Principles Of Biochemistry

by Horton, Robert A; Moran, Laurence A.; Scrimgeour, Gray; Perry, Marc; Rawn, David

• ISBN13: 9780131453067
• ISBN10: 0131453068
• Edition: 4th
• Format: Hardcover
• Copyright: 2005-06-29
• Publisher: Prentice Hall

Summary

This concise, introductory text focuses on the basic principles of biochemistry, filling the gap between the encyclopedic volumes and the cursory overview texts.Principles of Biochemistry, 4/ehas a well-deserved reputation for being the most accurate biochemistry textbook in the market. Widely praised in its previous edition for currency, and clarity of exposition, the new edition has been thoroughly revised and updated to reflect recent changes in this dynamic discipline.

Table of Contents

Preface	xxv
PART ONE Introduction
Introduction to Biochemistry	1	(25)
Biochemistry Is a Modern Science	2	(1)
The Chemical Elements of Life	3	(2)
Many Important Macromolecules Are Polymers	5	(6)
Proteins	6	(1)
Polysaccharides	7	(2)
Nucleic Acids	9	(1)
Lipids and Membranes	10	(1)
The Energetics of Life	11	(4)
Reaction Rates and Equilibria	12	(1)
Thermodynamics	13	(2)
Equilibrium Constants and Standard Gibbs Free Energy Changes	15	(1)
Biochemistry and Evolution	15	(1)
The Cell Is the Basic Unit of Life	16	(1)
Prokaryotic Cells: Structural Features	17	(1)
Eukaryotic Cells: Structural Features	18	(4)
The Nucleus	18	(1)
The Endoplasmic Reticulum and Golgi Apparatus	19	(1)
Mitochondria and Chloroplasts	20	(1)
Specialized Vesicles	21	(1)
The Cytoskeleton	22	(1)
A Picture of the Living Cell	22	(2)
Biochemistry Is Multidisciplinary	24	(2)
Appendix: The Special Terminology of Biochemistry	24	(1)
Selected Readings	25	(1)
Water	26	(26)
The Water Molecule Is Polar	27	(1)
Hydrogen Bonding in Water	28	(2)
Water Is an Excellent Solvent	30	(2)
Ionic and Polar Substances Dissolve in Water	30	(1)
Cellular Concentrations and Diffusion	31	(1)
Osmotic Pressure	31	(1)
Nonpolar Substances Are Insoluble in Water	32	(1)
Noncovalent Interactions	33	(3)
Charge--charge Interactions	33	(1)
Hydrogen Bonds	34	(1)
Van der Waals Forces	35	(1)
Hydrophobic Interactions	36	(1)
Water Is Nucleophilic	36	(1)
Ionization of Water	37	(2)
The pH Scale	39	(2)
Box 2.1 The little ``p'' in pH.	40	(1)
Acid Dissociation Constants of Weak Acids	41	(5)
Buffered Solutions Resist Changes in pH	46	(6)
Summary	49	(1)
Problems	49	(2)
Selected Readings	51	(1)
PART TWO Structure and Function
Amino Acids and the Primary Structures of Proteins	52	(32)
General Structure of Amino Acids	53	(2)
Structures of the 20 Common Amino Acids	55	(6)
Box 3.1 An Alternative Nomenclature	56	(1)
Aliphatic R Groups	57	(1)
Box 3.2 Common Names of Amino Acids	57	(1)
Aromatic R Groups	58	(1)
Sulfur-Containing R Groups	58	(1)
Side Chains with Alcohol Groups	59	(1)
Basic R Groups	59	(1)
Acidic R Groups and Their Amide Derivatives	60	(1)
The Hydrophobicity of Amino Acid Side Chains	60	(1)
Other Amino Acids and Amino Acid Derivatives	61	(1)
Ionization of Amino Acids	62	(4)
Peptide Bonds Link Amino Acids in Proteins	66	(1)
Protein Purification Techniques	67	(2)
Analytical Techniques	69	(3)
Amino Acid Composition of Proteins	72	(1)
Determining the Sequence of Amino Acid Residues	73	(2)
Protein Sequencing Strategies	75	(3)
