myosin) or a microtubule (dynein and kinesin).
MPF (mitosis-promoting factor) A heterodimeric protein, composed of a cyclin and cyclin-dependent kinase (Cdk), that triggers entrance of a cell into mitosis by inducing chromatin condensation and nuclear-envelope breakdown; originally called maturation-promoting factor.
mRNA (messenger RNA) Any RNA that specifies the order of amino acids in a protein. It is produced by transcription of DNA by RNA polymerase and, in RNA viruses, by transcription of viral RNA. In eukaryotes, the initial RNA product (primary transcript) undergoes processing to yield functional mRNA, which is transported to the cytoplasm. See also translation.
MTOC (microtubule-organizing center) General term for any structure (e.g., the centrosome) that organizes microtubules in nonmitotic (interphase) cells. (Figure 19-5)

Figure 19-5. Microtubule-organizing center. (a) Fluorescence micrograph of a Chinese hamster ovary cell stained with antibodies specific for tubulin and a centrosomal protein. The microtubules (green) are seen to radiate from a central point, the microtubule-organizing center (MTOC), near the nucleus. The MTOC (yellow) is detected with an antibody to Cep135, a protein in the pericentriolar material. (b) Electron micrograph of the MTOC in an animal cell. The pair of centrioles (red), C and C¡¬, in the center are oriented at right angles; thus one is seen in cross section, and one longitudinally. Surrounding the centrioles is a cloud of material, the pericentriolar (PC) matrix, which contains £^-tubulin and pericentrin. Embedded within the MTOC, but not contacting the centrioles, are the (−) ends of microtubules (MT; yellow). [Part (a) courtesy of R. Kuriyama; part (b) from B. R. Brinkley, 1987, in Encyclopedia of Neuroscience, vol. II, Birkhauser Press, p. 665; courtesy of B. R. Brinkley.]

multiadhesive matrix proteins Group of long flexible proteins that bind to other components of the extracellular matrix (collagen, polysaccharides) and to cell-surface receptors, thereby cross-linking the matrix to the cell membrane.
multimeric For proteins, containing several polypeptide chains (or subunits).
mutagen A chemical or physical agent that induces mutations.
mutation In genetics, a permanent, heritable change in the nucleotide sequence of a chromosome, usually in a single gene; commonly leads to a change in or loss of the normal function of the gene product.
myelin sheath Stacked specialized cell membrane that forms an insulating layer around vertebrate axons and increases the speed of impulse conduction. (Figures 21-15 and 21-16)

Figure 21-15. Two views of the myelin sheath. (a) Electron micrograph of a cross section of the axon of a myelinated peripheral neuron. It is surrounded by the Schwann cell (SN) that produced the myelin sheath, which can contain 50 ¡V 100 membrane layers. (b) Freeze-fracture preparation of a cut section of the rat sciatic nerve viewed in a scanning electron microscope. The axon of each neuron in the nerve is surrounded by a myelin sheath (MS). The axonal cytoplasm contains abundant filaments ¡X mostly microtubules and intermediate filaments ¡X that run longitudinally and serve to make the axon rigid. [Part (a) from P. C. Cross and K. L. Mercer, 1993, Cell and Tissue Ultrastructure, A Functional Perspective, W. H. Freeman and Company, p. 137. Part (b) from R. G. Kessel and R. H. Kardon, 1979, Tissues and Organs: A Text-Atlas of Scanning Electron Microscopy, W. H. Freeman and Company, p. 80.]

Figure 21-16. Formation and structure of a myelin sheath in the peripheral nervous system. (a) By wrapping itself around several axons simultaneously, a single Schwann cell can form a myelin sheath around multiple axons. As the Schwann cell continues to wrap around the axon, all the spaces between its plasma membranes, both cytosolic and exoplasmic, are reduced. Eventually all cytosol is forced out and a structure of compact stacked plasma membranes is formed. (b) The compaction of these membranes is generated mainly by P_o protein, which is synthesized only in myelinating Schwann cells. The 124-amino acid exoplasmic domain of P_o protein, which is folded like an immunoglobulin domain, associates with similar domains emanating from the opposite membrane surface. These interactions ¡§zipper¡¨ together the membrane surfaces, forming the close exoplasmic opposition. Membrane interactions are stabilized by a tryptophan residue on the tip of the exoplasmic domain, which binds to lipids in the opposite membrane. The close apposition of the cytosolic faces of the membrane may result from binding of the cytosolic tail of each P_o protein (green) to phospholipids in the opposite membrane. [Part (b) adapted from L. Shapiro et al., 1996, Neuron 17:435, and G. Lemke, 1996, Nature 383:395.]

myofibril Long, highly organized bundle of actin and myosin filaments and other proteins that constitute the basic structural unit of muscle cells (myofibers) (Figure 22-26)

Figure 22-26. Structure of cartilage proteoglycan aggregate. (a) Electron micrograph of a proteoglycan aggregate from fetal bovine epiphyseal cartilage. Aggrecan core proteins are bound at ≈40-nm intervals to a molecule of hyaluronan. Numerous keratan sulfate and chondroitin sulfate chains are attached to the aggrecan core proteins. (b) Diagram of detailed structure of an aggrecan monomer. The N-terminal domain of the core protein binds to a hyaluronan (HA) molecule. Binding is facilitated by a link protein, which binds to both the hyaluronan disaccharide and the aggrecan core protein. Each aggrecan core protein has 127 Ser-Gly sequences at which the glycosaminoglycan chains are added; 30 short keratan sulfate chains and 97 longer chondroitin sulfate chains are added to each core protein molecule in aggrecan. [Part (a) from J. A. Buckwalter and L. Rosenberg, 1983, Coll. Rel. Res. 3:489; courtesy of L. Rosenberg.]

myosin One of a family of motor proteins with a globular head region and coiled-coil tail region that has actin-stimulated ATPase activity; drives movement along actin filaments during muscle contraction and cytokinesis (myosin II) and mediates vesicle translocation (myosins I and V). (Figure 18-20)

Figure 18-20. Structure of various myosin molecules. (a) The three major myosin proteins are organized into head, neck, and tail domains, which carry out different functions. The head domain binds actin and has ATPase activity. The light chains, bound to the neck domain, regulate the head domain. The tail domain dictates the specific role of each myosin in the cell. Note that myosin II, the form that functions in muscle contraction, is a dimer with a long rigid coiled-coil tail. (b) Proteolysis of myosin II reveals its domain structure. For example, most proteases cleave myosin II at the base of the neck domain to generate a paired-head and neck fragment, called heavy meromyosin (HMM), and a rodlike tail fragment, called light meromyosin (LMM). Further digestion of HMM with papain splits off the neck region (S2 fragment) and leads to separation of the two head domains into single myosin head fragments (S1 fragments).

