Donald Voet received a Ph.D. in chemistry from Harvard University and did postdoctoral research in the Biology Department at MIT. Don took up a faculty position in the department of chemistry at the University of Pennsylvania, upon completing his postdoctoral work. He has been a visiting scholar at Oxford University, the University of California San Diego, and the Weismann Institute of Science in Israel.

Judith Voet received her Ph.D. from Brandeis University and did postdoctoral research at the University of Pennsylvania, Haverford College and the Fox Chase Cancer Center. She taught at the University of Delaware before moving to Swarthmore College. Together with Don Voet, she is Co-Editor-in-Chief of the journal Biochemistry and Molecular Biology Education.

Guide to Media Resources xvi

Part I Introduction and background 1

Chapter 1 Life 3

1. The Origin of Life 3

2. Evolution of Cells 9

3. Biochemistry: A Prologue 18

4. Genetics: An Overview 23

Chapter 2 Aqueous Solutions and Bioenergetics 36

1. Properties of Water 37

2. Acids, Bases, and Buffers 40

3. First Law of Thermodynamics: Energy is Conserved 45

4. Second Law of Thermodynamics: The Universe Tends Toward Maximum Disorder 46

5. Chemical Equilibria 49

Appendix: Concentration Dependence of Free Energy 52

Part II Biomolecules 57

Chapter 3 Amino Acids 59

1. The Amino Acids of Proteins 59

2. Stereochemistry of Amino Acids 64

3. Chemical Properties of Amino Acids 69

4. "Nonstandard" Amino Acids 71

Chapter 4 Nucleic Acids, Gene Expression, and Recombinant DNA Technology 75

1. Nucleotides and Nucleic Acids 76

2. DNA Is the Carrier of Genetic Information 78

3. Double Helical DNA 81

4. Forces Stabilizing Nucleic Acid Structures 95

5. Supercoiled DNA 101

6. Gene Expression and Replication: An Overview 113

7. Molecular Cloning 122

Chapter 5 Techniques of Protein and Nucleic Acid Purification 150

1. Protein Isolation 150

2. Protein Solubility 154

3. Chromatographic Separations 156

4. Electrophoresis 167

5. Ultracentrifugation 173

6. Nucleic Acid Fractionation 178

Chapter 6 Covalent Structures of Proteins and Nucleic Acids 184

1. Primary Structure Determination of Proteins 185

2. Chemical Synthesis of Polypeptides 196

3. Nucleic Acid Sequencing 201

4. Chemical Synthesis of Oligonucleotides 210

5. Chemical Evolution 214

6. Bioinformatics: An Introduction 223

Chapter 7 Three-Dimensional Structures of Proteins 241

1. Secondary Structure 241

2. Fibrous Proteins 253

3. Globular Proteins 260

4. Protein Stability 280

5. Quaternary Structure 288

Appendix: Viewing Stereo Pictures 292

Chapter 8 Protein Folding, Dynamics, and Structural Evolution 300

1. Protein Folding: Theory and Experiment 300

2. Folding Accessory Proteins 312

3. Protein Structure Prediction and Design 324

4. Protein Dynamics 328

5. Conformational Diseases: Amyloid and Prions 331

6. Structural Evolution 338

Chapter 9 Chemical and Biological Aspects of Hemoglobin 346

1. Hemoglobin and Myoglobin Function 346

2. Structure and Mechanism 355

3. Abnormal Hemoglobins 364

4. Allosteric Regulation 371

Appendix: Derivations of Symmetry Model Equations 377

Chapter 10 Sugars and Polysaccharides 382

1. Monosaccharides 382

2. Polysaccharides 388

3. Glycoproteins 396

Chapter 11 Lipids and Membranes 409

1. Lipid Classification 409

2. Lipid Aggregates and their Properties 416

3. Biological Membranes 421

4. Membrane Assembly and Protein Targeting 440

5. Lipoproteins 468

Part III MECHANISMS OF ENZYME ACTION 485

Chapter 12 Enzyme Kinetics 487

1. Historical Perspective 488

2. Substrate Specificity 489

3. Coenzymes 492

4. Control of Enzymatic Activity 493

5. A Primer of Enzyme Nomenclature 498

6. Chemical Kinetics 498

7. Enzyme Kinetics 503

8. Inhibition 508

9. Effects of pH 512

10. Bisubstrate Reactions 513

Appendix: Derivations of Michaelis-Menten Equation Variants 516

Chapter 13 Enzymatic Catalysis and Drug Design 523

1. Catalytic Mechanisms 523

2. Lysozyme 534

3. Serine Proteases 541

4. Drug Design 553

Part IV METABOLISM 573

Chapter 14 Introduction to Metabolism 575

1. Metabolic Pathways 576

