Efnisyfirlit

• Title Page
• Copyright Page
• Brief Contents
• Contents
• Preface
• Acknowledgments for the Global Edition
• About the Authors
• Tools of Biochemistry
• Foundation Figures
• Chapter 1: Biochemistry and the Language of Chemistry
• 1.1. The Science of Biochemistry
• The Origins of Biochemistry
• The Tools of Biochemistry
• Biochemistry as a Discipline and an Interdisciplinary Science
• 1.2. The Elements and Molecules of Living Systems
• The Chemical Elements of Cells and Organisms
• The Origin of Biomolecules and Cells
• The Complexity and Size of Biological Molecules
• The Biopolymers: Proteins, Nucleic Acids, and Carbohydrates
• Lipids and Membranes
• 1.3. Distinguishing Characteristics of Living Systems
• 1.4. The Unit of Biological Organization: The Cell
• 1.5. Biochemistry and the Information Explosion
• Chapter 2: The Chemical Foundation of Life: Weak Interactions in an Aqueous Environment
• 2.1. The Importance of Noncovalent Interactions in Biochemistry
• 2.2. The Nature of Noncovalent Interactions
• Charge–Charge Interactions
• Dipole and Induced Dipole Interactions
• Van der Waals Interactions
• Hydrogen Bonds
• 2.3. The Role of Water in Biological Processes
• The Structure and Properties of Water
• Water as a Solvent
• Ionic Compounds in Aqueous Solution
• Hydrophilic Molecules in Aqueous Solution
• Hydrophobic Molecules in Aqueous Solution
• Amphipathic Molecules in Aqueous Solution
• 2.4. Acid–Base Equilibria
• Acids and Bases: Proton Donors and Acceptors
• Ionization of Water and the Ion Product
• The pH Scale and the Physiological pH Range
• Weak Acid and Base Equilibria: Ka and pKa
• Titration of Weak Acids: The Henderson–Hasselbalch Equation
• Buffer Solutions
• Molecules with Multiple Ionizing Groups
• 2.5. Interactions Between Macroions in Solution
• Solubility of Macroions and pH
• The Influence of Small Ions: Ionic Strength
• Tools of Biochemistry: 2A Electrophoresis and Isoelectric Focusing
• Foundation Figure: Biomolecules: Structure and Function
• Chapter 3: The Energetics of Life
• 3.1. Free Energy
• Thermodynamic Systems
• The First Law of Thermodynamics and Enthalpy
• The Driving Force for a Process
• Entropy
• The Second Law of Thermodynamics
• 3.2. Free Energy: The Second Law in Open Systems
• Free Energy Defined in Terms of Enthalpy and Entropy Changes in the System
• An Example of the Interplay of Enthalpy and Entropy: The Transition Between Liquid Water and Ice
• The Interplay of Enthalpy and Entropy: A Summary
• Free Energy and Useful Work
• 3.3. The Relationships Between Free Energy, the Equilibrium State, and Nonequilibrium Concentrations
• Equilibrium, Le Chatelier’s Principle, and the Standard State
• Changes in Concentration and .G
• .G versus .G°, Q versus K, and Homeostasis versus Equilibrium
• Water, H+ in Buffered Solutions, and the “Biochemical Standard State”
• 3.4. Free Energy in Biological Systems
• Organic Phosphate Compounds as Energy Transducers
• Phosphoryl Group Transfer Potential
• Free Energy and Concentration Gradients: A Close Look at Diffusion Through a Membrane
• .G and Oxidation/Reduction Reactions in Cells
• Quantification of Reducing Power: Standard Reduction Potential
• Standard Free Energy Changes in Oxidation–Reduction Reactions
• Calculating Free Energy Changes for Biological Oxidations under Nonequilibrium Conditions
• A Brief Overview of Free Energy Changes in Cells
• Chapter 4: Nucleic Acids
• 4.1. Nucleic Acids— Informational Macromolecules
• The Two Types of Nucleic Acid: DNA and RNA
• Properties of the Nucleotides
• Stability and Formation of the Phosphodiester Linkage
• 4.2. Primary Structure of Nucleic Acids
• The Nature and Significance of Primary Structure
• DNA as the Genetic Substance: Early Evidence
• 4.3. Secondary and Tertiary Structures of Nucleic Acids
• The DNA Double Helix
• Data Leading Toward the Watson–Crick Double-Helix Model
• X-Ray Analysis of DNA Fibers
• Semiconservative Nature of DNA Replication
• Alternative Nucleic Acid Structures: B and A Helices
• DNA and RNA Molecules in Vivo
• DNA Molecules
• Circular DNA and Supercoiling
• Single-Stranded Polynucleotides
• 4.4. Alternative Secondary Structures of DNA
• Left-Handed DNA (Z-DNA)
• Hairpins and Cruciforms
• Triple Helices
• G-Quadruplexes
• 4.5. The Helix-to-Random Coil Transition: Nucleic Acid Denaturation
• 4.6. The Biological Functions of Nucleic Acids: A Preview of Genetic Biochemistry
• Genetic Information Storage: The Genome
• Replication: DNA to DNA
• Transcription: DNA to RNA
• Translation: RNA to Protein
• Tools of Biochemistry: 4A Manipulating DNA
• Tools of Biochemistry: 4B An Introduction to X-Ray Diffraction
• Chapter 5: Introduction to Proteins: The Primary Level of Protein Structure
• 5.1. Amino Acids
• Structure of the a-Amino Acids
• Stereochemistry of the a-Amino Acids
• Properties of Amino Acid Side Chains: Classes of a-Amino Acids
• Amino Acids with Nonpolar Aliphatic Side Chains
