Alcohol dehydrogenase: enzymology and metabolism.
Alcohol dehydrogenase (ADH), the principal enzyme responsible for ethanol oxidation, constitutes a complex family in humans. Based on structural and kinetic features, ADH can be divided into five classes. Low-Km class I beta-ADH and gamma-ADH show genetic polymorphism among racial populations. The allozymes exhibit distinct maximal activities due to single amino acid exchanges at different sites in the coenzyme-binding domain. Class IV mu-ADH also shows ethnic variability: it is detected in the stomach mucosa of Caucasians but not detectable in about 70% of Orientals. Class I, II, IV and V ADH isozymes exhibit tissue-specific distribution. Approximately 50% of Orientals lack the activity of the mitochondrial low-Km aldehyde dehydrogenase (ALDH2). Ethanol- and acetaldehyde-oxidizing activities of the liver, lung, and gastrointestinal tract appear to be correlated with their isozyme patterns of ADH and ALDH and with the allozymes. The frequencies of the alleles ADH(2)2 and ADH(3)1, coding for the high-Vmax beta 2- and gamma 1-ADH respectively, and of the mutant ALDH(2)2 in the Oriental subjects with alcoholism or alcoholic cirrhosis are significantly lower than those in healthy controls. These genotyping results support the current notion that genetic variation in ADH and ALDH may influence drinking behavior and susceptibility for alcoholism and possibly alcohol-induced organ injury by modulating the rate of metabolism of ethanol and acetaldehyde.
Yin
S J
SJ
Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, Republic of China.
D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000437:Alcoholism / Q000201:enzymology* / Q000235:genetics; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000483:Alleles; D000431:Ethanol / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D007700:Kinetics; D008104:Liver Cirrhosis, Alcoholic / Q000201:enzymology / Q000235:genetics; D011110:Polymorphism, Genetic; D014018:Tissue Distribution
D000431:Ethanol; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase