Biochemical Pharmacology of Ethanol

Mammalian Liver Alcohol Dehydrogenases.- 1. Physical and Chemical Properties of Alcohol Dehydrogenases from Livers of Horse, Man and Rat.- a. Molecular Weight, Subunit Composition, Ultraviolet Absorption, Catalytic Sites Per Mole, Zn++ Content, Sulfhydryl Groups, End Groups, Residues Per Subunit, Heterogeneity.- b. The Role of Zinc.- c. X-ray Crystallography.- d. Coenzyme Binding.- e. Conformational Changes.- f. Ternary Complexes: Significance and Use.- g. Substrate Specificity.- h. Catalytic Mechanism.- 2. Structure-Function Relationship in Isoenzymes.- a. Alcohol Dehydrogenase from Horse Liver.- b. Alcohol Dehydrogenase from Human Liver.- c. Alcohol Dehydrogenase from Rat, Rhesus Monkey and Other Species.- d. Significance of Steroid Activity.- Summary.- References.- Microsomal Ethanol Oxidation: Activity in Vitro and in Vivo.- 1. In Vitro Activity.- a. Evidence of Mixed Function Oxidase Activity.- b. Hydrogen Peroxide Dependence of the Ethanol Oxidizing Reaction.- c. The Role of Catalase in MEOS.- d. Separation of Catalase from Microsomal Components.- 2. In Vivo Activity.- 3. Conclusion.- Summary.- References.- Pathways of Ethanol Metabolism in Perfused Rat Liver.- 1. Alcohol Dehydrogenase Pathway.- a. Hydrogen Shuttle Mechanisms.- b. Rate-Limiting Step for the Alcohol Dehydrogenase Reaction.- c. Quantitation of Alcohol Dehydrogenase-Dependent Ethanol Oxidation.- 2. Quantitation of Catalase-Dependent Ethanol Oxidation.- a. Activation of Ethanol Utilization by Hydrogen Peroxide-Generating Substrates.- 3. Microsomal Ethanol Oxidizing System (MEOS).- 4. Adaptive Increase in Ethanol Utilization Following Chronic Ethanol Pretreatment.- Summary.- References.- Rate-Limiting Steps in Ethanol Metabolism and Approaches to Changing These Rates Biochemically.- 1. Metabolism of Ethanol.- 2. Liver Alcohol Dehydrogenase.- 3. Acetaldehyde Dehydrogenase.- 4. Transport and Oxidation of Reducing Equivalents.- 5. Lipogenesis.- 6. Inhibition of Ethanol Metabolism.- 7. Acceleration of Ethanol Metabolism.- Summary.- References.- Metabolic Correlates of Ethanol, Acetaldehyde, Acetate and Methanol in Humans and Animals.- A. Biological Properties of Ethanol.- 1. Ethanol Acts both as a Narcotic and as an Aberrant Nutrient.- 2. Competition for Coenzymes.- 3. Competitive Inhibitions of Enzyme Catalyzed Reactions.- a. Accumulation of Methanol in Ethanol-Drinking Subjects.- b. Biogenic Amine Condensation Products.- c. Shift in the Metabolism of Biogenic Amines.- B. Effects of Ethanol oN Liver Metabolism.- 1. Inhibition of Carbon Dioxide Formation.- 2. Suppression of Respiratory Quotient.- 3. Ethanol Inhibits its Own Intermediary Metabolism.- 4. Effects of Ethanol on the Metabolism of Glucose in the Liver.- C. Comparison of the Effects of Ethanol on Liver and BRAIN Metabolism.- 1. Diverse Effects of Ethanol on Brain and Liver Monoamine Oxidase.- D. Blood Concentrations of Ethanol, Acetaldehyde, Acetate and Methanol During Acute and Chronic Administration of Alcoholic Beverages in Humans and Animals.- 1. Subjects.- 2. Blood Ethanol Levels.- 3. Acetaldehyde.- a. Methodological Considerations.- b. Nonenzymatic Formation of Acetaldehyde.- 4. Acetaldehyde: Human Investigations.- a. Chronic Studies.- b. Acute Studies.- 5. Acetaldehyde: Animal Studies.- a. Methodology.- b. Sex, Strain and Alcohol Preference.- c. Acetaldehyde in Brain.- 6. Acetate.- 7. Methanol Accumulation.- Summary.- References.- Alcohol and Aldehyde Metabolism in Brain.- A. Attempts to Demonstrate Ethanol Metabolism in Brain.- 1. Oxygen Consumption and Carbon Dioxide Production.- 2. Conversion of Ethanol to Amino Acids in Brain.- 3. Histochemical Techniques.- B. Enzymes Which May Metabolize Ethanol in Brain.- 1. Catalase.- 2. Alcohol Dehydrogenase.- 3. Ethanol Metabolism and Redox Changes in Brain.- C. Aldehyde metabolism in Brain — Oxidation and Reduction.- 1. Substrate Specificity and Reaction Mechanism of Aldehyde Dehydrogenase — Oxidation.- 2. Activation and Inhibition of Aldehyde Dehydrogenase, Activity.- 3. Subcellular Distribution and Isozymes of Aldehyde Dehydrogenase.- 4. Reduction of Aldehydes to Alcohols in Brain.- 5. Characteristics of Aldehyde Reductase in Brain.- Summary.- References.- Effects of Ethanol on Brain Metabolism.- Effects on Intermediary Metabolism.