• Amino Acids with Nonpolar Aromatic Side Chains
• Amino Acids with Polar Side Chains
• Amino Acids with Positively Charged (Basic) Side Chains
• Amino Acids with Negatively Charged (Acidic) Side Chains
• Rare Genetically Encoded Amino Acids
• Modified Amino Acids
• 5.2. Peptides and the Peptide Bond
• The Structure of the Peptide Bond
• Stability and Formation of the Peptide Bond
• Peptides
• Polypeptides as Polyampholytes
• 5.3. Proteins: Polypeptides of Defined Sequence
• 5.4. From Gene to Protein
• The Genetic Code
• Posttranslational Processing of Proteins
• 5.5. From Gene Sequence to Protein Function
• 5.6. Protein Sequence Homology
• Tools of Biochemistry: 5A Protein Expression and Purification
• Tools of Biochemistry: 5B Mass, Sequence, and Amino Acid Analyses of Purified Proteins
• Chapter 6: The Three-Dimensional Structure of Proteins
• 6.1. Secondary Structure: Regular Ways to Fold the Polypeptide Chain
• Theoretical Descriptions of Regular Polypeptide Structures
• a Helices and ß Sheets
• Describing the Structures: Helices and Sheets
• Amphipathic Helices and Sheets
• Ramachandran Plots
• 6.2. Fibrous Proteins: Structural Materials of Cells and Tissues
• The Keratins
• Fibroin
• Collagen
• 6.3. Globular Proteins: Tertiary Structure and Functional Diversity
• Different Folding for Different Functions
• Different Modes of Display Aid Our Understanding of Protein Structure
• Varieties of Globular Protein Structure: Patterns of Main-Chain Folding
• 6.4. Factors Determining Secondary and Tertiary Structure
• The Information for Protein Folding
• The Thermodynamics of Folding
• Conformational Entropy
• Charge–Charge Interactions
• Internal Hydrogen Bonds
• Van der Waals Interactions
• The Hydrophobic Effect
• Disulfide Bonds and Protein Stability
• Prosthetic Groups, Ion-Binding, and Protein Stability
• 6.5. Dynamics of Globular Protein Structure
• Kinetics of Protein Folding
• The “Energy Landscape” Model of Protein Folding
• Intermediate and Off-Pathway States in Protein Folding
• Chaperones Faciliate Protein Folding in Vivo
• Protein Misfolding and Disease
• 6.6. Prediction of Protein Secondary and Tertiary Structure
• Prediction of Secondary Structure
• Tertiary Structure Prediction: Computer Simulation of Folding
• 6.7. Quaternary Structure of Proteins
• Symmetry in Multisubunit Proteins: Homotypic Protein–Protein Interactions
• Heterotypic Protein–Protein Interactions
• Tools of Biochemistry: 6A Spectroscopic Methods for Studying Macromolecular Conformation in Solution
• Tools of Biochemistry: 6B Determining Molecular Masses and the Number of Subunits in a Protein Molec
• Foundation Figure: Protein Structure and Function
• Chapter 7: Protein Function and Evolution
• 7.1. Binding a Specific Target: Antibody Structure and Function
• 7.2. The Adaptive Immune Response
• 7.3. The Structure of Antibodies
• 7.4. Antibody:Antigen Interactions
• Shape and Charge Complementarity
• Generation of Antibody Diversity
• 7.5. The Immunoglobulin Superfamily
• 7.6. The Challenge of Developing an AIDS Vaccine
• 7.7. Antibodies and Immunoconjugates as Potential Cancer Treatments
• 7.8. Oxygen Transport from Lungs to Tissues: Protein Conformational Change Enhances Function
• 7.9. The Oxygen-Binding Sites in Myoglobin and Hemoglobin
• Analysis of Oxygen Binding by Myoglobin
• 7.10. The Role of Conformational Change in Oxygen Transport
• Cooperative Binding and Allostery
• Models for the Allosteric Change in Hemoglobin
• Changes in Hemoglobin Structure Accompanying Oxygen Binding
• A Closer Look at the Allosteric Change in Hemoglobin
• 7.11. Allosteric Effectors of Hemoglobin Promote Efficient Oxygen Delivery to Tissues
• Response to pH Changes: The Bohr Effect
• Carbon Dioxide Transport
• Response to Chloride Ion at the a-Globin N-Terminus
• 2,3-Bisphosphoglycerate
• 7.12. Myoglobin and Hemoglobin as Examples of the Evolution of Protein Function
• The Structure of Eukaryotic Genes: Exons and Introns
• 7.13. Mechanisms of Protein Mutation
• Substitution of DNA Nucleotides
• Nucleotide Deletions or Insertions
• Gene Duplications and Rearrangements
• Evolution of the Myoglobin–Hemoglobin Family of Proteins
• 7.14. Hemoglobin Variants and Their Inheritance: Genetic Diseases
• Pathological Effects of Variant Hemoglobins
• 7.15. Protein Function Requiring Large Conformational Changes: Muscle Contraction
• 7.16. Actin and Myosin
• Actin
• Myosin
• 7.17. The Structure of Muscle
• 7.18. The Mechanism of Contraction
• Regulation of Contraction: The Role of Calcium
• Tools of Biochemistry: 7A Immunological Methods
• Chapter 8: Enzymes: Biological Catalysts
• 8.1. Enzymes As Biological Catalysts
• 8.2. The Diversity of Enzyme Function
• 8.3. Chemical Reaction Rates and the Effects of Catalysts
• Reaction Rates, Rate Constants, and Reaction Order
• First-Order Reactions
• Second-Order Reactions
• Transition States and Reaction Rates