Comparisons of the Primary Structures of Proteins Reveal Evolutionary Relationships	78	(6)
Summary	81	(1)
Problems	81	(2)
Selected Readings	83	(1)
Proteins: Three-Dimensional Structure and Function	84	(45)
There Are Four Levels of Protein Structure	86	(1)
Methods for Determining Protein Structure	87	(3)
The Conformation of the Peptide Group	90	(2)
The α Helix	92	(3)
β Strands and β Sheets	95	(2)
Loops and Turns	97	(1)
Teritary Structure of Proteins	98	(6)
Supersecondary Structures	99	(1)
Domains	100	(4)
Domain Structure and Function	104	(1)
Quaternary Structure	104	(3)
Protein Denaturation and Renaturation	107	(3)
Protein Folding and Stability	110	(5)
The Hydrophobic Effect	110	(1)
Hydrogen Bonding	111	(1)
Van der Waals Interactions and Charge--Charge Interactions	112	(1)
Protein Folding Is Assisted by Molecular Chaperones	112	(3)
Collagen, a Fibrous Protein	115	(1)
Structures of Myoglobin and Hemoglobin	116	(2)
Oxygen Binding to Myoglobin and Hemoglobin	118	(5)
Oxygen Binds Reversibly to Heme	118	(1)
Oxygen-Binding Curves of Myoglobin and Hemoglobin	119	(2)
Hemoglobin Is an Allosteric Protein	121	(2)
Antibodies Bind Specific Antigens	123	(6)
Summary	125	(1)
Problems	125	(2)
Selected Readings	127	(2)
Properties of Enzymes	129	(29)
The Six Classes of Enzymes	130	(2)
Kinetic Experiments Reveal Enzyme Properties	132	(3)
Chemical Kinetics	133	(1)
Enzyme Kinetics	134	(1)
The Michaelis--Menten Equation	135	(4)
Derivation of the Michaelis--Menten Equation	137	(1)
The Catalytic Constant kcat	138	(1)
The Meanings of Km	138	(1)
Kinetic Constants Indicate Enzyme Activity and Catalytic Proficiency	139	(1)
Measurement of Km and Vmax	140	(1)
Kinetics of Multisubstrate Reactions	141	(1)
Box 5.1 Hyperbolas versus Straight Lines	141	(1)
Reversible Enzyme Inhibition	142	(5)
Competitive Inhibition	143	(2)
Uncompetitive Inhibition	145	(1)
Noncompetitive Inhibition	146	(1)
Uses of Enzyme Inhibition	146	(1)
Irreversible Enzyme Inhibition	147	(1)
Allosteric Enzymes	148	(1)
Regulation of Enzyme Activity	148	(6)
Phosphofructokinase Is an Allosteric Enzyme	149	(1)
General Properties of Allosteric Enzymes	150	(2)
Two Theories of Allosteric Regulation	152	(1)
Regulation by Covalent Modification	153	(1)
Multienzyme Complexes and Multifunctional Enzymes	154	(4)
Summary	154	(1)
Problems	155	(2)
Selected Readings	157	(1)
Mechanisms of Enzymes	158	(34)
The Terminology of Mechanistic Chemistry	158	(2)
Nucleophilic Substitutions	159	(1)
Cleavage Reactions	160	(1)
Oxidation---Reduction Reactions	160	(1)
Catalysts Stabilize Transition States	160	(2)
Chemical Modes of Enzymatic Catalysis	162	(5)
Box 6.1 Site-Directed Mutagenesis Modifies Enzymes	163	(1)
Polar Amino Acid Residues in Active Sites	163	(1)
Acid-Base Catalysis	164	(1)
Covalent Catalysis	165	(1)
pH Affects Enzymatic Rates	166	(1)
Diffusion-Controlled Reactions	167	(4)
Triose Phosphate Isomerase	167	(3)
Superoxide Dismutase	170	(1)
Binding Modes of Enzymatic Catalysis	171	(7)
The Proximity Effect	172	(1)
Weak Binding of Substrates of Enzymes	172	(2)
Induced Fit	174	(1)
Transition-State Stabilization	175	(3)
Lysozyme	178	(4)
Box 6.2 Proposed Transition State for a Bimolecular Reaction	181	(1)
Properties of Serine Proteases	182	(10)
Zymogens Are Inactive Enzyme Precursors	182	(1)
