Biochemical and Genetic Studies in ALDH1-Deficient Subjects
At least nine isoenzymes of aldehyde dehydrogenase (E.C.184.108.40.206.) have been identified in man based on their enzymatic characteristics and physiochemical properties (Yoshida et al., 1990). Liver mitochondrial aldehyde dehydrogenase (ALDH2) probably plays a major role in acetaldehyde metabolism as its low km (1–2μM) is compatible with the circulating acetaldehyde levels after alcohol ingestion in both normal subjects and alcohol abusers (Arthur et al.,1984: Schumate et al., 1967; Kelding et al., 1983; Mezey and Tubon, 1971; Peters et al.,1987). The ALDH2 gene is 44 kbp in length and contains at least 12 exons which encode 517 amino acid residues (Hsu et al., 1988). These precisely match the reported protein sequence of ALDH2 (Hempel et al., 1985). A point mutation (C→A) leads to the formation of an enzymatically inactive subunit in exon 12 of the genetic sequence (Yoshida et al., 1984). This occurs in over 50% of Orientals (Goedde et al., 1979) and such individuals suffer an alcohol-flush reaction after ingestion of small amounts of ethanol. This is attributable to high circulating acetaldehyde concentrations (in excess of 15 µmol) and causes clinical symptoms such as increase in blood pressure and pulse rate (Wolffe, 1973).
KeywordsAldehyde Dehydrogenase ALDHI Activity ALDH2 Gene Alcohol Sensitivity Acetaldehyde Metabolism
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- Goedde, H.W., Harada, S. and Agarwal, D.P., 1979, Racial differences in alcohol sensitivity: a new hypothesis. Hum. Genet., 5: 331–334.Google Scholar
- Haroda,S., Agarwal, D.P. and Goedde, H.W., 1982, Human aldehyde dehydrogenase: 3,4-dihydroxy-phenyl-acetaldehyde metabolizing isoenzymes. In: Enzymology of Carbonyl Metabolism’, Vol. 1. Ed. H. Weiner & B. Wermuth Publ. A.R.Liss New York, USA pp 147–153.Google Scholar
- Peters, T.J., Ward, RJ., Rideout, J. and Lim, C.K., 1987, Blood acetaldehyde and ethanol levels in alcoholism, in: ‘Genetics and Alcoholism’, Ed Goedde, H.W. & Agarwal, D.P. Publ. A.Liss New York USA. pp 215–230.Google Scholar
- Tipton, K.F., Henehan, G.T.M. and Harrington, M.C., 1989, Cellular and intracellular distribution of aldehyde dehydrogenases. in: ‘Human Metabolism of Alcohol’, Vol 2. ed K.E.Crow & R.D.Batt. Publ. CRC.Press Boca Raton. pp 105–116.Google Scholar
- Wolffe, P.H., 1973, Vasomotor sensitivity to alcohol in diverse mongoloid populations. Amer J Hum Genet., 25: 193–199.Google Scholar
- Yoshida, A., 1990, Genetic polymorphisms of alcohol metabolizing enzymes and their significance for alcohol-related problems, in: ‘Alcoholism: A Molecular Perspective’, ed. T.N.Palmer, Publ Plenum U.K. pp 118–128.Google Scholar