Main description:

Alcohol abuse and alcoholism represents one of the major health, social, and economic issues facing not only America but much of the world. Problems with alcohol appear to be a common curse, afflicting almost all industrialized nations as well as the developing countries. In the United States today at least 10 million people suffer the misuse. It is estimated that 205,000 individuals die prematurely each year from a variety of ethanol-induced factors, including cirrhosis, cancer, heart disease, suicide, homi­ cide, and highway fatalities and other accidents. In purely economic terms, the alcohol-related cost to our society in 1975 is estimated at nearly $43 billion in lost production, medical expenses, motor vehicle accidents, fire losses, and the maintenance of social mechanisms to deal with these problems. But the economic impact pales in comparision with the psychological pain and anguish brought to alcoholics and their family and friends. The disease of alcoholism bears a close relation to the topic of our dedication, for it is equally insidious and sadistic, it destroys humanity and rational thought, and it brings terror, pain, and death.

Contents:

I. Distribution and Elimination of Ethanol.- 1 Factors Affecting the Distribution and Measurement of Ethanol in the Body.- A. Introduction.- B. Comparative Blood Ethanol Levels in Animals and Man.- C. Distribution of Ethanol in Body Tissues.- D. Methods of Ethanol Determination.- E. Alteration of Blood Ethanol Concentration: Summary.- F. Conclusions.- G. References.- 2 Chronopharmacokinetics of Ethanol.- A. Introduction.- B. Elimination Kinetics of Ethanol.- C. Chronopharmacology of Ethanol.- D. Theoretical Chronopharmacokinetics of Ethanol.- E. Conclusions and Implications.- F. References.- II. Enzymology and Metabolism of Ethanol.- 3 Metalloenzymes and Ethanol Metabolism: Liver Alcohol Dehydrogenase.- A. Introduction.- B. Horse Liver Alcohol Dehydrogenase—A Zinc Metalloenzyme.- C. Human Liver Alcohol Dehydrogenase.- D. Summary and Conclusions.- E. References.- 4 Enzymatic Pathways of Ethanol Metabolism.- A. Introduction.- B. Alcohol Dehydrogenase.- C. Catalase.- D. Microsomal Ethanol-Oxidizing System.- E. Summary and Conclusions.- F. References.- 5 Nonethanol Substrates of Alcohol Dehydrogenase.- A. Introduction.- B. Kinetic Mechanism of ADH.- C. Primary Alcohols.- D. Aldehyde Reduction.- E. Secondary Alcohols and Ketones.- F. Steroids.- G. Effect of the Substrate Structure on the Rate of Ternary Complex Interconversion.- H. Substrate Structure and Substrate Inhibition.- I. Diamond Lattice Section Models of Substrate-Binding Area of the Active Site.- J. Biological Occurrence of ADH Substrates and Physiological Role of ADH.- K. Conclusions.- L. References.- 6 Aldehyde Dehydrogenase: Mechanism of Action and Possible Physiological Roles.- A. Introduction.- B. The Reaction.- C. The Enzyme.- D. Inhibitors of Aldehyde Dehydrogenase.- E. High- and Low-Km Forms of Aldehyde Dehydrogenase.- F. Substrates for Aldehyde Dehydrogenase.- G. Induction of Aldehyde Dehydrogenase by Ethanol.- H. Summary and Conclusions.- I. References.- 7 Acetaldehyde Metabolism.- A. Introduction.- B. Levels of Acetaldehyde in the Body after Ingestion of Ethanol.- C. Rate of Acetaldehyde Metabolism in Various Organs.- D. Enzyme Responsible for the Oxidation of Acetaldehyde and Its Subcellular Localization.- E. Regulation of Acetaldehyde Metabolism.- F. Summary and Conclusions.- G. References.- 8 Methanol: Its Metabolism and Toxicity.- A. Introduction.- B. Methanol Oxidation.- C. Formaldehyde Metabolism.- D. Formate Metabolism.- E. Basis of the Toxicity of Methanol.- F. Treatment of Methanol Poisoning.- G. Summary and Conclusions.- H. References.- III. Effects of Ethanol on Intermediary Metabolism.