Biochemistry: Concepts and Connections

✍ Scribed by Appling, Dean R

• Publisher: Pearson Education Limited
• Year: 2016
• Tongue: English
• Leaves: 926
• Category: Library

✦ Synopsis

NOTE: You are purchasing a standalone product; MasteringChemistry does not come packaged with this content. If you would like to purchase both the physical text and MasteringChemistry search for ISBN-10: 0321839765/ISBN-13: 9780321839763. That package includes ISBN-10: 0133871975 /ISBN-13: 9780133871975 and ISBN-10: 0321839927ISBN-13: 9780321839923.
"For one or two semester biochemistry courses (science majors)."" "A highly visual, precise and fresh approach to guide today's mixed-science majors to a deeper understanding of biochemistry"Biochemistry: Concepts and Connections"engages students in the rapidly evolving field of biochemistry, better preparing them for the challenges of 21st century science through quantitative reasoning skills and a rich, chemical perspective on biological processes. This concise first edition teaches mixed-science-majors the chemical logic underlying the mechanisms, pathways, and processes in living cells through groundbreaking biochemical art and a clear narrative that illustrates biochemistry's relation to all other life sciences. Integration of biochemistry's experimental underpinnings alongside the presentation of modern techniques encourages students to appreciate and consider how their understanding of biochemistry can and will contribute to solving problems in medicine, agricultural sciences, environmental sciences, and forensics. The text is fully integrated with MasteringChemistry to provide support for students before, during, and after class. Highlights include interactive animations and tutorials based on the textbook's biochemical art program and Foundation Figures to help students visualize complex processes, apply, and test conceptual understanding as well as quantitative reasoning.
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✦ Table of Contents

Cover......Page 1
Title page......Page 2
Copyright page......Page 3
Brief contents......Page 4
Contents......Page 5
Preface......Page 20
About the Authors......Page 23
Tools of Biochemistry......Page 24
Foundation Figures......Page 25
Chapter 1......Page 35
Biochemistry and the Language of Chemistry......Page 36
The Origins of Biochemistry......Page 37
Biochemistry as a Discipline and an Interdisciplinary Science......Page 39
The Chemical Elements of Cells and Organisms......Page 40
The Origin of Biomolecules and Cells......Page 41
The Biopolymers: Proteins, Nucleic Acids, and Carbohydrates......Page 42
Lipids and Membranes......Page 44
1.3 Distinguishing Characteristics of Living Systems......Page 45
1.4 The Unit of Biological Organization: The Cell......Page 46
1.5 Biochemistry and the Information Explosion......Page 47
Chapter 2......Page 51
The Chemical Foundation of Life: Weak Interactions in an Aqueous Environment......Page 52
2.1 The Importance of Noncovalent Interactions in Biochemistry......Page 53
2.2 The Nature of Noncovalent Interactions......Page 54
Charge–Charge Interactions......Page 55
Dipole and Induced-Dipole Interactions......Page 56
Van der Waals Interactions......Page 57
Hydrogen Bonds......Page 58
The Structure and Properties of Water......Page 59
Hydrophilic Molecules in Aqueous Solution......Page 61
Amphipathic Molecules in Aqueous Solution......Page 62
Ionization of Water and the Ion Product......Page 63
The pH Scale and the Physiological pH Range......Page 65
Titration of Weak Acids: The Henderson–Hasselbalch Equation......Page 66
Buffer Solutions......Page 67
Molecules with Multiple Ionizing Groups......Page 68
Solubility of Macroions and pH......Page 71
The Influence of Small Ions: Ionic Strength......Page 73
Tools Of Biochemistry 2A Electrophoresis and Isoelectric Focusing......Page 77