Substrate Specificity of Serine Proteases	183	(1)
Serine Proteases Use Both the Chemical and the Binding Modes of Catalysis	184	(4)
Summary	188	(1)
Problems	188	(3)
Selected Readings	191	(1)
Coenzymes and Vitamins	192	(30)
Many Enzymes Require Inorganic Cations	193	(1)
Coenzyme Classification	193	(3)
Box 7.1 Vitamin C: A Vitamin but Not a Coenzyme	195	(1)
ATP and Other Nucleotide Cosubstrates	196	(1)
NADP and NAD	197	(3)
Box 7.2 NAD Binding to Dehydrogenases	199	(1)
FAD and FMN	200	(1)
Coenzyme A	201	(1)
Thiamine Pyrophosphate	202	(1)
Pyridoxal Phosphate	203	(4)
Biotin	207	(1)
Tetrahydrofolate	208	(2)
Cobalamin	210	(1)
Lipoamide	211	(1)
Lipid Vitamins	212	(2)
Vitamin A	213	(1)
Vitamin D	213	(1)
Vitamin E	213	(1)
Vitamin K	214	(1)
Ubiquinone	214	(1)
Protein Coenzymes	215	(1)
Cytochromes	216	(6)
Summary	218	(1)
Problems	219	(2)
Selected Readings	221	(1)
Carbohydrates	222	(31)
Most Monosaccharides Are Chiral Compounds	223	(3)
Cyclization of Aldoses and Ketoses	226	(3)
Conformations of Monosaccharides	229	(2)
Derivatives of Monosaccharides	231	(3)
Sugar Phosphates	231	(1)
Deoxy Sugars	231	(1)
Amino Sugars	231	(1)
Sugar Alcohols	232	(1)
Sugar Acids	233	(1)
Ascorbic Acid	234	(1)
Disaccharides and Other Glycosides	234	(3)
Structures of Disaccharides	234	(2)
Reducing and Nonreducing Sugars	236	(1)
Nucleosides and Other Glycosides	236	(1)
Polysaccharides	237	(4)
Starch and Glycogen	237	(2)
Cellulose and Chitin	239	(2)
Glycoconjugates	241	(12)
Proteoglycans	241	(2)
Box 8.1 Nodulation Factors Are Lipo-oligosaccharides	243	(1)
Peptidoglycans	243	(1)
Glycoproteins	244	(4)
Box 8.2 ABO Blood Group	248	(1)
Summary	249	(1)
Problems	250	(2)
Selected Readings	252	(1)
Lipids and Membranes	253	(43)
Structural and Functional Diversity of Lipids	253	(1)
Fatty Acids	254	(4)
Box 9.1 Common Names of Fatty Acids	255	(1)
Box 9.2 Trans Fatty Acids and Margarine	256	(2)
Triacylglycerols	258	(1)
Glycerophospholipids	259	(3)
Sphingolipids	262	(2)
Steroids	264	(1)
Other Biologically Important Lipids	265	(2)
Biological Membranes Are Composed of Lipid Bilayers and Proteins	267	(4)
Box 9.3 Special Nonaqueous Techniques Must Be Used to Study Lipids	268	(1)
Lipid Bilayers	269	(1)
Fluid Mosaic Model of Biological Membranes	270	(1)
Lipid Bilayers and Membranes Are Dynamic Structures	271	(3)
Three Classes of Membrane Proteins	274	(4)
Box 9.4 New Lipid Vesicles, or Liposomes	275	(3)
Membrane Transport	278	(6)
Thermodynamics of Membrane Transport	279	(1)
Pores and Channels	280	(1)
Passive Transport	281	(1)
Active Transport	281	(2)
Endocytosis and Exocytosis	283	(1)
Box 9.5 The Hot Spice of Chili Peppers	284	(1)
Transduction of Extracellular Signals	284	(12)
G Proteins Are Signal Transducers	285	(2)
The Adenylyl Cyclase Signaling Pathway	287	(1)
The Inositol--Phospholipid Signaling Pathway	288	(1)
Box 9.6 Bacterial Toxins and G Proteins	289	(2)
Receptor Tyrosine Kinases	291	(1)
Summary	292	(1)
Problems	292	(2)
Selected Readings	294	(2)
PART THREE Metabolism and Bioenergetics
Introduction to Metabolism	296	(31)
Metabolism Is the Sum of Cellular Reactions	296	(2)
Metabolic Pathways	298	(6)
Pathways Are Sequences of Reactions	299	(1)
Metabolism Proceeds by Discrete Steps	300	(1)
Metabolic Pathways Are Regulated	301	(2)
