Biochemistry

Cover......Page 1
Biochemistry, Fourth Edition......Page 2
Copyright......Page 3
Contents in Brief
......Page 6
Contents......Page 7
Preface......Page 28
1.1 What Are the Distinctive Properties of Living Systems?......Page 36
1.2 What Kinds of Molecules Are Biomolecules?......Page 39
1.3 What Is the Structural Organization of Complex Biomolecules?......Page 40
1.4 How Do the Properties of Biomolecules Reflect Their Fitness to the Living Condition?......Page 44
1.5 What Is the Organization and Structure of Cells?......Page 52
1.6 What Are Viruses?......Page 56
SUMMARY......Page 60
PROBLEMS......Page 61
FURTHER READING......Page 62
2.1 What Are the Properties of Water?......Page 63
2.2 What Is pH?......Page 70
2.3 What Are Buffers, and What Do They Do?......Page 76
2.4 What Properties of Water Give It a Unique Role in the Environment?......Page 79
PROBLEMS......Page 80
FURTHER READING......Page 82
3.1 What Are the Basic Concepts of Thermodynamics?......Page 83
3.3 What Is the Effect of pH on Standard-State Free Energies?......Page 89
3.4 What Can Thermodynamic Parameters Tell Us About Biochemical Events?......Page 90
3.5 What Are the Characteristics of High-Energy Biomolecules?......Page 91
3.6 What Are the Complex Equilibria Involved in ATP Hydrolysis?......Page 98
3.8 What Is the Daily Human Requirement for ATP?......Page 101
PROBLEMS......Page 103
FURTHER READING......Page 104
4.1 What Are the Structures and Properties of Amino Acids?......Page 105
4.2 What Are the Acid–Base Properties of Amino Acids?......Page 111
4.4 What Are the Optical and Stereochemical Properties of Amino Acids?......Page 114
4.5 What Are the Spectroscopic Properties of Amino Acids?......Page 117
4.6 How Are Amino Acid Mixtures Separated and Analyzed?......Page 120
4.7 What Is the Fundamental Structural Pattern in Proteins?......Page 121
PROBLEMS......Page 126
FURTHER READING......Page 127
5.1 What Architectural Arrangements Characterize Protein Structure?......Page 128
5.2 How Are Proteins Isolated and Purified from Cells?......Page 132
5.3 How Is the Amino Acid Analysis of Proteins Performed?......Page 134
5.4 How Is the Primary Structure of a Protein Determined?......Page 135
5.5 What Is the Nature of Amino Acid Sequences?......Page 145
5.6 Can Polypeptides Be Synthesized in the Laboratory?......Page 152
5.7 Do Proteins Have Chemical Groups Other Than Amino Acids?......Page 154
5.8 What Are the Many Biological Functions of Proteins?......Page 155
SUMMARY......Page 158
PROBLEMS......Page 159
FURTHER READING......Page 161
Appendix to Chapter 5: Protein Techniques......Page 162
6.1 What Noncovalent Interactions Stabilize the Higher Levels of Protein Structure?......Page 169
6.3 What Are the Elements of Secondary Structure in Proteins, and How Are They Formed?......Page 171
6.4 How Do Polypeptides Fold into Three-Dimensional Protein Structures?......Page 181
6.5 How Do Protein Subunits Interact at the Quaternary Level of Protein Structure?......Page 208
PROBLEMS......Page 214
FURTHER READING......Page 215
7.1 How Are Carbohydrates Named?......Page 216
7.2 What Is the Structure and Chemistry of Monosaccharides?......Page 217
7.3 What Is the Structure and Chemistry of Oligosaccharides?......Page 226
7.4 What Is the Structure and Chemistry of Polysaccharides?......Page 229
7.5 What Are Glycoproteins, and How Do They Function in Cells?......Page 239
7.6 How Do Proteoglycans Modulate Processes in Cells and Organisms?......Page 244
7.7 Do Carbohydrates Provide a Structural Code?......Page 248