Foundation figure Biomolecules: Structure and Function......Page 79
Chapter 3......Page 81
The Energetics of Life......Page 82
The First Law of Thermodynamics and Enthalpy......Page 83
The Driving Force for a Process......Page 84
Entropy......Page 85
Free Energy Defined in Terms of Enthalpy and Entropy Changes in the System......Page 86
The Interplay of Enthalpy and Entropy: A Summary......Page 87
Free Energy and Useful Work......Page 88
Changes in Concentration and ΔG......Page 89
ΔG versus ΔG°, Q versus K, and Homeostasis versus Equilibrium......Page 90
Water, H+ in Buffered Solutions, and the “Biochemical Standard State"......Page 92
Organic Phosphate Compounds as Energy Transducers......Page 93
Free Energy and Concentration Gradients: A Close Look at Diffusion Through a Membrane......Page 96
Quantification of Reducing Power: Standard Reduction Potential......Page 97
Calculating Free Energy Changes for Biological Oxidations under Nonequilibrium Conditions......Page 99
A Brief Overview of Free Energy Changes in Cells......Page 100
Chapter 4......Page 105
Nucleic Acids......Page 106
The Two Types of Nucleic Acid: DNA and RNA......Page 107
Properties of the Nucleotides......Page 110
Stability and Formation of the Phosphodiester Linkage......Page 111
The Nature and Significance of Primary Structure......Page 112
DNA as the Genetic Substance: Early Evidence......Page 113
X-Ray Analysis of DNA Fibers......Page 114
Semiconservative Nature of DNA Replication......Page 116
Alternative Nucleic Acid Structures: B and A Helices......Page 118
DNA Molecules......Page 119
Circular DNA and Supercoiling......Page 120
Single-Stranded Polynucleotides......Page 122
Left-Handed DNA (Z-DNA)......Page 123
Hairpins and Cruciforms......Page 124
G-Quadruplexes......Page 125
4.5 The Helix-to-Random Coil Transition: Nucleic Acid Denaturation......Page 126
Replication: DNA to DNA......Page 127
Translation: RNA to Protein......Page 128
Tools Of Biochemistry 4A Manipulating DNA......Page 132
Tools Of Biochemistry 4B An Introduction to X-Ray Diffraction......Page 137
Chapter 5......Page 141
Introduction to Proteins: The Primary Level of Protein Structure......Page 142
Stereochemistry of the a-Amino Acids......Page 144
Amino Acids with Nonpolar Aromatic Side Chains......Page 148
Amino Acids with Positively Charged (Basic) Side Chains......Page 149
The Structure of the Peptide Bond......Page 150
Stability and Formation of the Peptide Bond......Page 151
Peptides......Page 152
Polypeptides as Polyampholytes......Page 153
5.3 Proteins: Polypeptides of Defined Sequence......Page 154
The Genetic Code......Page 156
Post-translational Processing of Proteins......Page 157
5.5 From Gene Sequence to Protein Function......Page 158
5.6 Protein Sequence Homology......Page 160
Tools Of Biochemistry 5A Protein Expression and Purification......Page 164
Tools Of Biochemistry 5B Mass, Sequence, and Amino Acid Analyses of Purified Proteins......Page 171
Chapter 6......Page 177
The Three-Dimensional Structure of Proteins......Page 178
Theoretical Descriptions of Regular Polypeptide Structures......Page 179
Describing the Structures: Helices and Sheets......Page 181
Amphipathic Helices and Sheets......Page 182
Ramachandran Plots......Page 183
The Keratins......Page 185
Fibroin......Page 186
Collagen......Page 187
Different Modes of Display Aid Our Understanding of Protein Structure......Page 189
Varieties of Globular Protein Structure: Patterns of Main-Chain Folding......Page 190
The Thermodynamics of Folding......Page 194
Charge–Charge Interactions......Page 195
The Hydrophobic Effect......Page 196
Disulfide Bonds and Protein Stability......Page 197
Prosthetic Groups, Ion-binding, and Protein Stability......Page 198
The “Energy Landscape” Model of Protein Folding......Page 199
Chaperones Faciliate Protein Folding in Vivo......Page 201
