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Integration of Metabolism, Energetics, and Signal Transduction : Unifying Foundations in Cell Growth and Death, Cancer, Atherosclerosis, and Alzheimer Disease - Robert K. Ockner

Integration of Metabolism, Energetics, and Signal Transduction

Unifying Foundations in Cell Growth and Death, Cancer, Atherosclerosis, and Alzheimer Disease

Hardcover

Published: 1st April 2004
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This book demonstrates how metabolism and energetics are directly linked to those signal transduction pathways that are essential to survival of the cell, the organism, and the species. Recurring patterns of interaction among metabolism, energetics, and signal transduction are fundamental in diverse aspects of human health and disease. This book explores these phenomena in relation to cell growth and death, cancer, atherosclerosis and Alzheimer disease. Part I of the book explores the origins and theory of integration.

Topics covered in Part II include: nutrient and energy metabolism in cell proliferation; fatty acids and growth regulation; mitochondrial function in cell growth and death; metabolic effects of antiproliferative agents; fatty acids and mitochondria, cell growth and injury; metabolism and gene expression.

Part III of the book deals with energetics of neuronal activation; utilization of oxidizable substrates in the brain; astrocyte metabolism and astrocyte-neuron interaction; neuronal energy metabolism in the brain; astroctyes as metabolic buffer and mediator of neuronal injury; and metabolic factors in the pathogenesis of Alzheimer Disease.

"Dr. Ockner has written a fascinating and original book which explores potential metabolic links to neurodegeneration. He takes a fresh look at metabolic pathways involving interaction between astrocyte and neuron that are important for brain health and may play a significant role in the pathogenesis of Alzheimer disease and other normal and pathological phenomena. Dr. Ockner has a distinguished research career in fatty acid metabolism and the fatty acid binding proteins and writes with clarity upon this under-explored aspect of the brain in health and disease. Not only is his book important for understanding links between systemic and cerebral metabolism in neurodegeneration, but is a must read for scientists with an interest in the connection between metabolic pathways and brain function."

a "Bruce Miller, M.D.

