Fundamentals of biochemistry: life at the molecular level [Fourth edition] 9780470547847, 9781118129180, 4705478479, 0470547847, 9781118474747, 1118474740

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Fundamentals of biochemistry: life at the molecular level [Fourth edition]
 9780470547847, 9781118129180, 4705478479, 0470547847, 9781118474747, 1118474740

Table of contents :
Cover......Page 1
Fundamentals of Biochemistry: Life at the Molecular Level......Page 5
©......Page 6
About the Authors......Page 7
Brief Contents......Page 8
CONTENTS......Page 9
Preface......Page 19
Acknowledgments......Page 24
Guide to Media Resources......Page 27
Clinical Applications......Page 33
1 Introduction to the Chemistry of Life......Page 35
A. Biological Molecules Arose From Inorganic Materials......Page 36
B. Complex Self-replicating Systems Evolved from Simple Molecules......Page 37
2 Cellular Architecture......Page 39
A. Cells Carry Out Metabolic Reactions......Page 40
B. There are Two Types of Cells: Prokaryotes and Eukaryotes......Page 41
C. Molecular Data Reveal Three Evolutionary Domains of Organisms......Page 43
Box 1-1 Pathways of Discovery: Lynn Margulis and the Theory of Endosymbiosis......Page 44
A. The First law of Thermodynamics States That Energy is Conserved......Page 45
C. The Free Energy Change Determines the Spontaneity of a Process......Page 47
D. Free Energy Changes Can Be Calculated from Equilibrium Concentrations......Page 49
E. Life Obeys the Laws of Thermodynamics......Page 52
Box 1-2 Perspectives in Biochemistry: Biochemical Conventions......Page 46
2 Water......Page 56
A. Water is a Polar Molecule......Page 57
B. Hydrophilic Substances Dissolve in Water......Page 59
C. The Hydrophobic Effect Causes Nonpolar Substances to Aggregate in Water......Page 60
D. Water Moves by Osmosis and Solutes Move by Diffusion......Page 62
A. Water Ionizes to Form H+ and OH-......Page 64
Box 2-1 Perspectives in Biochemistry: The Consequences of Ocean Acidification......Page 66
C. Buffers Resist Changes in pH......Page 68
Box 2-2 Biochemistry in Health and Disease: The Blood Buffering System......Page 71
3 Nucleotides, Nucleic Acids, and Genetic Information......Page 74
1 Nucleotides......Page 75
A. Nucleic Acids Are Polymers of Nucleotides......Page 78
B. DNA Forms a Double Helix......Page 79
3 Overview of Nucleic Acid Function......Page 82
B. Genes Direct Protein Synthesis......Page 83
4 Nucleic Acid Sequencing......Page 85
A. Restriction Endonucleases Cleave DNA at Specific Sequences......Page 86
B. Electrophoresis Separates Nucleic Acids According to Size......Page 88
C. Traditional DNA Sequencing Uses the Chain-Terminator Method......Page 89
Box 3-1 Pathways of Discovery: Francis Collins and the Gene for Cystic Fibrosis......Page 92
E. Evolution Results from Sequence Mutations......Page 94
A. Cloned DNA Is an Amplified Copy......Page 96
B. DNA Libraries Are Collections of Cloned DNA......Page 100
C. DNA Is Amplified by the Polymerase Chain Reaction......Page 101
D. Recombinant DNA Technology Has Numerous Practical Applications......Page 102
Box 3-2 Perspectives in Biochemistry: DNA Fingerprinting......Page 103
Box 3-3 Perspectives in Biochemistry: Ethical Aspects of Recombinant DNA Technology......Page 105
4 Amino Acids......Page 110
Box 4-1 Pathways of Discovery: William C. Rose and the Discovery of Threonine......Page 111
C. Amino Acid Side Chains are Nonpolar, Polar, or Charged......Page 114
D. The pK Values of Ionizable Groups Depend on Nearby Groups......Page 116
E. Amino Acid Names Are Abbreviated......Page 117
2 Stereochemistry......Page 118
3 Amino Acid Derivatives......Page 121
B. Some Amino Acids Are Biologically Active......Page 122
Box 4-2 Perspectives in Biochemistry: The RS System......Page 120
Box 4-3 Perspectives in Biochemistry: Green Fluorescent Protein......Page 123
5 Proteins: Primary Structure......Page 127
1 Polypeptide Diversity......Page 128
2 Protein Purification and Analysis......Page 129
A. Purifying a Protein Requires a Strategy......Page 130
B. Salting Out Separates Proteins by Their Solubility......Page 132
C. Chromatography Involves Interaction with Mobile and Stationary Phases......Page 133
D. Electrophoresis Separates Molecules According to Charge and Size......Page 136
E. Ultracentrifugation Separates Molecules by Mass......Page 138
A. The First Step Is to Separate Subunits......Page 140