Protein Misfolding and Disease......Page 203
Tertiary Structure Prediction: Computer Simulation of Folding......Page 204
Symmetry in Multisubunit Proteins: Homotypic Protein–Protein Interactions......Page 205
Heterotypic Protein–Protein Interactions......Page 207
Tools Of Biochemistry 6A Spectroscopic Methods for Studying Macromolecular Conformation in Solution......Page 211
Tools Of Biochemistry 6B Determining Molecular Masses and the Number of Subunits in a Protein Molecule......Page 218
Foundation figure Protein Structure and Function......Page 221
Chapter 7......Page 223
Protein Function and Evolution......Page 224
7.2 The Adaptive Immune Response......Page 225
7.3 The Structure of Antibodies......Page 226
7.4 Antibody:Antigen Interactions......Page 228
Shape and Charge Complementarity......Page 229
Generation of Antibody Diversity......Page 230
7.6 The Challenge of Developing an AIDS Vaccine......Page 231
7.7 Antibodies and Immunoconjugates as Potential Cancer Treatments......Page 232
7.8 Oxygen Transport from Lungs to Tissues: Protein Conformational Change Enhances Function......Page 233
7.9 The Oxygen Binding Sites in Myoglobin and Hemoglobin......Page 234
Analysis of Oxygen Binding by Myoglobin......Page 235
Cooperative Binding and Allostery......Page 237
Models for the Allosteric Change in Hemoglobin......Page 239
Changes in Hemoglobin Structure Accompanying Oxygen Binding......Page 240
A Closer Look at the Allosteric Change in Hemoglobin......Page 241
Response to pH Changes: The Bohr Effect......Page 244
2,3-Bisphosphoglycerate......Page 245
The Structure of Eukaryotic Genes: Exons and Introns......Page 247
Nucleotide Deletions or Insertions......Page 248
Evolution of the Myoglobin–Hemoglobin Family of Proteins......Page 249
7.14 Hemoglobin Variants and Their Inheritance: Genetic Diseases......Page 251
Pathological Effects of Variant Hemoglobins......Page 252
Actin......Page 253
Myosin......Page 254
7.18 The Mechanism of Contraction......Page 256
Regulation of Contraction: The Role of Calcium......Page 259
Tools of Biochemistry 7A Immunological Methods......Page 263
Chapter 8......Page 265
Enzymes: Biological Catalysts......Page 266
8.2 The Diversity of Enzyme Function......Page 267
First-Order Reactions......Page 268
Second-Order Reactions......Page 269
Transition States and Reaction Rates......Page 270
Transition State Theory Applied to Enzymatic Catalysis......Page 272
Models for Substrate Binding and Catalysis......Page 273
Mechanisms for Achieving Rate Acceleration......Page 274
Case Study #1: Lysozyme......Page 276
Case Study #2: Chymotrypsin, a Serine Protease......Page 278
Coenzyme Function in Catalysis......Page 280
8.6 The Kinetics of Enzymatic Catalysis......Page 282
Reaction Rate for a Simple Enzyme-Catalyzed Reaction: Michaelis–Menten Kinetics......Page 283
Interpreting KM, kcat, and kcat/KM......Page 284
Analysis of Kinetic Data: Testing the Michaelis–Menten Model......Page 286
8.7 Enzyme Inhibition......Page 287
Competitive Inhibition......Page 288
Uncompetitive Inhibition......Page 290
Mixed Inhibition......Page 291
Irreversible Inhibition......Page 292
Feedback Control......Page 293
Heteroallostery......Page 294
Aspartate Carbamoyltransferase: An Example of an Allosteric Enzyme......Page 295
Pancreatic Proteases: Activation by Irreversible Protein Backbone Cleavage......Page 297
8.10 Nonprotein Biocatalysts: Catalytic Nucleic Acids......Page 298
Tools Of Biochemistry 8A How to Measure the Rates of Enzyme-Catalyzed Reactions......Page 302
Foundation figure Regulation of Enzyme Activity......Page 305
Chapter 9......Page 307
Carbohydrates: Sugars, Saccharides, Glycans......Page 308
Aldoses and Ketoses......Page 309
Enantiomers......Page 310
Tetrose Diastereomers......Page 311
Pentose Rings......Page 312
Hexose Rings......Page 315
