Abstract
Forty autopsy livers from Japanese individuals were studied concerning alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) isozymes using electrophoretic and enzyme assay methods. A remarkably high frequency (85%) was found for the atypical ADH phenotype. The gene frequencies of ADH22 and ADH32 were .625 and .05, respectively. The usual ALDH phenotype showed two major isozyme bands, a faster migrating (low Km for acetaldehyde) and a slower migrating isozyme (high Km for acetaldehyde). Fifty-two percent of the specimens had an unusual phenotype of ALDH, which showed only the slower migrating isozyme. The usual phenotype was inhibited about 20%--30% by disulfiram and the unusual type up to 90%. Such a high incidence in the Japanese of the unusual phenotype, which lacks in the low Km isozyme, suggests that the initial intoxicating symptoms after alcohol drinking in these subjects might be due to delayed oxidation of acetaldehyde rather than its higher-than-normal production by typical or atypical ADH.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Azevedo E. S., Da Silva C. B., Tavares-Neto J. Human alcohol dehydrogenase ADH1, ADH2 and ADH3 loci in a mixed population of Bahia, Brazil. Ann Hum Genet. 1976 Jan;39(3):321–327. doi: 10.1111/j.1469-1809.1976.tb00136.x. [DOI] [PubMed] [Google Scholar]
- Fukui M., Wakasugi C. Liver alcohol dehydrogenase in a Japanese population. Nihon Hoigaku Zasshi. 1972 Jan;26(1):46–51. [PubMed] [Google Scholar]
- Goedde H. W., Agarwal D. P., Harada S. Alcohol metabolizing enzymes: studies of isozymes in human biopsies and cultured fibroblasts. Clin Genet. 1979 Jul;16(1):29–33. doi: 10.1111/j.1399-0004.1979.tb00845.x. [DOI] [PubMed] [Google Scholar]
- Greenfield N. J., Pietruszko R. Two aldehyde dehydrogenases from human liver. Isolation via affinity chromatography and characterization of the isozymes. Biochim Biophys Acta. 1977 Jul 8;483(1):35–45. doi: 10.1016/0005-2744(77)90005-5. [DOI] [PubMed] [Google Scholar]
- Harada S., Agarwal D. P., Goedde H. W. Human liver alcohol dehydrogenase isoenzyme variations. Improved separation methods using prolonged high voltage starch-gel electrophoresis and isoelectric focusing. Hum Genet. 1978 Jan 19;40(2):215–220. doi: 10.1007/BF00272304. [DOI] [PubMed] [Google Scholar]
- Harada S., Agarwal D. P., Goedde H. W. Isozyme variations in acetaldehyde dehydrogenase (e.c.1.2.1.3) in human tissues. Hum Genet. 1978 Oct 31;44(2):181–185. doi: 10.1007/BF00295411. [DOI] [PubMed] [Google Scholar]
- Korsten M. A., Matsuzaki S., Feinman L., Lieber C. S. High blood acetaldehyde levels after ethanol administration. Difference between alcoholic and nonalcoholic subjects. N Engl J Med. 1975 Feb 20;292(8):386–389. doi: 10.1056/NEJM197502202920802. [DOI] [PubMed] [Google Scholar]
- Petersen D. R., Collins A. C., Deitrich R. A. Role of liver cytosolic aldehyde dehydrogenase isozymes in control of blood acetaldehyde concentrations. J Pharmacol Exp Ther. 1977 May;201(2):471–481. [PubMed] [Google Scholar]
- Raskin N. H. Editorial: Alcoholism or acetaldehydism? N Engl J Med. 1975 Feb 20;292(8):422–423. doi: 10.1056/NEJM197502202920811. [DOI] [PubMed] [Google Scholar]
- Schenker T. M., Teeple L. J., Von Wartburg J. P. Heterogeneity and polymorphism of human-liver alcohol dehydrogenase. Eur J Biochem. 1971 Dec;24(2):271–279. doi: 10.1111/j.1432-1033.1971.tb19681.x. [DOI] [PubMed] [Google Scholar]
- Smith M., Hopkinson D. A., Harris H. Alcohol dehydrogenase isozymes in adult human stomach and liver: evidence for activity of the ADH 3 locus. Ann Hum Genet. 1972 Mar;35(3):243–253. doi: 10.1111/j.1469-1809.1957.tb01398.x. [DOI] [PubMed] [Google Scholar]
- Smith M., Hopkinson D. A., Harris H. Developmental changes and polymorphism in human alcohol dehydrogenase. Ann Hum Genet. 1971 Feb;34(3):251–271. doi: 10.1111/j.1469-1809.1971.tb00238.x. [DOI] [PubMed] [Google Scholar]
- Smith M., Hopkinson D. A., Harris H. Studies on the properties of the human alcohol dehydrogenase isozymes determined by the different loci ADH1, ADH2, ADH3. Ann Hum Genet. 1973 Jul;37(1):49–67. doi: 10.1111/j.1469-1809.1973.tb01814.x. [DOI] [PubMed] [Google Scholar]
- Stamatoyannopoulos G., Chen S. H., Fukui M. Liver alcohol dehydrogenase in Japanese: high population frequency of atypical form and its possible role in alcohol sensitivity. Am J Hum Genet. 1975 Nov;27(6):789–796. [PMC free article] [PubMed] [Google Scholar]
- von Wartburg J. P., Papenberg J., Aebi H. An atypical human alcohol dehydrogenase. Can J Biochem. 1965 Jul;43(7):889–898. doi: 10.1139/o65-102. [DOI] [PubMed] [Google Scholar]