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Preface xv
Acknowledgments xix
Part I Introduction
1 Introduction to the Chemistry of Life 1
1 The Origin of Life 2
2 Cellular Architecture 5
3 Thermodynamics 11
Box 1-1 Pathways of Discovery Lynn Margulis and the Theory of Endosymbiosis 10
Box 1-2 Perspectives in Biochemistry Biochemical Conventions 12
2 Water 23
1 Physical Properties of Water 24
2 Chemical Properties of Water 31
Box 2-1 Perspectives in Biochemistry the Consequences of Ocean Acidification 34
Box 2-2 Biochemistry in Health and Disease the Blood Buffering System 38
Part II Biomolecules
3 Nucleotides, Nucleic Acids, and Genetic Information 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
Box 3-1 Pathways to Discovery Francis Collins and the Gene for Cystic Fibrosis 61
Box 3-2 Perspectives in Biochemistry DNA Fingerprinting 73
Box 3-3 Perspectives in Biochemistry Ethical Aspects of Recombinant DNA Technology 75
4 Amino Acids 80
1 Amino Acid Structure 81
2 Stereochemistry 88
3 Amino Acid Derivatives 91
Box 4-1 Pathways to Discovery William C. Rose and the Discovery of Threonine 81
Box 4-2 Perspectives in Biochemistry The RS System 90
Box 4-3 Perspectives in Biochemistry Green Fluorescent Protein 93
5 Proteins: Primary Structure 97
1 Polypeptide Diversity 98
2 Protein Purification and Analysis 99
3 Protein Sequencing 110
4 Protein Evolution 119
Box 5-1 Pathways of Discovery Frederick Sanger and Protein Sequencing 112
6 Proteins: Three-Dimensional Structure 131
1 Secondary Structure 132
2 Tertiary Structure 145
3 Quaternary Structure and Symmetry 158
4 Protein Stability 160
5 Protein Folding 165
Box 6-1 Pathways of Discovery Linus Pauling and Structural Biochemistry 136
Box 6-2 Biochemistry in Health and Disease Collagen Diseases 143
Box 6-3 Perspectives in Biochemistry Thermostable Proteins 162
Box 6-4 Perspectives in Biochemistry Protein Structure Prediction and Protein Design 167
7 Protein Function: Myoglobin and Hemoglobin, Muscle Contraction, and Antibodies 180
1 Oxygen Binding to Myoglobin and Hemoglobin 181
2 Muscle Contraction 200
3 Antibodies 212
Box 7-1 Perspectives in Biochemistry Other Oxygen-Transport Proteins 185
Box 7-2 Pathways of Discovery Max Perutz and the Structure and Function of Hemoglobin 186
Box 7-3 Biochemistry in Health and Disease High-Altitude Adaptation 195
Box 7-4 Pathways of Discovery Hugh Huxley and the Sliding Filament Model 203
Box 7-5 Perspectives in Biochemistry Monoclonal Antibodies 216
8 Carbohydrates 221
1 Monosaccharides 222
2 Polysaccharides 228
3 Glycoproteins 234
Box 8-1 Biochemistry in Health and Disease Lactose Intolerance 228
Box 8-2 Perspectives in Biochemistry Artificial Sweeteners 229
Box 8-3 Biochemistry in Health and Disease Peptidoglycan-Specific Antibiotics 238
9 Lipids and Biological Membranes 245
1 Lipid Classification 246
2 Lipid Bilayers 259
3 Membrane Proteins 262
4 Membrane Structure and Assembly 269
Box 9-1 Biochemistry in Health and Disease Lung Surfactant 251
Box 9-2 Pathways of Discovery Richard Henderson and the Structure of Bacteriorhodopsin 265
Box 9-3 Biochemistry in Health and Disease Tetanus and Botulinum Toxins Specifically Cleave SNAREs 286
10 Membrane Transport 293
1 Thermodynamics of Transport 294
2 Passive-Mediated Transport 295
3 Active Transport 309
Box 10-1 Perspectives in Biochemistry Gap Junctions 306
Box 10-2 Perspectives in Biochemistry Differentiating Mediated and Nonmediated Transport 308