C. Edman Degradation Removes a Peptide’s First Amino Acid Residue......Page 144
D. Mass Spectrometry Determines the Molecular Masses of Peptides......Page 147
E. Reconstructed Protein Sequences Are Stored in Databases......Page 148
4 Protein Evolution......Page 150
A. Protein Sequences Reveal Evolutionary Relationships......Page 151
B. Proteins Evolve by the Duplication of Genes or Gene Segments......Page 153
Box 5-1 Pathways of Discovery: Frederick Sanger and Protein Sequencing......Page 142
6 Proteins: Three-Dimensional Structure......Page 161
A. The Planar Peptide Group Limits Polypeptide Conformations......Page 162
B. The Most Common Regular Secondary Structures are the α Helix and the β Sheet......Page 165
C. Fibrous Proteins Have Repeating Secondary Structures......Page 170
D. Most Proteins Include Nonrepetitive Structure......Page 174
A. Most Protein Structures Are Determined by X-Ray Crystallography or Nuclear Magnetic Resonance......Page 176
B. Side Chain Location Varies with Polarity......Page 180
C. Tertiary Structures Contain Combinations of Secondary Structure......Page 182
D. Structure Is Conserved More than Sequence......Page 185
E. Structural Bioinformatics Provides Tools for Storing, Visualizing, and Comparing Protein Structural Information......Page 186
3 Quaternary Structure and Symmetry......Page 189
4 Protein Stability......Page 190
A. Proteins Are Stabilized by Several Forces......Page 191
Box 6-3 Perspectives in Biochemistry: Thermostable Proteins......Page 193
C. Proteins Are Dynamic Structures......Page 195
A. Proteins Follow Folding Pathways......Page 196
B. Molecular Chaperones Assist Protein Folding......Page 200
C. Some Diseases Are Caused by Protein Misfolding......Page 203
Box 6-1 Pathways of Discovery: Linus Pauling and Structural Biochemistry......Page 166
Box 6-2 Biochemistry in Health and Disease: Collagen Diseases......Page 173
Box 6-4 Perspectives in Biochemistry: Protein Structure Prediction and Protein Design......Page 199
7 Protein Function: Myoglobin and Hemoglobin, Muscle Contraction, and Antibodies......Page 210
A. Myoglobin Is a Monomeric Oxygen-Binding Protein......Page 211
Box 7-1 Perspectives in Biochemistry: Other Oxygen-Transport Proteins......Page 215
C. Oxygen Binds Cooperatively to Hemoglobin......Page 218
D. Hemoglobin’s Two Conformations Exhibit Different Affinities for Oxygen......Page 220
E. Mutations May Alter Hemoglobin’s Structure and Function......Page 227
2 Muscle Contraction......Page 230
A. Muscle Consists of Interdigitated Thick and Thin Filaments......Page 231
B. Muscle Contraction Occurs when Myosin Heads Walk up Thin Filaments......Page 238
C. Actin Forms Microfilaments in Nonmuscle Cells......Page 240
A. Antibodies Have Constant and Variable Regions......Page 242
B. Antibodies Recognize a Huge Variety of Antigens......Page 244
Box 7-2 Pathways of Discovery: Max Perutz and the Structure and Function of Hemoglobin......Page 216
Box 7-3 Biochemistry in Health and Disease: High-Altitude Adaptation......Page 225
Box 7-4 Pathways of Discovery: Hugh Huxley and the Sliding Filament Model......Page 233
Box 7-5 Perspectives in Biochemistry: Monoclonal Antibodies......Page 246
8 Carbohydrates......Page 251
A. Monosaccharides Are Aldoses or Ketoses......Page 252
B. Monosaccharides Vary in Configuration and Conformation......Page 253
C. Sugars Can Be Modified and Covalently Linked......Page 255
Box 8-1 Biochemistry in Health and Disease: Lactose Intolerance......Page 258
B. Cellulose and Chitin Are Structural Polysaccharides......Page 260
C. Starch and Glycogen Are Storage Polysaccharides......Page 261
D. Glycosaminoglycans Form Highly Hydrated Gels......Page 262
3 Glycoproteins......Page 264
B. Bacterial Cells Walls Are Made of Peptidoglycan......Page 265
Box 8-3 Biochemistry in Health and Disease: Peptidoglycan-Specific Antibiotics......Page 268
D. Oligosaccharides May Determine Glycoprotein Structure, Function, and Recognition......Page 270
Box 8-2 Perspectives in Biochemistry: Artificial Sweeteners......Page 259
9 Lipids and Biological Membranes......Page 275
A. The Properties of Fatty Acids Depend on Their Hydrocarbon Chains......Page 276
B. Triacylglycerols Contain Three Esterified Fatty Acids......Page 278
C. Glycerophospholipids Are Amphipathic......Page 279
D. Sphingolipids Are Amino Alcohol Derivatives......Page 282
E. Steroids Contain Four Fused Rings......Page 283
