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.

Preface xii

Acknowledgments xv

PART I INTRODUCTION

1 Life, Cell and Thermodynamics 1

1 The Origin of Life 2

2 Cellular Architecture 5

3 Thermodynamics 11

2 Physical and Chemical Properties of Water 23

1 Physical Properties of Water 24

2 Chemical Properties of Water 31

PART I I BIOMOLECULES

3 Overview of DNA Structure, Function, and Engineering 42

1 Nucleotides 43

2 Introduction to Nucleic Acid Structure 46

3 Overview of Nucleic Acid Function 50

4 Nucleic Acid Sequencing 53

5 Manipulating DNA 66

4 Amino Acids 80

1 Amino Acid Structure 81

2 Stereochemistry 88

3 Amino Acid Derivatives 91

5 Polypeptide Analysis, Sequencing and Evolution 97

1 Polypeptide Diversity 98

2 Protein Purifi cation and Analysis 99

3 Protein Sequencing 110

4 Protein Evolution 119

6 Proteins: Structure and Folding 131

1 Secondary Structure 132

2 Tertiary Structure 145

3 Quaternary Structure and Symmetry 158

4 Protein Stability 160

5 Protein Folding 165

7 Physiological Activities of Proteins 180

1 Oxygen Binding to Myoglobin and Hemoglobin 181

2 Muscle Contraction 200

3 Antibodies 212

8 Saccharide Chemistry 221

1 Monosaccharides 222

2 Polysaccharides 228

3 Glycoproteins 234

9 Lipids, Bilayer and Membranes 245

1 Lipid Classifi cation 246

2 Lipid Bilayers 259

3 Membrane Proteins 262

4 Membrane Structure and Assembly 269

10 Passive and Active Transport 293

1 Thermodynamics of Transport 294

2 Passive-Mediated Transport 295

3 Active Transport 309

PART I I I ENZYMES

11 Mechanisms of Enzyme Action 322

1 General Properties of Enzymes 323

2 Activation Energy and the Reaction Coordinate 327

3 Catalytic Mechanisms 330

4 Lysozyme 339

5 Serine Proteases 345

12 Properties of Enzymes 361

1 Reaction Kinetics 362

2 Enzyme Inhibition 374

3 Control of Enzyme Activity 382

4 Drug Design 391

13 Hormones and Signal Transduction 402

1 Hormones 403

2 Receptor Tyrosine Kinases 408

3 Heterotrimeric G Proteins 423

4 The Phosphoinositide Pathway 432

PART IV METABOLISM

14 Bioenergetics 442

1 Overview of Metabolism 443

2 “High-Energy” Compounds 452

3 Oxidation–Reduction Reactions 462

4 Experimental Approaches to the Study of Metabolism 468

15 Glycolysis and the Pentose Phosphate Pathway 478

1 Overview of Glycolysis 479

2 The Reactions of Glycolysis 481

3 Fermentation: The Anaerobic Fate of Pyruvate 497

4 Regulation of Glycolysis 502

5 Metabolism of Hexoses Other than Glucose 508

6 The Pentose Phosphate Pathway 512

16 Additional Pathways in Carbohydrate Metabolism 523

1 Glycogen Breakdown 524

2 Glycogen Synthesis 532

3 Control of Glycogen Metabolism 536

4 Gluconeogenesis 544

5 Other Carbohydrate Biosynthetic Pathways 551

17 The Citric Acid Cycle 558

1 Overview of the Citric Acid Cycle 559

2 Synthesis of Acetyl-Coenzyme A 562

3 Enzymes of the Citric Acid Cycle 568

4 Regulation of the Citric Acid Cycle 575

5 Reactions Related to the Citric Acid Cycle 579

18 Mitochondrial ATP Synthesis 588

1 The Mitochondrion 589

2 Electron Transport 593

3 Oxidative Phosphorylation 609

4 Control of Oxidative Metabolism 620

19 Photosynthesis 630

1 Chloroplasts 631

2 The Light Reactions 635

3 The Dark Reactions 651

20 Synthesis and Degradation of lipids 664

1 Lipid Digestion, Absorption, and Transport 664

2 Fatty Acid Oxidation 671

3 Ketone Bodies 685

4 Fatty Acid Biosynthesis 686

5 Regulation of Fatty Acid Metabolism 697

6 Synthesis of Other Lipids 700

7 Cholesterol Metabolism 706

21 Synthesis and Degradation of Amino Acids 718

1 Protein Degradation 719

2 Amino Acid Deamination 724

3 The Urea Cycle 728

4 Breakdown of Amino Acids 733

5 Amino Acid Biosynthesis 746

6 Other Products of Amino Acid Metabolism 758

7 Nitrogen Fixation 764

22 Regulation of Fuel Metabolism 773

1 Organ Specialization 774

2 Hormonal Control of Fuel Metabolism 781

3 Metabolic Homeostasis: The Regulation of Energy Metabolism, Appetite, and Body Weight 786

4 Disturbances in Fuel Metabolism 790

PART V GENE EXPRESSION AND REPLICATION

23 Nucleotide Synthesis and Degradation 802

1 Synthesis of Purine Ribonucleotides 802

2 Synthesis of Pyrimidine Ribonucleotides 809

3 Formation of Deoxyribonucleotides 812

4 Nucleotide Degradation 820

24 DNA structure and Interactions with Proteins 831

1 The DNA Helix 832

2 Forces Stabilizing Nucleic Acid Structures 848

3 Fractionation of Nucleic Acids 856

4 DNA–Protein Interactions 859

5 Eukaryotic Chromosome Structure 868

25 DNA Synthesis and Repair 879

1 Overview of DNA Replication 880

2 Prokaryotic DNA Replication 882

3 Eukaryotic DNA Replication 898

4 DNA Damage 904

5 DNA Repair 909

6 Recombination 916

26 RNA Metabolism 938

1 Prokaryotic RNA Transcription 939

2 Transcription in Eukaryotes 948

3 Posttranscriptional Processing 961

27 The Genetic Code and Translation 982

1 The Genetic Code 983

2 Transfer RNA and Its Aminoacylation 988

3 Ribosomes 996

4 Translation 1004

5 Posttranslational Processing 1024

28 Gene Expression in Prokaryotes and Eukaryotes 1033

1 Genome Organization 1034

2 Regulation of Prokaryotic Gene Expression 1043

3 Regulation of Eukaryotic Gene Expression 1052

4 The Cell Cycle, Cancer, Apoptosis, and Development 1080

Glossary G-1 Index I-1

SOLUTIONS to Odd-Numbered Problems SP-1

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