Professor of Neurology

Clinical director of the Memory and Aging Center

University of California, San Francisco

Prologuep. 1
Disparate Themes: Origins and Integrationp. 3
Fatty Acids, Mitochondria, and Signal Transduction: Integrated Control of Cell Proliferation, Injury, and Deathp. 11
Introduction to Part IIp. 13
Nutrient and Energy Metabolism in Cell Proliferationp. 19
Introductionp. 19
Intermediary Metabolism: General Considerationsp. 19
ATP Generation, Carbohydrate Metabolism, and Cell Growthp. 22
Aerobic Glycolysis, Mitochondrial Respiration, and Oxidative Phosphorylationp. 23
Wingless/Wnt-Like Signaling: Convergence of Antecedents and the Unpredictablep. 27
Broader Significance of wg/Wnt-Like Signalingp. 31
Lithiump. 33
Reactive Oxygen Speciesp. 33
Referencesp. 35
Fatty Acids and Growth Regulationp. 47
Introductionp. 47
Omega-6 ([omega]-6) Fatty Acidsp. 48
Omega-3 ([omega]-3) Fatty Acidsp. 51
Metabolic Effectsp. 51
Growth Effectsp. 52
Fatty Acids, Modulation of Cell Growth, and the AMP-Activated Protein Kinasep. 53
AMP-Activated Protein Kinasep. 57
Stoichiometric Considerationsp. 58
Metabolic Interaction Between Tumor and Host: Cancer Cachexiap. 61
Referencesp. 64
Mitochondrial Function in Cell Growth and Deathp. 77
Introductionp. 77
Peroxisome Proliferator-Activated Receptors (PPAR) and Ligands: Mitochondrial Redox, Macrophages, and Mitosisp. 78
PPAR[alpha]p. 78
PPAR[gamma]p. 84
PPAR[delta]p. 85
Mitochondrial Function in Apoptosisp. 85
The Bcl-2 Protein Familyp. 88
wg/Wnt-Like Signaling: Convergence of Mitochondria, p53, and Telomerasep. 90
Mitochondria and FasL-Independent Activation of Fasp. 93
Apoptosis and the Cell Cycle: Chronic Viral Hepatitis and Cancerp. 95
Referencesp. 98
Metabolic Effects of Antiproliferative Agentsp. 121
Introductionp. 121
Butyratep. 121
Transforming Growth Factor-[beta] (TGF[beta])p. 125
Salicylates and Other Nonsteroidal Anti-Inflammatory Drugs (NSAIDS)p. 127
Referencesp. 132
Fatty Acids and Mitochondria, Cell Growth and Injury: Broader Implicationsp. 143
Introductionp. 143
Adverse Effects of Fatty Acids on Mitochondrial Function and Cell Redox Balancep. 143
Origins of Intramitochondrial Oxidative Stressp. 145
Consequences of Intramitochondrial Oxidative Stress: Atherosclerosis and Beyondp. 148
Atherosclerosis and Arterial Hypertensionp. 149
Oxidized LDLp. 149
The Endothelial Lesionp. 150
Beneficial Effects of "Statin" Hypolipidemic Agentsp. 152
Adverse Effects of Fatty Acid Oxidation-Induced ROS in Various Organsp. 154
Ischemia-Reperfusion Injury and Heat Shock/Stress Responsep. 156
Paradoxical Benefits of Adversityp. 156
Referencesp. 160
Metabolism and Gene Expression in Liver Regenerationp. 177
Introductionp. 177
Systemic Metabolic Responses to 70% Hepatectomyp. 177
Early Changes in Hepatocellular Metabolism and Gene Expressionp. 180
Ensuing Modulation of Systemic and Hepatocellular Metabolismp. 182
Effects of Proinflammatory Cytokines: TNF[alpha] vs. Insulinp. 184
Completion of Regeneration and Cell Cycle Exitp. 189
Referencesp. 190
Part II Conclusionsp. 201
Fatty Acids, Ketone Bodies, and Brain Metabolism: Implications for Neuronal Function and Alzheimer Diseasep. 205
Introduction to Part IIIp. 207
Energetics of Neuronal Activationp. 209
Introduction - Relevant Principles of Intermediary Metabolismp. 209
Energy-Consuming Events in Neuronal Activationp. 212
Mitochondrial Function and the Generation of ATPp. 213
Referencesp. 214
Utilization of Oxidizable Substrates in Brainp. 217
Introductionp. 217
Glucosep. 218
Ketone Bodiesp. 220
Fatty Acid Utilization in Brain and the Regulation of Appetitep. 226
Uptake of Fatty Acids from Plasmap. 226
Oxidation of Fatty Acidsp. 228
Fatty Acid Oxidation and Regulation of Feeding Behaviorp. 233
Cytokines and the Brainp. 237
Referencesp. 241
Astrocyte Metabolism and Astrocyte-Neuron Interactionp. 255
Introductionp. 255
Carbohydrate Metabolismp. 255
Amino Acid Metabolism and the Glutamine Shuttlep. 259
Fatty Acids, Antioxidant Defense, HIV Dementia, and Cell Proliferationp. 262
Astrocyte-Neuron Interaction and Oxidative Stressp. 264
HIV Dementiap. 267
Cell Proliferation and Tumorigenesisp. 268
Referencesp. 269
Neuronal Energy Metabolism in Brain: Astrocyte as Metabolic "Buffer" and Mediator of Neuronal Injuryp. 277
Introductionp. 277
Activation-Related Glucose and Oxygen Consumptionp. 278
Increases in Plasma Concentrations of Ketone Bodies and FFAp. 279
Ketogenic Diet and Control of Seizure Activityp. 280
Synaptic Transmission, Long-Term Potentiation, and Excitotoxicityp. 282
Energetic Considerations in Synaptic Transmissionp. 282
Augmented Glutamate Exposure: Long-Term Potentiation and Excitotoxicityp. 285
Long-Term Potentiationp. 285
Excitotoxicity--Origins of Oxidative Stressp. 288
Referencesp. 293
Pathogenesis of Alzheimer Disease: Metabolic Factorsp. 303
Introductionp. 303
Genetic Determinantsp. 305
Apolipoprotein E Isoformsp. 305
Presenilin and Amyloid Precursor Protein Mutationsp. 306
Association of Alzheimer Disease with Type II Diabetes Mellitusp. 307
Cerebral Metabolism and Insulin Signalingp. 309
Glycolysis and the Citric Acid Cycle in Alzheimer Diseasep. 310
Wingless/Wnt-Like Signal Transduction and Effects of Lithiump. 314
Wingless/Wnt-Like Signalingp. 315
Neuroprotection and Cell Cycle-Linked Neuronal Deathp. 316
Neurochemical Effects of Lithiump. 320
Metabolic Determinants in Alzheimer Disease: Synthesisp. 321
Oxidative Stress and [beta] Amyloid: A "Vicious Cycle" of Multiple Interacting Determinantsp. 321
[beta] Amyloidp. 322
Oxidative Stressp. 323
Genetic Factorsp. 323
Changes in Fatty Acid and Ketone Body Metabolismp. 324
Neuroprotective Responses and the "Vicious Cycle"p. 325
Hypothesized Role of Fatty Acid Metabolism in Neurodegenerationp. 326
Integrated Model of Alzheimer Disease Pathogenesisp. 329
Referencesp. 330
Part III Conclusionsp. 355
Epiloguep. 359
Looking Back, Looking Aheadp. 361
Indexp. 369
Table of Contents provided by Rittenhouse. All Rights Reserved.

ISBN: 9780306484711
ISBN-10: 0306484714
Series: Bioengineering, Mechanics, and Materials: Principles and Applications in Sport S.
Audience: Professional
Format: Hardcover
Language: English
Number Of Pages: 387
Published: 1st April 2004
Publisher: Springer Science+Business Media
Country of Publication: US
Dimensions (cm): 24.8 x 16.5  x 2.54
Weight (kg): 0.97