Phosphate Esters......Page 316
Glycosides......Page 317
Distinguishing Features of Different Disaccharides......Page 318
Writing the Structure of Disaccharides......Page 319
Stability and Formation of the Glycosidic Bond......Page 320
9.4 Polysaccharides......Page 321
Storage Polysaccharides......Page 322
Cellulose......Page 323
Chitin......Page 324
Nonstructural Roles of Glycosaminoglycans......Page 325
Bacterial Cell Wall Polysaccharides; Peptidoglycan......Page 326
O-Linked Glycans......Page 327
Blood Group Antigens......Page 328
Influenza Neuraminidase, a Target for Antiviral Drugs......Page 329
Tools Of Biochemistry 9A The Emerging Field of Glycomics......Page 332
Chapter 10......Page 333
Lipids, Membranes, and Cellular Transport......Page 334
Fatty Acids......Page 335
Triacylglycerols: Fats......Page 337
10.2 The Lipid Constituents of Biological Membranes......Page 338
Glycerophospholipids......Page 339
Sphingolipids and Glycosphingolipids......Page 340
Cholesterol......Page 341
10.3 The Structure and Properties of Membranes and Membrane Proteins......Page 342
Motion in Synthetic Membranes......Page 343
The Asymmetry of Membranes......Page 344
Characteristics of Membrane Proteins......Page 345
Insertion of Proteins into Membranes......Page 346
Evolution of the Fluid Mosaic Model of Membrane Structure......Page 348
The Thermodynamics of Transport......Page 350
Nonmediated Transport: Diffusion......Page 351
Carriers......Page 352
Permeases......Page 353
Pore-Facilitated Transport......Page 354
Ion Selectivity and Gating......Page 355
10.5 Ion Pumps: Direct Coupling of ATP Hydrolysis to Transport......Page 357
10.6 Ion Transporters and Disease......Page 359
10.7 Cotransport Systems......Page 360
The Resting Potential......Page 361
The Action Potential......Page 362
Toxins and Neurotransmission......Page 363
Chapter 11......Page 367
Chemical Logic of Metabolism......Page 368
11.1 A First Look at Metabolism......Page 369
Central Pathways of Energy Metabolism......Page 370
Distinct Pathways for Biosynthesis and Degradation......Page 373
Nucleophilic Substitutions......Page 374
Carbonyl Condensations......Page 375
11.4 Bioenergetics of Metabolic Pathways......Page 377
Energy Yields, Respiratory Quotients, and Reducing Equivalents......Page 378
ATP as a Free Energy Currency......Page 379
Metabolite Concentrations and Solvent Capacity......Page 381
Thermodynamic Properties of ATP......Page 382
Kinetic Control of Substrate Cycles......Page 383
Other High-Energy Phosphate Compounds......Page 384
Control of Enzyme Levels......Page 385
Compartmentation......Page 386
Distributive Control of Metabolism......Page 388
Whole Cells......Page 389
Metabolic Probes......Page 390
Tools Of Biochemistry 11A Metabolomics......Page 394
Tools Of Biochemistry 11B Radioactive and Stable Isotopes......Page 397
Foundation Figure Enzyme Kinetics and Drug Action......Page 399
Chapter 12......Page 401
Carbohydrate Metabolism: Glycolysis, Gluconeogenesis, Glycogen Metabolism, and the Pentose Phosphate Pathway......Page 402
Anaerobic and Aerobic Glycolysis......Page 404
Reaction 1: The First ATP Investment......Page 406
Reaction 4: Cleavage to Two Triose Phosphates......Page 408
Reaction 5: Isomerization of Dihydroxyacetone Phosphate......Page 409
Reaction 6: Generation of the First Energy-Rich Compound......Page 410
Reaction 8: Preparing for Synthesis of the Next High-Energy Compound......Page 411
Reaction 10: The Second Substrate-Level Phosphorylation......Page 412
Lactate Metabolism......Page 413
Ethanol Metabolism......Page 415
12.4 Energy and Electron Balance Sheets......Page 416
Physiological Need for Glucose Synthesis in Animals......Page 417
Bypass 1: Conversion of Pyruvate to Phosphoenolpyruvate......Page 418
Bypass 3: Conversion of Glucose-6-phosphate to Glucose......Page 419
Lactate......Page 420