N

NAD+ (nicotinic adenine dinucleotide) A widely used coenzyme that participates in oxidation reactions by accepting two electrons from a donor molecule and one H+ from the solution. The reduced form, NADH, transfers electrons to carriers that function in oxidative phosphorylation. (Figure 16-4)

Figure 16-4. Structures of the electron-carrying coenzymes NAD⁺ and NADH. Nicotinamide adenine dinucleotide (NAD⁺) and the related nicotinamide adenine dinucleotide phosphate (NADP⁺) accept only pairs of electrons; reduction to NADH or NADPH involves the transfer of two electrons simultaneously. In most oxidation-reduction reactions in biological systems, a pair of hydrogen atoms (two protons and two electrons) are removed from a molecule. One of the protons and both electrons are transferred to NAD⁺; the other proton is released into solution. Thus the overall reaction is sometimes written NAD⁺ + 2 H⁺ + 2 e⁻ ↔ NADH + H⁺. NADP is identical in structure with NAD except for the presence of an additional phosphate group. However, NAD and NADP participate in different sets of enzymatically catalyzed reactions.

NADP+ (nicotinic adenine dinucleotide phosphate) Phosphorylated form of NAD+, which is used extensively as an electron carrier in biosynthetic pathways and during photosynthesis.
Nernst equation Mathematical expression that defines the electric potential E across a membrane as directly proportional to the logarithm of the ratio of the ion concentrations on either side of the membrane and inversely proportional to the valency of the ions.
neuron (nerve cell) Any of the impulse-conducting cells of the ner-vous system. A typical neuron contains a cell body; several short, branched processes (dendrites); and one long process (axon). (Figure 21-1)

neuropeptide A peptide secreted by neurons that functions as a signaling molecule either at a synapse or elsewhere. These molecules have diverse, often long-lived effects in contrast to neurotransmitters.
neurotransmitter Extracellular signaling molecule that is released by the presynaptic neuron at a chemical synapse and relays the signal to the postsynaptic cell. The response elicited by a neurotransmitter, either excitatory or inhibitory, is determined by its receptor on the postsynaptic cell. Examples include acetylcholine, dopamine, GABA (£^-aminobutyric acid), and serotonin. (Figure 21-28)

noncovalent bond Any relatively weak chemical bond that does not involve an intimate sharing of electrons. Multiple noncovalent bonds often stabilize the conformation of macromolecules and mediate highly specific interactions between molecules.
nonpolar Referring to a molecule or structure that lacks any net electric charge or asymmetric distribution of positive and negative charges. Nonpolar molecules generally are insoluble in water.
Northern blotting Technique for detecting specific RNAs separated by electrophoresis by hybridization to a labeled DNA probe. See also Southern blotting.
nuclear envelope Double-membrane structure surrounding the nucleus; the outer membrane is continuous with the endoplasmic reticulum and the two membranes are perforated by nuclear pores. (Figures 5-42 and 5-50)

Figure 5-42. Structure of animal cells. (a) Electron micrograph of a thin section of a hormone-secreting cell from the rat pituitary stained with osmium tetroxide, which preferentially binds cell membranes. The subcellular features typical of many animal cells are clearly visible. (b) Drawing of a ¡§typical¡¨ animal cell. Not every animal cell contains all the organelles, granules, and fibrous structures shown here, and other substructures can be present in some cells. Animal cells also differ considerably in shape and in the prominence of various organelles and substructures. [Part (a) courtesy of Biophoto Associates.]

Figure 5-50. A freeze-fracture preparation of an onion root-tip cell, showing the nucleus and pores in the nuclear membrane, which traverse the inner and outer nuclear membranes. [Courtesy of D. Branton.]

nuclear lamina Fibrous network on the inner surface of the inner nuclear membrane composed of lamin filaments. (Figure 13-15)

nuclear pore complex (NPC) Large, multiprotein structure in the nuclear envelope through which ions and small molecules can diffuse and which mediates the active transport of ribonucleoproteins and large proteins between the nucleus and cytoplasm. (Figure 11-28)

Figure 11-28. Nuclear pore complex. (a) Nuclear envelopes of Xenopus oocytes visualized by field emission in-lens scanning electron microscopy. Left: Cytoplasmic face of nuclear pore complexes (NPCs). Middle: Nucleoplasmic face of NPCs, showing the ¡§basket¡¨ structure. Right: Nucleoplasmic face of the nuclear envelope after removal of the nuclear membrane by mild detergent treatment. The nuclear lamin network, which inserts into the nuclear ring of the NPC, is exposed by this treatment. (b) Cut-away model of the NPC. [Part (a) from V. Doye and E. Hurt, 1997, Curr. Opin. Cell Biol. 9401; courtesy of M. W. Goldberg and T. D. Allen. Part (b) adapted from M. Ohno et al., 1998, Cell 92:327.]

nuclear receptor General term for intracellular receptors that bind lipid-soluble hormones (e.g., steroid hormones); also called steroid receptor superfamily. Following ligand binding, the hormonereceptor complex translocates to the nucleus and functions as a transcription factor. (Figure 10-67)

Figure 10-67. Model of hormone-dependent gene activation by the glucocorticoid receptor (GR). In the absence of hormone, GR is bound in a complex with Hsp90 in the cytoplasm via its ligand-binding domain (light purple). When hormone is present, it diffuses through the plasma membrane and binds to the GR ligand-binding domain, causing a conformational change in the ligand-binding domain that releases the receptor from Hsp90. The receptor with bound ligand is then translocated into the nucleus where its DNA-binding domain (orange) binds to response elements, allowing the activation domain (green) to stimulate transcription of target genes.
nucleic acid A polymer of nucleotides linked by phosphodiester bonds. DNA and RNA are the primary nucleic acids in cells.
nucleocapsid A viral capsid plus the enclosed nucleic acid.
nucleolus Large structure in the nucleus of eukaryotic cells where rRNA synthesis and processing occurs and ribosome subunits are assembled.
nucleoside A small molecule composed of a purine or pyrimidine base linked to a pentose (either ribose or deoxyribose). (Table 4-1)

Table 4-1. Naming Nucleosides and Nucleotides

nucleosome Small structural unit of chromatin consisting of a disk-shaped core of histone proteins around which a 146-bp segment of DNA is wrapped. (Figure 9-31)

Figure 9-31. Solenoid model of the 30-nm condensed chromatin fiber in a side view. The octameric histone core (see Figure 9-30) is shown as an orange disk. Each nucleosome associates with one H1 molecule, and the fiber coils into a solenoid structure with a diameter of 30 nm. [Adapted from M. Grunstein, 1992, Sci. Am. 267:68]

nucleotide A nucleoside with one or more phosphate groups linked via an ester bond to the sugar moiety. DNA and RNA are polymers of nucleotides. (Figure 4-1a and Table 4-1)

Figure 4-1. All Nucleotides have a common structure. (a) Chemical structure of adenosine 5¡¬-monophosphate (AMP), a nucleotide that is present in RNA. All nucleotides are composed of a phosphate moiety, containing up to three phosphate groups, linked to the 5¡¬ hydroxyl of a pentose sugar, whose 1¡¬ carbon is linked to an organic base. By convention, the carbon atoms of the pentoses are numbered with primes. In natural nucleotides, the 1¡¬ carbon is joined by a £] linkage to the base, which is in the plane above the furanose ring, as is the phosphate. (b) Haworth projections of ribose and deoxyribose, the pentoses in nucleic acids.