2. Organic Reaction Mechanisms 579

3. Experimental Approaches to the Study of Metabolism 585

4. Thermodynamics of Phosphate Compounds 594

5. Oxidation-Reduction Reactions 600

6. Thermodynamics of Life 603

Chapter 15 Glycolysis and Other Related Pathways 609

1. The Glycolytic Pathway 610

2. The Reactions of Glycolysis 613

3. Fermentation: The Anaerobic Fate of Pyruvate 630

4. Metabolic Regulation and Control 635

5. Metabolism of Hexoses Other Than Glucose 646

6. The Pentose Phosphate Pathway 649

7. Gluconeogenesis 655

8. Biosynthesis of Oligosaccharides and Glycoproteins 664

Chapter 16 Glycogen Metabolism 682

1. Glycogen Breakdown 683

2. Glycogen Synthesis 688

3. Control of Glycogen Metabolism 691

4. Glycogen Storage Diseases 710

Chapter 17 Signal Transduction 715

1. Hormones 715

2. Heterotrimeric G Proteins 732

3. Tyrosine Kinase-Based Signaling 743

4. The Phosphoinositide Cascade 768

Chapter 18 Transport through Membranes 788

1. Thermodynamics of Transport 788

2. Kinetics and Mechanisms of Transport 789

3. ATP-Driven Active Transport 802

4. Ion Gradient-Driven Active Transport 812

5. Neurotransmission 816

Chapter 19 Citric Acid Cycle 833

1. Cycle Overview 833

2. Metabolic Sources of Acetyl-Coenzyme A 836

3. Enzymes of the Citric Acid Cycle 850

4. Regulation of the Citric Acid Cycle 858

5. The Amphibolic Nature of the Citric Acid Cycle 861

6. The Glyoxylate Cycle 862

Chapter 20 Electron Transport and Oxidative Phosphorylation 868

1. The Mitochondrion 869

2. Electron Transport 873

3. Oxidative Phosphorylation 890

4. Control of ATP Production 907

Chapter 21 Photosynthesis: Bioinorganic Chemistry and Physiology 916

1. Chloroplasts 917

2. Light Reactions 918

3. Dark Reactions 942

Chapter 22 Lipid Metabolism 956

1. Lipid Digestion, Absorption, and Transport 956

2. Fatty Acid Oxidation 961

3. Ketone Bodies 976

4. Fatty Acid Biosynthesis 981

5. Regulation of Fatty Acid Metabolism 992

6. Cholesterol Metabolism 994

7. Eicosanoid Metabolism: Prostaglandins, Prostacyclins, Thromboxanes, Leukotrienes, and Lipoxins 1012

8. Phospholipid and Glycolipid Metabolism 1023

9. Metabolic Homeostasis: Regulation of Appetite, Energy Expenditure, and Body Weight 1033

Chapter 23 Amino Acid Metabolism 1045

1. Amino Acid Deamination 1046

2. Metabolic Breakdown of Individual Amino Acids 1051

3. The Urea Cycle 1069

4. Amino Acids as Biosynthetic Precursors 1073

5. Amino Acid Biosynthesis 1091

Chapter 24 Nucleotide Metabolism 1110

1. Synthesis of Purine Ribonucleotides 1110

2. Synthesis of Pyrimidine Ribonucleotides 1118

3. Formation of Deoxyribonucleotides 1122

4. Nucleotide Degradation 1133

5. Biosynthesis of Nucleotide Coenzymes 1139

Part V Expression and Transmission of Genetic Information 1147

Chapter 25 D NA Replication, Repair, and Recombination 1149

1. DNA Replication: An Overview 1149

2. Enzymes of Replication 1152

3. Prokaryotic Replication 1165

4. Eukaryotic Replication 1177

5. Repair of DNA 1189

6. Recombination and Mobile Genetic Elements 1201

7. DNA Methylation and Trinucleotide Repeat Expansions 1222

Chapter 26 Transcription 1236

1. The Role of RNA in Protein Synthesis 1237

2. RNA Polymerase 1241

3. Control of Transcription in Prokaryotes 1259

4. Post-Transcriptional Processing 1277

Chapter 27 Translation 1314

1. The Genetic Code 1314

2. Transfer RNA and Its Aminoacylation 1321

3. Ribosomes and Polypeptide Synthesis 1338

4. Control of Eukaryotic Translation 1374

5. Post-Translational Modification 1379

*Chapter 28 Eukaryotic Gene Expression W-1

1. Chromosome Structure W-1

2. Genomic Organization W-12

3. Control of Expression W-25

4. Cell Differentiation and Growth W-59

*Chapter 29 Viruses: Paradigms for Cellular Functions W-84

1. Tobacco Mosaic Virus W-86

2. Icosahedral Viruses W-91

3. Bacteriophage Lambda W-103

4. Influenza Virus W-123

*Chapter 30 Molecular Physiology W-136

1. Blood Clotting W-136

2. Immunity W-150

3. Motility: Muscles, Vesicle Transport, Cilia, and Flagella W-182

Index I-1

*Chapters 28, 29 and 30 are available on our book companion website, [...]