Evolution of Metabolic Pathways	303	(1)
Major Pathways in Cells	304	(2)
Compartmentation and Interorgan Metabolism	306	(2)
Actual Gibbs Free Energy Change, Not Standard Free Energy Change, Determines the Spontaneity of Metabolic Reactions	308	(2)
The Free Energy of ATP	310	(3)
The Metabolic Roles of ATP	313	(4)
Phosphoryl-Group Transfer	314	(1)
Production of ATP by Phosphoryl Group Transfer	315	(1)
Nucleotidyl Group Transfer	316	(1)
Thioesters Have High Free Energies of Hydrolysis	317	(1)
Reduced Coenzymes Conserve Energy from Biological Oxidations	318	(5)
Gibbs Free Energy Change Is Related to Reduction Potential	319	(3)
Electron Transfer from NADH Provides Free Energy	322	(1)
Box 10.1 NAD and NADH Differ in Their Ultraviolet Absorption Spectra	322	(1)
Experimental Methods for Studying Metabolism	323	(4)
Summary	324	(1)
Problems	324	(2)
Selected Readings	326	(1)
Glycolysis	327	(30)
The Enzymatic Reactions of Glycolysis	328	(1)
The Ten Enzyme-Catalyzed Steps of Glycolysis	328	(12)
Box 11.1 A Brief History of the Glycolytic Pathway	332	(6)
Box 11.2 Formation of 2,3-Bisphosphoglycerate in Red Blood Cells	338	(2)
Box 11.3 Arsenate Poisoning	340	(1)
The Fate of Pyruvate	340	(3)
Metabolism of Pyruvate to Ethanol	341	(1)
Reduction of Pyruvate to Lactate	342	(1)
Free Energy Changes in Glycolysis	343	(1)
Regulation of Glycolysis	344	(6)
Regulation of Hexose Transporters	344	(2)
Regulation of Hexokinase	346	(1)
Box 11.4 Glucose 6-Phosphate Has a Pivotal Metabolic Role in the Liver	346	(1)
Regulation of Phosphofructokinase-1	347	(1)
Regulation of Pyruvate Kinase	348	(2)
The Pasteur Effect	350	(1)
Other Sugars Can Enter Glycolysis	350	(2)
Fructose Is Converted to Glyceraldehyde 3-Phosphate	350	(1)
Galactose Is Converted to Glucose 1-Phosphate	351	(1)
Mannose Is Converted to Fructose 6-Phosphate	352	(1)
The Entner--Doudoroff Pathway in Bacteria	352	(5)
Summary	354	(1)
Problems	354	(1)
Selected Readings	355	(2)
Gluconeogenesis, The Pentose Phosphate Pathway, and Glycogen Metabolism	357	(27)
Gluconeogenesis	358	(4)
Pyruvate Carboxylase	359	(1)
Phosphoenolpyruvate Carboxykinase	360	(1)
Fructose 1,6-bisphosphatase	361	(1)
Glucose 6-phosphatase	361	(1)
Precursors for Gluconeogenesis	362	(2)
Lactate	362	(1)
Amino Acids	363	(1)
Glycerol	363	(1)
Propionate and Lactate	363	(1)
Acetate	364	(1)
Regulation of Gluconeogenesis	364	(2)
Box 12.1 Glucose Is Sometimes Converted to Sorbitol	366	(1)
The Pentose Phosphate Pathway	366	(5)
Oxidative Stage	368	(1)
Nonoxidative Stage	368	(1)
Box 12.2 Glucose 6-phosphate Dehydrogenase Deficiency in Humans	369	(1)
Interconversions Catalyzed by Transketolase and Transaldolase	370	(1)
Glycogen Metabolism	371	(3)
Glycogen Synthesis	371	(1)
Glycogen Degradation	372	(2)
Regulation of Glycogen Metabolism	374	(5)
Hormones Regulate Glycogen Metabolism	375	(1)
Reciprocal Regulation of Glycogen Phosphorylase and Glycogen Synthase	375	(1)
Intracellular Regulation of Glycogen Metabolism Involves Interconvertible Enzymes	376	(2)
Box 12.3 Glycogen Storage Diseases	378	(1)
Maintenance of Glucose Levels in Mammals	379	(5)
Summary	381	(1)
Problems	382	(1)
Selected Readings	383	(1)
The Citric Acid Cycle	384	(31)
Conversion of Pyruvate to Acetyl CoA	385	(6)
The Citric Acid Cycle Oxidizes Acetyl CoA	391	(2)