Table 4-1. Naming Nucleosides and Nucleotides

nucleus Large membrane-bounded organelle in eukaryotic cells that contains DNA organized into chromosomes; synthesis and processing of RNA and ribosome assembly occur in the nucleus.

O

Okazaki fragments Short (<1000 bases), single-stranded DNA fragments that are formed during synthesis of the lagging strand in DNA replication and are rapidly joined by DNA ligase to form a continuous DNA strand. (Figure 12-9)

oncogene A gene whose product is involved either in transforming cells in culture or in inducing cancer in animals. Most oncogenes are mutant forms of normal genes (proto-oncogenes) involved in the control of cell growth or division.
oocyte Developing egg cell.
operator Short DNA sequence in a bacterial or viral genome that binds a repressor protein and controls transcription of an adjacent gene. (Figure 10-2)

Figure 10-2. Jacob and Monod model of transcriptional regulation of the lac operon by lac repressor. When lac repressor binds to a DNA sequence called the operator (O), which lies just upstream of the lacZ gene, transcription of the operon by RNA polymerase is blocked. Binding of lactose to the repressor causes a conformational change in the repressor, so that it no longer binds to the operator. RNA polymerase then is free to bind to the promoter (P) and initiate transcription of the lac genes; the resulting polycistronic mRNA is translated into the encoded proteins. [Adapted from A. J. F. Griffiths et al., 1993, An Introduction to Genetic Analysis,5th ed., W. H. Freeman and Co.]

operon In bacterial DNA, a cluster of contiguous genes transcribed from one promoter that gives rise to a polycistronic mRNA.
organelle Any membrane-limited structure found in the cytoplasm of eukaryotic cells.
osmosis Net movement of water across a semipermeable membrane from a solution of lesser to one of greater solute concentration. The membrane must be permeable to water but not to solute molecules.
osmotic pressure Hydrostatic pressure that must be applied to the more concentrated solution to stop the net flow of water across a semipermeable membrane separating solutions of different concentrations. (Figure 15-30)

Figure 15-30. Experimental system for demonstrating osmotic pressure. Solutions A and B are separated by a membrane that is permeable to water but impermeable to all solutes. If C_B (the total concentration of solutes in solution B) is greater than C_A, water will tend to flow across the membrane from solution A to solution B. The osmotic pressure p between the solutions is the hydrostatic pressure that would have to be applied to solution B to prevent this water flow. From the van't Hoff equation, p = RT(C_B − C_A).

oxidation Loss of electrons from an atom or molecule as occurs when hydrogen is removed from a molecule or oxygen is added. The opposite of reduction.
oxidation potential The voltage change when an atom or molecule loses an electron.
oxidative phosphorylation The phosphorylation of ADP to form ATP driven by the transfer of electrons to oxygen (O2) in bacteria and mitochondria. This process involves generation of a proton-motive force during electron transport, and its subsequent use to power ATP synthesis. (Figure 16-9)

Figure 16-9. Summary of the aerobic oxidation of pyruvate in mitochondria. The outer membrane is not shown because it is freely permeable to all metabolites. Specific transport proteins (ovals) in the inner membrane import pyruvate (tan), ADP (green), and P_i (purple) into the matrix and export ATP. NADH generated in the cytosol is not transported directly to the matrix because the inner membrane is impermeable to NAD⁺ and NADH; instead, a shuttle system (red oval) transports electrons from cytosolic NADH to NAD⁺ in the matrix (see Figure 16-13). O₂ diffuses into the matrix and CO₂ diffuses out. HSCoA denotes free coenzyme A (CoA), and SCoA denotes CoA when it is esterified. Fatty acids are linked to CoA on the outer mitochondrial membrane. Subsequently, the fatty acyl group is removed from the CoA, linked to a carnitine carrier that transports it across the inner membrane, and then the fatty acid is reattached to a CoA on the matrix side of the inner membrane (blue oval). Oxidation of pyruvate in the citric acid cycle generates NADH and FADH₂. Electrons from these reduced coenzymes are transferred via four electron transport complexes (blue rectangles) to O₂ concomitant with transport of H⁺ ions from the matrix to the intermembrane space, generating the proton-motive force. The F₀F₁ complex (orange) then harnesses the proton-motive force to synthesize ATP. Blue arrows indicate electron flow; red arrows indicate transmembrane movement of metabolites.

P

passive (simple) diffusionNet movement of a molecule across a membrane down its concentration gradient at a rate proportional to the gradient and the permeability of the membrane.
patch clamping Technique for determining ion flow through a single ion channel or across the membrane of an entire cell by use of a micropipette whose tip is applied to a small patch of the cell membrane. (Figures 21-19 and 21-20)

Figure 21-19. Outline of the patch-clamping technique. (a) Basic patch-clamping arrangement for measuring current flow through individual ion channels in the plasma membrane of a living cell. The patch electrode, filled with a current-conducting saline solution, is applied, with a slight suction, to the plasma membrane. The 0.5-£gm-diameter tip covers a region that contains only one or a few ion channels. The second electrode is inserted into the cytosol. The recording device measures current flow only through the channels in the patch of plasma membrane. (b) Photomicrograph of the cell body of a cultured neuron and the tip of a patch pipette touching the cell membrane. [Part (b) from B. Sakmann, 1992, Neuron 8:613 (Nobel lecture); also published in E. Neher and B. Sakmann, 1992, Sci. Am. 266(3):44.]

Figure 21-20. Different patch-clamping configurations. The effects of different ion concentrations and other substances within and outside the cell on current flow through single channels can be measured on intact cells or isolated patches (a, b, d). In the whole-cell configuration (c), the piece of membrane in the patch is ruptured, allowing measurement of current flow through all of the ion channels. The effect of different solutes on channels is studied most easily with isolated, detached patches (b, d). [Adapted from B. Hille, 1992, Ionic Channels of Excitable Membranes, 2d ed., Sinauer Associates, p. 89.]

