DONALD VOET

JUDITH G. VOET

BIOCHEMISTRYSECOND EDITION

JOHN WILEY & SONS, INC.New York Chichester Brisbane

Toronto Singapore

1995, by John Wiley & Sons, Inc.

:0-471-58651-X

I. INTRODUCTION AND IV. METABOLISM 411BACKGROUND 1

15. Introduction to Metabolism 4121. Life 2 16. Glycolysis 4432. Aqueous Solutions 29 17. Glycogen Metabolism 4843. Thermodynamic Principles: A Review 42 18. Transport through Membranes 513

19. The Citric Acid Cycle 53820. Electron Transport and Oxidative

Phosphorylation 56321. Other Pathways of Carbohydrate

II. BIOMOLECULES 55Metabolism 599

22. Photosynthesis 626

4. Amino Acids 56 23. Lipid Metabolism 662

5. Techniques of Protein Purification 71 24. Amino Acid Metabolism 727

6. Covalent Structures of Proteins 105 25. Energy Metabolism: Integration and Organ7. Three-Dimensional Structures of Proteins 141 Specialization 785

8. Protein Folding, Dynamics, and Structural 26. Nucleotide Metabolism 795

Evolution 191

9. Hemoglobin: Protein Function inV. EXPRESSION AND TRANSMISSIONMicrocosm 215

10. Sugars and Polysaccharides 251 OF GENETIC INFORMATION 829

11. Lipids and Membranes 277 27. DNA: The Vehicle of Inheritance 83028. Nucleic Acid Structures and

Manipulation 848

29. Transcription 915

30. Translation 959

III. MECHANISMS OF ENZYME 31. DNA Replication, Repair, and

ACTION 331Recombination 1020

32. Viruses: Paradigms for Cellular12. Introduction to Enzymes 332 Functions 1074

13. Rates of Enzymatic Reactions 345 33. Eukaryotic Gene Expression 1123

14. Enzymatic Catalysis 371 34. Molecular Physiology 1196

I. INTRODUCTION AND 7. Three-Dimensional Structures of Proteins 141BACKGROUND 1 1. Secondary Structure 141

2. Fibrous Proteins 1531. Life 2 3. Globular Proteins 1621. Prokaryotes 2 4. Protein Stability 1742. Eukaryotes 6 5. Quaternary Structure 1803. Biochemistry: A Prologue 13 Appendix: Viewing Stereo Pictures 1854. The Origin of Life 185. The Biochemical Literature 24 8. Protein Folding, Dynamics, and Structural

Evolution 1912. Aqueous Solutions 29 1. Protein Folding: Theory and Experiment 1911. Properties of Water 29 2. Protein Dynamics 2052. Acids, Bases, and Buffers 34 3. Structural Evolution 208

3. Thermodynamic Principles: A Review 42 9. Hemoglobin: Protein Function in1. First Law of Thermodynamics: Energy is Conserved 43 Microcosm 2152. Second Law of Thermodynamics: The Universe Tends 1. Hemoglobin Function 216

Towards Maximum Disorder 44 2. Structure and Mechanism 2233. Free Energy: The Indicator of Spontaneity 47 3. Abnormal Hemoglobins 2354. Chemical Equilibria 48 4. Allosteric Regulation 241Appendix: Concentration Dependence of Free Energy 51 Appendix: Derivation of Symmetry Model Equations 247

10. Sugars and Polysaccharides 251

II. BIOMOLECULES 55 I. Monosaccharides 2522. Polysaccharides 258

4. Amino Acids 56 3. Glycoproteins 266

1. Amino Acids of Proteins 562. Optical Activity 62 11. Lipids and Membranes 2773. "Nonstandard" Amino Acids 6 7

1. Lipid Classification 2782. Properties of Lipid Aggregates 285

5. Techniques of Protein Purification 71 3. Biological Membranes 2901. Protein Isolation 72 4. Membrane Assembly and Protein Targeting 305

2. Solubilities of Proteins 75 5. Lipid-Linked Proteins and Lipoproteins 314

3. Chromatographic Separations 784. Electrophoresis 895. Ultracentrifugation 97 III. MECHANISMS OF ENZYME

ACTION 3316. Covalent Structures of Proteins 105

1. Primary Structure Determination 106 12. Introduction to Enzymes 3322. Protein Modification 119 1. Historical Perspective 3333. Chemical Evolution 123 2. Substrate Specificity 3334. Polypeptide Synthesis 132 3. Coenzymes 337

4. Regulation of Enzymatic Activity 338 3. Enzymes of the Citric Acid Cycle 5485. A Primer of Enzyme Nomenclature 343 4. Regulation of the Citric Acid Cycle 557

5. The Amphibolic Nature of the Citric Acid Cycle 559

13. Rates of Enzymatic Reactions 345

1. Chemical Kinetics 346 20. Electron Transport and Oxidative2. Enzyme Kinetics 351 Phosphorylation 5633. Inhibition 3554. Effects of pH 360 1. The Mitochondrion 564

5. Bisubstrate Reactions 362 2. Electron Transport 568

Appendix: Derivations of Michaelis-Menten Equation 3. Oxidative Phosphorylation 582