F. Other Lipids Perform a Variety of Metabolic Roles......Page 286
A. Bilayer Formation Is Driven by the Hydrophobic Effect......Page 289
B. Lipid Bilayers Have Fluidlike Properties......Page 290
A. Integral Membrane Proteins Interact with Hydrophobic Lipids......Page 292
B. Lipid-Linked Proteins Are Anchored to the Bilayer......Page 297
C. Peripheral Membrane Proteins Associate Loosely with Membranes......Page 298
A. The Fluid Mosaic Model Accounts for Lateral Diffusion......Page 299
B. The Membrane Skeleton Helps Define Cell Shape......Page 301
C. Membrane Lipids Are Distributed Asymmetrically......Page 304
D. The Secretory Pathway Generates Secreted and Transmembrane Proteins......Page 306
E. Intracellular Vesicles Transport Proteins......Page 310
F. Proteins Mediate Vesicle Fusion......Page 314
Box 9-1 Biochemistry in Health and Disease: Lung Surfactant......Page 280
Box 9-2 Pathways of Discovery: Richard Henderson and the Structure of Bacteriorhodopsin......Page 295
Box 9-3 Biochemistry in Health and Disease: Tetanus and Botulinum Toxins Specifically Cleave SNAREs......Page 316
1 Thermodynamics of Transport......Page 322
A. Ionophores Carry Ions across Membranes......Page 324
B. Porins Contain β Barrels......Page 325
C. Ion Channels Are Highly Selective......Page 326
D. Aquaporins Mediate the Transmembrane Movement of Water......Page 333
E. Transport Proteins Alternate between Two Conformations......Page 334
A. The (Na+ – K+) – ATPase Transports Ions in Opposite Directions......Page 338
Box 10-3 Biochemistry in Health and Disease: The Action of Cardiac Glycosides......Page 340
C. ABC Transporters Are Responsible for Drug Resistance......Page 342
D. Active Transport May Be Driven by Ion Gradients......Page 343
Box 10-1 Perspectives in Biochemistry: Gap Junctions......Page 335
Box 10-2 Perspectives in Biochemistry: Differentiating Mediated and Nonmediated Transport......Page 337
11 Enzymatic Catalysis......Page 349
1 General Properties of Enzymes......Page 350
B. Enzymes Act on Specific Substrates......Page 351
C. Some Enzymes Require Cofactors......Page 353
2 Activation Energy and the Reaction Coordinate......Page 354
A. Acid–Base Catalysis Occurs by Proton Transfer......Page 357
B. Covalent Catalysis Usually Requires a Nucleophile......Page 361
C. Metal Ion Cofactors Act as Catalysts......Page 362
D. Catalysis Can Occur through Proximity and Orientation Effects......Page 363
E. Enzymes Catalyze Reactions by Preferentially Binding the Transition State......Page 365
4 Lysozyme......Page 366
A. Lysozyme’s Catalytic Site Was Identified through Model Building......Page 367
B. The Lysozyme Reaction Proceeds via a Covalent Intermediate......Page 369
A. Active Site Residues Were Identified by Chemical Labeling......Page 373
Box 11-3 Biochemistry in Health and Disease: Nerve Poisons......Page 374
C. Serine Proteases Use Several Catalytic Mechanisms......Page 379
D. Zymogens Are Inactive Enzyme Precursors......Page 383
Box 11-1 Perspectives in Biochemistry: Drawing Reaction Mechanisms......Page 358
Box 11-2 Perspectives in Biochemistry: Effects of pH on Enzyme Activity......Page 359
Box 11-4 Biochemistry in Health and Disease: The Blood Coagulation Cascade......Page 384
1 Reaction Kinetics......Page 389
A. Chemical Kinetics Is Described by Rate Equations......Page 390
B. Enzyme Kinetics Often Follows the Michaelis–Menten Equation......Page 392
Box 12-2 Perspectives in Biochemistry: Kinetics and Transition State Theory......Page 397
D. Bisubstrate Reactions Follow One of Several Rate Equations......Page 400
A. Competitive Inhibition Involves Inhibitor Binding at an Enzyme’s Substrate Binding Site......Page 402
B. Uncompetitive Inhibition Involves Inhibitor Binding to the Enzyme–Substrate Complex......Page 408
C. Mixed Inhibition Involves Inhibitor Binding to Both the Free Enzyme and the Enzyme–Substrate Complex......Page 409
3 Control of Enzyme Activity......Page 410
A. Allosteric Control Involves Binding at a Site Other than the Active Site......Page 411
B. Control by Covalent Modification Usually Involves Protein Phosphorylation......Page 415
4 Drug Design......Page 419
A. Drug Discovery Employs a Variety of Techniques......Page 420
C. Clinical Trials Test for Efficacy and Safety......Page 421
D. Cytochromes P450 Are Often Implicated in Adverse Drug Reactions......Page 423
Box 12-1 Pathways of Discovery: J.B.S. Haldane and Enzyme Action......Page 394