The Pasteur Effect......Page 421
Reciprocal Regulation of Glycolysis and Gluconeogenesis......Page 422
Fructose-2,6-bisphosphate and the Control of Glycolysis and Gluconeogenesis......Page 423
Regulation at the Hexokinase/Glucose-6-Phosphatase Substrate Cycle......Page 426
Disaccharide Metabolism......Page 427
Hydrolytic and Phosphorolytic Cleavages......Page 428
Glycogen Breakdown......Page 429
Biosynthesis of UDP-Glucose......Page 430
The Glycogen Synthase Reaction......Page 431
Structure of Glycogen Phosphorylase......Page 432
Cyclic AMP–Dependent Protein Kinase......Page 433
Calmodulin......Page 434
Control of Glycogen Synthase Activity......Page 435
Congenital Defects of Glycogen Metabolism in Humans......Page 436
12.10 A Biosynthetic Pathway That Oxidizes Glucose: The Pentose Phosphate Pathway......Page 437
Production of Six-Carbon and Three-Carbon Sugar Phosphates......Page 438
Tailoring the Pentose Phosphate Pathway to Specific Needs......Page 440
Regulation of the Pentose Phosphate Pathway......Page 441
Human Genetic Disorders Involving Pentose Phosphate Pathway Enzymes......Page 442
Chapter 13......Page 447
The Citric Acid Cycle......Page 448
The Three Stages of Respiration......Page 450
Chemical Strategy of the Citric Acid Cycle......Page 451
Overview of Pyruvate Oxidation and the Pyruvate Dehydrogenase Complex......Page 453
Coenzymes Involved in Pyruvate Oxidation and the Citric Acid Cycle......Page 454
Nicotinamide Adenine Dinucleotide (NAD+)......Page 455
Coenzyme A: Activation of Acyl Groups......Page 456
Action of the Pyruvate Dehydrogenase Complex......Page 457
Step 1: Introduction of Two Carbon Atoms as Acetyl-CoA......Page 460
Step 2: Isomerization of Citrate......Page 461
Step 4: Conservation of Energy in NADH by a Second Oxidative Decarboxylation......Page 462
Step 6: A Flavin-Dependent Dehydrogenation......Page 463
13.4 Stoichiometry and Energetics of the Citric Acid Cycle......Page 464
Control of Pyruvate Oxidation......Page 465
13.6 Organization and Evolution of the Citric Acid Cycle......Page 467
13.8 Anaplerotic Sequences: The Need to Replace Cycle Intermediates......Page 468
Reactions Involving Amino Acids......Page 469
13.9 The Glyoxylate Cycle: An Anabolic Variant of the Citric Acid Cycle......Page 470
Tools Of Biochemistry 13A Detecting and Analyzing Protein–Protein Interactions......Page 475
Chapter 14......Page 477
Electron Transport, Oxidative Phosphorylation, and Oxygen Metabolism......Page 478
14.2 Free Energy Changes in Biological Oxidations......Page 480
Iron–Sulfur Proteins......Page 483
Cytochromes......Page 484
Respiratory Complexes......Page 485
NADH–Coenzyme Q Reductase (Complex I)......Page 486
Succinate–Coenzyme Q Reductase (Complex II)......Page 487
Coenzyme Q:Cytochrome c Oxidoreductase (Complex III)......Page 488
The P/O Ratio: Energetics of Oxidative Phosphorylation......Page 490
Oxidative Reactions That Drive ATP Synthesis......Page 491
Mechanism of Oxidative Phosphorylation: Chemiosmotic Coupling......Page 492
Membranes Can Establish Proton Gradients......Page 493
Discovery and Reconstitution of ATP Synthase......Page 494
Mechanism of ATP Synthesis......Page 496
14.5 Respiratory States and Respiratory Control......Page 499
Transport of Substrates and Products into and out of Mitochondria......Page 502
Shuttling Cytoplasmic Reducing Equivalents into Mitochondria......Page 503
14.8 The Mitochondrial Genome, Evolution, and Disease......Page 504
Formation of Reactive Oxygen Species......Page 506
Dealing with Oxidative Stress......Page 507
Foundation figure Intermediary Metabolism......Page 511
Chapter 15......Page 513
Photosynthesis......Page 514
15.1 The Basic Processes of Photosynthesis......Page 517
15.2 The Chloroplast......Page 518
The Light-Absorbing Pigments......Page 519
The Light-Gathering Structures......Page 520
