FUNCTIONAL METABOLISM: REGULATION AND ADAPTATION -- CONTENTS -- Preface -- Contributors -- Chapter 1 Principles of Metabolic Control -- Key Concepts -- Metabolic Renaissance In Post Genome Era? -- Metabolic Engineering -- Metabolic Regulation versus Metabolic Control -- Complexity of Metabolism and Concept of Biochemical Unity -- Basis of Metabolic Control -- Pacemaker Enzymes -- Identification of a Pacemaker Enzyme -- Enzyme Purification -- Cautionary Note about Relating In Vitro Kinetic Studies of a Purified Enzyme to Its In Vivo Function and Control -- Compartmentation of Metabolism -- Formulation of a Theory of Metabolic Control -- Metabolic Control Analysis -- Mechanisms of Metabolic Control -- Coarse Metabolic Control -- Fine Metabolic Control -- Concluding Remarks -- Chapter 2 Enzymes: The Basis of Catalysis -- Introduction -- Enzyme Structure -- Thermodynamics and Kinetic Theory of Enzyme Function -- Thermodynamic Aspects of Kinetic Function: Processes Not Under Enzyme Control -- Cellular Equilibria and Enzymes -- Reaction Rate Theories -- How Enzymes Influence Reaction Rates -- How Enzyme-Catalyzed Reactions Occur: Lysozyme as a Model of Transition State Theory -- When Enzymes Need Extra Help: Coenzymes and Their Functions -- Coenzymes That Transfer High Energy Phosphate -- Coenzymes That Accept and Donate Electrons -- Coenzymes That Activate Substrates -- Kinetic Mechanisms of Enzyme Action -- Development of Rate Equations: Simple Solution Kinetics -- The Haldane Relationship -- Multisubstrate Reactions -- Cooperative Enzyme Mechanism -- Allosteric Enzyme Activation and Inhibition -- Enzyme Inhibition -- Temperature Effects on Enzyme Function -- Estimating Kinetic Parameters from Enzyme Velocity Data (the Influence of Error Structure) -- Chapter 3 Enzymes in the Cell: What's Really Going On? -- Introduction.

Basic Enzyme Mechanism Under In Vivo Conditions -- Effect of Enzyme-Substrate Binding -- Effect of Reaction Reversibility -- Effect of Substrate and Product Binding Combined with Reaction Reversibility -- Time Course of the Complete Enzyme Mechanism -- Simple Enzyme Systems -- Simple Enzyme Pathways under In Vivo Conditions -- Thought Experiment: Regulating Flux In Vivo -- Mathematical Modeling of the Linear System -- Branch Points and Irreversible Enzymes in Pathways -- Simple Enzyme Pathways and Crossover Plots -- Basics of Metabolic Control Analysis -- MCA Analysis and Metabolic Pathways -- Controlling Pathway Flux under In Vivo Conditions: Direct Calculation of Control Coefficients -- Controlling Pathway Flux under In Vivo Conditions: Indirect Calculations of Control Coefficients -- Relating Flux Control Coefficients to Pathway Regulation -- Potential of an Enzyme to Be Regulated -- Metabolic Simulation -- Supply versus Demand -- Feedback Inhibition -- Formation of Multienzyme Complexes -- Chapter 4 Signal Transduction Pathways and the Control of Cellular Responses to External Stimuli -- Function and Structure of Signaling Pathways -- Protein Kinases and Protein Phosphatases -- Cascades and Cross-talk -- Amplification and Signal Thresholds -- Signal Transmission via Protein Kinases -- Kinase Signaling Networks for Serine/Threonine Phosphorylation -- Second-Messenger-Dependent Protein Kinases -- Function and Regulation of Protein Phosphatases -- Serine-Threonine Protein Phosphatases -- Coordinated Action of Protein Kinases and Protein Phosphatases -- Protein Phosphorylation and Regulation of Glycogen Metabolism -- Protein Phosphorylation and Regulation of Smooth Muscle Contraction -- Chapter 5 Tyrosine Phosphorylation and the Control of Cellular Information -- Protein Tyrosine Kinases -- Protein-Binding Modules and Specificity.

Protein Tyrosine Phosphatases -- Direct Modulation of PTP Activity -- Recruitment of PTPs to RPTKs -- From Membrane to Nucleus: Intracellular Signal Transmission -- ERK Pathway -- SAPK/JNK Pathway -- p38 Pathway -- Cross-talk in MAPK Signaling -- Signaling through Space and Time: The MAPK Cascade as a Cellular Switch -- Role of Scaffolding Proteins -- Transcription Factors Linked to Signaling Pathways -- MAPK Nuclear Targets -- Nuclear Factor-kB -- Second Messengers and Transcriptional Activation -- Coordinated Control of Cellular Events: Insulin Signaling -- Conclusion -- Chapter 6 Control of Transcription in Eukaryotic Cells -- Introduction -- Basal Transcription Machinery -- Upstream Factors -- Inducible Factors -- DNA-Binding Domains -- Dimerization Domains -- Activation Domains -- Repression Domains -- Ligand-Binding Domains -- Nuclear Localization Signal -- Nuclear Export Signal -- Regulation of Transcription Factors -- Examples of Transcription Factors Involved in Metabolic Control -- Factors Repressed by Oxidative Conditions -- Factors Activated by Oxidative Conditions -- Redox Factors -- Conclusions -- Chapter 7 Translational Controls and Protein Synthesis in Eukaryotic Cells -- Introduction -- Basic Elements of Translation -- Posttranscriptional mRNA Processing -- Ribosomes -- Translation Initiation -- Translation Elongation -- Regulation of Translation -- Regulation at the Level of mRNA -- Regulation of Translation Initiation -- Regulation of Elongation -- Regulation at the Level of the Ribosome -- Conclusions -- Chapter 8 The Mitochondria: Powerhouse of the Cell -- Introduction -- Mitochondrial History -- Structure -- Energy Metabolism -- Pyruvate Dehydrogenase Complex -- Tricarboxylic Acid Cycle -- Branch Points: The TCA Cycle In Vivo -- Glyoxylate Cycle -- Urea Cycle -- Fatty Acid Oxidation -- Ketogenesis.

