Alcoholism pp 127-138 | Cite as

Genetic Polymorphisms of Alcohol Metabolizing Enzymes and Their Significance for Alcohol-Related Problems

  • A. Yoshida
Part of the NATO ASI Series book series (NSSA, volume 206)


Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) isozymes not only play a role in alcohol detoxification, but also participate in metabolism of neurotransmitters, fatty acids and glutathione, and in clearance of biogenic toxic substances. Genetic abnormalities, and consequent alteration of activity and kinetic properties of any one of the ADH and ALDH isozymes would potentially affect one’s sensitivity to alcohol and vulnerability in developing alcohol-related problems.


Aldehyde Dehydrogenase Alcoholic Liver Disease Ethanol Oxidation Restriction Fragment Length Polymorphism ALDH2 Gene 
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  1. Blum, K., Noble, E. P., Sheridan, P. J., Montgomery, A., Ritchie, T., Jagadeeswaran, P., Nogami, H., Briggs, A. H., and Cohn, J. B., 1990, Allelic association of human dopamine D2 receptor gene in alcoholism, JAMA, 263: 2055.PubMedCrossRefGoogle Scholar
  2. Consalvi, V., Mdrdh, G., and Vallee, B. L., 1986, Human alcohol dehydrogenases and serotonin metabolism, Biochem.Biophys.Res.Comm., 139: 1009.PubMedCrossRefGoogle Scholar
  3. Eckey, R., Agarwal, D. P., Saha, N., and Goedde, H. W., 1986, Detection and partial characterization of a variant of cytosolic aldehyde dehydrogenase isozyme, Hum.Genet. 72: 95.PubMedCrossRefGoogle Scholar
  4. Esterbauer, H., Zollner, H., and Lang, J., 1985, Metabolism of the lipid peroxidation product 4-hydroxynonenal by isolated hepatocytes and liver cytosolic fractions, Biochem.J., 228: 363.PubMedGoogle Scholar
  5. Frezza, M., di Padova, C., Possato, G., Terpin, M., Baraona, E., and Lieber, C. S., 1990, High blood alcohol levels in women: The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism, New Eng.J.Med., 322: 95.PubMedCrossRefGoogle Scholar
  6. Goedde, H. W., Agarwal, D. P., Harada, S., Rothhammer, F., Whittaker, J.O., and Lisker, R., 1986, Aldehyde dehydrogenase polymorphism in North American, South American and Mexican Indian populations, Am.J.Hum.Genet. 38: 395.PubMedGoogle Scholar
  7. Hafer, G., Agarwal, D. P., and Goedde, H. W., 1987, Human brain aldehyde dehydrogenase: Activity with DOPAL and isozyme distribution, Alcohol, 4: 413.PubMedCrossRefGoogle Scholar
  8. Harada, S., 1990, Genetic polymorphism of aldehyde dehydrogenase and its physiological significance to alcohol metabolism, Prog.Clin.Biol.Res., 344: 289.PubMedGoogle Scholar
  9. Harada, S., Muramatsu, T., and Agarwal, D. P., and Goedde, H. W., 1989, Polymorphism of aldehyde dehydrogenase in human saliva, Prog.Clin.Biol. Res., 190: 133.Google Scholar
  10. Hsu, L. C., Bendel, R. E., and Yoshida, A., 1987, Direct detection of usual and atypical alleles on human aldehyde dehydrogenase-2 (ALDH2) locus, Am.J. Hum.Genet., 41: 1987Google Scholar
  11. Hsu, L. C., Chang, W-C., and Yoshida, A., 1989, Cloning of a new human aldehyde dehydrogenase gene and comparison with liver cytosolic ALDH1 and mitochondria) ALDH2 genes, Am.J.Hum.Genet., 45: A196.Google Scholar
  12. lkuta, T., Shibuya, A., and Yoshida, A., 1988, Direct determination of usual (Caucasian type) and atypical (Oriental type) alleles of class I human alcohol dehydrogenase-2 locus, Bioch.Genet., 26: 519.CrossRefGoogle Scholar
  13. Julià, P., Farrés, J., and Parés, X., 1987, Characterization of three isozymes of rat alcohol dehydrogenase: Tissue distribution and physical and enzymatic properties, Eur.J.Bioch., 162: 179.CrossRefGoogle Scholar
  14. Keung, W-M., 1988, A genuine organ specific alcohol dehydrogenase from hamster testes: Isolation, characterization and developmental changes, Bioch.Biophys.Res.Comm., 156: 38.CrossRefGoogle Scholar
  15. Koivusalo, M., Baumann, M., and Votila, L., 1989, Evidence for the identity of glutathione-dependent formaldehyde dehydrogenase and class III alcohol dehydrogenase, FEBS Lett., 257: 105.PubMedCrossRefGoogle Scholar