Box 12-3 Biochemistry in Health and Disease: HIV Enzyme Inhibitors......Page 404
13 Biochemical Signaling......Page 430
1 Hormones......Page 431
B. Epinephrine and Norepinephrine Prepare the Body for Action......Page 432
C. Steroid Hormones Regulate a Wide Variety of Metabolic and Sexual Processes......Page 434
D. Growth Hormone Binds to Receptors in Muscle, Bone, and Cartilage......Page 435
2 Receptor Tyrosine Kinases......Page 436
A. Receptor Tyrosine Kinases Transmit Signals across the Cell Membrane......Page 437
B. Kinase Cascades Relay Signals to the Nucleus......Page 440
C. Some Receptors are Associated with Nonreceptor Tyrosine Kinases......Page 445
D. Protein Phosphatases Are Signaling Proteins in Their Own Right......Page 448
3 Heterotrimeric G Proteins......Page 451
A. G Protein–Coupled Receptors Contain Seven Transmembrane Receptors......Page 452
B. Heterotrimeric G Proteins Dissociate on Activation......Page 454
C. Adenylate Cyclase Synthesizes cAMP to Activate Protein Kinase A......Page 456
D. Phosphodiesterases Limit Second Messenger Activity......Page 458
4 The Phosphoinositide Pathway......Page 460
A. Ligand Binding Results in the Cytoplasmic Release of the Second Messengers IP3 and Ca2+......Page 461
B. Calmodulin Is a Ca2+ - Activated Switch......Page 462
C. DAG Is a Lipid-Soluble Second Messenger......Page 464
D. Epilog: Complex Systems Have Emergent Properties......Page 465
Box 13-1 Pathways of Discovery: Rosalyn Yalow and the Radioimmunoassay (RIA)......Page 433
Box 13-2 Perspectives in Biochemistry: Receptor–Ligand Binding Can Be Quantitated......Page 438
Box 13-3 Biochemistry in Health and Disease: Oncogenes and Cancer......Page 444
Box 13-4 Biochemistry in Health and Disease: Drugs and Toxins That Affect Cell Signaling......Page 459
14 Introduction to Metabolism......Page 470
A. Nutrition Involves Food Intake and Use......Page 471
B. Vitamins and Minerals Assist Metabolic Reactions......Page 472
C. Metabolic Pathways Consist of Series of Enzymatic Reactions......Page 473
D. Thermodynamics Dictates the Direction and Regulatory Capacity of Metabolic Pathways......Page 477
E. Metabolic Flux Must Be Controlled......Page 478
2 “High-Energy” Compounds......Page 480
A. ATP Has a High Phosphoryl Group-Transfer Potential......Page 482
Box 14-3 Perspectives in Biochemistry: ATP and ΔG......Page 483
C. Some Other Phosphorylated Compounds Have High Phosphoryl Group-Transfer Potentials......Page 486
D. Thioesters Are Energy-Rich Compounds......Page 489
A. NAD+ and FAD Are Electron Carriers......Page 490
B. The Nernst Equation Describes Oxidation–Reduction Reactions......Page 491
C. Spontaneity Can Be Determined by Measuring Reduction Potential Differences......Page 493
A. Labeled Metabolites Can Be Traced......Page 496
C. Systems Biology Has Entered the Study of Metabolism......Page 498
Box 14-1 Perspectives in Biochemistry: Oxidation States of Carbon......Page 475
Box 14-2 Pathways of Discovery: Fritz Lipmann and “High-Energy” Compounds......Page 481
15 Glucose Catabolism......Page 506
Box 15-1 Pathways of Discovery: Otto Warburg and Studies of Metabolism......Page 507
A. Hexokinase Uses the First ATP......Page 509
B. Phosphoglucose Isomerase Converts Glucose-6-Phosphate to Fructose-6-Phosphate......Page 510
D. Aldolase Converts a 6-Carbon Compound to Two 3-Carbon Compounds......Page 512
E. Triose Phosphate Isomerase Interconverts Dihydroxyacetone Phosphate and Glyceraldehyde-3-Phosphate......Page 513
F. Glyceraldehyde-3-Phosphate Dehydrogenase Forms the First “High-Energy” Intermediate......Page 517
G. Phosphoglycerate Kinase Generates the First ATP......Page 519
H. Phosphoglycerate Mutase Interconverts 3-Phosphoglycerate and 2-Phosphoglycerate......Page 520
I. Enolase Forms the Second “High-Energy” Intermediate......Page 521
Box 15-2 Perspectives in Biochemistry: Synthesis of 2,3-Bisphosphoglycerate in Erythrocytes and Its Effect on the Oxygen Carrying Capacity of the Blood......Page 522
3 Fermentation: The Anaerobic Fate of Pyruvate......Page 525
B. Alcoholic Fermentation Converts Pyruvate to Ethanol and CO2......Page 526
C. Fermentation Is Energetically Favorable......Page 529
Box 15-3 Perspectives in Biochemistry: Glycolytic ATP Production in Muscle......Page 530
A. Phosphofructokinase Is the Major Flux-Controlling Enzyme of Glycolysis in Muscle......Page 531
B. Substrate Cycling Fine-tunes Flux Control......Page 534