Photochemistry in Plants and Algae: Two Photosystems in Series......Page 522
Photosystem II: The Splitting of Water......Page 524
Photosystem I: Production of NADPH......Page 526
Summation of the Two Systems: The Overall Reaction and ATP Generation......Page 527
Evolution of Photosynthesis......Page 529
15.4 The Dark Reactions: The Calvin Cycle......Page 530
Incorporation of CO2 into a Three-Carbon Sugar......Page 531
Stage II: Regeneration of the Acceptor......Page 532
Regulation of Photosynthesis......Page 533
15.6 Photorespiration and the C4 Cycle......Page 534
Chapter 16......Page 539
Lipid Metabolism......Page 540
Fat Digestion and Absorption......Page 542
Classification and Functions of Lipoproteins......Page 544
Transport and Utilization of Lipoproteins......Page 545
Cholesterol Transport and Utilization in Animals......Page 546
The LDL Receptor and Cholesterol Homeostasis......Page 547
Cholesterol, LDL, and Atherosclerosis......Page 549
Early Experiments......Page 550
Fatty Acid Activation and Transport into Mitochondria......Page 552
The B-Oxidation Pathway......Page 553
Reaction 4: Thiolytic Cleavage......Page 554
Oxidation of Unsaturated Fatty Acids......Page 555
Oxidation of Fatty Acids with Odd-Numbered Carbon Chains......Page 556
Ketogenesis......Page 557
Relationship of Fatty Acid Synthesis to Carbohydrate Metabolism......Page 558
Synthesis of Malonyl-CoA......Page 559
Malonyl-CoA to Palmitate......Page 560
Multifunctional Proteins in Fatty Acid Synthesis......Page 562
Fatty Acid Desaturation......Page 563
Control of Fatty Acid Synthesis......Page 565
16.4 Biosynthesis of Triacylglycerols......Page 566
16.5 Glycerophospholipids......Page 567
16.6 Sphingolipids......Page 568
Steroids: Some Structural Considerations......Page 569
Stage 1: Formation of Mevalonate......Page 570
Stage 2: Synthesis of Squalene from Mevalonate......Page 571
Control of Cholesterol Biosynthesis......Page 572
Vitamin D......Page 574
Vitamin A......Page 575
Vitamin K......Page 576
16.8 Eicosanoids: Prostaglandins, Thromboxanes, and Leukotrienes......Page 577
Chapter 17......Page 581
Interorgan and Intracellular Coordination of Energy Metabolism in Vertebrates......Page 582
Brain......Page 583
Blood......Page 585
Actions of the Major Hormones......Page 586
Glucagon......Page 587
AMP-Activated Protein Kinase (AMPK)......Page 588
Mammalian Target of Rapamycin (mTOR)......Page 589
Sirtuins......Page 590
Endocrine Regulation of Energy Homeostasis......Page 591
17.3 Responses to Metabolic Stress: Starvation, Diabetes......Page 592
Starvation......Page 593
Diabetes......Page 594
Chapter 18......Page 597
Amino Acid and Nitrogen Metabolism......Page 598
Biological Nitrogen Fixation......Page 600
Glutamine Synthetase: Generation of Biologically Active Amide Nitrogen......Page 602
Protein Turnover......Page 603
Chemical Signals for Turnover—Ubiquitination......Page 604
Pyridoxal Phosphate......Page 605
Discovery and Chemistry of Folic Acid......Page 606
Conversion of Folic Acid to Tetrahydrofolate......Page 607
Tetrahydrofolate in the Metabolism of One-Carbon Units......Page 608
B12 Coenzymes and Pernicious Anemia......Page 610
Detoxification and Excretion of Ammonia......Page 611
The Krebs–Henseleit Urea Cycle......Page 612
Pyruvate Family of Glucogenic Amino Acids......Page 614
Succinyl-CoA Family of Glucogenic Amino Acids......Page 616
Phenylalanine and Tyrosine Degradation......Page 618
Amino Acid Biosynthetic Pathways......Page 620
Synthesis of Valine, Leucine, and Isoleucine from Pyruvate......Page 621
S-Adenosylmethionine and Biological Methylation......Page 622
Precursor Functions of Glutamate......Page 624
Tryptophan and Tyrosine Are Precursors of Neurotransmitters and Biological Regulators......Page 625
Chapter 19......Page 631
Nucleotide Metabolism......Page 632
Biosynthetic Routes: De Novo and Salvage Pathways......Page 633