Variants 366 4. Control of ATP Production 593

14. Enzymatic Catalysis 371 21. Other Pathways of Carbohydrate1. Catalytic Mechanisms 371 Metabolism 5992. Lysozyme 381 1. Gluconeogenesis 5993. Serine Proteases 389 2. The Glyoxylate Pathway 6064. Glutathione Reductase 400 3. Biosynthesis of Oligosaccharides and Glycoproteins 608

4. The Pentose Phosphate Pathway 617IV. METABOLISM 411

15. Introduction to Metabolism 412 22. Photosynthesis 626

1. Metabolic Pathways 414 1. Chloroplasts 6272. Organic Reaction Mechanisms 415 2. Light Reactions 6283. Experimental Approaches to the Study of 3. Dark Reactions 649

Metabolism 4214. Thermodynamics of Phosphate Compounds 4285. Oxidation - Reduction Reactions 434 23. Lipid Metabolism 6626. Thermodynamics of Life 437 1. Lipid Digestion, Absorption, and Transport 662

2. Fatty Acid Oxidation 66616. Glycolysis 443 3. Ketone Bodies 678

1. The Glycolytic Pathway 444 4. Fatty Acid Biosynthesis 680

2. The Reactions of Glycolysis 447 5. Regulation of Fatty Acid Metabolism 688

3. Fermentation: The Anaerobic Fate of Pyruvate 464 6. Cholesterol Metabolism 690

4. Control of Metabolic Flux 470 7. Arachidonate Metabolism: Prostaglandins, Prostacyclins,Thromboxanes, and Leukotrienes 7045. Metabolism of Hexoses Other Than Glucose 476

8. Phospholipid and Glycolipid Metabolism 713

17. Glycogen Metabolism 484

1. Glycogen Breakdown 485 24. Amino Acid Metabolism 727

2. Glycogen Synthesis 491 1. Amino Acid Deamination 7283. Control of Glycogen Metabolism 493 2. The Urea Cycle 7314. Glycogen Storage Diseases 507 3. Metabolic Breakdown of Individual Amino Acids 735

4. Amino Acids as Biosynthetic Precursors 749

18. Transport Through Membranes 513 5. Amino Acid Biosynthesis 764

1. Thermodynamics of Transport 5136. Nitrogen Fixation 776

2. Kinetics and Mechanisms of Transport 514

3. ATP-Driven Active Transport 524 25. Energy Metabolism: Integration and Organ4. Ion Gradient-Driven Active Transport 531 Specialization 785

1. Major Pathways and Strategies of Energy Metabolism:19. Citric Acid Cycle 538 A Summary 785

1. Cycle Overview 538 2. Organ Specialization 788

2. Metabolic Sources of Acetyl-Coenzyme A 541 3. Metabolic Adaptation 792

26. Nucleotide Metabolism 795 4. Control of Eukaryotic Translation 1004

1. Chemical Structures of Nucleotides, Nucleosides, and 5. Posttranslational Modification 1007

Bases 795 6. Protein Degradation 1010

2. Synthesis of Purine Ribonucleotides 797

3. Synthesis of Pyrimidine Ribonucleotides 803 31. DNA Replication, Repair, and4. Formation of Deoxyribonucleotides 806 Recombination 10205. Nucleotide Degradation 8166. Biosynthesis of Nucleotide Coenzymes 822 1. DNA Replication: An Overview 1020

2. Enzymes of Replication 10243. Prokaryotic Replication Mechanisms 1030

V. THE EXPRESSION AND 4. Eukaryotic DNA Replication 1038TRANSMISSION OF GENETIC 5. Repair of DNA 1046

INFORMATION 829 6. Recombination and Mobile Genetic Elements 10537. DNA Methylation and Trinucleotide Repeat

27. DNA: The Vehicle of Inheritance 830 Expansions 1065

1. Genetics: A Review 8302. DNA Is the Carrier of Genetic Information 844 32. Viruses: Paradigms for Cellular

Functions 1074

28. Nucleic Acid Structures and 1. Tobacco Mosaic Virus 1076Manipulation 848 2. Spherical Viruses 1081

1. Chemical Structure and Base Composition 849 3. Bacteriophage Ä 1089

2. Double Helical Structures 850 4. Influenza Virus 1105

3. Forces Stabilizing Nucleic Acid Structures 862 5. Subviral Pathogens 1113

4. Nucleic Acid Fractionation 870

5. Supercoiled DNA 873 33. Eukaryotic Gene Expression 11236. Nucleic Acid Sequencing 882

1. Chromosome Structure 11247. Chemical Synthesis of Oligonucleotides 8968. Molecular Cloning 897

2. Genomic Organization 11333. Control of Expression 11484. Cell Differentiation 1168

29. Transcription 915

1. The Role of RNA in Protein Synthesis 916 34. Molecular Physiology 11962. RNA Polymerase 9193. Control of Transcription in Prokaryotes 930

1. Blood Clotting 1196

4. Posttranscriptional Processing 9441 Immunity 12073. Motility: Muscles, Cilia, and Flagella 12344. Biochemical Communications: Hormones and

30. Translation 959 Neurotransmission 1261

1. The Genetic Code 9592. Transfer RNA and its Aminoacylation 9673. Ribosomes 981 Index 1311