The role of alcohol dehydrogenase and aldehyde dehydrogenase isozymes in alcohol metabolism, alcohol sensitivity, and alcoholism.
Isozymes of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were studied in human organs and tissues using sensitive analytical techniques. Both ADH and ALDH showed an extensive polymorphism among different racial groups. In liver extracts and other tissues of Japanese an isozyme of ALDH (ALDH I) with a low Km for acetaldehyde was found to be deficient. The ALDH isozyme deficiency might account for the marked initial sensitivity to alcohol in Orientals owing to their impaired acetaldehyde oxidizing capacity. Significantly low erythrocyte ALDH activity was noted more frequently in chronic alcoholics than in healthy controls. After subcellular fractionation of livers from alcoholics a preferential damage of mitochondrial ALDH isozyme was observed. The metabolism of acetaldehyde has received considerable attention in the past few years, owing to the toxic effects of this substance. Rapid progress has been made in the understanding of the multiple molecular forms of ADH and ALDH in human tissues. Our recent studies have demonstrated that the isozymes of ALDH may play an important role in the pathogenesis of alcohol-related organ damage and in the biological sensitivity to alcohol in certain ethnic groups. A possible protection of ALDH I deficiency against alcoholism in Japanese has been discussed. More recent reports [Imprain et al, 1982; Jones, 1982] indicate that, in addition to the enzymatically active ALDH II, tissues from Orientals deficient in ALDH I isozyme contain enzymatically inactive, immunologically cross-reactive material homologous with ALDH I. Thus, the absence of ALDH I isozyme is not due to a regulatory mutation, a gene deletion, or a nonsense mutation, but probably results from a structural mutation.(ABSTRACT TRUNCATED AT 250 WORDS)
D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D000435:Alcoholic Intoxication / Q000235:genetics*; D000437:Alcoholism / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D000444:Aldehyde Dehydrogenase; D000445:Aldehyde Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism*; D014644:Genetic Variation; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D007564:Japan; D008099:Liver / Q000201:enzymology; D009928:Organ Specificity; D011110:Polymorphism, Genetic
D007527:Isoenzymes; D000431:Ethanol; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D000445:Aldehyde Oxidoreductases; D000444:Aldehyde Dehydrogenase