A. Fructose Is Converted to Fructose-6-Phosphate or Glyceraldehyde-3-Phosphate......Page 536
B. Galactose Is Converted to Glucose-6-Phosphate......Page 538
6. The Pentose Phosphate Pathway......Page 540
A. Oxidative Reactions Produce NADPH in Stage 1......Page 542
C. Stage 3 Involves Carbon–Carbon Bond Cleavage and Formation......Page 543
Box 15-4 Biochemistry in Health and Disease: Glucose-6-Phosphate Dehydrogenase Deficiency......Page 546
16 Glycogen Metabolism and Gluconeogenesis......Page 551
1. Glycogen Breakdown......Page 552
A. Glycogen Phosphorylase Degrades Glycogen to Glucose-1-Phosphate......Page 553
B. Glycogen Debranching Enzyme Acts as a Glucosyltransferase......Page 556
C. Phosphoglucomutase Interconverts Glucose-1-Phosphate and Glucose-6-Phosphate......Page 557
A. UDP–Glucose Pyrophosphorylase Activates Glucosyl Units......Page 560
B. Glycogen Synthase Extends Glycogen Chains......Page 561
C. Glycogen Branching Enzyme Transfers Seven-Residue Glycogen Segments......Page 563
B. Glycogen Phosphorylase and Glycogen Synthase Undergo Control by Covalent Modification......Page 564
C. Glycogen Metabolism Is Subject to Hormonal Control......Page 570
4. Gluconeogenesis......Page 572
A. Pyruvate Is Converted to Phosphoenolpyruvate in Two Steps......Page 573
C. Gluconeogenesis and Glycolysis Are Independently Regulated......Page 577
Box 16-4 Perspectives in Biochemistry: Lactose Synthesis......Page 579
Box 16-1 Pathways of Discovery: Carl and Gerty Cori and Glucose Metabolism......Page 554
Box 16-2 Biochemistry in Health and Disease: Glycogen Storage Diseases......Page 558
Box 16-3 Perspectives in Biochemistry: Optimizing Glycogen Structure......Page 565
17 Citric Acid Cycle......Page 585
1. Overview of the Citric Acid Cycle......Page 586
A. Pyruvate Dehydrogenase Is a Multienzyme Complex......Page 589
B. The Pyruvate Dehydrogenase Complex Catalyzes Five Reactions......Page 591
Box 17-2 Biochemistry in Health and Disease: Arsenic Poisoning......Page 595
B. Aconitase Interconverts Citrate and Isocitrate......Page 597
D. α-Ketoglutarate Dehydrogenase Resembles Pyruvate Dehydrogenase......Page 598
E. Succinyl-CoA Synthetase Produces GTP......Page 599
H. Malate Dehydrogenase Regenerates Oxaloacetate......Page 601
4. Regulation of the Citric Acid Cycle......Page 602
A. Pyruvate Dehydrogenase Is Regulated by Product Inhibition and Covalent Modification......Page 603
B. Three Enzymes Control the Rate of the Citric Acid Cycle......Page 604
A. Other Pathways Use Citric Acid Cycle Intermediates......Page 606
C. The Glyoxylate Cycle Shares Some Steps with the Citric Acid Cycle......Page 608
Box 17-1 Pathways of Discovery: Hans Krebs and the Citric Acid Cycle......Page 588
Box 17-3 Perspectives in Biochemistry: Evolution of the Citric Acid Cycle......Page 610
18 Electron Transport and Oxidative Phosphorylation......Page 615
A. Mitochondria Contain a Highly Folded Inner Membrane......Page 617
B. Ions and Metabolites Enter Mitochondria via Transporters......Page 618
A. Electron Transport Is an Exergonic Process......Page 621
B. Electron Carriers Operate in Sequence......Page 622
C. Complex I Accepts Electrons from NADH......Page 624
D. Complex II Contributes Electrons to Coenzyme Q......Page 629
Box 18-1 Perspectives in Biochemistry: Cytochromes Are Electron-Transport Heme Proteins......Page 630
F. Complex IV Reduces Oxygen to Water......Page 634
3. Oxidative Phosphorylation......Page 637
A. The Chemiosmotic Theory Links Electron Transport to ATP Synthesis......Page 638
B. ATP Synthase Is Driven by the Flow of Protons......Page 641
C. The P/O Ratio Relates the Amount of ATP Synthesized to the Amount of Oxygen Reduced......Page 646
D. Oxidative Phosphorylation Can Be Uncoupled from Electron Transport......Page 647
4. Control of Oxidative Metabolism......Page 648
A. The Rate of Oxidative Phosphorylation Depends on the ATP and NADH Concentrations......Page 650
B Aerobic Metabolism Has Some Disadvantages......Page 651
Box 18-2 Pathways of Discovery: Peter Mitchell and the Chemiosmotic Theory......Page 639
Box 18-3 Perspectives in Biochemistry: Bacterial Electron Transport and Oxidative Phosphorylation......Page 640
Box 18-4 Perspectives in Biochemistry: Uncoupling in Brown Adipose Tissue Generates Heat......Page 649
Box 18-5 Biochemistry in Health and Disease: Oxygen Deprivation in Heart Attack and Stroke......Page 653