The Citric Acid Cycle Enzymes	393	(10)
Box 13.1 Where Do the Electrons Come From?	394	(3)
Box 13.2 Three-point Attachment of Prochiral Substrates to Enzymes	397	(5)
Box 13.3 Converting One Enzyme into Another	402	(1)
Reduced Coenzymes Can Fuel the Production of ATP	403	(1)
Regulation of the Citric Acid Cycle	404	(2)
The Citric Acid Cycle Isn't Always a ``Cycle''	406	(1)
The Glyoxylate Pathway	407	(3)
Evolution of the Citric Acid Cycle	410	(5)
Summary	354	(1)
Problems	354	(1)
Selected Readings	355	(60)
Electron Transport and ATP Synthesis	415	(29)
Overview of Membrane-associated Electron Transport and ATP Synthesis	416	(1)
The Mitochondrion	416	(2)
The Chemiosmotic Theory and the Protonmotive Force	418	(3)
Historical Background: The Chemiosmotic Theory	418	(2)
The Protonmotive Force	420	(1)
Electron Transport	421	(3)
``Complexes I Through IV	421	(3)
Cofactors in Electron Transport	424	(1)
Complex I	424	(1)
Complex II	425	(2)
Complex III	427	(2)
Complex IV	429	(3)
Complex V: ATP Synthase	432	(3)
Box 14.1 Proton Leaks and Heat Production	435	(1)
Active Transport of ATP, ADP, and Pi Across the Mitochondrial Membrane	435	(1)
The P/O Ratio	436	(1)
NADH Shuttle Mechanisms in Eukaryotes	436	(3)
Box 14.2 The High Cost of Living	439	(1)
Other Terminal Electron Acceptors and Donors	439	(1)
Superoxide Anions	440	(4)
Summary	441	(1)
Problems	441	(1)
Selected Readings	442	(2)
Photosynthesis	444	(35)
Light-Gathering Pigments	445	(4)
Bacterial Photosystems	449	(11)
Photosystem II	449	(3)
Photosystem I	452	(2)
Coupled Photosystems and Cytochrome bf	454	(4)
Reduction Potentials and Gibbs Free Energy in Photosynthesis	458	(1)
Photosynthesis Takes Place within Internal Membranes	459	(1)
Plant Photosynthesis	460	(4)
Chloroplasts	460	(1)
Box 15.1 Bacteriorhodopsin	461	(2)
Plant Photosystems	463	(1)
Organization of Chloroplast Photosystems	463	(1)
Fixation of CO2: The Calvin Cycle	464	(7)
The Calvin Cycle	465	(1)
Rubisco: Ribulose 1,5-bisphosphate Carboxylase-oxygenase	465	(4)
Oxygenation of Ribulose 1,5-Bisphosphate	469	(1)
Calvin Cycle: Reduction and Regeneration Stages	470	(1)
Box 15.2 Building a Better Rubisco	470	(1)
Sucrose and Starch Metabolism in Plants	471	(2)
Additional Carbon-Fixation Pathways	473	(6)
Box 15.3 Gregor Mendel's Wrinkled Peas	473	(1)
The C4 Pathway	474	(1)
Crassulacean Acid Metabolism (CAM)	474	(2)
Carbon Fixation in Bacteria	476	(1)
Summary	477	(1)
Problems	477	(1)
Selected Readings	478	(1)
Lipid Metabolism	479	(41)
Fatty Acid Synthesis	480	(5)
Synthesis of Malonyl ACP and Acetyl ACP	480	(1)
The Initiation Reaction of Fatty Acid Synthesis	481	(1)
The Elongation Reactions of Fatty Acid Synthesis	482	(1)
Activation of Fatty Acids	483	(1)
Fatty Acid Extension and Desaturation	484	(1)
Synthesis of Triacylglycerols and Glycerophospholipids	485	(3)
Synthesis of Eicosanoids	488	(2)
Box 16.1 The Search for a Replacement for Aspirin	490	(1)
Synthesis of Ether Lipids	490	(1)
Synthesis of Sphingolipids	491	(4)
Box 16.2 Lysosomal Storage Diseases	493	(1)
Box 16.3 Regulating Cholesterol Levels	494	(1)
Synthesis of Cholesterol	495	(3)
Stage 1: Acetyl CoA to Isopentenyl Diphosphate	495	(1)
Stage 2: Isopentenyl Diphosphate to Squalene	496	(1)
Stage 3: Squalene to Cholesterol	496	(1)
