Research on alcohol metabolism: a historical perspective.

The primary enzymatic steps in ethanol metabolism to acetaldehyde, acetate and CO2 + water have been known for many decades, but only a few clinical implications were recognized, such as the risk of malnutrition due to use of alcohol as a source of calories, and the use of disulfiram and other ALDH blockers in the treatment of alcoholism. In the last four decades, however, further understanding of alcohol metabolism has led to recognition of the changes secondary to altered NAD:NADH ratio; to ethanol oxidation by, and induction of, the microsomal cytochrome P450IIE1 system; to fatty acid ethyl ester formation; to the increase in hepatic O2 consumption; and to the formation of acetaldehyde-protein adducts and antibodies to these. This new knowledge has led to important progress in relation to the pathogenesis and treatment of alcoholic liver disease, and to potentially valuable new diagnostic procedures for detecting heavy drinking and incipient alcoholic tissue damage. These advances demonstrate strikingly how basic research into fundamental biological processes can yield important and unanticipated practical benefits.