Box 10-3 Biochemistry in Health and Disease The Action of Cardiac Glycosides 312
Part III Enzymes
11 Enzymatic Catalysis 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
Box 11-1 Perspectives in Biochemistry Drawing Reaction Mechanisms 331
Box 11-2 Perspectives in Biochemistry Effects of pH on Enzyme Activity 332
Box 11-3 Biochemistry in Health and Disease Nerve Poisons 346
Box 11-4 Biochemistry in Health and Disease the Blood Coagulation Cascade 356
12 Enzyme Kinetics, Inhibition, and Control 361
1 Reaction Kinetics 362
2 Enzyme Inhibition 374
3 Control of Enzyme Activity 382
4 Drug Design 391
Box 12-1 Pathways of Discovery J.B.S. Haldane and Enzyme Action 366
Box 12-2 Perspectives in Biochemistry Kinetics and Transition State Theory 369
Box 12-3 Biochemistry in Health and Disease HIV Enzyme Inhibitors 376
13 Biochemical Signaling 402
1 Hormones 403
2 Receptor Tyrosine Kinases 408
3 Heterotrimeric G Proteins 423
4 The Phosphoinositide Pathway 432
Box 13-1 Pathways of Discovery Rosalyn Yalow and the Radioimmunoassay (RIA) 404
Box 13-2 Perspectives in Biochemistry Receptor–Ligand Binding Can Be Quantitated 410
Box 13-3 Biochemistry in Health and Disease Oncogenes and Cancer 416
Box 13-4 Biochemistry in Health and Disease Drugs and Toxins That Affect Cell Signaling 431
Part IV Metabolism
14 Introduction to Metabolism 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
Box 14-1 Perspectives in Biochemistry Oxidation States of Carbon 447
Box 14-2 Pathways of Discovery Fritz Lipmann and “High-Energy” Compounds 453
Box 14-3 Perspectives in Biochemistry ATP and ΔG 455
15 Glucose Catabolism 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
Box 15-1 Pathways of Discovery Otto Warburg and Studies of Metabolism 479
Box 15-2 Perspectives in Biochemistry Synthesis of 2,3-Bisphosphoglycerate in Erythrocytes and Its Effect on the Oxygen Carrying Capacity of the Blood 494
Box 15-3 Perspectives in Biochemistry Glycolytic ATP Production in Muscle 502
Box 15-4 Biochemistry in Health and Disease Glucose-6-Phosphate Dehydrogenase Deficiency 518
16 Glycogen Metabolism and Gluconeogenesis 523
1 Glycogen Breakdown 524
2 Glycogen Synthesis 532
3 Control of Glycogen Metabolism 536
4 Gluconeogenesis 544
5 Other Carbohydrate Biosynthetic Pathways 551
Box 16-1 Pathways of Discovery Carl and Gerty Cori and Glucose Metabolism 526
Box 16-2 Biochemistry in Health and Disease Glycogen Storage Diseases 530
Box 16-3 Perspectives in Biochemistry Optimizing Glycogen Structure 537
Box 16-4 Perspectives in Biochemistry Lactose Synthesis 552
17 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
Box 17-1 Pathways of Discovery Hans Krebs and the Citric Acid Cycle 561
Box 17-2 Biochemistry in Health and Disease Arsenic Poisoning 568
Box 17-3 Perspectives in Biochemistry Evolution of the Citric Acid Cycle 582
18 Electron Transport and Oxidative Phosphorylation 588
1 The Mitochondrion 589
2 Electron Transport 593
3 Oxidative Phosphorylation 609
4 Control of Oxidative Metabolism 620
Box 18-1 Perspectives in Biochemistry Cytochromes are Electron-Transport Heme Proteins 602
Box 18-2 Pathways of Discovery Peter Mitchell and the Chemiosmotic Theory 611
Box 18-3 Perspectives in Biochemistry Bacterial Electron Transport and Oxidative Phosphorylation 612
Box 18-4 Perspectives in Biochemistry Uncoupling in Brown Adipose Tissue Generates Heat 621
Box 18-5 Biochemistry in Health and Disease Oxygen Deprivation in Heart Attack and Stroke 625
19 Photosynthesis 630
1 Chloroplasts 631