Other Products of Isoprenoid Metabolism	496	(2)
Fatty Acid Oxidation	498	(8)
The Reactions of β-Oxidation	499	(1)
Fatty Acid Synthesis and β-Oxidation	500	(1)
Transport of Fatty Acyl CoA into Mitochondria	501	(1)
Box 16.4 A Trifunctional Enzyme for β-Oxidation	502	(1)
ATP Generation from Fatty Acid Oxidation	502	(2)
β-Oxidation of Odd-Chain and Unsaturated Fatty Acids	504	(2)
Eukaryotic Lipids Are Made at a Variety of Sites	506	(1)
Lipid Metabolism Is Regulated by Hormones in Mammals	507	(2)
Absorption and Mobilization of Fuel Lipids in Mammals	509	(4)
Absorption of Dietary Lipids	509	(1)
Lipoproteins	510	(3)
Box 16.5 Lipoprotein Lipase and Coronary Heart Disease	513	(1)
Serum Albumin	513	(1)
Ketone Bodies Are Fuel Molecules	513	(7)
Ketone Bodies Are Synthesized in the Liver	514	(1)
Ketone Bodies Are Oxidized in Mitochondria	515	(1)
Box 16.6 Altered Carbohydrate and Lipid Metabolism in Diabetes	516	(1)
Summary	517	(1)
Problems	517	(2)
Selected Readings	519	(1)
Amino Acid Metabolism	520	(37)
The Nitrogen Cycle and Nitrogen Fixation	521	(2)
Assimilation of Ammonia	523	(3)
Ammonia Is Incorporated into Glutamate and Glutamine	524	(1)
Transamination Reactions	524	(2)
Synthesis of Amino Acids	526	(10)
Aspartate and Asparagine	526	(1)
Box 17.1 Childhood Acute Lymphoblastic Leukemia Can Be Treated with Asparaginase	526	(1)
Lysine, Methionine, and Threonine	527	(1)
Alanine, Valine, Leucine, and Isoleucine	528	(1)
Glutamate, Glutamine, Arginine, and Proline	529	(1)
Serine, Glycine, and Cysteine	530	(1)
Phenylalanine, Tyrosine, and Tryptophan	531	(4)
Box 17.2 Genetically Modified Food
Box 17.3 Essential and Nonessential Amino Acids in Animals
Histidine	535	(1)
Amino Acids as Metabolic Precursors	536	(2)
Products Derived from Glutamate, Glutamine, and Aspartate	536	(1)
Products Derived from Serine and Glycine	536	(1)
Synthesis of Nitric Oxide from Arginine	536	(2)
Protein Turnover	538	(1)
Box 17.4 Apoptosis---Programmed Cell Death	538	(1)
Amino Acid Catabolism	539	(10)
Alanine, Asparagine, Aspartate, Glutamate, and Glutamine	541	(1)
Arginine, Histidine, and Proline	541	(1)
Glycine and Serine	542	(1)
Threonine	543	(1)
The Branched-Chain Amino Acids	543	(2)
Methionine	545	(1)
Cysteine	546	(1)
Phenylalanine, Tryptophan, and Tyrosine	546	(1)
Box 17.5 Phenylketonuria, a Defect in Tyrosine Formation	546	(2)
Lysine	548	(1)
Box 17.6 Diseases of Amino Acid Metabolism	548	(1)
The Urea Cycle Converts Ammonia into Urea	549	(4)
Synthesis of Carbamoyl Phosphate	549	(1)
The Reactions of the Urea Cycle	549	(1)
Ancillary Reactions of the Urea Cycle	550	(1)
Box 17.7 The Liver Is Organized for Removing Toxic Ammonia	551	(2)
Renal Glutamine Metabolism Produces Bicarbonate	553	(4)
Summary	554	(1)
Problems	555	(1)
Selected Readings	556	(1)
Nucleotide Metabolism	557	(26)
Synthesis of Purine Nucleotides	558	(3)
Other Purine Nucleotides Are Synthesized from IMP	561	(2)
Box 18.1 Common Names of the Bases	561	(2)
Synthesis of Pyrimidine Nucleotides	563	(5)
The Pathway for Pyrimidine Synthesis	564	(1)
Box 18.2 How Some Enzymes Transfer Ammonia from Glutamine	565	(1)
Regulation of Pyrimidine Synthesis	566	(2)
CTP Is Synthesized from UMP	568	(1)
Reduction of Ribonucleotides to Deoxyribonucleotides	569	(1)
Methylation of dUMP Produces dTMP	570	(3)