PCR (polymerase chain reaction) Technique for amplifying a specific DNA segment in a complex mixture by multiple cycles of DNA synthesis from short oligonucleotide primers followed by brief heat treatment to separate the complementary strands. (Figure 7-38)

Figure 7-38. The polymerase chain reaction. The starting material is a double-stranded DNA. Large numbers of primers are added, each with the sequence found in one strand at the end of the region to be amplified. The thermostable Taq polymerase and dNTPs are also added. In the first cycle, heating to 95 ¢XC melts the double-stranded DNA and subsequent cooling to 60 ¢XC then allows the excess primers to hybridize (anneal) to their complementary sequences in the target DNA. The Taq polymerase then extends each primer from its 3¡¬ end by polymerization of dNTPs, generating newly synthesized strands (wavy lines) that extend in the 3¡¬ direction to the 5¡¬ end of the template restriction fragment. In the second cycle, the original and newly made DNA strands are separated at 95 ¢XC and primers annealed to their complementary sequences at 60 ¢XC. (For simplicity, subsequent events involving only newly made strands are shown; these soon greatly outnumber the original strands.) Each annealed primer again is extended by Taq polymerase to the end of the other primer sequence at the 5¡¬ end of the template strand. Thus the strands (amplimers) synthesized in this cycle exactly equal the length of region to be amplified. In the third cycle, two double-stranded DNA molecules are generated equal to the sequence of the region to be amplified. These two are doubled in the fourth cycle and are doubled again with each successive cycle. [Adapted from J. D. Watson et al., 1992, Recombinant DNA, 2d ed., Scientific American Books.]

pentose A five-carbon monosaccharide. The pentoses ribose and deoxyribose are present in RNA and DNA, respectively.
peptide A small polymer usually containing fewer than 30 amino acids connected by peptide bonds.
peptide bond Covalent bond that links adjacent amino acid residues in proteins; formed by a condensation reaction between the amino group of one amino acid and the carboxyl group of another with release of a water molecule. (Figure 3-3)

Figure 3-3. The peptide bond. (a) A condensation reaction between two amino acids forms the peptide bond, which links all the adjacent residues in a protein chain. (b) Side-chain groups (R) extend from the backbone of a protein chain, in which the amino N, £\ carbon, carbonyl carbon sequence is repeated throughout.

peripheral membrane protein Any protein that associates with the cytosolic or exoplasmic face of a membrane but does not enter the hydrophobic core of the phospholipid bilayer; also called extrinsic protein. See also integral membrane protein. (Figure 3-32)

peroxisome Small organelle in eukaryotic cells whose functions include degradation of fatty acids and amino acids by means of reactions that generate hydrogen peroxide, which is converted to water and oxygen by catalase.
pH A measure of the acidity or alkalinity of a solution defined as the negative logarithm of the hydrogen ion concentration in moles per liter: pH=−log [H⁺]. Neutrality is equivalent to a pH of 7; values below this are acidic and those above are alkaline. (Table 2-3)

Table 2-3. The pH Scale



	Concentration of H⁺ Ions (mol/L)	pH	Example


Increasing acidity	10⁻⁰	0
	10⁻¹	1	Gastric fluids
	10⁻²	2	Lemon juice
	10⁻³	3	Vinegar
	10⁻⁴	4	Acid soil
	10⁻⁵	5	Lysosomes
	10⁻⁶	6	Cytoplasm of contracting muscle
Neutral	10⁻⁷	7	Pure water and cytoplasm
	10⁻⁸	8	Sea water
	10⁻⁹	9	Very alkaline natural soil
	10⁻¹⁰	10	Alkaline lakes
	10⁻¹¹	11	Household ammonia
Increasing alkalinity	10⁻¹²	12	Lime (saturated solution)
	10⁻¹³	13
	10⁻¹⁴	14

phage See bacteriophage.
phagocytosis Process by which relatively large particles (e.g., bacterial cells) are internalized by certain eukaryotic cells.
phenotype The observable characteristics of a cell or organism as distinct from its genotype.
pheromone A signaling molecule released by an individual that can alter the behavior or gene expression of other individuals of the same species. The yeast £\ and a mating-type factors are well-studied examples.
phosphatase An enzyme that removes a phosphate group from a substrate by hydrolysis. Phosphoprotein phosphatases act with protein kinases to control the activity of many cellular proteins.
phosphoanhydride bond A type of high-energy bond formed between two phosphate groups, such as the £^ and £] phosphates and the £] and £\ phosphates in ATP. (Figure 2-24)

Figure 2-24. In adenosine triphosphate (ATP), two high-energy phosphoanhydride bonds (red) link the three phosphate groups.

phosphodiester bond A covalent bond in which two hydroxyl groups form ester linkages to the same phosphate group; joins adjacent nucleotides in DNA and RNA.
phosphoinositides A family of membrane-bound lipids containing phosphorylated inositol derivatives that are important in signal-transduction pathways in eukaryotic cells. (Figure 20-29)

Figure 20-29. Yeast two-hybrid system for detecting proteins that interact. (a) Recombinant DNA techniques can be used to prepare genes that encode hybrid (chimeric) proteins consisting of the DNA-binding domain (purple) or activation domain (orange) of a transcription factor fused to one of two interacting proteins, referred to as the ¡§bait¡¨ domain (pink) and ¡§fish¡¨ domain (green). (b) If yeast cells are transfected with genes encoding both hybrids, the bait and fish portions of the chimeric proteins interact to produce a functional transcriptional activator. One end of this protein complex binds to the upstream activating sequence (UAS) of a test gene (in this example, the HIS3 gene); the other end, consisting of the activation domain, stimulates assembly of the transcription-initiation complex (gray) at the promoter (yellow). (c) This strategy can be used to screen a cDNA library for clones expressing proteins that interact with a protein of interest, in this case Ras. This approach requires two types of plasmids: The bait plasmid includes a DNA sequence encoding the DNA-binding domain of a transcription factor (purple) connected to the coding sequence for Ras (pink). The fish plasmids contain individual cDNAs (green) from a library connected to the coding sequence for the activation domain (orange). Each type of plasmid also contains a wild-type selection gene (e.g., TRP1 or LEU2). Both types of plasmids are transfected into yeast cells with mutations in genes required for tryptophan, leucine, and histidine biosynthesis (trp1, leu2, his3 cells) and then grown in the absence of tryptophan and leucine. Only cells that contain the bait plasmid and at least one fish plasmid survive under these selection conditions. The cells that survive then are plated on medium lacking histidine; only cells that contain the bait plasmid and a fish plasmid encoding a protein that binds to Ras are able to grow, thus identifying cDNAs encoding Ras-binding proteins. [See A. B. Vojtek et al., 1993, Cell 74:205; S. Fields and O. Song, 1989, Nature 340:245.]

phospholipid bilayer A symmetrical two-layer structure, found in all biomembranes, in which the polar head groups of phospholipids are exposed to the aqueous medium, while the nonpolar hydrocarbon chains of the fatty acids are in the center. (Figure 5-30)

Figure 5-30. A space-filling model of a typical phospholipid bilayer. The hydrophobic interior is generated by the fatty acyl side chains. Some of these chains have bends caused by doublebonds. The different polar head groups all lie on the outer, aqueous surface of the bilayer. [From L. Stryer, 1995, Biochemistry,4th ed., W.H Freeman and Company, p 270; courtsey of L.Stryer.]