PROBLEMS......Page 251
FURTHER READING......Page 253
8.1 What Are the Structures and Chemistry of Fatty Acids?......Page 254
8.2 What Are the Structures and Chemistry of Triacylglycerols?......Page 257
8.3 What Are the Structures and Chemistry of Glycerophospholipids?......Page 258
8.4 What Are Sphingolipids, and How Are They Important for Higher Animals?......Page 262
8.6 What Are Terpenes, and What Is Their Relevance to Biological Systems?......Page 264
8.7 What Are Steroids, and What Are Their Cellular Functions?......Page 268
8.8 How Do Lipids and Their Metabolites Act as Biological Signals?......Page 269
8.9 What Can Lipidomics Tell Us about Cell,Tissue, and Organ Physiology?......Page 272
PROBLEMS......Page 274
FURTHER READING......Page 276
9.1 What Are the Chemical and Physical Properties of Membranes?......Page 277
9.2 What Are the Structure and Chemistry of Membrane Proteins?......Page 283
9.3 How Are Biological Membranes Organized?......Page 295
9.4 What Are the Dynamic Processes That Modulate Membrane Function?......Page 296
9.5 How Does Transport Occur Across Biological Membranes?......Page 304
9.7 How Does Facilitated Diffusion Occur?......Page 306
9.8 How Does Energy Input Drive Active Transport Processes?......Page 312
9.9 How Are Certain Transport Processes Driven by Light Energy?......Page 320
9.10 How Is Secondary Active Transport Driven by Ion Gradients?......Page 321
SUMMARY......Page 322
PROBLEMS......Page 323
FURTHER READING......Page 324
10.1 What Are the Structure and Chemistry of Nitrogenous Bases?......Page 326
10.2 What Are Nucleosides?......Page 329
10.3 What Are the Structure and Chemistry of Nucleotides?......Page 330
10.4 What Are Nucleic Acids?......Page 332
10.5 What Are the Different Classes of Nucleic Acids?......Page 334
10.6 Are Nucleic Acids Susceptible to Hydrolysis?......Page 342
SUMMARY......Page 348
PROBLEMS......Page 349
FURTHER READING......Page 350
11.1 How Do Scientists Determine the Primary Structure of Nucleic Acids?......Page 351
11.2 What Sorts of Secondary Structures Can Double-Stranded DNA Molecules Adopt?......Page 355
11.3 Can the Secondary Structure of DNA Be Denatured and Renatured?......Page 365
11.4 Can DNA Adopt Structures of Higher Complexity?......Page 368
11.5 What Is the Structure of Eukaryotic Chromosomes?......Page 371
11.6 Can Nucleic Acids Be Synthesized Chemically?......Page 374
11.7 What Are the Secondary and Tertiary Structures of RNA?......Page 376
SUMMARY......Page 385
PROBLEMS......Page 386
FURTHER READING......Page 387
12.1 What Does It Mean “To Clone”?......Page 389
12.2 What Is a DNA Library?......Page 395
12.3 Can the Cloned Genes in Libraries Be Expressed?......Page 404
12.4 What Is the Polymerase Chain Reaction (PCR)?......Page 408
12.6 Is It Possible to Make Directed Changes in the Heredity of an Organism?......Page 410
SUMMARY......Page 414
PROBLEMS......Page 415
FURTHER READING......Page 416
13 Enzymes—Kinetics and Specificity......Page 417
13.1 What Characteristic Features Define Enzymes?......Page 418
13.2 Can the Rate of an Enzyme-Catalyzed Reaction Be Defined in a Mathematical Way?......Page 421
13.3 What Equations Define the Kinetics of Enzyme-Catalyzed Reactions?......Page 424
13.4 What Can Be Learned from the Inhibition of Enzyme Activity?......Page 432
13.5 What Is the Kinetic Behavior of Enzymes Catalyzing Bimolecular Reactions?......Page 438
13.6 How Can Enzymes Be So Specific?......Page 444
13.7 Are All Enzymes Proteins?......Page 445
13.8 Is It Possible to Design an Enzyme to Catalyze Any Desired Reaction?......Page 449
