Functional Metabolism: Regulation and Adaptation

614 Pages·2004·58.57 MB·English

by  Kenneth B. Storey

FUNCTIONAL METABOLISM:
REGULATION AND ADAPTATION
EDITED BY
Kenneth B. Storey, Ph.D.
Institute of Biochemistry
Carleton University
Ottawa, Ontario
Canada
(wW) ILEY-LISS
W
A JOHN WILEY & SONS, INC., PUBLICATION
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FUNCTIONAL METABOLISM
This Page Intentionally Left Blank
FUNCTIONAL METABOLISM:
REGULATION AND ADAPTATION
EDITED BY
Kenneth B. Storey, Ph.D.
Institute of Biochemistry
Carleton University
Ottawa, Ontario
Canada
(wW) ILEY-LISS
W
A JOHN WILEY & SONS, INC., PUBLICATION
This book is printed on acid-free paper. @
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Library of Congress Cataloging-in-PublicationD ata:
Functional metabolism: regulation and adaption/edited by Kenneth B. Storey
p. ; cm.
lncludes bibliographical references and index.
ISBN 0-47 1-4 1090-X (pbk. : alk. paper)
1, Metabolisrn-Regulation. 2. Homeostasis. 3. Adaption (Physiology) 4.
Cellular signal transduction.
[DNLM: 1. Metabolism-physiology. 2. Cells-ultrastructure. 3. Metabolic
Diseases-genetics. 4. Molecular Biology-methods. QU 120 F979 20041 I.
Storey, K. B. (Kenneth B.)
QP171.F86 2004
572'.4-dc22
2003027397
Printed in the United States of America
109 8 7 6 5 4 3 2 1
CONTENTS
Prefnce xv
Contributors xvii
Chapter 1 Principles of Metabolic Control
Willianz C. Plnxton
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 5
Compartmentation of Metabolism 5
Formulation of a Theory of Metabolic Control 6
Metabolic Control Analysis 6
Mechanisms of Metabolic Control 7
Coarse Metabolic Control 8
Fine Metabolic Control 9
Concluding Remarks 23
Chapter 2 Enzymes: The Basis of Catalysis 25
Stephen P.J. Brooks
Introduction 25
Enzyme Structure 25
Thermodynamics and Kinetic Theory of Enzyme Function 27
Thermodynamic Aspects of Kinetic Function: Processes Not Under Enzyme Control 27
Cellular Equilibria and Enzymes 29
Reaction Rate Theories 29
How Enzymes Influence Reaction Rates 31
How Enzyme-Catalyzed Reactions Occur: Lysozyme as a Model of Transition State Theory 33
V
vi CONTENTS
When Enzymes Need Extra Help: Coenzymes and Their Functions 35
Coenzymes That Transfer High Energy Phosphate 35
Coenzymes That Accept and Donate Electrons 37
Coenzymes That Activate Substrates 37
Kinetic Mechanisms of Enzyme Action 37
Development of Rate Equations: Simple Solution Kinetics 39
The Haldane Relationship 41
Multisubstrate Reactions 42
Cooperative Enzyme Mechanism 43
Allosteric Enzyme Activation and Inhibition 46
Enzyme Inhibition 47
Temperature Effects on Enzyme Function 49
Estimating Kinetic Parameters from Enzyme Velocity Data (the Influence of Error Structure) 5 0
Chapter 3 Enzymes in the Cell: What’s Really Going On? 55
Stephen P.J . Brook5
Introduction 55
Basic Enzyme Mechanism Under In Vivo Conditions 55
Effect of Enzyme-Substrate Binding 5.5
Effect of Reaction Reversibility 57
Effect of Substrate and Product Binding Combined with Reaction Reversibility 57
Time Course of the Complete Enzyme Mechanism 59
Simple Enzyme Systems 62
Simple Enzyme Pathways under In Vivo Conditions 63
Thought Experiment: Regulating Flux In Vivo 65
Mathematical Modeling of the Linear System 67
Branch Points and Irreversible Enzymes in Pathways 68
Simple Enzyme Pathways and Crossover Plots 68
Basics of Metabolic Control Analysis 69
MCA Analysis and Metabolic Pathways 73
Controlling Pathway Flux under In Vivo Conditions: Direct Calculation of Control Coefficients 73
Controlling Pathway Flux under In Vivo Conditions: Indirect Calculations of Control Coefficients 76
Relating Flux Control Coefficients to Pathway Regulation 77
Potential of an Enzyme to Be Regulated 79
Metabolic Simulation 82
Supply versus Demand 82
Feedback Inhibition 83
Formation of Multienzyme Complexes 84
Chapter 4 Signal Transduction Pathways and the Control of Cellular Responses to External Stimuli 87
