Alcohol Metabolism, Alcohol Intolerance, and Alcoholism

1 Introduction.- 2 Alcohol Metabolism: Biochemistry and Genetic Variations.- 2.1Absorption, Body Distribution, and Elimination of Ethanol.- 2.1.1 Absorption.- 2.1.2 Tissue Distribution.- 2.1.3 Excretion and Elimination.- 2.2 Biochemical Pathways of Ethanol Degradation.- 2.2.1 Microsomal Ethanol-Oxidizing System.- 2.2.2 Catalase.- 2.2.3 Alcohol Dehydrogenase (ADH).- 2.2.4 Aldehyde Dehydrogenase (ALDH).- 3 Alcohol-Metabolizing Enzymes and Acute Reactions to Alcohol.- 3.1Ethanol- and Acetaldehyde-Mediated Acute Response to Alcohol.- 3.2 Ethnic Differences in Acute Response to Alcohol 53.- 3.2.1 Familial Resemblances in Flushing Response.- 3.3 Mechanism of Alcohol Sensitivity.- 3.3.1 Relationship to Ethanol- and Acetaldehyde-Oxidizing Capacity.- 3.3.2 Alcohol Absorption Rate.- 3.3.3 Alcohol Metabolism and Clearance Rate.- 3.3.4 Variation in ADH.- 3.3.5 Variation in ALDH.- 3.3.6 Prostaglandin- and Histamine-Mediated Flushing Reactions to Alcohol.- 3.4 Racial-Ethnic Patterns of Alcohol Abuse and Alcoholism.- 3.4.1 Drinking Patterns and Ethnic Background.- 3.4.2 Correlations Between Flushing Response, ALDHI Isozyme Abnormality, Alcohol Use, and Alcoholism.- 3.4.3 Aldehyde Dehydrogenase I Isozyme Abnormality and Alcoholism.- 3.4.4 Gene-Culture Coevolution of Alcohol Usage.- 3.4.5 Implications.- 4Biochemical Aspects of Alcoholism.- 4.1 Alcohol-Related Metabolic Derangements.- 4.1.1 Organ Dysfunction.- 4.2 Metabolic Changes.- 4.2.1 Lipid Metabolism.- 4.2.2 Protein Metabolism.- 4.2.3 Carbohydrate Metabolism.- 4.2.4 Endocrine Effects of Alcohol.- 4.2.5 Carcinogenetic and Mutagenic Effects of Ethanol.- 4.3Changes in Alcohol-Metabolizing Enzymes in Alcohol-Related Disorders.- 4.3.1 Alcohol Dehydrogenase.- 4.3.2 Microsomal Ethanol-Oxidizing System.- 4.3.3 Aldehyde Dehydrogenase.- 4.4Biochemical Markers of Alcohol Abuse and Alcoholism.- 4.4.1 Conventional Markers.- 4.4.2 Test Combinations.- 4.4.3 Coming Markers.- 5Neuropsychopharmacology of Alcoholism.- 5.1 Alcohol Effects in the CNS.- 5.1.1 Electrophysiological Actions of Ethanol.- 5.1.2Neuropsychological Impairments in Alcoholics.- 5.2Addiction, Tolerance, and Dependence.- 5.2.1 Biochemical Basis of Addiction to Ethanol.- 5.2.2 Biogenic Amine-Aldehyde Condensation Products.- 5.2.3 Membrane Actions.- 5.2.4 Alcohol and Neurotransmitters.- 5.2.5 Neuropeptide Effects on Tolerance.- 5.2.6 Role of Prostaglandins in Alcoholism.- 5.3Metabolic Factors.- 5.3.1 Alcohol Metabolism in the Brain.- 5.3.2 Acetaldehyde Metabolism in the Brain.- 5.3.3 Metabolism of Biogenic Aldehydes.- 6Genetic Factors in Alcoholism.- 6.1 Ethnic and Cultural Variables.- 6.2 Familial and Nonfamilial Alcoholism.- 6.3 Genetic Contributions.- 6.3.1 Family Studies.- 6.3.2 Adoption Studies.- 6.3.3 Twin Studies.- 6.3.4 What Is Inherited.- 6.3.5 Mode of Inheritance.- 6.4Genetic and Environmental Interactions in Alcoholism.- 6.5Biological Mediators of Alcoholism.- 6.5.1 Biomedical Markers of Alcoholism.- 6.5.2 Characterization of High-Risk and Low-Risk Individuals.- 6.5.3 Some Baseline Metabolic Differences Presaging Alcoholism.- 6.5.4 Neurophysiological and Neuropsychological Differences.- 6.5.5 Metabolic Variables.- 6.5.6 Genetic and Serological Markers of Alcoholism.- 6.5.7 Altered Alcohol Metabolism.- 6.5.8 Adenylate Cyclase.- 7Experimental Section.- 7.1Subjects and Materials.- 7.1.1 Patients.- 7.1.2 Healthy Subjects.- 7.1.3 Biopsy Material.- 7.1.4 Autopsy Material.- 7.1.5 Blood Samples.- 7.1.6 Hair Root Follicles.- 7.2Methods.- 7.2.1 Alcohol Sensitivity Questionnaire.- 7.2.2 Alcohol Dehydrogenase.- 7.2.3 Aldehyde Dehydrogenase.- 7.2.4 Protein Determination.- 7.2.5 Separation of Erythrocytes Based on Cell Age.- 7.2.6 Densitometry.- 7.2.7 Cloning and Sequencing of ALDH I-cDNA.- 7.2.8 Chromosomal Localization of ALDH I Isozyme.- 7.2.9 Genotyping of ALDH I Alleles.- References 145.- Subject Index 179.