• Transition State Theory Applied to Enzymatic Catalysis
• 8.4. How Enzymes Act as Catalysts: Principles and Examples
• Models for Substrate Binding and Catalysis
• Mechanisms for Achieving Rate Acceleration
• Case Study #1: Lysozyme
• Case Study #2: Chymotrypsin, a Serine Protease
• 8.5. Coenzymes, Vitamins, and Essential Metals
• Coenzyme Function in Catalysis
• Metal Ions in Enzymes
• 8.6. The Kinetics of Enzymatic Catalysis
• Reaction Rate for a Simple Enzyme-Catalyzed Reaction: Michaelis–Menten Kinetics
• Interpreting KM, kcat, and kcat/KM
• Enzyme Mutants May Affect kcat and KM Differently
• Analysis of Kinetic Data: Testing the Michaelis–Menten Model
• 8.7. Enzyme Inhibition
• Reversible Inhibition
• Competitive Inhibition
• Uncompetitive Inhibition
• Mixed Inhibition
• Irreversible Inhibition
• Multisubstrate Reactions
• Random Substrate Binding
• Ordered Substrate Binding
• The Ping-Pong Mechanism
• Qualitative Interpretation of KM and Vmax: Application to Multisubstrate Reaction Mechanisms
• 8.8. The Regulation of Enzyme Activity
• Substrate-Level Control
• Feedback Control
• Allosteric Enzymes
• Homoallostery
• Heteroallostery
• Aspartate Carbamoyltransferase: An Example of an Allosteric Enzyme
• 8.9. Covalent Modifications Used to Regulate Enzyme Activity
• Pancreatic Proteases: Activation by Irreversible Protein Backbone Cleavage
• 8.10. Nonprotein Biocatalysts: Catalytic Nucleic Acids
• Tools of Biochemistry: 8A How to Measure the Rates of Enzyme-Catalyzed Reactions
• Foundation Figure: Regulation of Enzyme Activity
• Chapter 9: Carbohydrates: Sugars, Saccharides, Glycans
• 9.1. Monosaccharides
• Aldoses and Ketoses
• Enantiomers
• Alternative Designations for Enantiomers: d–l and R–S
• Monosaccharide Enantiomers in Nature
• Diastereomers
• Tetrose Diastereomers
• Pentose Diastereomers
• Hexose Diastereomers
• Aldose Ring Structures
• Pentose Rings
• Hexose Rings
• Sugars with More Than Six Carbons
• 9.2. Derivatives of the Monosaccharides
• Phosphate Esters
• Lactones and Acids
• Alditols
• Amino Sugars
• Glycosides
• 9.3. Oligosaccharides
• Oligosaccharide Structures
• Distinguishing Features of Different Disaccharides
• Writing the Structure of Disaccharides
• Stability and Formation of the Glycosidic Bond
• 9.4. Polysaccharides
• Storage Polysaccharides
• Structural Polysaccharides
• Cellulose
• Chitin
• Glycosaminoglycans
• The Proteoglycan Complex
• Nonstructural Roles of Glycosaminoglycans
• Bacterial Cell Wall Polysaccharides; Peptidoglycan
• 9.5. Glycoproteins
• N-Linked and O-Linked Glycoproteins
• N-Linked Glycans
• O-Linked Glycans
• Blood Group Antigens
• Erythropoetin: A Glycoprotein with Both O- and N-Linked Oligosaccharides
• Influenza Neuraminidase, a Target for Antiviral Drugs
• Tools of Biochemistry: 9A The Emerging Field of Glycomics
• Chapter 10: Lipids, Membranes, and Cellular Transport
• 10.1. The Molecular Structure and Behavior of Lipids
• Fatty Acids
• Triacylglycerols: Fats
• Soaps and Detergents
• Waxes
• 10.2. The Lipid Constituents of Biological Membranes
• Glycerophospholipids
• Sphingolipids and Glycosphingolipids
• Glycoglycerolipids
• Cholesterol
• 10.3. The Structure and Properties of Membranes and Membrane Proteins
• Motion in Membranes
• Motion in Synthetic Membranes
• Motion in Biological Membranes
• The Asymmetry of Membranes
• Characteristics of Membrane Proteins
• Insertion of Proteins into Membranes
• Evolution of the Fluid Mosaic Model of Membrane Structure
• 10.4. Transport Across Membranes
• The Thermodynamics of Transport
• Nonmediated Transport: Diffusion
• Facilitated Transport: Accelerated Diffusion
• Carriers
• Permeases
• Pore-Facilitated Transport
• Ion Selectivity and Gating
• Active Transport: Transport Against a Concentration Gradient
• 10.5. Ion Pumps: Direct Coupling of ATP Hydrolysis to Transport
• 10.6. Ion Transporters and Disease
• 10.7. Cotransport Systems
• 10.8. Excitable Membranes, Action Potentials, and Neurotransmission
• The Resting Potential
• The Action Potential
• Toxins and Neurotransmission
• Foundation Figure: Targeting Pain and Inflammation through Drug Design
• Chapter 11: Chemical Logic of Metabolism
• 11.1. A First Look at Metabolism
• 11.2. Freeways on the Metabolic Road Map
• Central Pathways of Energy Metabolism
• Distinct Pathways for Biosynthesis and Degradation
• 11.3. Biochemical Reaction Types
• Nucleophilic Substitutions
• Nucleophilic Additions
• Carbonyl Condensations
• Eliminations
• Oxidations and Reductions
• 11.4. Bioenergetics of Metabolic Pathways
• Oxidation as a Metabolic Energy Source
• Biological Oxidations: Energy Release in Small Increments
• Energy Yields, Respiratory Quotients, and Reducing Equivalents
• ATP as a Free Energy Currency
• Metabolite Concentrations and Solvent Capacity
• Thermodynamic Properties of ATP
• The Important Differences Between .G and .G°
• Kinetic Control of Substrate Cycles
• Other High-Energy Phosphate Compounds