Justin A. MncDonald
Function and Structure of Signaling Pathways 87
Protein Kinases and Protein Phosphatases 90
Cascades and Cross-talk 92
Amplification and Signal Thresholds 94
Signal Transmission via Protein Kinases 94
Kinase Signaling Networks for Serine/Threonine Phosphorylation 100
Second-Messenger-Dependent Protein Kinases 102
Function and Regulation of Protein Phosphatases 115
Serine-Threonine Protein Phosphatases 116
Coordinated Action of Protein Kinases and Protein Phosphatases 120
Protein Phosphorylation and Regulation of Glycogen Metabolism 120
CONTENTS vii
Protein Phosphorylation and Regulation of Smooth Muscle Contraction 120
Chapter 5 Tyrosine Phosphorylation and the Control of Cellular Information 125
Justin A. MacDonald
Protein Tyrosine Kinases 125
Protein-Binding Modules and Specificity 128
Protein Tyrosine Phosphatases 132
Direct Modulation of PTP Activity 132
Recruitment of PTPs to RPTKs 133
From Membrane to Nucleus: Intracellular Signal Transmission 133
ERK Pathway 134
SAPK/JNK Pathway 139
p38 Pathway 139
Cross-talk in MAPK Signaling 140
Signaling through Space and Time: The MAPK Cascade as a Cellular Switch 140
Role of Scaffolding Proteins 141
Transcription Factors Linked to Signaling Pathways 146
MAPK Nuclear Targets 146
Nuclear Factor-& 146
Second Messengers and Transcriptional Activation 147
Coordinated Control of Cellular Events: Insulin Signaling 148
Conclusion 150
Chapter 6 Control of Transcription in Eukaryotic Cells 153
William C. Willmore
Introduction 153
Basal Transcription Machinery 153
Upstream Factors 157
Inducible Factors 157
DNA-Binding Domains 158
Dimerization Domains 165
Activation Domains 166
Repression Domains 168
Ligand-Binding Domains 169
Nuclear Localization Signal 169
Nuclear Export Signal 171
Regulation of Transcription Factors 171
Examples of Transcription Factors Involved in Metabolic Control 173
Factors Repressed by Oxidative Conditions 173
Factors Activated by Oxidative Conditions 183
Redox Factors 185
Conclusions 187
Chapter 7 Translational Controls and Protein Synthesis in Eukaryotic Cells 189
William G. Willmore
Introduction 189
Basic Elements of Translation 189
Posttranscriptional mRNA Processing 189
Ribosomes 192
Translation Initiation 195
Translation Elongation 196
Regulation of Translation 197
viii CONTENTS
Regulation at the Level of mRNA i97
Regulation of Translation Initiation 286
Regulation of Elongation 209
Regulation at the Level of the Ribosome 209
Conclusions 210
Chapter 8 The Mitochondria: Powerhouse of the Cell 21 1
Ki M J. Co\van
Introduction 21 1
Mitochondri a1 Hi story 21 1
Structure 212
Energy Metabolism 213
Pyruvate Dehydrogenase Complex 213
Tricarboxylic Acid Cycle 216
Branch Points: The TCA Cycle h Vivo 220
Clyoxylate Cycle 220
Urea Cycle 22 1
Fatty Acid Oxidation 222
Ketogcnesis 223
Amino Acid Degradation as a Fuel for TCA Cycle 224
Respiratory Chain 224
Metabolic Control Analysis 226
Uncoupling for Thermogenesis 227
ATP-ADP Translocase Release Ratio 228
Mitochondrial Import of Proteins 228
Mitochondrial Oxygen Sensing 230
Calcium Signaling and the Mitochondria 23 1
Aging, Disease, and the Mitochondria 233
Apoptosis 234
Conclusion 240
Chapter 9 Human Energy Metabolism in Health and Disease 243
Steven C. Greeiicvaj
Introduction 243
Human Carbohydrate Metabolism 243
Clycolysis 245
Gluconeogenesis 245
Glycogen Metabolism 246
Regulation of Carbohydrate Metabolism 246
Transcriptional Regulation of Carbohydrate Metabolism 249
Pyruvate Dehydrogenase 250
Human Lipid Metabolism 25 1
Lipogenesis 252
Regulation of Lipogenesis 253
Transcriptional Regulation of Lipogenesis 255
Lipolysis 256
Regulation of Lipolysis 258
Ketogenesis 259
Human Protein Metabolism 259
Amino Acid Metabolism, the Urea Cycle, and Gluconeogenesis 260
Regulation of Protein Metabolism 262
Transcriptional Regulation of Protein Metabolism 262