PRPP, a Central Metabolite in De Novo and Salvage Pathways......Page 634
Synthesis of the Purine Ring......Page 635
Synthesis of ATP and GTP from Inosine Monophosphate......Page 637
Uric Acid, a Primary End Product......Page 638
Gout......Page 639
Severe Combined Immunodeficiency Disease......Page 640
Glutamine-dependent Amidotransferases......Page 641
19.5 Deoxyribonucleotide Metabolism......Page 643
RNR Structure and Mechanism......Page 644
Regulation of Ribonucleotide Reductase Activity......Page 646
Regulation of dNTP Pools by Selective dNTP Degradation......Page 647
Biosynthesis of Thymine Deoxyribonucleotides......Page 648
Salvage Routes to Deoxyribonucleotides......Page 649
Thymidylate Synthase: A Target Enzyme for Chemotherapy......Page 650
19.6 Virus-Directed Alterations of Nucleotide Metabolism......Page 652
19.7 Other Medically Useful Analogs......Page 654
Chapter 20......Page 657
Mechanisms of Signal Transduction......Page 658
20.1 An Overview of Hormone Action......Page 659
Hierarchical Nature of Hormonal Control......Page 660
Receptors and Adenylate Cyclase as Distinct Components of Signal Transduction Systems......Page 661
Structural Analysis of G Protein-coupled Receptors......Page 662
Actions of G Proteins......Page 663
The Versatility of G Proteins......Page 664
Effectors......Page 665
Cyclic GMP and Nitric Oxide......Page 666
Phosphoinositides......Page 667
20.3 Receptor Tyrosine Kinases and Insulin Signaling......Page 669
20.4 Hormones and Gene Expression: Nuclear Receptors......Page 672
Oncogenes in Human Tumors......Page 674
The Cancer Genome Mutational Landscape......Page 676
The Cholinergic Synapse......Page 677
Fast and Slow Synaptic Transmission......Page 678
Actions of Specific Neurotransmitters......Page 679
Peptide Neurotransmitters and Neurohormones......Page 680
Foundation Figure Cell Signaling and Protein Regulation......Page 683
Chapter 21......Page 685
Genes, Genomes, and Chromosomes......Page 686
Bacterial Genomes—The Nucleoid......Page 687
Genome Sizes......Page 688
Repetitive Sequences......Page 689
Duplications of Functional Genes......Page 690
Multiple Variants of a Gene......Page 691
The Nucleus......Page 692
Histones and Nonhistone Chromosomal Proteins......Page 693
The Nucleosome......Page 694
Restriction and Modification......Page 696
Properties of Restriction and Modification Enzymes......Page 697
Mapping Large Genomes......Page 699
Generating Physical Maps......Page 700
Southern Transfer and DNA Fingerprinting......Page 701
Locating Genes on the Human Genome......Page 702
Size of the Human Genome......Page 703
Tools Of Biochemistry 21A Polymerase Chain Reaction......Page 707
Chapter 22......Page 709
DNA Replication......Page 710
22.1 Early Insights into DNA Replication......Page 711
Structure and Activities of DNA Polymerase I......Page 712
Multiple Activities in a Single Polypeptide Chain......Page 713
Discovery of Additional DNA Polymerases......Page 714
Structure and Mechanism of DNA Polymerases......Page 715
Replication Proteins in Addition to DNA Polymerase......Page 716
Discontinuous DNA Synthesis......Page 717
The DNA Polymerase III Holoenzyme......Page 719
Clamp Loading Complex......Page 720
Helicases: Unwinding DNA Ahead of the Fork......Page 721
Actions of Type I and Type II Topoisomerases......Page 722
The Four Topoisomerases of E. coli......Page 724
DNA Polymerases......Page 725
Other Eukaryotic Replication Proteins......Page 726
Initiation of E. coli DNA Replication at oric......Page 727
Initiation of Eukaryotic Replication......Page 728
Linear Virus Genome Replication......Page 729
Telomerase......Page 730
Polymerase Insertion Specificity......Page 731
RNA-dependent RNA Replicases......Page 733
Replication of Retroviral Genomes......Page 734
Chapter 23......Page 737
DNA Repair, Recombination, and Rearrangement......Page 738