• Other High-Energy Nucleotides
• Adenylate Energy Charge
• 11.5. Major Metabolic Control Mechanisms
• Control of Enzyme Levels
• Control of Enzyme Activity
• Compartmentation
• Hormonal Regulation
• Distributive Control of Metabolism
• 11.6 Experimental Analysis of Metabolism
• Goals of the Study of Metabolism
• Levels of Organization at Which Metabolism Is Studied
• Whole Organisms
• Isolated or Perfused Organs
• Whole Cells
• Cell-Free Systems
• Purified Components
• Systems Level
• Metabolic Probes
• Tools of Biochemistry: 11A Metabolomics
• Tools of Biochemistry: 11B Radioactive and Stable Isotopes
• Foundation Figure: Enzyme Kinetics and Drug Action
• Chapter 12: Carbohydrate Metabolism: Glycolysis, Gluconeogenesis, Glycogen Metabolism, and the Pento
• 12.1. An Overview of Glycolysis
• Relation of Glycolysis to Other Pathways
• Anaerobic and Aerobic Glycolysis
• Chemical Strategy of Glycolysis
• 12.2. Reactions of Glycolysis
• Reactions 1–5: The Energy Investment Phase
• Reaction 1: The First ATP Investment
• Reaction 2: Isomerization of Glucose-6-Phosphate
• Reaction 3: The Second Investment of ATP
• Reaction 4: Cleavage to Two Triose Phosphates
• Reaction 5: Isomerization of Dihydroxyacetone Phosphate
• Reactions 6–10: The Energy Generation Phase
• Reaction 6: Generation of the First Energy-Rich Compound
• Reaction 7: The First Substrate-Level Phosphorylation
• Reaction 8: Preparing for Synthesis of the Next High-Energy Compound
• Reaction 9: Synthesis of the Second High-Energy Compound
• Reaction 10: The Second Substrate-Level Phosphorylation
• 12.3. Metabolic Fates of Pyruvate
• Lactate Metabolism
• Isozymes of Lactate Dehydrogenase
• Ethanol Metabolism
• 12.4. Energy and Electron Balance Sheets
• 12.5. Gluconeogenesis
• Physiological Need for Glucose Synthesis in Animals
• Enzymatic Relationship of Gluconeogenesis to Glycolysis
• Bypass 1: Conversion of Pyruvate to Phosphoenolpyruvate
• Bypass 2: Conversion of Fructose-1,6-bisphosphate to Fructose-6-phosphate
• Bypass 3: Conversion of Glucose-6-phosphate to Glucose
• Stoichiometry and Energy Balance of Gluconeogenesis
• Gluconeogenesis
• Reversal of Glycolysis
• Substrates for Gluconeogenesis
• Lactate
• Amino Acids
• Ethanol Consumption and Gluconeogenesis
• 12.6. Coordinated Regulation of Glycolysis and Gluconeogenesis
• The Pasteur Effect
• Reciprocal Regulation of Glycolysis and Gluconeogenesis
• Regulation at the Phosphofructokinase/ Fructose-1,6-Bisphosphatase Substrate Cycle
• Fructose-2,6-bisphosphate and the Control of Glycolysis and Gluconeogenesis
• Regulation at the Pyruvate Kinase/Pyruvate Carboxylase + PEPCK Substrate Cycle
• Regulation at the Hexokinase/Glucose-6-Phosphatase Substrate Cycle
• 12.7. Entry of Other Sugars into the Glycolytic Pathway
• Monosaccharide Metabolism
• Galactose Utilization
• Fructose Utilization
• Disaccharide Metabolism
• Glycerol Metabolism
• Polysaccharide Metabolism
• Hydrolytic and Phosphorolytic Cleavages
• Starch and Glycogen Digestion
• 12.8. Glycogen Metabolism in Muscle and Liver
• Glycogen Breakdown
• Glycogen Biosynthesis
• Biosynthesis of UDP-Glucose
• The Glycogen Synthase Reaction
• Formation of Branches
• 12.9. Coordinated Regulation of Glycogen Metabolism
• Structure of Glycogen Phosphorylase
• Control of Phosphorylase Activity
• Proteins in the Glycogenolytic Cascade
• Cyclic AMP–Dependent Protein Kinase
• Phosphorylase b Kinase
• Calmodulin
• Nonhormonal Control of Glycogenolysis
• Control of Glycogen Synthase Activity
• Congenital Defects of Glycogen Metabolism in Humans
• 12.10. A Biosynthetic Pathway That Oxidizes Glucose: The Pentose Phosphate Pathway
• The Oxidative Phase: Generating Reducing Power as NADPH
• The Nonoxidative Phase: Alternative Fates of Pentose Phosphates
• Production of Six-Carbon and Three-Carbon Sugar Phosphates
• Tailoring the Pentose Phosphate Pathway to Specific Needs
• Regulation of the Pentose Phosphate Pathway
• Human Genetic Disorders Involving Pentose Phosphate Pathway Enzymes
• Chapter 13: The Citric Acid Cycle
• 13.1. Overview of Pyruvate Oxidation and the Citric Acid Cycle
• The Three Stages of Respiration
• Chemical Strategy of the Citric Acid Cycle
• Discovery of the Citric Acid Cycle
• 13.2. Pyruvate Oxidation: A Major Entry Route for Carbon into the Citric Acid Cycle
• Overview of Pyruvate Oxidation and the Pyruvate Dehydrogenase Complex
• Coenzymes Involved in Pyruvate Oxidation and the Citric Acid Cycle
• Thiamine Pyrophosphate (TPP)
• Lipoic Acid (Lipoamide)
• Coenzyme A: Activation of Acyl Groups
• Flavin Adenine Dinucleotide (FAD)
• Nicotinamide Adenine Dinucleotide (NAD+)
• Action of the Pyruvate Dehydrogenase Complex
• 13.3. The Citric Acid Cycle
• Step 1: Introduction of Two Carbon Atoms as Acetyl-CoA
• Step 2: Isomerization of Citrate
• Step 3: Conservation of the Energy Released by an Oxidative Decarboxylation in the Reduced Electron
