Genetics of Human Alcohol and Aldehyde Dehydrogenases

  • Moyra Smith


During the past 5 years considerable progress has been made in the elucidation of the biochemical genetics of human alcohol dehydrogenases (ADH) and human aldehyde dehydrogenases (ALDH). In particular, progress has been made in determining the number of gene loci coding for these enzymes and the tissue distribution of the enzymes. In addition, a number of allelic variants of specific forms of alcohol and aldehyde dehydrogenases have been described. Studies have been done on different population groups to determine the frequencies of some of these variants. The relationship of the presence of variant forms of alcohol and aldehyde dehydrogenases to altered alcohol tolerance has been investigated. Efficient procedures for purifying alcohol and aldehyde dehydrogenases have been defined. As a result, detailed studies on the kinetics of separated isozymes and amino acid sequence determinations have been possible. To date, complete amino acid sequence data have been obtained for three ADH isozymes and one ALDH isozyme, while partial amino acid sequence data have been published on a second ALDH isozyme. Antibodies to specific forms of aldehyde dehydrogenase have been used to determine the nature of the genetic variation in mitochondrial ALDH.


Fetal Liver Aldehyde Dehydrogenase Amino Acid Sequence Data Amino Acid Sequence Determination ADH3 Isozyme 
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  1. Adinolfi, A., and Hopkinson, D. A., 1978, Blue Sepharose chromatography of human alcohol dehydrogenase: Evidence for interlocus and interallelic differences in affinity characteristics, Ann. Hum. Genet. 41:399–407.PubMedCrossRefGoogle Scholar
  2. Adinolfi, A., and Hopkinson, D. A., 1979, Affinity characteristics of human alcohol dehydrogenase (ADH) isozymes, Ann. Hum. Genet. 43:109–119.PubMedCrossRefGoogle Scholar
  3. Adinolfi, A., Adinolfi, M., Hopkinson, D. A., and Harris, H., 1978, Immunological properties of the human alcohol dehydrogenase (ADH) isozymes, J. Immunogenet. 5:283–296.PubMedCrossRefGoogle Scholar
  4. Adinolfi, A., Adinolfi, M., and Hopkinson, D. A., 1984, Immunological and biochemical characterization of the human alcohol dehydrogenase chi ADH isozyme, Ann. Hum. Genet. 48:1–10.PubMedCrossRefGoogle Scholar
  5. Agarwal, D. P., Meier-Tackman, D., Harada, S., and Goedde, H. W., 1981, A search for the Indianapolis variant of human alcohol dehydrogenase in liver samples from Northern Germany and Japan, Hum. Genet. 50:170–171.CrossRefGoogle Scholar
  6. Agarwal, D. P., Tobar-Rojas, L., Harada, S., and Goedde, H. W., 1983, Comparative study of erythrocyte aldehyde dehydrogenase in alcoholics and control subjects, Pharmacol. Biochem. Behav. 18:89–95.PubMedCrossRefGoogle Scholar
  7. Azevedo, E. S., da Silva, M. C., and Tavares-Neto, J., 1975, Human alcohol dehydrogenase ADH1, ADH2, and ADH3 loci in a mixed population of Bahia, Brazil, Ann. Hum. Genet. 39:321–327.CrossRefGoogle Scholar
  8. Bilanchone, V., Duester, G., and Smith, M., 1985, Developmental and tissue specific variation in human class I ADH mRNA, Nucleic Acid Res. (submitted).Google Scholar
  9. Blair, A. H., and Vallee, B. L., 1966, Some catalytic properties of human liver alcohol dehydrogenase isoenzymes, Biochemistry 5:2026–2034.PubMedCrossRefGoogle Scholar