2 The Light Reactions 635
3 The Dark Reactions 651
Box 19-1 Perspectives in Biochemistry Segregation of PSI and PSII 649
20 Lipid Metabolism 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
Box 20-1 Biochemistry in Health and Disease Vitamin B12 Deficiency 680
Box 20-2 Pathways of Discovery Dorothy Crowfoot Hodgkin and the Structure of Vitamin B12 680
Box 20-3 Perspectives in Biochemistry Polyketide Synthesis 694
Box 20-4 Biochemistry in Health and Disease Sphingolipid Degradation and Lipid Storage Diseases 706
21 Amino Acid Metabolism 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
Box 21-1 Biochemistry in Health and Disease Homocysteine, a Marker of Disease 740
Box 21-2 Biochemistry in Health and Disease Phenylketonuria and Alcaptonuria Result from Defects in Phenylalanine Degradation 746
Box 21-3 Biochemistry in Health and Disease the Porphyrias 760
22 Mammalian Fuel Metabolism: Integration and Regulation 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
Box 22-1 Biochemistry in Health and Disease The Intestinal Microbiome 777
Box 22-2 Pathways of Discovery Frederick Banting and Charles Best and the Discovery of Insulin 794
Part V Gene Expression and Replication
23 Nucleotide Metabolism 802
1 Synthesis of Purine Ribonucleotides 802
2 Synthesis of Pyrimidine Ribonucleotides 809
3 Formation of Deoxyribonucleotides 812
4 Nucleotide Degradation 820
Box 23-1 Biochemistry in Health and Disease Inhibition of Thymidylate Synthesis in Cancer Therapy 821
Box 23-2 Pathways of Discovery Gertrude Elion and Purine Derivatives 826
24 Nucleic Acid Structure 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
Box 24-1 Pathways of Discovery Rosalind Franklin and the Structure of DNA 833
Box 24-2 Biochemistry in Health and Disease Inhibitors of Topoisomerases as Antibiotics and Anticancer Chemotherapeutic Agents 848
Box 24-3 Perspectives in Biochemistry The RNA World 854
25 DNA Replication, Repair, and Recombination 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
Box 25-1 Pathways of Discovery Arthur Kornberg and DNA Polymerase I 883
Box 25-2 Perspectives in Biochemistry Reverse Transcriptase 900
Box 25-3 Biochemistry in Health and Disease Telomerase, Aging, and Cancer 905
Box 25-4 Perspectives in Biochemistry DNA Methylation 908
Box 25-5 Perspectives in Biochemistry Why Doesn’t DNA Contain Uracil? 911
26 Transcription and RNA Processing 938
1 Prokaryotic RNA Transcription 939
2 Transcription in Eukaryotes 948
3 Posttranscriptional Processing 961
Box 26-1 Perspectives in Biochemistry Collisions between DNA Polymerase and RNA Polymerase 945
Box 26-2 Biochemistry in Health and Disease Inhibitors of Transcription 950
Box 26-3 Pathways of Discovery Richard Roberts and Phillip Sharp and the Discovery of Introns 964
27 Protein Synthesis 982
1 The Genetic Code 983
2 Transfer RNA and Its Aminoacylation 988
3 Ribosomes 996
4 Translation 1004
5 Posttranslational Processing 1024
Box 27-1 Perspectives in Biochemistry Evolution of the Genetic Code 986
Box 27-2 Perspectives in Biochemistry Expanding the Genetic Code 996
Box 27-3 Biochemistry in Health and Disease the Effects of Antibiotics on Protein Synthesis 1020
28 Regulation of Gene Expression 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
Box 28-1 Biochemistry in Health and Disease Trinucleotide Repeat Diseases 1040
Box 28-2 Perspectives in Biochemistry X Chromosome Inactivation 1053
Box 28-3 Perspectives in Biochemistry Nonsense-Mediated Decay 1070
Glossary G-1
Index I-1