phospholipids The major class of lipids present in biomembranes, usually composed of two fatty acid chains esterified to two of the carbons of glycerol phosphate, with the phosphate esterified to one of various polar groups. (Figure 5-27)

Figure 5-27. Structures of two types of phospholipids and a glycolipid. The hydrophobic portions of all molecules are shown in yellow; the hydrophilic, in green. (a) Phosphatidylcholine is a typical phosphoglyceride. The fatty acyl side chains can be saturated, or they can contain one or more double bonds. Common alcohols found in these phospholipids are shown in Figure 5-28. (b) Sphingomyelins are a group of phospholipids that lack a glycerol backbone; a sphingomyelin may contain a different fatty acyl side chain than oleic acid (shown here). Linkage of sphingosine (outlined by black dots) to a fatty acid via an amide bond forms a ceramide. (c) Glucosylcerebroside, one of the simplest glycolipids, consists of the ceramide formed from sphingosine and oleic acid linked to a single glucose residue. This glycolipid is abundant in the myelin sheath.

photosynthesis Complex series of reactions occurring in some bacteria and plant chloroplasts whereby light energy is used to generate carbohydrates from CO2, usually with the consumption of H2O and evolution of O2.
pI See isoelectric point.
pinocytosis The nonspecific uptake of small droplets of extracellular fluid into endocytic vesicles.
plaque assay Technique for determining the number of infectious viral particles in a sample by culturing a diluted sample on a layer of susceptible host cells and then counting the clear areas of lysed cells (plaques) that develop. (Figure 6-14)

Figure 6-14. Plaque assay for determining number of infectious particles in a viral suspension. (a) Each lesion, or plaque, which develops where a single virion initially infected a single cell, constitutes a pure viral clone. (b) Plate illuminated from behind shows plaques formed by £f bacteriophage plated on E. coli. (c) Plate showing plaques produced by poliovirus plated on HeLa cells. [Part (b) courtesy of Barbara Morris; part (c) from S. E. Luria et al., 1978, General Virology, 3d ed., Wiley, p. 26.]

plasma membrane The membrane surrounding a cell that separates the cell from its external environment, consisting of a phospholipid bilayer and associated proteins. (Figure 3-32)

plasmid Small, circular extrachromosomal DNA molecule capable of autonomous replication in a cell. Commonly used as a cloning vector.
plasmodesmata (sing. plasmodesma) Tubelike cell junctions that interconnect the cytoplasm of adjacent plant cells and are functionally analogous to gap junctions in animal cells. (Figure 22-36)

Figure 22-36. The structure of plasmodesmata. A plasmodesma is a plasma membrane ¡V lined channel through the cell wall. Note the desmotubule, an extension of the endoplasmic reticulum, and the annulus, a ring of cytosol that interconnects the cytosol of adjacent cells. Not shown is a gating complex that fills the channel and controls transport of materials through plasmodesmata.

point mutation Change of a single nucleotide in DNA, especially in a region coding for protein; can result in formation of a codon specifying a different amino acid or a stop codon, or a shift in the reading frame. (Figure 8-4)

Figure 8-4. Different types of mutations. (a) Point mutations, which involve alteration in a single base pair, and small deletions generally directly affect the function of only one gene. A wild-type peptide sequence and the mRNA and DNA encoding it are shown at the top. Altered nucleotides and amino acid residues are highlighted in green. Missense mutations lead to a change in a single amino acid in the encoded protein. In a nonsense mutation, a nucleotide base change leads to the formation of a stop codon (purple). This results in premature termination of translation, thereby generating a truncated protein. Frameshift mutations involve the addition or deletion of any number of nucleotides that is not a multiple of three, causing a change in the reading frame. Consequently, completely unrelated amino acid residues are incorporated into the protein prior to encountering a stop codon. (b) Chromosomal abnormalities involve alterations in large segments of DNA. Presumably these abnormalities arise owing to errors in the mechanisms for repairing double-strand breaks in DNA. Chromosomes (I or II) are shown as single thick lines with the regions involved in a particular abnormality highlighted in green or purple. Inversions occur when a break is rejoined to the correct chromosome but in an incorrect orientation; deletions, when a segment of DNA is lost; translocations, when breaks are rejoined to the wrong chromosomes; and insertions, when a segment from one chromosome is inserted into another chromosome.

polar Referring to a molecule or structure with a net electric charge or asymmetric distribution of positive and negative charges. Polar molecules are usually soluble in water.
polarity Presence of functional and/or structural differences in distinct regions of a cell or cellular component.
polymer Any large molecule composed of multiple identical or similar units (monomers) linked by covalent bonds.
polymerase chain reaction See PCR.
polypeptide Linear polymer of amino acids connected by peptide bonds. Proteins are large polypeptides, and the two terms commonly are used interchangeably.
polyribosome A complex containing several ribosomes all translating a single messenger RNA; also called polysome.
polysaccharide Linear or branched polymer of monosaccharides, linked by glycosidic bonds, usually containing more than 15 residues. Examples include glycogen, cellulose, and glycosaminoglycans.
positional cloning Isolation and cloning of the normal form of a mutation-defined gene (i.e., a gene identified by genetic analysis of mutants).
pre-mRNA Precursor messenger RNA; the primary transcript and intermediates in RNA processing.
pre-rRNA Large precursor ribosomal RNA that is synthesized in the nucleolus of eukaryotic cells and processed to yield three of the four RNAs present in ribosomes. (Figure 11-50)

Figure 11-50. Processing of pre-rRNA and assembly of ribosomes in eukaryotes. (a) Major intermediates and times required for various steps in pre-rRNA processing in higher eukaryotes. Ribosomal and nucleolar proteins associate with 45S pre-rRNA soon after its synthesis, forming an 80S pre-rRNP. Synthesis of 5S rRNA occurs outside of the nucleolus. The extensive secondary structure of rRNAs (see Figure 4-33) is not represented here. Note that RNA constitutes about two-thirds of the mass of the ribosomal subunits, and protein about one-third. (b) Pathway for processing of 6.6-kb (35S) pre-rRNA primary transcript in S. cerevisiae. The transcribed spacer regions (tan), which are discarded during processing, separate the regions corresponding to the mature 18S, 5.8S, and 25S rRNAs. All of the intermediates diagrammed have been identified; their sizes are indicated in red type. [Part (b) adapted from S. Chu et al., 1994, Proc. Nat'l. Acad. Sci. USA 91:659.]