  10. Bosron, W. F., Li, T. K., Dafeldecker, W. P., and Vallee, B. L., 1979a, Human liver pi alcohol dehydrogenase kinetic and molecular properties, Biochemistry 18:1101–1105.PubMedCrossRefGoogle Scholar
  11. Bosron, W. F., Li, T. K., and Vallee, B. L., 1979b, Heterogeneity and new molecular forms of human liver alcohol dehydrogenase, Biochem. Biophys. Res. Commun. 91:1549–1555.PubMedCrossRefGoogle Scholar
  12. Bosron, W. F., Li, T. K., and Vallee, B. L., 1980, New molecular forms of liver alcohol dehydrogenase: Isolation and characterization of ADH Indianapolis, Proc. Natl. Acad. Sci. USA 77:5784–5788.PubMedCrossRefGoogle Scholar
  13. Bosron, W. F., Crabb, D. W., and Li, T. K., 1983a, Relationship between kinetics of liver alcohol dehydrogenase and alcohol metabolism, Pharmacol. Biochem. Behav. 18:223–227.PubMedCrossRefGoogle Scholar
  14. Bosron, W. F., Magnes, L. J., and Li, T. K., 1983b, Human liver alcohol dehydrogenase: ADH Indianapolis results from genetic polymorphism at the ADH2 gene locus, Biochem. Genet. 21:735–744.PubMedCrossRefGoogle Scholar
  15. Bühler, R., Pestalozzi, D., Hess, M., and von Wartburg, J. P., 1983, Localization of alcohol dehydrogenase in human tissue: An immunohistochemical study, Pharmacol. Biochem. Behav. 18:55–59.PubMedCrossRefGoogle Scholar
  16. Bühler, R., Hempel, J., von Wartburg, J. P., and Jornvall, H., 1984a, Atypical human alcohol dehydrogenase: the beta 2 Berne sub-unit has an amino acid exchange that is identical to the one in the beta 2 Oriental chain, FEBS Lett. 173:360–366.PubMedCrossRefGoogle Scholar
  17. Bühler, R., Hempel, J., Kaiser, R., De Zalenski, C., von Wartburg, J. P., and Jornvall, H., 1984b, Human liver alcohol dheydrogenase 2: The primary structure of the gamma 1 protein chain. Eur. J. Biochem. 145:447–453.PubMedCrossRefGoogle Scholar
  18. Bühler, R., Hempel, J., Kaiser, R., von Wartburg, J. P., and Vallee, B. L., 1984c, Human alcohol dehydrogenase: Structural differences between beta and gamma sub-units suggest parallel duplications in isoenzyme evolution and predominant expression of separate gene descendants in livers of different mammals, Proc. Natl. Acad. Sci. USA 81:6320–6324.PubMedCrossRefGoogle Scholar
  19. Carlock, L., Hiroshige, S., and Smith, M., 1985, Assignment of the gene coding for class III ADH to human chromosome 4: 4q21–4q25, Cytogenet. Cell Genet., 46:(in press).Google Scholar
  20. Castle, S. L., and Board, P. G., 1982, Electrophoretic investigation of formaldehyde dehydrogenase in human tissues, Hum. Hered. 32:222–224.PubMedCrossRefGoogle Scholar
  21. Duester, G., Hatfield, G. W., Buhler, R., Hempel, J., Jornvall, H., and Smith, M., 1984, Molecular cloning and characterization of a cDNA for the beta sub-unit of human alcohol dehydrogenase, Proc. Natl. Acad. Sci. USA 81:4055–4059.PubMedCrossRefGoogle Scholar
  22. Duester, G., Hatfield, G. W., and Smith, M., 1985a, Molecular genetic analysis of human alcohol dehydrogenase, Alcohol, 2:53–56.PubMedCrossRefGoogle Scholar
  23. Duester, G., Smith, M., Bilanchone, V., and Hatfield, G. W., 1985b, Organization, structure and expression of the genes encoding human alpha, beta, and gamma alcohol dehydrogenase, J. Biol. Chem. (in press).Google Scholar
  24. Forte-McRobbie, C. M., and Pietruszko, R., 1985, Purification and characterization of a high Km liver aldehyde dehydrogenase, J. Biol. Chem. (in press).Google Scholar
  25. Fukui, M., and Wakasugi, C., 1972, Liver alcohol dehydrogenase in a Japanese population, Jpn. J. Legal Med. 26:46–51.Google Scholar