PROBLEMS......Page 450
FURTHER READING......Page 452
14.1 What Are the Magnitudes of Enzyme-Induced Rate Accelerations?......Page 454
14.2 What Role Does Transition-State Stabilization Play in Enzyme Catalysis?......Page 455
14.3 How Does Destabilization of ES Affect Enzyme Catalysis?......Page 456
14.4 How Tightly Do Transition-State Analogs Bind to the Active Site?......Page 458
14.5 What Are the Mechanisms of Catalysis?......Page 461
14.6 What Can Be Learned from Typical Enzyme Mechanisms?......Page 468
SUMMARY......Page 483
PROBLEMS......Page 484
FURTHER READING......Page 486
15.1 What Factors Influence Enzymatic Activity?......Page 487
15.2 What Are the General Features of Allosteric Regulation?......Page 491
15.3 Can Allosteric Regulation Be Explained by Conformational Changes in Proteins?......Page 492
15.4 What Kinds of Covalent Modification Regulate the Activity of Enzymes?......Page 494
15.5 Is the Activity of Some Enzymes Controlled by Both Allosteric Regulation and Covalent Modification?......Page 497
Special Focus: Is There an Example in Nature That Exemplifies the Relationship Between Quaternary Structure and the Emergence of Allosteric Properties? Hemoglobin and Myoglobin—Paradigms of Protein Structure and Function......Page 502
SUMMARY......Page 513
PROBLEMS......Page 514
FURTHER READING......Page 515
16.2 What Is the Molecular Mechanism of Muscle Contraction?......Page 516
16.3 What Are the Molecular Motors That Orchestrate the Mechanochemistry of Microtubules?......Page 525
16.4 How Do Molecular Motors Unwind DNA?......Page 533
16.5 How Do Bacterial Flagella Use a Proton Gradient to Drive Rotation?......Page 538
SUMMARY......Page 542
PROBLEMS......Page 543
FURTHER READING......Page 544
17.1 Is Metabolism Similar in Different Organisms?......Page 546
17.2 What Can Be Learned from Metabolic Maps?......Page 548
17.3 How Do Anabolic and Catabolic Processes Form the Core of Metabolic Pathways?......Page 552
17.4 What Experiments Can Be Used to Elucidate Metabolic Pathways?......Page 558
17.5 What Can the Metabolome Tell Us about a Biological System?......Page 564
17.6 What Food Substances Form the Basis of Human Nutrition?......Page 566
SUMMARY......Page 567
FURTHER READING......Page 568
18.1 What Are the Essential Features of Glycolysis?......Page 570
18.3 What Are the Chemical Principles and Features of the First Phase of Glycolysis?......Page 572
18.4 What Are the Chemical Principles and Features of the Second Phase of Glycolysis?......Page 581
18.5 What Are the Metabolic Fates of NADH and Pyruvate Produced in Glycolysis?......Page 587
18.7 Are Substrates Other Than Glucose Used in Glycolysis?......Page 589
18.8 How Do Cells Respond to Hypoxic Stress?......Page 594
SUMMARY......Page 595
PROBLEMS......Page 596
FURTHER READING......Page 597
19 The Tricarboxylic Acid Cycle......Page 598
19.1 What Is the Chemical Logic of the TCA Cycle?......Page 599
19.2 How Is Pyruvate Oxidatively Decarboxylated to Acetyl-CoA?......Page 601
19.3 How Are Two CO[sub(2)] Molecules Produced from Acetyl-CoA?......Page 606
19.4 How Is Oxaloacetate Regenerated to Complete the TCA Cycle?......Page 610
19.5 What Are the Energetic Consequences of the TCA Cycle?......Page 613
19.6 Can the TCA Cycle Provide Intermediates for Biosynthesis?......Page 616
19.7 What Are the Anaplerotic, or “Filling Up,” Reactions?......Page 617
19.8 How Is the TCA Cycle Regulated?......Page 619
19.9 Can Any Organisms Use Acetate as Their Sole Carbon Source?......Page 622