Types and Consequences of DNA Damage......Page 739
O6-Alkylguanine Alkyltransferase......Page 741
Nucleotide Excision Repair: Excinucleases......Page 742
Replacement of Uracil in DNA by BER......Page 743
Repair of Oxidative Damage to DNA......Page 744
Mismatch Repair......Page 745
Daughter-strand Gap Repair......Page 747
Site-specific Recombination......Page 749
Models for Recombination......Page 750
Proteins Involved in Homologous Recombination......Page 751
Immunoglobulin Synthesis: Generating Antibody Diversity......Page 753
Transposable Genetic Elements......Page 755
Gene Amplification......Page 756
Foundation figure Antibody Diversity and Use as Therapeutics......Page 761
Chapter 24......Page 763
Transcription and Post-transcriptional Processing......Page 764
The Predicted Existence of Messenger RNA......Page 765
T2 Bacteriophage and the Demonstration of Messenger RNA......Page 766
RNA Dynamics in Uninfected Cells......Page 767
Biological Role of RNA Polymerase......Page 768
Structure of RNA Polymerase......Page 769
Initiation of Transcription: Interactions with Promoters......Page 770
Initiation and Elongation: Incorporation of Ribonucleotides......Page 772
Factor-Independent Termination......Page 773
24.4 Transcription in Eukaryotic Cells......Page 774
RNA Polymerase II: Transcription of Structural Genes......Page 775
Transcriptional Elongation......Page 778
Post-transcriptional Processing in the Synthesis of Bacterial rRNAs and tRNAs......Page 779
tRNA Processing......Page 780
Splicing......Page 781
Alternative Splicing......Page 783
Tools Of Biochemistry 24A DNA Microarrays......Page 786
Tools Of Biochemistry 24B Chromatin Immunoprecipitation......Page 787
Chapter 25......Page 789
Information Decoding: Translation and Posttranslational Protein Processing......Page 790
25.1 An Overview of Translation......Page 791
How the Code Was Deciphered......Page 792
Features of the Code......Page 793
The Wobble Hypothesis......Page 794
Messenger RNA......Page 795
Transfer RNA......Page 796
Aminoacyl-tRNA Synthetases: The First Step in Protein Synthesis......Page 798
Components of Ribosomes......Page 800
Ribosomal RNA Structure......Page 802
Internal Structure of the Ribosome......Page 803
Initiation......Page 804
Elongation......Page 805
Termination......Page 807
Suppression of Nonsense Mutations......Page 808
25.5 Inhibition of Translation by Antibiotics......Page 809
25.6 Translation in Eukaryotes......Page 810
25.8 The Final Stages in Protein Synthesis: Folding and Covalent Modification......Page 811
Covalent Modification......Page 812
Proteins Synthesized in the Cytoplasm......Page 813
Role of the Golgi Complex......Page 815
Chapter 26......Page 819
Regulation of Gene Expression......Page 820
The Lactose Operon—Earliest Insights into Transcriptional Regulation......Page 821
The Repressor Binding Site......Page 823
The CRP–DNA Complex......Page 825
Bacteriophage l: Multiple Operators, Dual Repressors, Interspersed Promoters and Operators......Page 826
The SOS Regulon: Activation of Multiple Operons by a Common Set of Environmental Signals......Page 828
Biosynthetic Operons: Ligand-Activated Repressors and Attenuation......Page 829
Chromatin and Transcription......Page 831
Transcriptional Control Sites and Genes......Page 832
Nucleosome Remodeling Complexes......Page 833
Transcription Initiation......Page 834
DNA Methylation in Eukaryotes......Page 835
DNA Methylation and Gene Silencing......Page 836
26.4 Regulation of Translation......Page 837
Regulation of Eukaryotic Translation......Page 838
26.5 RNA Interference......Page 839
Small Interfering RNAs......Page 840
26.7 RNA Editing......Page 841
Foundation Figure Information Flow in Biological Systems......Page 845
Answers to Selected Problems......Page 848
Glossary......Page 864
Credits......Page 880
Index......Page 882