Figure 4-33. Two-dimensional map of the secondary structure of the small (16S) rRNA from bacteria, showing the location of base-paired stems and loops. In general, the length and position of the stem-loops are very similar in all species, although the exact sequence varies from species to species. The most highly conserved regions are represented as red lines, and the numbered stem-loops unique to prokaryotes are preceded by a P. Eukaryotic small (18S) rRNAs exhibit a generally similar pattern of stem-loops, although, as with prokaryotes, a few are unique. [Adapted from E. Huysmans and R. DeWachter, 1987, Nucl. Acids Res. 14:73].

primary structure In proteins, the linear arrangement (sequence) of amino acids and the location of covalent (mostly disulfide) bonds within a polypeptide chain.
primary transcript Initial RNA product, containing introns and exons, produced by transcription of DNA. Many primary transcripts must undergo RNA processing to form the physiologically active RNA species.
primase A specialized RNA polymerase that synthesizes short stretches of RNA used as primers for DNA synthesis.
primer A short nucleic acid sequence containing a free 3¡¬ hydroxyl group that forms base pairs with a complementary template strand and functions as the starting point for addition of nucleotides to copy the template strand.
probe Defined RNA or DNA fragment, radioactively or chemically labeled, that is used to detect specific nucleic acid sequences by hybridization.
prokaryotes Class of organisms, including the eubacteria and archaea, that lack a true membrane-limited nucleus and other organelles. See also eukaryotes.
promoter DNA sequence that determines the site of transcription initiation for an RNA polymerase.
promoter-proximal element Any regulatory sequence in eukaryotic DNA that is located within 200 base pairs of the transcription start site. Transcription of many genes is controlled by multiple promoter-proximal elements. (Figure 10-34)

prophase Earliest stage in mitosis during which the chromosomes condense and the centrioles begin moving toward the spindle poles. (Figure 19-34)

prosthetic group A nonpeptide organic molecule or metal ion that binds tightly and specifically with a protein and is required for its activity, such as heme in hemoglobin. See also coenzyme.
proteasome Large multifunctional protease complex in the cytosol that degrades intracellular proteins marked for destruction by attachment of multiple ubiquitin molecules. (Figure 3-18)

Figure 3-18. Ubiquitin-mediated proteolytic pathway. (a) A conjugating enzyme catalyzes formation of a peptide bond between ubiquitin (Ub) and the side-chain ¡VNH₂ of a lysine residue in a target protein. Additional Ub molecules are added, forming a multiubiquitin chain. This chain is thought to direct the tagged protein to a proteasome, which cleaves the protein into numerous small peptide fragments. (b) Computer-generated image reveals cylindrical structure of a proteasome with a cap at each end of a core. Proteolysis of ubiquitin-tagged proteins occurs along the inner wall of the core. [Part (b) from W. Baumeister et al., 1998, Cell 92:357. Courtesy of W. Baumeister.]

protein A linear polymer of amino acids linked together in a specific sequence and usually containing more than 50 residues. Proteins form the key structural elements in cells and participate in nearly all cellular activities.
proteoglycans A group of glycoproteins that contain a core protein to which is attached one or more glycosaminoglycans. They are found in nearly all extracellular matrices, and some are attached to the plasma membrane. (Figures 22-26 and 22-27)

Figure 22-27. Schematic diagram of the cell-surface proteoglycan syndecan-4. The core protein in all syndecan proteoglycans (syndecan-1, -2, -3, and -4) spans the plasma membrane and dimerizes through the cytoplasmic domain. Syndecan core proteins range in size from 20,000 MW (syndecan-4) to 45,000 MW (syndecan-3) because of differences in their extracellular domains, but their membrane-spanning and cytosolic domains are similar. The syndecans contain three heparan sulfate chains and sometimes chondroitin sulfate.

proton-motive force The energy equivalent of the proton (H+) concentration gradient and electric potential gradient across a membrane; used to drive ATP synthesis by ATP synthase, transport of molecules against their concentration gradient, and movement of bacterial flagella.
proto-oncogene A normal cellular gene that encodes a protein usually involved in regulation of cell growth or proliferation and that can be mutated into a cancer-promoting oncogene, either by changing the protein-coding segment or by altering its expression.
pulse-chase A type of experiment in which a radioactive small molecule is added to a cell for a brief period (the pulse) and then is replaced with an excess of the unlabeled form of same small molecule (the chase). Used to detect changes in the cellular location of a molecule or its metabolic fate over time.
pump Any transmembrane protein that mediates the active transport of an ion or small molecule across a biomembrane. (Table 15-2)

Table 15-2. Comparison of Major Classes of ATP-Powered Ion and Small-Molecule Pumps



P Class	F Class	V Class	ABC Class


Substances Transported

H⁺, Na⁺, K⁺, Ca²⁺	H⁺ only	H⁺ only	Ions and various small molecules
Structural and Functional Features

Large catalytic £\ subunits (often two) become phosphorylated during solute transport; smaller £] subunits may regulate transport.	Multiple transmembrane and cytosolic subunits generally function to synthesize ATP on £] cytosolic subunits powered by movement of H⁺ down an electrochemical gradient.	Multiple transmembrane and cytosolic subunits generally use energy released by ATP hydrolysis to pump H⁺ ions from cytosol to organelle lumens, acidifying them.	Two transmembrane domains form the pathway for solute; two cytosolic ATP-binding domains couple ATP hydrolysis to solute movement. Domains may be in one or separate subunits.
Location of Specific Pumps

Plasma membrane of plants, fungi, bacteria (H⁺ pump)	Bacterial plasma membranes	Vacuolar membranes in plants, yeast, other fungi	Bacterial plasma membranes (amino acid, sugar, and peptide transporters)
Plasma membrane of higher eukaryotes (Na⁺/K⁺ pump)	Inner mitochondrial membrane	Endosomal and lysosomal membrane in animal cells	Mammalian endoplasmic reticulum (transporters of peptides associated with antigen presentation by MHC proteins)
Apical plasma membrane of mammalian stomach cells (H⁺/K⁺ pump)	Thylakoid membrane of chloroplast	Plasma membrane of certain acid-secreting animal cells (e.g., osteoclasts and some kidney tubule cells)
Plasma membrane of all eukaryotic cells (Ca²⁺ pump)			Mammalian plasma membranes (transporters of small molecules, phospholipids, small lipidlike drugs)
Sarcoplasmic reticulum membrane in muscle cells (Ca²⁺ pump)

purines A class of nitrogenous compounds containing two fused heterocyclic rings. Two purines, adenine and guanine, commonly are found in DNA and RNA. (Figure 4-2)

Figure 4-2. The chemical structures of the principal bases in nucleic acids. In nucleic acids and nucleotides, nitrogen 9 of purines and nitrogen 1 of pyrimidines (red) are bonded to the 1¡¬ carbon of ribose or deoxyribose.

pyrimidines A class of nitrogenous compounds containing one heterocyclic ring. Two pyrimidines, cytosine and thymine, commonly are found in DNA; in RNA, uracil replaces thymine. (Figure 4-2)

Q

quaternary structure The number and relative positions of the polypeptide chains in multisubunit proteins.
quiescent Referring to a cell that has exited the cell cycle and is in the G0 state.