• Step 4: Conservation of Energy in NADH by a Second Oxidative Decarboxylation
• Step 5: A Substrate-Level Phosphorylation
• Step 6: A Flavin-Dependent Dehydrogenation
• Step 7: Hydration of a Carbon–Carbon Double Bond
• Step 8: An Oxidation that Regenerates Oxaloacetate
• 13.4. Stoichiometry and Energetics of the Citric Acid Cycle
• 13.5. Regulation of Pyruvate Dehydrogenase and the Citric Acid Cycle
• Control of Pyruvate Oxidation
• Control of the Citric Acid Cycle
• 13.6. Organization and Evolution of the Citric Acid Cycle
• 13.7. Citric Acid Cycle Malfunction as a Cause of Human Disease
• 13.8. Anaplerotic Sequences: The Need to Replace Cycle Intermediates
• Reactions that Replenish Oxaloacetate
• The Malic Enzyme
• Reactions Involving Amino Acids
• 13.9. The Glyoxylate Cycle: An Anabolic Variant of the Citric Acid Cycle
• Tools of Biochemistry: 13A Detecting and Analyzing Protein–Protein Interactions
• Chapter 14: Electron Transport, Oxidative Phosphorylation, and Oxygen Metabolism
• 14.1. The Mitochondrion: Scene of the Action
• 14.2. Free Energy Changes in Biological Oxidations
• 14.3. Electron Transport
• Electron Carriers in the Respiratory Chain
• Flavoproteins
• Iron–Sulfur Proteins
• Coenzyme Q
• Cytochromes
• Respiratory Complexes
• NADH–Coenzyme Q Reductase (Complex I)
• Succinate–Coenzyme Q Reductase (Complex II; Succinate Dehydrogenase)
• Coenzyme Q:Cytochrome c Oxidoreductase (Complex III)
• Cytochrome c Oxidase (Complex IV)
• 14.4. Oxidative Phosphorylation
• The P/O Ratio: Energetics of Oxidative Phosphorylation
• Oxidative Reactions That Drive ATP Synthesis
• Mechanism of Oxidative Phosphorylation: Chemiosmotic Coupling
• A Closer Look at Chemiosmotic Coupling: The Experimental Evidence
• Membranes Can Establish Proton Gradients
• An Intact Inner Membrane Is Required for Oxidative Phosphorylation
• Key Electron Transport Proteins Span the Inner Membrane
• Uncouplers Act by Dissipating the Proton Gradient
• Generation of a Proton Gradient Permits ATP Synthesis Without Electron Transport
• Complex V: The Enzyme System for ATP Synthesis
• Discovery and Reconstitution of ATP Synthase
• Structure of the Mitochondrial F1ATP Synthase Complex
• Mechanism of ATP Synthesis
• 14.5. Respiratory States and Respiratory Control
• 14.6. Mitochondrial Transport Systems
• Transport of Substrates and Products into and out of Mitochondria
• Shuttling Cytoplasmic Reducing Equivalents into Mitochondria
• 14.7. Energy Yields from Oxidative Metabolism
• 14.8. The Mitochondrial Genome, Evolution, and Disease
• 14.9. Oxygen as a Substrate for Other Metabolic Reactions
• Oxidases and Oxygenases
• Cytochrome P450 Monooxygenase
• Reactive Oxygen Species, Antioxidant Defenses, and Human Disease
• Formation of Reactive Oxygen Species
• Dealing with Oxidative Stress
• Foundation Figure: Intermediary Metabolism
• Chapter 15: Photosynthesis
• 15.1. The Basic Processes of Photosynthesis
• 15.2. The Chloroplast
• 15.3. The Light Reactions
• Absorption of Light: The Light-Harvesting System
• The Energy of Light
• The Light-Absorbing Pigments
• The Light-Gathering Structures
• Photochemistry in Plants and Algae: Two Photosystems in Series
• Photosystem II: The Splitting of Water
• Photosystem I: Production of NADPH
• Summation of the Two Systems: The Overall Reaction and NADPH and ATP Generation
• An Alternative Light Reaction Mechanism: Cyclic Electron Flow
• Reaction Center Complexes in Photosynthetic Bacteria
• Evolution of Photosynthesis
• 15.4. The Carbon Reactions: The Calvin Cycle
• Stage I: Carbon Dioxide Fixation and Sugar Production
• Incorporation of CO2 into a Three-Carbon Sugar
• Formation of Hexose Sugars
• Stage II: Regeneration of the Acceptor
• 15.5. A Summary of the Light and Carbon Reactions in Two-System Photosynthesis
• The Overall Reaction and the Efficiency of Photosynthesis
• Regulation of Photosynthesis
• 15.6. Photorespiration and the C4 Cycle
• Chapter 16: Lipid Metabolism
• Part I: Bioenergetic Aspects of Lipid Metabolism
• 16.1. Utilization and Transport of Fat and Cholesterol
• Fats as Energy Reserves
• Fat Digestion and Absorption
• Transport of Fat to Tissues: Lipoproteins
• Classification and Functions of Lipoproteins
• Transport and Utilization of Lipoproteins
• Cholesterol Transport and Utilization in Animals
• The LDL Receptor and Cholesterol Homeostasis
• Cholesterol, LDL, and Atherosclerosis
• Mobilization of Stored Fat for Energy Generation
• 16.2. Fatty Acid Oxidation
• Early Experiments
• Fatty Acid Activation and Transport into Mitochondria
• The ß-Oxidation Pathway
• Reaction 1: The Initial Dehydrogenation
• Reactions 2 and 3: Hydration and Dehydrogenation
• Reaction 4: Thiolytic Cleavage
• Mitochondrial ß-Oxidation Involves Multiple Isozymes
• Energy Yield from Fatty Acid Oxidation
• Oxidation of Unsaturated Fatty Acids
• Oxidation of Fatty Acids with Odd-Numbered Carbon Chains
• Control of Fatty Acid Oxidation
• Ketogenesis