- 9 Ethanol Metabolism in Perfused Liver and Isolated Hepatocytes with Associated Methodologies.- A. Introduction.- B. Methodology for the Study of Hepatic Ethanol Metabolism.- C. Advantages and Limitations of the Methods.- D. Comparative Rates of Ethanol Utilization.- E. Factors Controlling the Rate of Hepatic Ethanol Metabolism.- F. Summary and Conclusions.- G. References.- 10 Effect of Acute and Chronic Administration of Ethanol on the Redox States of Brain and Liver.- A. Introduction.- B. Basic Aspects of the Redox State.- C. Measurement of the Redox State.- D. Effect of Acute Ethanol Administration on the Liver Redox State.- E. Effect of Chronic Ethanol Administration on the Liver Redox State.- F. Effect of Acute and Chronic Ethanol Administration on the Brain Redox State.- G. Summary and Conclusions.- H. Appendix: List of Symbols and Abbreviations.- I. References.- 11 Control of Ethanol Oxidation and Its Interaction with Other Metabolic Systems.- A. Introduction.- B. Basic Theoretical Aspects of Metabolic Control.- C. Control of Alcohol Dehydrogenase: Properties of the Purified Enzymes.- D. Control of Alcohol Dehydrogenase in Vivo and in Perfused Liver and Hepatocyte Systems.- E. Generation and Control of the Redox State and Acetaldehyde Levels.- F. Determination of Rate-Limiting Reactions: The Use of Inhibitors.- G. Summary and Conclusions.- H. References.- 12 Effects of Ethanol on the Intermediary Metabolism of Liver and Brain.- A. Introduction.- B. Carbohydrate Metabolism.- C. Nitrogen Metabolism in Liver.- D. Lipid Metabolism.- E. One-Carbon Metabolism.- F. Summary and Conclusions.- G. References.- 13 Amino Acids and Ethanol.- A. Introduction.- B. Effects of Ethanol on the Digestion and Absorption of Amino Acids.- C. Effects of Ethanol on Amino Acid Transport.- D. Plasma Amino Acids in the Alcoholic.- E. Metabolism of Individual Amino Acids in the Alcoholic.- F. Dietary Requirements for Amino Acids in the Alcoholic.- G. Amino Acids and the Pathogenesis of Hepatic Encephalopathy.- H. Amino Acids and Hyperalimentation in Patients with Hepatic Insufficiency.- I. Summary and Conclusions.- J. References.- IV. Biochemistry of Ethanol-Induced Liver Damage and Disease.- 14 Role of Mitochondrial Damage in Alcoholic Liver Disease.- A. Introduction.- B. Morphologic Evidence of Mitochondrial Injury.- C. Changes in Mitochondrial Functional Integrity.- D. Summary and Conclusions.- E. References.- 15 Hypermetabolic State, Oxygen Availability, and Alcohol-Induced Liver Damage.- A. Relationship between Ethanol Metabolism and Oxygen Consumption.- B. Increased Ethanol Metabolism and Oxygen Demand following Chronic Ethanol Ingestion.- C. Oxygen Availability and Alcoholic Liver Damage.- D. Summary and Conclusions.- E. References.- 16 Effect of Ethanol and Ethanol-Related Diseases on Biliary Lipid Metabolism.- A. Introduction.- B. Cholesterol, Bile Acid, and Lecithin Metabolism.- C. Ethanol and Biliary Lipid Metabolism.- D. Cholesterol and Bile Acid Metabolism in Ethanol-Related Diseases.- E. Summary and Conclusions.- F. References.- 17 Ethanol and Hepatic Fibrogenesis.- A. Introduction.- B. Hepatic Collagen Synthesis.- C. Hepatic Collagen Degradation.- D. Deficiency of Nutrients and Hepatic Fibrosis.- E. Prevention and Therapy of Hepatic Fibrosis in Alcoholism.- F. Summary and Conclusions.- G. References.- 18 Biochemistry of Hepatic Coma in Alcohol-Induced Liver Disease and Other Types of Hepatic Dysfunction.- A. Introduction.- B. Definition of Hepatic Coma.- C. Normal Consciousness.- D. Current Hypotheses of the Mechanism(s) of Hepatic Encephalopathy.- E. Accumulation of Toxins.- F. Depletion of Vital Substrate(s) and Sensitivity of the Brain.- G. Conclusions.- H. References.- V. Effects of Ethanol on the Metabolism of Brain.