- 1. Effects on Glycolysis.- 2. Energy-Rich Phosphates.- 3. Oxygen Consumption.- 4. Carbon Dioxide Production.- 5. Tricarboxylic Acid Cycle Inhibition.- 6. Lipid Metabolism.- 7. Amino Acid and Protein Metabolism.- Summary.- References.- Effects of Ethanol on Protein Synthesis.- A. Cardiac Protein Synthesis, Ethanol and Nutrition.- 1. Amino Acid Availability and Cardiac Protein Synthesis.- 2. Effects of Ethanol or Metabolites on the Heart.- a. Ethanol and Cardiac Metabolic Effects.- b. Ethanol and Cardiac Protein Synthesis.- B. Hepatic Protein Synthesis.- a. Albumin Synthesizing Mechanism.- b. Factors Influencing Hepatic Albumin Production.- c. Clinical Liver Disease.- d. Amino Acids and Nutritional Effects on Albumin Synthesis.- Summary.- References.- The Effects of Aliphatic Alcohols on the Biophysical and Biochemical Correlates of Membrane Function.- 1. Interactions of Alcohols with Membranes.- a. Membrane Protection.- b. Membrane Expansion.- c. Membrane Disordering.- d. Lipid Disorganization.- 2. Alcohols and the Electrical Properties of Membranes and Related Biochemical Events.- 3.Alcohols and the Active Transport of Cations and the Na-K ATPase.- 4. Alcohols and Calcium and Magnesium Metabolism.- 5. Concluding Remarks.- Summary.- References.- Interactions of Ethanol with Cyclic Amp.- 1. Acute Effects of Ethanol on the Cyclic AMP System.- a. Effects of Ethanol on Adenylate Cyclase.- b. Effects of Ethanol on Phosphodiesterases.- c. Effect of Ethanol on ATP Levels and ATPase Activity.- d. Effects of Ethanol on Cyclic AMP Levels.- 2. Changes of the Cyclic AMP System after Chronic Ethanol Administration.- a. Changes in the Central Nervous System.- b. Changes in the Peripheral Organs.- 3. Possible Role of Cyclic AMP in Ethanol Effects.- a. Ethanol-Induced Fatty Liver.- b. Implication of Cyclic AMP System in the Central Effects of Ethanol.- 4. Conclusions.- Summary.- References.- Alcohol, Aldehydes and Biogenic Amines.- 1. Biogenic Amine Catabolism and the Effects of Ethanol and Acetaldehyde.- 2. Effects of Ethanol and Acetaldehyde on Biogenic Amine Turnover and Steady-State Levels in Brain.- 3. Effects of Ethanol on the Uptake of Transmitters by Brain Tissue In Vitro.- 4. The Effect of Ethanol on the Urinary Excretion of the Biogenic Amines and their Metabolites.- Summary.- References.- Formation of Aberrant Neurotransmitters and Its Implication for Alcohol Addiction and Intoxication.- 1. Storage and Release of False Neurotransmitters.- 2. False Neurotransmitters and Alcoholism.- 3. Formation and Inhibition of Tetrahydroisoquinoline Derivatives.- 4. Newer Concepts Related to the Involvement of Biogenic Amines in Alcoholism.- Summary.- References.- Interaction of Biogenic Amines with Ethanol.- 1. Effects of Ethanol on Monamine Metabolism.- 2. Aberrant Neurotransmitters: Hypothetical Role in Alcoholism.- 3. Serotonergic Regulation of Respiratory Depression Induced by Ethanol.- 4. Discussion and Critique.- Summary.- References.- Some Endocrine Aspects of Alcoholism.- 1. The Adrenal Cortex.- 2. Aldosterone.- 3. Cortisol.- 4. Sex Hormone Metabolism.- 5. Insulin.- 6. Miscellaneous.- Summary.- References.- Marihuana VS. Alcohol: A Pharmacologic Comparison.- 1. Drug Classification.- 2. Behavior.- 3. Pharmacology.- 4. Toxicity.- 5. Therapeutic Effects.- Summary.- References.- Induction of Physical Dependence on Alcohol in Rodents.- 1. Experimental Conditions Necessary for Induction of Physical Dependence.- 2. Objective Criteria of Physical Dependence (Physical signs induced by withdrawal).- a. Quantification.- 3. Methods for Induction of Physical Dependence.- a. Criteria.- b. Supplementary Measures.- c. Liquid Diet Procedures.- d. Changes in Behavior.- e. Inhalation of Ethanol.- f. Gastric Intubation.- g. Intravascular Catheterization.- Conclusion.- Summary.- References.- Induction of Physical Dependence Upon Alcohol in Nonhuman Primates.- 1. The Concept of Physical Dependence.- 2. Measurement of Physical Dependence.- 3. Infusion Procedures.- 4. Intubation Procedures.- 5. Nonvolitional Oral Intake.- 6. Miscellaneous Procedures.- 7. Discussion.- Summary.- References.- Genetic Determinants of Alcohol Addiction.- 1. Biological Variation.- 2. Family Studies.- 3. Twin Studies.- 4. Adoption Studies.- 5. Genetic Marker Studies.- 6. Comment.- Summary.- References.- List of Contributors.