19 Photosynthesis......Page 657
A. The Light Reactions Take Place in the Thylakoid Membrane......Page 658
B. Pigment Molecules Absorb Light......Page 659
A. Light Energy Is Transformed to Chemical Energy......Page 662
B. Electron Transport in Photosynthetic Bacteria Follows a Circular Path......Page 664
C Two-Center Electron Transport Is a Linear Pathway That Produces O2 and NADPH......Page 666
Box 19-1 Perspectives in Biochemistry: Segregation of PSI and PSII......Page 676
A. The Calvin Cycle Fixes CO2......Page 678
B. Calvin Cycle Products Are Converted to Starch, Sucrose, and Cellulose......Page 682
C. The Calvin Cycle Is Controlled Indirectly by Light......Page 683
D. Photorespiration Competes with Photosynthesis......Page 685
1. Lipid Digestion, Absorption, and Transport......Page 691
A. Triacylglycerols Are Digested before They Are Absorbed......Page 692
B. Lipids Are Transported as Lipoproteins......Page 694
2. Fatty Acid Oxidation......Page 698
B. Carnitine Carries Acyl Groups across the Mitochondrial Membrane......Page 699
C. β Oxidation Degrades Fatty Acids to Acetyl-CoA......Page 701
D. Oxidation of Unsaturated Fatty Acids Requires Additional Enzymes......Page 703
E. Oxidation of Odd-Chain Fatty Acids Yields Propionyl-CoA......Page 704
F. Peroxisomal β Oxidation Differs from Mitochondrial β Oxidation......Page 711
3. Ketone Bodies......Page 712
4. Fatty Acid Biosynthesis......Page 714
A. Mitochondrial Acetyl-CoA Must Be Transported into the Cytosol......Page 715
B. Acetyl-CoA Carboxylase Produces Malonyl-CoA......Page 716
C. Fatty Acid Synthase Catalyzes Seven Reactions......Page 717
D. Fatty Acids May Be Elongated and Desaturated......Page 723
E. Fatty Acids Are Esterified to Form Triacylglycerols......Page 724
5. Regulation of Fatty Acid Metabolism......Page 725
A. Glycerophospholipids Are Built from Intermediates of Triacylglycerol Synthesis......Page 728
B. Sphingolipids Are Built from Palmitoyl-CoA and Serine......Page 731
C. C20 Fatty Acids Are the Precursors of Prostaglandins......Page 732
Box 20-4 Biochemistry in Health and Disease: Sphingolipid Degradation and Lipid Storage Diseases......Page 734
A. Cholesterol Is Synthesized from Acetyl-CoA......Page 735
B. HMG-CoA Reductase Controls the Rate of Cholesterol Synthesis......Page 738
C. Abnormal Cholesterol Transport Leads to Atherosclerosis......Page 741
Box 20-1 Biochemistry in Health and Disease: Vitamin B12 Deficiency......Page 706
Box 20-2 Pathways of Discovery: Dorothy Crowfoot Hodgkin and the Structure of Vitamin B12......Page 708
Box 20-3 Perspectives in Biochemistry: Polyketide Synthesis......Page 722
21 Amino Acid Metabolism......Page 746
A. Lysosomes Degrade Many Proteins......Page 747
B. Ubiquitin Marks Proteins for Degradation......Page 748
C. The Proteasome Unfolds and Hydrolyzes Ubiquitinated Polypeptides......Page 749
2. Amino Acid Deamination......Page 752
A. Transamination Uses PLP to Transfer Amino Groups......Page 753
3. The Urea Cycle......Page 756
A. Five Enzymes Carry Out the Urea Cycle......Page 757
B. The Urea Cycle Is Regulated by Substrate Availability......Page 760
4. Breakdown of Amino Acids......Page 761
A. Alanine, Cysteine, Glycine, Serine, and Threonine Are Degraded to Pyruvate......Page 762
B. Asparagine and Aspartate Are Degraded to Oxaloacetate......Page 764
C. Arginine, Glutamate, Glutamine, Histidine, and Proline Are Degraded to α-Ketoglutarate......Page 765
Box 21-1 Biochemistry in Health and Disease: Homocysteine, a Marker of Disease......Page 766
E. Leucine and Lysine Are Degraded Only to Acetyl-CoA and/or Acetoacetate......Page 771
F. Tryptophan Is Degraded to Alanine and Acetoacetate......Page 772
G. Phenylalanine and Tyrosine Are Degraded to Fumarate and Acetoacetate......Page 773
Box 21-2 Biochemistry in Health and Disease: Phenylketonuria and Alcaptonuria Result from Defects in Phenylalanine Degradation......Page 774
A. Nonessential Amino Acids Are Synthesized from Common Metabolites......Page 776
B. Plants and Microorganisms Synthesize the Essential Amino Acids......Page 780
A. Heme Is Synthesized from Glycine and Succinyl-CoA......Page 786
B. Amino Acids Are Precursors of Physiologically Active Amines......Page 790
C. Nitric Oxide Is Derived from Arginine......Page 791
A. Nitrogenase Reduces N2 to NH3......Page 792
B. Fixed Nitrogen Is Assimilated into Biological Molecules......Page 796
Box 21-3 Biochemistry in Health and Disease: The Porphyrias......Page 788