• 16.3. Fatty Acid Biosynthesis
• Relationship of Fatty Acid Synthesis to Carbohydrate Metabolism
• Early Studies of Fatty Acid Synthesis
• Biosynthesis of Palmitate from Acetyl-CoA
• Synthesis of Malonyl-CoA
• Malonyl-CoA to Palmitate
• Multifunctional Proteins in Fatty Acid Synthesis
• Transport of Acetyl Units and Reducing Equivalents into the Cytosol
• Elongation of Fatty Acid Chains
• Fatty Acid Desaturation
• Control of Fatty Acid Synthesis
• 16.4. Biosynthesis of Triacylglycerols
• Part II: Metabolism of Membrane Lipids, Steroids, and Other Complex Lipids
• 16.5. Glycerophospholipids
• 16.6. Sphingolipids
• 16.7. Steroid Metabolism
• Steroids: Some Structural Considerations
• Biosynthesis of Cholesterol
• Early Studies of Cholesterol Biosynthesis
• Stage 1: Formation of Mevalonate
• Stage 2: Synthesis of Squalene from Mevalonate
• Stage 3: Cyclization of Squalene to Lanosterol and Its Conversion to Cholesterol
• Control of Cholesterol Biosynthesis
• Cholesterol Derivatives: Bile Acids, Steroid Hormones, and Vitamin D
• Bile Acids
• Steroid Hormones
• Vitamin D
• Lipid-Soluble Vitamins
• Vitamin A
• Vitamin E
• Vitamin K
• 16.8. Eicosanoids: Prostaglandins, Thromboxanes, and Leukotrienes
• Chapter 17: Interorgan and Intracellular Coordination of Energy Metabolism in Vertebrates
• 17.1. Interdependence of the Major Organs in Vertebrate Fuel Metabolism
• Fuel Inputs and Outputs
• Metabolic Division of Labor Among the Major Organs
• Brain
• Muscle
• Heart
• Adipose Tissue
• Liver
• Blood
• 17.2. Hormonal Regulation of Fuel Metabolism
• Actions of the Major Hormones
• Insulin
• Glucagon
• Epinephrine
• Coordination of Energy Homeostasis
• AMP-Activated Protein Kinase (AMPK)
• Mammalian Target of Rapamycin (mTOR)
• Sirtuins
• Endocrine Regulation of Energy Homeostasis
• 17.3. Responses to Metabolic Stress: Starvation, Diabetes
• Starvation
• Diabetes
• Foundation Figure: Energy Regulation
• Chapter 18: Amino Acid and Nitrogen Metabolism
• 18.1. Utilization of Inorganic Nitrogen: The Nitrogen Cycle
• Biological Nitrogen Fixation
• Nitrate Utilization
• 18.2. Utilization of Ammonia: Biogenesis of Organic Nitrogen
• Glutamate Dehydrogenase: Reductive Amination of a-Ketoglutarate
• Glutamine Synthetase: Generation of Biologically Active Amide Nitrogen
• Carbamoyl Phosphate Synthetase: Generation of an Intermediate for Arginine and Pyrimidine Synthesis
• 18.3. The Nitrogen Economy and Protein Turnover
• Metabolic Consequences of the Absence of Nitrogen Storage Compounds
• Protein Turnover
• Intracellular Proteases and Sites of Turnover
• Chemical Signals for Turnover—Ubiquitination
• 18.4. Coenzymes Involved in Nitrogen Metabolism
• Pyridoxal Phosphate
• Folic Acid Coenzymes and One-Carbon Metabolism
• Discovery and Chemistry of Folic Acid
• Conversion of Folic Acid to Tetrahydrofolate
• Tetrahydrofolate in the Metabolism of One-Carbon Units
• Folic Acid in the Prevention of Heart Disease and Birth Defects
• B12 Coenzymes
• B12 Coenzymes and Pernicious Anemia
• 18.5. Amino Acid Degradation and Metabolism of Nitrogenous End Products
• Transamination Reactions
• Detoxification and Excretion of Ammonia
• Transport of Ammonia to the Liver
• The Krebs–Henseleit Urea Cycle
• 18.6. Pathways of Amino Acid Degradation
• Pyruvate Family of Glucogenic Amino Acids
• Oxaloacetate Family of Glucogenic Amino Acids
• a-Ketoglutarate Family of Glucogenic Amino Acids
• Succinyl-CoA Family of Glucogenic Amino Acids
• Acetoacetate/Acetyl-CoA Family of Ketogenic Amino Acids
• Phenylalanine and Tyrosine Degradation
• 18.7. Amino Acid Biosynthesis
• Biosynthetic Capacities of Organisms
• Amino Acid Biosynthetic Pathways
• Synthesis of Glutamate, Aspartate, Alanine, Glutamine, and Asparagine
• Synthesis of Serine and Glycine from 3-Phosphoglycerate
• Synthesis of Valine, Leucine, and Isoleucine from Pyruvate
• 18.8. Amino Acids as Biosynthetic Precursors
• S-Adenosylmethionine and Biological Methylation
• Precursor Functions of Glutamate
• Arginine Is the Precursor for Nitric Oxide and Creatine Phosphate
• Tryptophan and Tyrosine Are Precursors of Neurotransmitters and Biological Regulators
• Chapter 19: Nucleotide Metabolism
• 19.1. Outlines of Pathways in Nucleotide Metabolism
• Biosynthetic Routes: De Novo and Salvage Pathways
• Nucleic Acid Degradation and the Importance of Nucleotide Salvage
• PRPP, a Central Metabolite in De Novo and Salvage Pathways
• 19.2. De Novo Biosynthesis of Purine Ribonucleotides
• Synthesis of the Purine Ring
• Enzyme Organization in the Purine Biosynthetic Pathway
• Synthesis of ATP and GTP from Inosine Monophosphate
• 19.3 Purine Catabolism and Its Medical Significance
• Uric Acid, a Primary End Product
• Medical Abnormalities of Purine Catabolism
• Gout
• Lesch–Nyhan Syndrome
• Severe Combined Immunodeficiency Disease
• 19.4. Pyrimidine Ribonucleotide Metabolism
• De Novo Biosynthesis of UTP and CTP
• Glutamine-Dependent Amidotransferases