Box 18.3 Free Radicals in the Reduction of Ribonucleotides	570	(2)
Box 18.4 Cancer Drugs Inhibit dTTP Synthesis	572	(1)
Salvage of Purines and Pyrimidines	573	(1)
Purine Catabolism	574	(4)
Box 18.5 Lesch-Nyhan Syndrome and Gout	574	(4)
The Purine Nucleotide Cycle in Muscle	578	(1)
Pyrimidine Catabolism	579	(4)
Summary	580	(1)
Problems	580	(1)
Selected Readings	581	(2)
PART FOUR Biological Information Flow
Nucleic Acids	583	(32)
Nucleotides Are the Building Blocks of Nucleic Acids	584	(6)
Ribose and Deoxyribose	584	(1)
Purines and Pyrimidines	585	(1)
Nucleosides	586	(1)
Nucleotides	587	(3)
DNA Is Double-Stranded	590	(7)
Nucleotides Are Joined by 3'--5' Phosphodiester Linkages	590	(2)
Two Antiparallel Strands Form a Double Helix	592	(3)
Weak Forces Stabilize the Double Helix	595	(2)
Conformations of Double-Stranded DNA	597	(1)
DNA Can Be Supercoiled	597	(2)
Cells Contain Several Kinds of RNA	599	(1)
DNA Is Packaged in Chromatin in Eukaryotic Cells	599	(6)
Nucleosomes	600	(1)
Box 19.1 Histones Can Be Acetylated and Deacetylated	601	(2)
Higher Levels of Chromatin Structure	603	(1)
Bacterial DNA Packaging	604	(1)
Nucleases and Hydrolysis of Nucleic Acids	605	(5)
Alkaline Hydrolysis of RNA	605	(1)
Ribonuclease-Catalyzed Hydrolysis of RNA	605	(3)
Restriction Endonucleases	608	(2)
EcoRI Binds Tightly to DNA	610	(1)
Uses of Restriction Endonucleases	610	(5)
Summary	612	(1)
Problems	612	(1)
Selected Readings	613	(2)
DNA Replication, Repair, and Recombination	615	(32)
Chromosomal DNA Replication Is Bidirectional	616	(2)
DNA Polymerase	618	(4)
Chain Elongation Is a Nucleotidyl-Group-Transfer Reaction	619	(2)
DNA Polymerase III Remains Bound to the Replication Fork	621	(1)
Proofreading Corrects Polymerization Errors	621	(1)
DNA Polymerase Synthesizes Two Strands Simultaneously	622	(4)
Lagging-Strand Synthesis Is Discontinuous	623	(1)
Each Okazaki Fragment Begins with an RNA Primer	623	(1)
Okazaki Fragments Are Joined by the Action of DNA Polymerase I and DNA Ligase	624	(2)
Model of the Replisome	626	(3)
Initiation and Termination of DNA Replication	629	(1)
DNA Replication in Eukaryotes	630	(4)
Box 20.1 Sequencing DNA Using Dideoxynucleotides	632	(2)
Repair of Damaged DNA	634	(5)
Repair after Photodimerization: An Example of Direct Repair	635	(1)
Excision Repair	635	(4)
Homologous Recombination	639	(8)
The Holliday Model of General Recombination	639	(1)
Recombination in E. coli	640	(1)
Recombination Can Be a Form of Repair	641	(2)
Box 20.2 Molecular Links Between DNA Repair and Breast Cancer	643	(1)
Summary	644	(1)
Problems	645	(1)
Selected Readings	646	(1)
Transcription and RNA Processing	647	(36)
Types of RNA	648	(1)
RNA Polymerase	649	(3)
RNA Polymerase Is an Oligomeric Protein	649	(1)
The Chain Elongation Reaction	650	(2)
Transcription Initiation	652	(4)
Genes Have a 5'→3' Orientation	652	(1)
The Transcription Complex Assembles at a Promoter	652	(3)
The σ Subunit Recognizes the Promoter	655	(1)
RNA Polymerase Changes Conformation	655	(1)
Transcription Termination	656	(3)
Transcription in Eukaryotes	659	(4)
Eukaryotic RNA Polymerases	659	(3)
Eukaryotic Transcription Factors	662	(1)
The Role of Chromatin in Eukaryotic Transcription	663	(1)
Transcription of Genes Is Regulated	663	(2)