R

radioisotope Unstable form of an atom that emits radiation as it decays. Several radioisotopes are commonly used experimentally as labels in biological molecules.
Ras protein A monomeric GTP-binding protein that functions in intracellular signaling pathways and is activated by ligand binding to receptor tyrosine kinasesand other cell-surface receptors. See also GTPase superfamily. (Figure 20-23)

Figure 20-23. Activation of Ras following binding of a hormone (e.g., EGF) to an RTK. The adapter protein GRB2 binds to a specific phosphotyrosine on the activated RTK and to Sos, which in turn interacts with the inactive Ras ¡P GDP. The guanine nucleotide ¡V exchange factor (GEF) activity of Sos then promotes formation of the active Ras ¡P GTP. Note that Ras is tethered to the membrane by a farnesyl anchor (see Figure 3-36b). [See L. Buday and J. Downward, 1993, Cell 73:611; J. P. Olivier et al., 1993, Cell 73:179; S. E. Egan et al., 1993, Nature 363:45; E. J. Lowenstein et al., 1992, Cell 70:431; M. A. Simon et al., 1993, Cell 73:169.]

Figure 3-36. Anchoring of integral proteins to the plasma membrane by membrane-embedded hydrocarbon groups (highlighted in red). (a) Thy-1 protein and several hydrolytic enzymes are anchored by glycosylphosphatidylinositol. This complex anchor is found only on the exoplasmic face. (b) Cytosolic proteins involved in signaling such as Ras are anchored to the cytosolic face of the membrane through farnesyl and palmitoyl groups. (c) Other cytosolic proteins are associated with the membrane through myristate and similar fatty acids attached to an N-terminal glycine residue.

reading frame The sequence of nucleotide triplets (codons) that runs from a specific translation start codon in a mRNA to a stop codon. Some mRNAs can be translated into different polypeptides by reading in two different reading frames. (Figure 4-21)

Figure 4-21. Example of how the genetic code ¡X an overlapping, commaless triplet code ¡X can be read in two different frames. If translation of the mRNA sequence shown begins at two different upstream start sites (not shown), then two overlapping reading frames are possible; in this case, the codons are shifted one base to the right in the lower frame. As a result, different amino acids are encoded by the same nucleotide sequence. Many instances of such overlaps have been discovered in viral and cellular genes of prokaryotes and eukaryotes. It is theoretically possible for the mRNA to have a third reading frame.

receptor Any protein that binds a specific extracellular signaling molecule (ligand) and then initiates a cellular response. Receptors for steroid hormones, which diffuse across the plasma membrane, are located within the cell; receptors for water-soluble hormones, peptide growth factors, and neurotransmitters are located in the plasma membrane with their ligand-binding domain exposed to the external medium.
receptor tyrosine kinase (RTK) Member of an important class of cell-surface receptors whose cytosolic domain has tyrosine-specific protein kinase activity. Ligand binding activates this kinase activity and initiates intracellular signaling pathways. (Figure 20-23)

recessive In genetics, referring to that allele of a gene that is not expressed in the phenotype when the dominant allele is present. Also refers to the phenotype of an individual (homozygote) carrying two recessive alleles. (Figure 8-1)

recombinant DNA Any DNA molecule formed by joining DNA fragments from different sources. Commonly produced by cutting DNA molecules with restriction enzymes and then joining the resulting fragments from different sources with DNA ligase.
recombination Any process in which chromosomes or DNA molecules are cleaved and the fragments are rejoined to give new combinations. Occurs naturally in cells as the result of the exchange (crossing over) of DNA sequences on maternal and paternal chromatids during meiosis; also is carried out in vitro with purified DNA and enzymes.
reduction Gain of electrons by an atom or molecule as occurs when hydrogen is added to a molecule or oxygen is removed. The opposite of oxidation.
reduction potential The voltage change when an atom or molecule gains an electron.
replication fork See growing fork.
replication origin Unique DNA segments present in an organism's genome at which DNA replication begins. Eukaryotic chromosomes contain multiple origins, whereas bacterial chromosomes and plasmids often contain just one.
replicon Region of DNA served by one replication origin.
resolution The minimum distance that can be distinguished by an optical apparatus; also called resolving power.
respiration General term for any cellular process involving the uptake of O2 coupled to production of CO2.
restriction enzyme (endonuclease) Any enzyme that recognizes and cleaves a specific short sequence, the restriction site, in double-stranded DNA molecules. These enzymes are widespread in bacteria and are used extensively in recombinant DNA technology. (Table 7-1 and Figure 7-5)

Table 7-1. Selected Restriction Endonucleases and Their Restriction-Site Sequences



Source Microorganism	Enzyme*	Recognition Site (¡õ)^†	Ends Produced


Arthrobacter luteus	AluI	AG¡õCT	Blunt
Bacillus amyloliquefaciens H	BamHI	G¡õGATCC	Sticky
Escherichia coli	EcoRI	G¡õAATTC	Sticky
Haemophilus gallinarum	HgaI	GACGC+5¡õ	^‡
Haemophilus influenzae	HindIII	A¡õAGCTT	Sticky
Haemophilus parahaemolyticus	HphI	GGTGA+8¡õ	^‡
Nocardia otitiscaviaruns	NotI	GC¡õGGCCGC	Sticky
Staphylococcus aureus 3A	Sau3AI	¡õGATC	Sticky
Serratia marcesens	SmaI	CCC¡õGGG	Blunt
Thermus aquaticus	TaqI	T¡õCGA	Sticky
. Enzymes are named with abbreviations of the bacterial strains from which they are isolated; the roman numeral indicates the enzyme's priority of discovery in that strain (for example, AluI was the first restriction enzyme to be isolated from Arthrobacter luteus). ^†. Recognition sequences are written 5¡¬¡÷3¡¬ (only one strand is given), with the cleavage site indicated by an arrow. Enzymes producing blunt ends cut both strands at the indicated site; those producing stick ends make staggered cuts, with cleavage occurring between the same nucleotides in each strand as shown in Figure 7-5a. ^‡. The cleavage sites for* HphI and HgaI occur several nucleotides away from the recognition sequence. HgaI cuts five nucleotides 3¡¬ to the GACGC sequence on the top strand and ten nucleotides 5¡¬ to the complementary GTGCG sequence on the bottom strand. HphI cuts eight nucleotides 3¡¬ to the GGTGA sequence on the top strand and seven nucleotides 5¡¬ to the complementary CCACT sequence on the bottom strand. SOURCE: R. J. Roberts, 1988, Nucl. Acids Res. 16(suppl):271.