22 Mammalian Fuel Metabolism: Integration and Regulation......Page 801
1. Organ Specialization......Page 802
A. The Brain Requires a Steady Supply of Glucose......Page 803
B. Muscle Utilizes Glucose, Fatty Acids, and Ketone Bodies......Page 804
D. Liver Is the Body’s Central Metabolic Clearinghouse......Page 806
F. Blood Transports Metabolites in Interorgan Metabolic Pathways......Page 808
2. Hormonal Control of Fuel Metabolism......Page 809
A. Insulin Release Is Triggered by Glucose......Page 810
B. Glucagon and Catecholamines Counter the Effects of Insulin......Page 811
A. AMP-Dependent Protein Kinase Is the Cell’s Fuel Gauge......Page 814
B. Adipocytes and Other Tissues Help Regulate Fuel Metabolism and Appetite......Page 816
C. Energy Expenditure Can Be Controlled by Adaptive Thermogenesis......Page 817
A. Starvation Leads to Metabolic Adjustments......Page 818
B. Diabetes Mellitus Is Characterized by High Blood Glucose Levels......Page 820
C. Obesity Is Usually Caused by Excessive Food Intake......Page 823
Box 22-1 Biochemistry in Health and Disease: The Intestinal Microbiome......Page 805
Box 22-2 Pathways of Discovery: Frederick Banting and Charles Best and the Discovery of Insulin......Page 822
23 Nucleotide Metabolism......Page 827
A. Purine Synthesis Yields Inosine Monophosphate......Page 828
B. IMP Is Converted to Adenine and Guanine Ribonucleotides......Page 831
C. Purine Nucleotide Biosynthesis Is Regulated at Several Steps......Page 832
D. Purines Can Be Salvaged......Page 833
A. UMP Is Synthesized in Six Steps......Page 834
C. Pyrimidine Nucleotide Biosynthesis Is Regulated at ATCase or Carbamoyl Phosphate Synthetase II......Page 836
3. Formation of Deoxyribonucleotides......Page 837
A. Ribonucleotide Reductase Converts Ribonucleotides to Deoxyribonucleotides......Page 838
B. dUMP Is Methylated to Form Thymine......Page 842
4. Nucleotide Degradation......Page 846
A. Purine Catabolism Yields Uric Acid......Page 848
B. Some Animals Degrade Uric Acid......Page 850
C. Pyrimidines Are Broken Down to Malonyl-CoA and Methylmalonyl-CoA......Page 852
Box 23-1 Biochemistry in Health and Disease: Inhibition of Thymidylate Synthesis in Cancer Therapy......Page 847
Box 23-2 Pathways of Discovery: Gertrude Elion and Purine Derivatives......Page 851
24 Nucleic Acid Structure......Page 855
A. DNA Can Adopt Different Conformations......Page 856
B. DNA Has Limited Flexibility......Page 862
C. DNA Can Be Supercoiled......Page 864
D. Topoisomerases Alter DNA Supercoiling......Page 866
Box 24-2 Biochemistry in Health and Disease: Inhibitors of Topoisomerases as Antibiotics and Anticancer Chemotherapeutic Agents......Page 872
A. Nucleic Acids Are Stabilized by Base Pairing, Stacking, and Ionic Interactions......Page 873
B. DNA Can Undergo Denaturation and Renaturation......Page 874
C. RNA Structures Are Highly Variable......Page 876
A. Nucleic Acids Can Be Purified by Chromatography......Page 880
B. Electrophoresis Separates Nucleic Acids by Size......Page 881
4. DNA–Protein Interactions......Page 883
A. Restriction Endonucleases Distort DNA on Binding......Page 884
B. Prokaryotic Repressors Often Include a DNA-Binding Helix......Page 885
C. Eukaryotic Transcription Factors May Include Zinc Fingers or Leucine Zippers......Page 888
A. DNA Coils around Histones to Form Nucleosomes......Page 892
B. Chromatin Forms Higher-Order Structures......Page 895
Box 24-1 Pathways of Discovery: Rosalind Franklin and the Structure of DNA......Page 857
Box 24-3 Perspectives in Biochemistry: The RNA World......Page 878
25 DNA Replication, Repair, and Recombination......Page 901
1. Overview of DNA Replication......Page 902
A. DNA Polymerases Add the Correctly Paired Nucleotide......Page 904
B. Replication Initiation Requires Helicase and Primase......Page 910
C. The Leading and Lagging Strands Are Synthesized Simultaneously......Page 913
D. Replication Terminates at Specific Sites......Page 916
E. DNA Is Replicated with High Fidelity......Page 917
A. Eukaryotes Use Several DNA Polymerases......Page 918
B. Eukaryotic DNA Is Replicated from Multiple Origins......Page 922
C. Telomerase Extends Chromosome Ends......Page 923
Box 25-3 Biochemistry in Health and Disease: Telomerase, Aging, and Cancer......Page 925
B. Many Mutagens Are Carcinogens......Page 927
A. Some Damage Can Be Directly Reversed......Page 929