  16. Li, T. K., Bosron, W. F., Defeldecker, W. P., Lange, L. G., and Vallee, B. L., 1977, Isolation of n-alcohol dehydrogenase of human liver: Is it a determinant of alcoholism?, Proc.Natl.Acad.Sci.U.S.A., 74: 4378.PubMedCrossRefGoogle Scholar
  17. Màrdh, G., and Vallee, B. L., 1986, Human class I alcohol dehydrogenase catalyze the interconversion of alcohols and aldehydes in the metabolism of dopamine, Biochem., 25: 7279.CrossRefGoogle Scholar
  18. Märdh, G., Falchuck, K. H., Auld, D. S., and Vallee, B. L., 1986, Testosterone allosterically regulates ethanol oxidation by homo-and heterodimeric y-subunitcontaining isozymes of human alcohol dehydrogenase, Proc.Natl.Acad.Sci.U.S.A., 83: 2836.PubMedCrossRefGoogle Scholar
  19. O’Dowd, B. F., Rothhammer, F., and Israel, Y., 1990, Genotyping of mitochondrial aldehyde dehydrogenase locus of native South American Indians, Alcoholism Clin.Exp.Res., in press.Google Scholar
  20. Ryzlak, M. T., and Pietruszko, R., 1987, Purification and characterization of aldehyde dehydrogenase from human brain, Arch.Bioch.Biophys., 255: 409.CrossRefGoogle Scholar
  21. Ryzlak, M. T., and Pietruszko, R., 1989, Human brain glyceraldehyde-3-phosphate dehydrogenase, succinic semialdehyde dehydrogenase and aldehyde dehydrogenase isozymes: Substrate specificity and sensitivity to disulfiram, Alcoholism:Clin.Exp.Res., 13: 755.CrossRefGoogle Scholar
  22. Shibuya, A., and Yoshida, A., 1988a, Frequency of the atypical aldehyde dehydrogenase-2 gene (ALDH22) in Japanese and Caucasians, Am.J.Hum.Genet., 43: 741.PubMedGoogle Scholar
  23. Shibuya, A., and Yoshida, A., 1988b, Genotypes of alcohol metabolizing enzymes in Japanese with alcoholic liver disease: A strong association of the usual Caucasian type aldehyde dehydrogenase gene (ALDH21) with the disease, Am.J.Hum.Genet., 34: 744.Google Scholar
  24. Shibuya, A., Yasunami, M., and Yoshida, A., 1989, Genotypes of alcohol dehydrogenase and aldehyde dehydrogenase loci in Japanese alcohol flushers and non-flushers, Hum.Genet., 82: 14.PubMedCrossRefGoogle Scholar
  25. Singh, S., Fritz, G., Fang, B., Harada, S., Paik, Y. K., Eckey, R., Agarwal, D. P., and Goedde, H. W., 1989, Inheritance of mitochondrial aldehyde dehydrogenase: Genotyping in Chinese, Japanese and South Korean families reveals dominance of the mutant allele, Hum.Genet., 83: 119.PubMedCrossRefGoogle Scholar
  26. Wagner, F. W., Burger, A. R., and Vallee, B. L., 1983, Kinetic properties of human liver alcohol dehydrogenase: Oxidation of alcohols by class I isozymes, Biochem., 22: 1857.CrossRefGoogle Scholar
  27. Wolff, P. H., 1973, Vasomotor sensitivity to alcohol in diverse Mongoloid populations, Am.J.Hum.Genet., 25: 193.PubMedGoogle Scholar
  28. Yin, S-J., Cheng, T-C., Chang, C-P., Chen, Y-J., Chao, Y-C., Tang, H-S., Chang, T-M., and Wu, C-W., 1988, Human stomach alcohol and aldehyde dehydrogenase (ALDH): A genetic model proposed for ALDH III isozymes, Bioch.Genet., 26: 345.Google Scholar
  29. Yoshida, A., 1983, A possible structural variant of human cytosolic aldehyde dehydrogenase with diminished activity, Am.J.Hum.Genet., 35: 1115.Google Scholar
  30. Yoshida, A., and Chen, S-H., 1989, Restriction fragment length polymorphism of human aldehyde dehydrogenase 1 and aldehyde dehydrogenase 2 loci, Hum. Genet., 83: 204.PubMedCrossRefGoogle Scholar
  31. Yoshida, A., Hsu, L. C., and Yasunami, M., 1990, Genetics of human alcoholmetabolizing enzymes, in: “Progress in Nucleic Acid Research and Molecular Biology,” W. Cohn and K. Moldave, eds., Academic Press, Orlando, in press.Google Scholar
  32. Yoshida, A., Shibuya, A., Davé, V., Nakayama, M., and Hayashi, A., 1990, Developmental changes of aldehyde dehydrogenase isozymes in human livers: Mitochondrial ALDH2 isozyme is expressed in fetal livers, Experientia, in press.Google Scholar
  33. Yoshida, A., Ward, R. J., and Peters, T. J., 1989, Cytosolic aldehyde dehydrogenase (ALDH1) variants found in alcohol flushers, Ann.Hum.Genet., 53: 1.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • A. Yoshida
    • 1
  1. 1.Department of Biochemical GeneticsBeckman Research Institute of the City of HopeDuarteUSA

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