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Lecturer Dr. Arthur Cederbaum Mount Sinai School of Medicine Department of Biochemistry Box 1020 One Gustave Levy Place New York, NY 10029 (212) 241-7285 acederb@smtplink.mssm.edu
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Lecturer Dr. Arthur Cederbaum Mount Sinai School of Medicine Department of Biochemistry Box 1020 One Gustave Levy Place New York, NY 10029 (212) 241-7285 acederb@smtplink.mssm.edu
Editor |
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The overall goal is to describe the pathways and factors which modulate blood alcohol levels and ethanol metabolism and describe how the body disposes of ethanol and its metabolites.
The various factors which play a role in the distribution of ethanol in the body, influence the absorption of ethanol when orally administered and contribute to first pass metabolism of ethanol will be described.
Most ethanol is oxidized in the liver and general principles and overall mechanisms for ethanol oxidation will be summarized. The kinetics of ethanol elimination in-vivo will be described as will various genetic and environmental factors which can modify the rate of ethanol metabolism.
The enzymatic pathways responsible for ethanol metabolism will be described, in particular, the properties and frequency of the human alcohol dehydrogenase alleles. Rate-limiting steps in the overall metabolism of ethanol, including the capacity and activity of alcohol dehydrogenase isoforms, and the necessity to reoxidize NADH by substrate shuttle pathways and the mitochondrial respiratory chain will be discussed.
The impact of ethanol metabolism on other liver metabolic pathways, on the hepatic redox state and on cytochrome P450-dependent metabolism of xenobiotics and drugs will be briefly described. Factors playing a role in the metabolic adaptation i.e., increased rate of ethanol metabolism by chronic alcoholics will be discussed.
Metabolism of acetaldehyde, the initial product formed by all biochemical pathways of ethanol metabolism will be summarized. The role of acetaldehyde in the toxic actions of ethanol and ethanol drinking behavior will be discussed.
Various factors which influence accurate determination of blood or breath alcohol levels and therefore complicate satisfactory forensic analyses will be described.
Despite much knowledge of ethanol pharmacokinetics and metabolism, numerous questions remain for further evaluation and research, including what regulates ethanol metabolism in-vivo, the role of ethanol metabolites in organ damage, functions and physiological substrates of the various ADH isoforms, population and gender differences in ethanol metabolism, developing markers to identify individuals susceptible to alcohol and other considerations are discussed.