• Multifunctional Enzymes in Eukaryotic Pyrimidine Metabolism
• 19.5 Deoxyribonucleotide Metabolism
• Reduction of Ribonucleotides to Deoxyribonucleotides
• RNR Structure and Mechanism
• Source of Electrons for Ribonucleotide Reduction
• Regulation of Ribonucleotide Reductase Activity
• Regulation of dNTP Pools by Selective dNTP Degradation
• Biosynthesis of Thymine Deoxyribonucleotides
• Salvage Routes to Deoxyribonucleotides
• Thymidylate Synthase: A Target Enzyme for Chemotherapy
• 19.6. Virus-Directed Alterations of Nucleotide Metabolism
• 19.7. Other Medically Useful Analogs
• Chapter 20: Mechanisms of Signal Transduction
• 20.1. An Overview of Hormone Action
• Chemical Nature of Hormones and Other Signaling Agents
• Hierarchical Nature of Hormonal Control
• Hormone Biosynthesis
• 20.2. Modular Nature of Signal Transduction Systems: G Protein-Coupled Signaling
• Receptors
• Receptors as Defined by Interactions with Drugs
• Receptors and Adenylate Cyclase as Distinct Components of Signal Transduction Systems
• Structural Analysis of G Protein-Coupled Receptors
• Transducers: G Proteins
• Actions of G Proteins
• Structure of G Proteins
• Consequences of Blocking GTPase
• The Versatility of G Proteins
• Interaction of GPCRs with G Proteins
• G Proteins in the Visual Process
• Effectors
• Second Messengers
• Cyclic AMP
• Cyclic GMP and Nitric Oxide
• Phosphoinositides
• 20.3. Receptor Tyrosine Kinases and Insulin Signaling
• 20.4. Hormones and Gene Expression: Nuclear Receptors
• 20.5. Signal Transduction, Growth Control, and Cancer
• Viral and Cellular Oncogenes
• Oncogenes in Human Tumors
• The Cancer Genome Mutational Landscape
• 20.6. Neurotransmission
• The Cholinergic Synapse
• Fast and Slow Synaptic Transmission
• Actions of Specific Neurotransmitters
• Drugs That Act in the Synaptic Cleft
• Peptide Neurotransmitters and Neurohormones
• Foundation Figure: Cell Signaling and Protein Regulation
• Chapter 21: Genes, Genomes, and Chromosomes
• 21.1. Bacterial and Viral Genomes
• Viral Genomes
• Bacterial Genomes— The Nucleoid
• 21.2. Eukaryotic Genomes
• Genome Sizes
• Repetitive Sequences
• Satellite DNA
• Duplications of Functional Genes
• Alu Elements
• Introns
• Gene Families
• Multiple Variants of a Gene
• Pseudogenes
• The ENCODE Project and the Concept of “Junk DNA”
• 21.3. Physical Organization of Eukaryotic Genes: Chromosomes and Chromatin
• The Nucleus
• Chromatin
• Histones and Nonhistone Chromosomal Proteins
• The Nucleosome
• Higher-order Chromatin Structure in the Nucleus
• 21.4. Nucleotide Sequence Analysis of Genomes
• Restriction and Modification
• Properties of Restriction and Modification Enzymes
• Determining Genome Nucleotide Sequences
• Mapping Large Genomes
• Generating Physical Maps
• The Principle of Southern Analysis
• Southern Transfer and DNA Fingerprinting
• Locating Genes on the Human Genome
• Sequence Analysis Using Artificial Chromosomes
• Size of the Human Genome
• Tools of Biochemistry: 21A Polymerase Chain Reaction
• Chapter 22: DNA Replication
• 22.1. Early Insights into DNA Replication
• 22.2. DNA Polymerases: Enzymes Catalyzing Polynucleotide Chain Elongation
• Structure and Activities of DNA Polymerase I
• DNA Substrates for the Polymerase Reaction
• Multiple Activities in a Single Polypeptide Chain
• Structure of DNA Polymerase I
• Discovery of Additional DNA Polymerases
• Structure and Mechanism of DNA Polymerases
• 22.3. Other Proteins at the Replication Fork
• Genetic Maps of E. coli and Bacteriophage T4
• Replication Proteins in Addition to DNA Polymerase
• Discontinuous DNA Synthesis
• RNA Primers
• Proteins at the Replication Fork
• The DNA Polymerase III Holoenzyme
• Sliding Clamp
• Clamp Loading Complex
• Single-Stranded DNA-Binding Proteins: Maintaining Optimal Template Conformation
• Helicases: Unwinding DNA Ahead of the Fork
• Topoisomerases: Relieving Torsional Stress
• Actions of Type I and Type II Topoisomerases
• The Four Topoisomerases of E. coli
• A Model of the Replisome
• 22.4. Eukaryotic DNA Replication
• DNA Polymerases
• Other Eukaryotic Replication Proteins
• Replication of Chromatin
• 22.5. Initiation of DNA Replication
• Initiation of E. coli DNA Replication at ori c
• Initiation of Eukaryotic Replication
• 22.6. Replication of Linear Genomes
• Linear Virus Genome Replication
• Telomerase
• 22.7. Fidelity of DNA Replication
• 3 Exonucleolytic Proofreading
• Polymerase Insertion Specificity
• DNA Precursor Metabolism and Genomic Stability
• Ribonucleotide Incorporation and Genomic Stability
• 22.8. RNA Viruses: The Replication of RNA Genomes
• RNA-Dependent RNA Replicases
• Replication of Retroviral Genomes
• Chapter 23: DNA Repair, Recombination, and Rearrangement
• 23.1. DNA Repair
• Types and Consequences of DNA Damage
• Direct Repair of Damaged DNA Bases: Photoreactivation and Alkyltransferases
• Photoreactivation
• O6-Alkylguanine Alkyltransferase
