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Factors Contributing to the Adaptive Increase in Ethanol Metabolism due to Chronic Consumption of Ethanol
Author(s) -
Cederbaum Arthur I.,
Dicker Elisa,
Lieber Charles S.,
Rubin Emanuel
Publication year - 1977
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1977.tb05762.x
Subject(s) - ethanol , acetaldehyde , ethanol metabolism , chemistry , alcohol dehydrogenase , biochemistry , ouabain , microsome , metabolism , medicine , alcohol , endocrinology , biology , enzyme , organic chemistry , sodium
SUMMARY Chronic ethanol consumption, in a diet which leads to a fatty liver, results in an increase in the rate of ethanol oxidation in isolated rat hepatocytes. The percent increase (30%‐40%) is similar to that previously found in vivo, in the same model system. 1,11 This increase does not correlate with the activity of alcohol dehydrogenase, which was slightly decreased after chronic ethanol consumption. 1,16 The increase in ethanol oxidation is not associated with a hypermetabolic state of the liver since oxygen consumption with a variety of substrates was not enhanced after chronic ethanol consumption. Approximately 40%‐50% of this increase persists in the presence of an inhibitor of alcohol dehydrogenase, inhibitors of mitochondrial oxygen consumption and inhibitors of the malate‐aspartate shuttle. The increase persists in the presence of ouabain, dinitrophenol and various shuttle metabolites (in the presence and absence of dinitrophenol). Chronic consumption of ethanol results in hypertrophy of the smooth endoplasmic reticulum and an adaptive increase in the ability of microsomal preparations to oxidize ethanol to acetaldehyde. 1,11 The fact that part of the increase in ethanol oxidation which occurs after chronic ethanol administration persists in the presence of the various additives discussed above, indicates that pathways that are independent of alcohol dehydrogenase contribute to this metabolic adaptation. These data extend the observation that the metabolic adaptation found after chronic ethanol consumption was not abolished by 2mM pyrazole. 1,26