SUMMARY......Page 624
PROBLEMS......Page 625
FURTHER READING......Page 626
20.1 Where in the Cell Do Electron Transport and Oxidative Phosphorylation Occur?......Page 627
20.2 What Are Reduction Potentials, and How Are They Used to Account for Free Energy Changes in Redox Reactions?......Page 628
20.3 How Is the Electron-Transport Chain Organized?......Page 632
20.5 How Does a Proton Gradient Drive the Synthesis of ATP?......Page 646
20.7 How Are the Electrons of Cytosolic NADH Fed into Electron Transport?......Page 655
20.8 How Do Mitochondria Mediate Apoptosis?......Page 659
SUMMARY......Page 661
PROBLEMS......Page 662
FURTHER READING......Page 663
21.1 What Are the General Properties of Photosynthesis?......Page 665
21.2 How Is Solar Energy Captured by Chlorophyll?......Page 668
21.3 What Kinds of Photosystems Are Used to Capture Light Energy?......Page 672
21.4 What Is the Molecular Architecture of Photosynthetic Reaction Centers?......Page 676
21.5 What Is the Quantum Yield of Photosynthesis?......Page 682
21.6 How Does Light Drive the Synthesis of ATP?......Page 683
21.7 How Is Carbon Dioxide Used to Make Organic Molecules?......Page 685
21.8 How Does Photorespiration Limit CO[sub(2)] Fixation?......Page 691
SUMMARY......Page 694
PROBLEMS......Page 695
FURTHER READING......Page 696
22.1 What Is Gluconeogenesis, and How Does It Operate?......Page 697
22.2 How Is Gluconeogenesis Regulated?......Page 704
22.3 How Are Glycogen and Starch Catabolized in Animals?......Page 708
22.4 How Is Glycogen Synthesized?......Page 710
22.5 How Is Glycogen Metabolism Controlled?......Page 713
22.6 Can Glucose Provide Electrons for Biosynthesis?......Page 718
PROBLEMS......Page 728
FURTHER READING......Page 730
23.1 How Are Fats Mobilized from Dietary Intake and Adipose Tissue?......Page 732
23.2 How Are Fatty Acids Broken Down?......Page 736
23.3 How Are Odd-Carbon Fatty Acids Oxidized?......Page 745
23.4 How Are Unsaturated Fatty Acids Oxidized?......Page 748
23.5 Are There Other Ways to Oxidize Fatty Acids?......Page 749
23.6 What Are Ketone Bodies, and What Role Do They Play in Metabolism?......Page 752
PROBLEMS......Page 754
FURTHER READING......Page 756
24.1 How Are Fatty Acids Synthesized?......Page 757
24.2 How Are Complex Lipids Synthesized?......Page 772
24.3 How Are Eicosanoids Synthesized, and What Are Their Functions?......Page 782
24.4 How Is Cholesterol Synthesized?......Page 785
24.5 How Are Lipids Transported Throughout the Body?......Page 792
24.6 How Are Bile Acids Biosynthesized?......Page 796
24.7 How Are Steroid Hormones Synthesized and Utilized?......Page 797
SUMMARY......Page 799
PROBLEMS......Page 800
FURTHER READING......Page 801
25.1 Which Metabolic Pathways Allow Organisms to Live on Inorganic Forms of Nitrogen?......Page 803
25.2 What Is the Metabolic Fate of Ammonium?......Page 809
25.3 What Regulatory Mechanisms Act on Escherichia coli Glutamine Synthetase?......Page 811
25.4 How Do Organisms Synthesize Amino Acids?......Page 814
25.5 How Does Amino Acid Catabolism Lead into Pathways of Energy Production?......Page 839
SUMMARY......Page 845
PROBLEMS......Page 846
FURTHER READING......Page 847
26.2 How Do Cells Synthesize Purines?......Page 848
26.4 How Are Purines Degraded?......Page 856
26.5 How Do Cells Synthesize Pyrimidines?......Page 861
26.7 How Do Cells Form the Deoxyribonucleotides That Are Necessary for DNA Synthesis?......Page 865
26.8 How Are Thymine Nucleotides Synthesized?......Page 868
SUMMARY......Page 871
PROBLEMS......Page 872