- 19 Ethanol, Acetaldehyde, and the Metabolism of Perfused Brain.- A. Introduction.- B. Perfused Brain Preparations.- C. Metabolism of [14C] Ethanol and [14C] Acetaldehyde by Perfused Brain.- D. Summary and Conclusions.- E. References.- 20 Studies on Ethanol’s Effects on Cells in Culture.- A. Introduction.- B. How Cell Cultures Can Aid in the Study of Ethanol.- C. Cytotoxic Effects of Ethanol on Cells in Culture.- D. Interactions of Ethanol with the Process of Active Transport.- E. Enzymatic Activity of Cells Exposed to Ethanol.- F. Further Studies on Ethanol and Cells in Culture.- G. Tolerance to and Dependence upon Ethanol and Other Depressant Drugs in Cell Cultures.- H. Summary and Conclusions.- I. References.- 21 Effects of Ethanol on Cerebral Protein and Ribonucleic Acid Synthesis.- A. Introduction.- B. Effects of Ethanol on Cerebral Protein Metabolism.- C. Effects of Ethanol on Cerebral Ribonucleic Acid Metabolism.- D. Summary and Conclusions.- E. References.- VI. Metabolic Effects of Ethanol on Various Organs of the Body.- 22 Biochemical and Pathological Derangements of the Gastrointestinal Tract following Acute and Chronic Ingestion of Ethanol.- A. Introduction.- B. Absorption of Ethanol in the Stomach and Intestine.- C. Ethanol and Gastric Emptying.- D. Ethanol and Gastric Secretion.- E. Effects of Ethanol on Gastric Mucosal Permeability, Transmural Ion Transport, Mucosal Potential Differences, and Blood Flow.- F. Effect of Ethanol on Breaking the Mucosal Barrier, Back Diffusion of Hydrogen Ions, and Leakage of Serum Proteins.- G. Gastric Injury Due to Acute Intake of Ethanol.- H. Alcoholism and Chronic Gastric Mucosal Injury.- I. Effects of Ethanol on Intestinal Transport of Nutrients and Synthesis of Triglycerides.- J. Effects of Ethanol on Intestinal Enzymes and Intermediate Metabolism.- K. Effects of Acute and Chronic Ethanol Administration on the Morphology of the Small Intestinal Mucosa and Intestinal Motility.- L. Alcoholism and Vitamin Deficiencies.- M. Summary and Conclusions.- N. References.- 23 Hyperlipemic Effects of Ethanol.- A. Introduction.- B. Factors Involved in Ethanol-Induced Changes in Plasma Lipids.- C. Clinical Implications of the Ethanol-Induced Changes in Plasma Lipids.- D. Summary and Conclusions.- E. References.- 24 Ethanol, Lipids, and Adipose Tissue Metabolism.- A. Introduction.- B. Normal Adipose Tissue Function.- C. Effects of Ethanol on Adipose Tissue Function.- D. Ethanol Metabolism in Adipose Tissue.- E. Summary and Conclusions.- F. References.- 25 Metabolic and Pathological Changes in Muscle during Acute and Chronic Administration of Ethanol.- A. Introduction.- B. Clinical and Morphologic Features.- C. Experimental Studies.- D. Summary and Conclusions.- E. References.- 26 Ethanol and the Immune Response.- A. Introduction.- B. Ethanol and Cellular Immunity.- C. Ethanol and Humoral Immunity.- D. Ethanol and Complement.- E. Summary and Conclusions.- F. References.- 27 Effect of Ethanol on Chromosomal Structure and Function.- A. Introduction.- B. Ethanol as a Mutagenic Agent in Plants.- C. Ethanol as a Mutagenic Agent in Animals.- D. Ethanol as a Teratogenic Agent.- E. Ethanol as a Carcinogenic Agent.- F. Ethanol as a Chromosome-Damaging Agent in Human and Mammalian Cells in Vitro.- G. Chromosome Damage in Alcoholics.- H. Factors Which Could Lead to the Elevation of the Frequency of Chromosomal Damage in Alcoholics.- I. Summary and Conclusions.- J. References.- 28 Biochemical Abnormalities Accompanying Alcoholism: Implications for the Clinical Diagnosis of Acute and Chronic Intoxication with Ethanol.- A. Introduction.- B. Tests Associated with Acute Intoxication.- C. Indirect Tests Associated with Chronic Intoxication.- D. Summary and Conclusions.- E. References.