Figure 7-5. Restriction-recognition sites are short DNA sequences recognized and cleaved by various restriction endonucleases. (a) EcoRI, a restriction enzyme from E. coli, makes staggered cuts at the specific 6-bp inverted repeat sequence shown. This cleavage yields fragments with single-stranded, complementary ¡§sticky¡¨ ends. Many other restriction enzymes also produce fragments with sticky ends. (b) Bacterial cells with restriction endonucleases also contain corresponding modification enzymes that methylate bases in the restriction-recognition site. For example, E. coli cells containing the EcoRI restriction enzyme also contain EcoRI methylase, a modification enzyme that catalyzes addition of a methyl group to two adenines in the EcoRI recognition sequence. The methylated restriction site is not cleaved by EcoRI, assuring that a cell making this restriction enzyme does not destroy its own DNA.

restriction fragment A defined DNA fragment resulting from cleavage with a particular restriction enzyme. These fragments are used in the production of recombinant DNA molecules and DNA cloning.
restriction point The point in late G1 of the cell cycle at which mammalian cells become committed to entering the S phase and completing the cycle even in the absence of growth factors.
retrotransposon Type of eukaryotic mobile DNA element whose movement in the genome is mediated by an RNA intermediate and involves a reverse transcription step. See also transposon.
retrovirus A type of eukaryotic virus containing an RNA genome that replicates in cells by first making a DNA copy of the RNA. This proviral DNA is inserted into cellular chromosomal DNA, and gives rise to further genomic RNA as well as the mRNAs for viral proteins. (Figure 6-22)

Figure 6-22. Retroviral life cycle. Retroviruses have two identical copies of a plus single-stranded RNA genome and an outer envelope containing protruding viral glycoproteins. After envelope glycoproteins on a virion interact with a specific host-cell membrane protein or group of proteins, the retroviral envelope fuses directly with the plasma membrane without first undergoing endocytosis (step 1). Following fusion, the nucleocapsid enters the cytoplasm of the cell; then deoxynucleoside triphosphates from the cytosol enter the nucleocapsid, where viral reverse transcriptase and other proteins copy the ssRNA genome of the virus into a dsDNA copy (step 2). The viral DNA copy is transported into the nucleus (only one host-cell chromosome is depicted) and integrated into one of many possible sites in the host-cell chromosomal DNA (step 3). The integrated viral DNA, referred to as a provirus, is transcribed by the host-cell RNA polymerase, generating mRNAs (light red) and genomic RNA molecules (dark red). The host-cell machinery translates the viral mRNAs into glycoproteins and nucleocapsid proteins (step 4). The latter assemble with genomic RNA to form progeny nucleocapsids, which interact with the membrane-bound viral glycoproteins, as illustrated in Figure 6-17. Eventually the host-cell membrane buds out and progeny virions are pinched off (step 5). See Figures 9-20 and 9-21 for details of the reverse transcription process and the transcription and processing of viral RNA.

reverse transcriptase Enzyme found in retroviruses that catalyzes synthesis of a double-stranded DNA from a single-stranded RNA template. (Figure 9-16)

Figure 9-16. Generation of LTRs during reverse transcription of retroviral genomic RNA. A complicated series of nine events generates a double-stranded DNA copy of the single-stranded RNA genome of a retrovirus (top). The genomic RNA is packaged in the virion with a retrovirus-specific cellular tRNA hybridized to a complementary sequence near its 5¡¬ end called the primer-binding site (PBS). The retroviral RNA has a short direct-repeat terminal sequence (R) at each end. The overall reaction is catalyzed by reverse transcriptase, which catalyzes polymerization of deoxyribonucleotides and digestion of the RNA strand in a DNA-RNA hybrid. The entire process yields a double-stranded DNA molecule that is longer than the template RNA and has a long terminal repeat (LTR) at each end. The different regions are not shown to scale. The PBS and R regions are actually much shorter than the U5 and U3 regions, and the central coding region is very much longer (≈7500 nucleotides) than the other regions. [See E. Gilboa et al., 1979, Cell 18:93.]

ribosomal RNA See rRNA.
ribosome A large complex comprising several different rRNA molecules and more than 50 proteins, organized into a large subunit and small subunit; the site of protein synthesis. (Figures 4-32 and 4-34)

Figure 4-32. The general structure of ribosomes in prokaryotes and eukaryotes. In all cells, each ribosome consists of a large and a small subunit. The two subunits contain rRNAs of different lengths, as well as a different set of proteins. All ribosomes contain two major rRNA molecules (dark red) ¡X 23S and 16S rRNA in bacteria, 28S and 18S rRNA in eukaryotes ¡X and one or two small RNAs (light red). The proteins are named L1, L2, etc., and S1, S2, etc., depending on whether they are found in the large or the small subunit.

Figure 4-34. Overall structure of the E. coli ribosome at 25-Å resolution inferred from cryoelectron microscopy and three-dimensional reconstruction based on the analysis of 4300 individual projections. (a) This model shows the shapes of the large (blue) and small (yellow) subunits of the ribosome with three aminoacyl-tRNAs (pink, green, yellow) superimposed at the A, P, and E sites. The roles of these tRNA-binding sites during protein synthesis are discussed later. Chemical cross-linking experiments have demonstrated that the mRNA (orange beads) passes close to the anticodon loops of the tRNAs and that the nascent polypeptide chain is buried in the tunnel in the large ribosomal subunit that begins within 10 ¡V 15 Å of the 3¡¬ aminoacylated end of the tRNAs. The tunnel termination site on the ribosome surface has also been accurately mapped. (b) Large panel shows a field of 70S ribosomes. Small panels (left) show cryoelectron microscopy images of a single 70S ribosome, small (30S) subunit, and large (50S) subunit. Small panels (right) show computer-derived averages of many dozens of images in the same orientation. Cryoelectron microscopy is carried out on unstained samples of ribosomes or subunits flash frozen as ¡§vitreous ices¡¨ (without ice crystals) in a very thin layer of water (Chapter 5). Individual images are analyzed by computer projections. [See R. K. Agrawal et al., Cell, in press; J. Frank, 1995, Nature 356:441; J. Frank et al., 1995, Biochem. Cell Biol. 73:757. Courtesy of J. Frank.]

ribozyme An RNA molecule or segment with catalytic activity.
RNA (ribonucleic acid) Linear, single-stranded polymer, composed of ribose nucleotides, that is synthesized by transcription of DNA or by copying of RNA. The three types of cellular RNA ¡X mRNA, rRNA, and tRNA ¡X play different roles in protein synthesis.
RNA editing Unusual type of RNA processing in which the sequence of a pre-mRNA is altered.
RNA polymerase An enzyme that copies one strand of DNA or RNA (the template strand) to make the complementary RNA strand using as substrates ribonucleoside triphosphates.
RNA processing Various modifications that occur to many but not all primary transcripts to yield functional RNA molecules.
RNA splicing A process that results in removal of introns and joining of exons in RNAs. See also spliceosome. (Figure 11-16)

Figure 11-16. Splicing of exons in pre-mRNA occurs via two transesterification reactions. In the first reaction, the ester bond between the 5¡¬ phosphorus of the intron and the 3¡¬ oxygen (red) of exon 1 is exchanged for an ester bond with the 2¡¬ oxygen (dark blue) of the branch-site A residue. In the second reaction, the ester bond between the 5&iex