Box 25-5 Perspectives in Biochemistry: Why Doesn’t DNA Contain Uracil?......Page 931
C. Nucleotide Excision Repair Removes a Segment of a DNA Strand......Page 932
D. Mismatch Repair Corrects Replication Errors......Page 933
E. Some DNA Repair Mechanisms Introduce Errors......Page 934
A. Homologous Recombination Involves Several Protein Complexes......Page 936
B. DNA Can Be Repaired by Recombination......Page 942
C. Transposition Rearranges Segments of DNA......Page 945
Box 25-1 Pathways of Discovery: Arthur Kornberg and DNA Polymerase I......Page 905
Box 25-2 Perspectives in Biochemistry: Reverse Transcriptase......Page 920
Box 25-4 Perspectives in Biochemistry: DNA Methylation......Page 928
26 Transcription and RNA Processing......Page 953
A. RNA Polymerase Resembles Other Polymerases......Page 954
B. Transcription Is Initiated at a Promoter......Page 957
C. The RNA Chain Grows from the 5' to 3' End......Page 958
D. Transcription Terminates at Specific Sites......Page 961
2. Transcription in Eukaryotes......Page 963
Box 26-2 Biochemistry in Health and Disease: Inhibitors of Transcription......Page 964
B. Each Polymerase Recognizes a Different Type of Promoter......Page 969
C. Transcription Factors Are Required to Initiate Transcription......Page 971
A. Messenger RNAs Undergo 5' Capping and Addition of a 3' Tail......Page 976
B. Splicing Removes Introns from Eukaryotic Genes......Page 978
C. Ribosomal RNA Precursors May Be Cleaved, Modified, and Spliced......Page 987
D. Transfer RNAs Are Processed by Nucleotide Removal, Addition, and Modification......Page 991
Box 26-1 Perspectives in Biochemistry: Collisions between DNA Polymerase and RNA Polymerase......Page 960
Box 26-3 Pathways of Discovery: Richard Roberts and Phillip Sharp and the Discovery of Introns......Page 979
27 Protein Synthesis......Page 996
A. Codons Are Triplets That Are Read Sequentially......Page 997
B. The Genetic Code Was Systematically Deciphered......Page 998
Box 27-1 Perspectives in Biochemistry: Evolution of the Genetic Code......Page 1000
A. All tRNAs Have a Similar Structure......Page 1002
B. Aminoacyl–tRNA Synthetases Attach Amino Acids to tRNAs......Page 1004
C. A tRNA May Recognize More than One Codon......Page 1008
Box 27-2 Perspectives in Biochemistry: Expanding the Genetic Code......Page 1010
A. The Prokaryotic Ribosome Consists of Two Subunits......Page 1011
B. The Eukaryotic Ribosome Is Larger and More Complex......Page 1016
4. Translation......Page 1018
A. Chain Initiation Requires an Initiator tRNA and Initiation Factors......Page 1020
B. The Ribosome Decodes the mRNA, Catalyzes Peptide Bond Formation, Then Moves to the Next Codon......Page 1025
C. Release Factors Terminate Translation......Page 1037
5. Posttranslational Processing......Page 1038
A. Ribosome-Associated Chaperones Help Proteins Fold......Page 1039
B. Newly Synthesized Proteins May Be Covalently Modified......Page 1040
Box 27-3 Biochemistry in Health and Disease: The Effects of Antibiotics on Protein Synthesis......Page 1034
28 Regulation of Gene Expression......Page 1047
A. Gene Number Varies among Organisms......Page 1048
B. Some Genes Occur in Clusters......Page 1051
C. Eukaryotic Genomes Contain Repetitive DNA Sequences......Page 1053
A. The lac Operon Is Controlled by a Repressor......Page 1057
B. Catabolite-Repressed Operons Can Be Activated......Page 1060
C. Attenuation Regulates Transcription Termination......Page 1062
D. Riboswitches Are Metabolite-Sensing RNAs......Page 1064
A. Chromatin Structure Influences Gene Expression......Page 1066
B. Eukaryotes Contain Multiple Transcriptional Activators......Page 1077
C. Posttranscriptional Control Mechanisms Include RNA Degradation......Page 1083
D. Antibody Diversity Results from Somatic Recombination and Hypermutation......Page 1090
A. Progress through the Cell Cycle Is Tightly Regulated......Page 1093
B. Tumor Suppressors Prevent Cancer......Page 1095
C. Apoptosis Is an Orderly Process......Page 1098
D. Development Has a Molecular Basis......Page 1102
Box 28-1 Biochemistry in Health and Disease: Trinucleotide Repeat Diseases......Page 1054
Box 28-2 Perspectives in Biochemistry: X Chromosome Inactivation......Page 1067
Box 28-3 Perspectives in Biochemistry: Nonsense-Mediated Decay......Page 1084
Solutions to Odd-Numbered Problems......Page 1113
Glossary......Page 1135
Index......Page 1159

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