Amino Acid Degradation as a Fuel for TCA Cycle -- Respiratory Chain -- Metabolic Control Analysis -- Uncoupling for Thermogenesis -- ATP-ADP Translocase Release Ratio -- Mitochondrial Import of Proteins -- Mitochondrial Oxygen Sensing -- Calcium Signaling and the Mitochondria -- Aging, Disease, and the Mitochondria -- Apoptosis -- Conclusion -- Chapter 9 Human Energy Metabolism in Health and Disease -- Introduction -- Human Carbohydrate Metabolism -- Glycolysis -- Gluconeogenesis -- Glycogen Metabolism -- Regulation of Carbohydrate Metabolism -- Transcriptional Regulation of Carbohydrate Metabolism -- Pyruvate Dehydrogenase -- Human Lipid Metabolism -- Lipogenesis -- Regulation of Lipogenesis -- Transcriptional Regulation of Lipogenesis -- Lipolysis -- Regulation of Lipolysis -- Ketogenesis -- Human Protein Metabolism -- Amino Acid Metabolism, the Urea Cycle, and Gluconeogenesis -- Regulation of Protein Metabolism -- Transcriptional Regulation of Protein Metabolism -- Human Energy Metabolism in the Fed State -- Human Energy Metabolism During Fasting and Starvation -- Cachexia -- Metabolic Changes in Cancer -- Chapter 10 Hormones in Human Metabolism and Disease -- Hormonal Regulation of Human Metabolism -- Introduction -- Insulin -- Glucagon -- Epinephrine and Norepinephrine -- Cortisol -- Growth Hormone -- Insulin-like Growth Factors -- Thyroid Hormone -- Leptin -- Hormonal Dysregulation and Human Disease -- Obesity -- Diabetes Mellitus -- Chapter 11 Skeletal Muscle Metabolism and Plasticity -- Introduction -- Skeletal Muscle Plasticity -- Dynamic State of Muscle Fibers -- Muscle Fiber Types -- Muscle Morphology: Fiber Size and Capillary Density -- Metabolic Profile -- Fuels and Their Control -- Energy Use and Production in Muscle -- Fuel Availability and Use -- Control and Integration of Fuel Use -- ADP in Energy Metabolism.

Carbohydrate Metabolism and Glucose Uptake -- Fatty Acid Transport and Entry into Muscle Cells -- Interplay between Lipid and Carbohydrate Metabolism -- Reactive Oxygen Species and Nitric Oxide: Role in Skeletal Muscle Function -- Perspectives -- Chapter 12 Oxygen in Biology and Biochemistry: Role of Free Radicals -- Free Radicals and Oxidizing Agents in Biology -- Free Radical Reactions in Biology -- Reactive Oxygen Species -- Reactive Nitrogen Species -- Antioxidant Defenses -- Enzymatic Antioxidants, Glutathione, and Thioredoxin -- Low-Molecular-Weight Antioxidants -- Lipid Peroxidation -- Introduction -- Initiation and Propagation Phases of Lipid Peroxidation -- Termination of Peroxidation Reaction and Its Consequences -- Antioxidants That Function against Lipid Peroxidation -- Protein Oxidation -- In Vitro Studies on Protein Oxidation -- Oxidation of Sulfur-Containing Residues and Tyrosine Residues -- Carbonyl Protein -- DNA Oxidative Damage -- DNA Damage: Introductory Remarks -- DNA as Target of Reactive Oxygen Species -- Oxidative Damage (and Repair) to DNA Bases -- Other Types of DNA Alterations, Including Strand Breaks and Fragmentation -- Biological Effects of DNA Damage -- Free Radicals and Signal Transduction -- Bacterial Regulons soxRS and oxyR -- Oxidants and Cellular Redox Signaling -- Oxygen Sensing and ROS -- Chapter 13 Oxidative Stress and Medical Sciences -- Oxidative Stress in Biology and Disease -- Free Radicals and Neuronal Disorders -- Oxidative Stress in Wilson's Disease, Friedrich's Ataxia, and ALS -- Parkinson's Disease (PD) and Oxidative Stress -- Alzheimer's Disease: The Free Radical Connection -- Inflammation and Oxidative Stress: An Outlook -- "Manufacturing" of Free Radicals by Phagocytes -- Oxidative Stress Induced by Phagocytes -- More on Microbial Killing: A Radical New Hypothesis.

Atherosclerosis and Free Radicals: To Be or Not Be?.