• Nucleotide Excision Repair: Excinucleases
• Base Excision Repair: DNA N-Glycosylases
• Replacement of Uracil in DNA by BER
• Repair of Oxidative Damage to DNA
• Mismatch Repair
• Double-Strand Break Repair
• Daughter-Strand Gap Repair
• Damage Response
• 23.2. Recombination
• Site-Specific Recombination
• Homologous Recombination
• Breaking and Joining of Chromosomes
• Models for Recombination
• Proteins Involved in Homologous Recombination
• 23.3. Gene Rearrangements
• Immunoglobulin Synthesis: Generating Antibody Diversity
• Transposable Genetic Elements
• Retroviruses
• Gene Amplification
• Tools of Biochemistry: 23A Manipulating the Genome
• Foundation Figure: Antibody Diversity and Use as Therapeutics
• Chapter 24: Transcription and Posttranscriptional Processing
• 24.1. DNA as the Template for RNA Synthesis
• The Predicted Existence of Messenger RNA
• T2 Bacteriophage and the Demonstration of Messenger RNA
• RNA Dynamics in Uninfected Cells
• 24.2. Enzymology of RNA Synthesis: RNA Polymerase
• Biological Role of RNA Polymerase
• Structure of RNA Polymerase
• 24.3. Mechanism of Transcription in Bacteria
• Initiation of Transcription: Interactions with Promoters
• Initiation and Elongation: Incorporation of Ribonucleotides
• Punctuation of Transcription: Termination
• Factor-Independent Termination
• Factor-Dependent Termination
• 24.4. Transcription in Eukaryotic Cells
• RNA Polymerase I: Transcription of the Major Ribosomal RNA Genes
• RNA Polymerase III: Transcription of Small RNA Genes
• RNA Polymerase II: Transcription of Structural Genes
• Chromatin Structure and Transcription
• Transcriptional Elongation
• Termination of Transcription
• 24.5. Posttranscriptional Processing
• Bacterial mRNA Turnover
• Posttranscriptional Processing in the Synthesis of Bacterial rRNAs and tRNAs
• rRNA Processing
• tRNA Processing
• Processing of Eukaryotic mRNA
• Capping
• Splicing
• Alternative Splicing
• Tools of Biochemistry: 24A Analyzing the Transcriptome
• Tools of Biochemistry: 24B Chromatin Immunoprecipitation
• Chapter 25: Information Decoding: Translation and Posttranslational Protein Processing
• 25.1. An Overview of Translation
• 25.2. The Genetic Code
• How the Code Was Deciphered
• Features of the Code
• Deviations from the Genetic Code
• The Wobble Hypothesis
• tRNA Abundance and Codon Bias
• Punctuation: Stopping and Starting
• 25.3. The Major Participants in Translation: mRNA, tRNA, and Ribosomes
• Messenger RNA
• Transfer RNA
• Aminoacyl-tRNA Synthetases: The First Step in Protein Synthesis
• The Ribosome and Its Associated Factors
• Soluble Protein Factors in Translation
• Components of Ribosomes
• Ribosomal RNA Structure
• Internal Structure of the Ribosome
• 25.4. Mechanism of Translation
• Initiation
• Elongation
• Termination
• Suppression of Nonsense Mutations
• 25.5. Inhibition of Translation by Antibiotics
• 25.6. Translation in Eukaryotes
• 25.7. Rate of Translation; Polyribosomes
• 25.8. The Final Stages in Protein Synthesis: Folding and Covalent Modification
• Chain Folding
• Covalent Modification
• 25.9. Protein Targeting in Eukaryotes
• Proteins Synthesized in the Cytoplasm
• Proteins Synthesized on the Rough Endoplasmic Reticulum
• Role of the Golgi Complex
• Chapter 26: Regulation of Gene Expression
• 26.1. Regulation of Transcription in Bacteria
• The Lactose Operon—Earliest Insights into Transcriptional Regulation
• Isolation and Properties of the Lactose Repressor
• The Repressor Binding Site
• Regulation of the lac Operon by Glucose: A Positive Control System
• The CRP–DNA Complex
• Some Other Bacterial Transcriptional Regulatory Systems: Variations on a Theme
• Bacteriophage .: Multiple Operators, Dual Repressors, Interspersed Promoters and Operators
• The SOS Regulon: Activation of Multiple Operons by a Common Set of Environmental Signals
• Biosynthetic Operons: Ligand-Activated Repressors and Attenuation
• Applicability of the Operon Model—Variations on a Theme
• 26.2. Transcriptional Regulation in Eukaryotes
• Chromatin and Transcription
• Transcriptional Control Sites and Genes
• Nucleosome Remodeling Complexes
• Transcription Initiation
• Regulation of the Elongation Cycle by RNA Polymerase Phosphorylation
• 26.3. DNA Methylation, Gene Silencing, and Epigenetics
• DNA Methylation in Eukaryotes
• DNA Methylation and Gene Silencing
• Genomic Distribution of Methylated Cytosines
• Other Proposed Epigenetic Phenomena
• 5-Hydroxymethylcytosine
• Chromatin Histone Modifications
• 26.4. Regulation of Translation
• Regulation of Bacterial Translation
• Regulation of Eukaryotic Translation
• Phosphorylation of Eukaryotic Initiation Factors
• Long Noncoding RNAs
• 26.5. RNA Interference
• MicroRNAs
• Small Interfering RNAs
• 26.6. Riboswitches
• 26.7. RNA Editing
• Foundation Figure: Information Flow in Biological Systems
• Appendix I: Answers to Selected Problems
• Appendix II: References
• Credits
• Index
• Back Cover