The lac Operon, an Example of Negative and Positive Regulation	665	(5)
lac Repressor Blocks Transcription	665	(2)
The Structure of lac Repressor	667	(1)
cAMP Regulatory Protein Activates Transcription	668	(2)
Posttranscriptional Modification of RNA	670	(4)
Transfer RNA Processing	671	(1)
Ribosomal RNA Processing	672	(2)
Eukaryotic mRNA Processing	674	(9)
Eukaryotic mRNA Molecules Have Modified Ends	674	(3)
Some Eukaryotic mRNA Precursors Are Spliced	677	(3)
Summary	680	(1)
Problems	680	(2)
Selected Readings	682	(1)
Protein Synthesis	683	(36)
The Genetic Code	683	(3)
Transfer RNA	686	(2)
The Three-Dimensional Structure of tRNA	686	(2)
tRNA Anticodons Base-Pair with mRNA Codons	688	(1)
Aminoacyl-tRNA Synthetases	688	(4)
The Aminoacyl-tRNA Synthetase Reaction	689	(1)
Specificity of Aminoacyl-tRNA Synthetases	689	(2)
Proofreading Activity of Aminoacyl-tRNA Synthetases	691	(1)
Ribosomes	692	(3)
Ribosomes Are Composed of Both Ribosomal RNA and Protein	693	(2)
Ribosomes Contain Two Aminoacyl-tRNA Binding Sites	695	(1)
Initiation of Translation	695	(2)
Initiator tRNA	695	(1)
Initiation Complexes Assemble Only at Initiation Codons	695	(1)
Initiation Factors Help Form the Initiation Complex	696	(1)
Translation Initiation in Eukaryotes	697	(1)
Chain Elongation Is a Three-Step Microcycle	697	(8)
Elongation Factors Dock an Aminoacyl-tRNA in the A Site	699	(1)
Peptidyl Transferase Catalyzes Peptide Bond Formation	700	(1)
Translocation Moves the Ribosome by One Codon	701	(4)
Termination of Translation	705	(1)
Protein Synthesis Is Energetically Expensive	705	(1)
Regulation of Protein Synthesis	705	(7)
Ribosomal Protein Synthesis Is Coupled to Ribosome Assembly in E. coli	706	(1)
Box 22.1 Some Antibiotics Inhibit Protein Synthesis	707	(1)
Globin Synthesis Depends on Heme Availability	707	(1)
The E. coli trp Operon Is Regulated by Repression and Attenuation	708	(4)
Posttranslational Processing	712	(7)
The Signal Hypothesis	712	(4)
Glycosylation of Proteins	716	(1)
Summary	716	(1)
Problems	717	(1)
Selected Readings	718	(1)
Recombinant DNA Technology	719	(30)
Making Recombinant DNA	719	(2)
Cloning Vectors	721	(6)
Plasmid Vectors	723	(1)
Bacteriophage λ Vectors	723	(1)
Shuttle Vectors	724	(1)
Yeast Artificial Chromosomes as Vectors	724	(3)
Identification of Host Cells Containing Recombinant DNA	727	(1)
Selection Strategies Use Marker Genes	727	(1)
Selection in Eukaryotes	727	(1)
Visual Markers: Insertional Inactivation of the β-Galactosidase Gene	727	(1)
Genomic Libraries	728	(1)
Box 23.1 The Human Genome Project	728	(1)
cDNA Libraries Are Made from Messenger RNA	729	(1)
Screening a Library	730	(3)
Chromosome Walking	733	(1)
Expression of Proteins Using Recombinant DNA Technology	734	(1)
Prokaryotic Expression Vectors	734	(1)
Expression of Proteins in Eukaryotes	734	(1)
Applications of Recombinant DNA Technology	735	(4)
Genetic Engineering of Plants	737	(1)
Genetic Engineering in Prokaryotes	737	(2)
Applications to Human Diseases	739	(2)
The Polymerase Chain Reaction Amplifies Selected DNA Sequences	741	(2)
Box 23.2 Medical Uses of PCR	741	(2)
Site-Directed Mutagenesis of Cloned DNA	743	(6)
Summary	744	(1)
Problems	745	(2)
Selected Readings	747	(2)
Solutions	749	(60)
Illustration Credits	809	(2)
Glossary	811	(16)
Index	827