FURTHER READING......Page 873
27.1 Can Systems Analysis Simplify the Complexity of Metabolism?......Page 874
27.2 What Underlying Principle Relates ATP Coupling to the Thermodynamics of Metabolism?......Page 876
27.3 Is There a Good Index of Cellular Energy Status?......Page 878
27.4 How Is Overall Energy Balance Regulated in Cells?......Page 880
27.5 How Is Metabolism Integrated in a Multicellular Organism?......Page 882
27.6 What Regulates Our Eating Behavior?......Page 888
27.7 Can You Really Live Longer by Eating Less?......Page 891
SUMMARY......Page 893
PROBLEMS......Page 894
FURTHER READING......Page 896
28.1 How Is DNA Replicated?......Page 897
28.2 What Are the Properties of DNA Polymerases?......Page 900
28.3 Why Are There So Many DNA Polymerases?......Page 905
28.4 How Is DNA Replicated in Eukaryotic Cells?......Page 906
28.5 How Are the Ends of Chromosomes Replicated?......Page 909
28.6 How Are RNA Genomes Replicated?......Page 911
28.7 How Is the Genetic Information Shuffled by Genetic Recombination?......Page 912
28.8 Can DNA Be Repaired?......Page 922
28.9 What Is the Molecular Basis of Mutation?......Page 926
28.10 Do Proteins Ever Behave as Genetic Agents?......Page 928
Special Focus: Gene Rearrangements and Immunology—Is It Possible to Generate Protein Diversity Using Genetic Recombination?......Page 930
SUMMARY......Page 937
PROBLEMS......Page 938
FURTHER READING......Page 939
29.1 How Are Genes Transcribed in Prokaryotes?......Page 941
29.2 How Is Transcription Regulated in Prokaryotes?......Page 947
29.3 How Are Genes Transcribed in Eukaryotes?......Page 959
29.4 How Do Gene Regulatory Proteins Recognize Specific DNA Sequences?......Page 970
29.5 How Are Eukaryotic Transcripts Processed and Delivered to the Ribosomes for Translation?......Page 974
29.6 Can We Propose a Unified Theory of Gene Expression?......Page 981
SUMMARY......Page 983
PROBLEMS......Page 984
FURTHER READING......Page 985
30.1 What Is the Genetic Code?......Page 987
30.2 How Is an Amino Acid Matched with Its Proper tRNA?......Page 988
30.3 What Are the Rules in Codon–Anticodon Pairing?......Page 993
30.4 What Is the Structure of Ribosomes, and How Are They Assembled?......Page 996
30.5 What Are the Mechanics of mRNA Translation?......Page 1000
30.6 How Are Proteins Synthesized in Eukaryotic Cells?......Page 1011
PROBLEMS......Page 1019
FURTHER READING......Page 1020
31.1 How Do Newly Synthesized Proteins Fold?......Page 1022
31.2 How Are Proteins Processed Following Translation?......Page 1028
31.3 How Do Proteins Find Their Proper Place in the Cell?......Page 1029
31.4 How Does Protein Degradation Regulate Cellular Levels of Specific Proteins?......Page 1033
PROBLEMS......Page 1040
FURTHER READING......Page 1041
32.1 What Are Hormones?......Page 1043
32.2 What Is Signal Transduction?......Page 1045
32.3 How Do Signal-Transducing Receptors Respond to the Hormonal Message?......Page 1048
32.4 How Are Receptor Signals Transduced?......Page 1059
32.5 How Do Effectors Convert the Signals to Actions in the Cell?......Page 1069
32.6 How Are Signaling Pathways Organized and Integrated?......Page 1072
32.7 How Do Neurotransmission Pathways Control the Function of Sensory Systems?......Page 1078
SUMMARY......Page 1091
PROBLEMS......Page 1092
FURTHER READING......Page 1093
Abbreviated Answers to Problems......Page 1096
Index......Page 1144
Common Abbreviations Used by Biochemists......Page 1179
The Standard Genetic Code......Page 1181
Icons and Colors in Illustrations......Page 1182
Back......Page 1183