  26. Goedde, H. W., Harada, S., and Agarwal, D. P., 1979a, Racial differences in alcohol sensitivity: A new hypothesis, Hum. Genet. 51:331–334.PubMedCrossRefGoogle Scholar
  27. Goedde, H. W., Agarwal, D. P., and Harada, S., 1979b, Alcohol metabolizing enzymes: Studies of isozymes in human biopsis and cultured fibroblasts, Clin. Genet. 16:29–33.PubMedCrossRefGoogle Scholar
  28. Greenfield, N. J., and Pietruszko, R., 1977, Two aldehyde dehydrogenases from human liver. Isolation via affinity chromatography and characterization of the isozymes, Biochim. Biophys. Acta 483:35–45.PubMedGoogle Scholar
  29. Harada, S., Agarwal, D. P., and Goedde, H. W., 1978, Human liver alcohol dehydrogenase isoenzyme variations, Hum. Genet. 40:215–220.PubMedCrossRefGoogle Scholar
  30. Harada, S., Misawa, S., Agarwal, D. P., and Goedde, H. W., 1980a, Liver alcohol dehydrogenase and aldehyde dehydrogenase in the Japanese: Isozyme variation and its possible role in alcohol intoxication, Am. J. Hum. Genet. 32:8–15.PubMedGoogle Scholar
  31. Harada, S., Agarwal, D., and Goedde, H. W., 1980b, electrophoretic and biochemical studies of human aldehyde dehydrogenase isozymes in various tissues, Life Sci. 26:1773–1780.PubMedCrossRefGoogle Scholar
  32. Hempel, J., Kaiser, R., and Jornvall, H., 1984a, Human liver mitochondrial aldehyde dehydrogenase: A C terminal segment positions and defines the structure corresponding to the one reported to differ in the Oriental enzyme variant, FEBS Lett. 173:367–373.PubMedCrossRefGoogle Scholar
  33. Hempel, J., Buhler, R., Kaiser, R., Holmquist, B., De Zalenski, C., von Wartburg, J. P., Vallee, B. L., and Jornvall, H., 1984b, Human liver alcohol dehydrogenase 1. The primary structure of the beta 1 beta 1 isoenzyme, Eur. J. Biochem. 145:437–455.PubMedCrossRefGoogle Scholar
  34. Hempel, J., von Bahr-Lindstrom, H., and Jornvall, H., 1984c, Aldehyde dehydrogenase from human liver: Primary structure of the cytoplasmic isoenzyme, Eur. J. Biochem. 141:21–35.PubMedCrossRefGoogle Scholar
  35. Hiroshige, S., Carlock, L., Wasmuth, J., and Smith, M., 1985, Regional assignment of human formaldehyde dehydrogenase (FDH) to the region 4q21–4q25, Cytogenet. Cell Genet., 41:(in press).Google Scholar
  36. Hsu, L. C., Mohandas, T., Yoshida, A. 1985a, Chromosomal assignment of ALDH1 and ALDH2 genes, Cytogenet. Cell Genet. 41:(in press).Google Scholar
  37. Hsu, L. C., Tani, K., Fujiyoshi, T., and Yoshida, A., 1985b, Cloning of cDNA for human aldehyde dehydrogenase 1 and aldehyde dehydrogenase 2, Proc. Nat. Acad. Sci. USA 82:3771–3775.PubMedCrossRefGoogle Scholar
  38. Ikuta, T., Fujiyoshi, T., Hsu, L., Kurachi, K., and Yoshida, A., 1984, Cloning of cDNAs for human alcohol and aldehyde dehydrogenase, Am. J. Hum. Genet. 36:141s.Google Scholar
  39. Impraim, C., Wang, G., and Yoshida, A., 1982, Structural mutation in a major human aldehyde dehydrogenase gene results in loss of enzyme activity, Am. J. Hum. Genet. 34:837–841.PubMedGoogle Scholar
  40. Jenkins, W. J., and Peters, T. J., 1983, The sub-cellular localisation of acetaldehyde dehydrogenase in human liver, Cell Biochem. Function 1:37–40.CrossRefGoogle Scholar
  41. Jones, G. L., and Teng, Y.-S., 1983, A chemical and enzymological account of the multiple forms of human liver aldehyde dehydrogenase, Biochem. Biophys. Acta 745:162–174.PubMedCrossRefGoogle Scholar
  42. Jörnvall, H., Hempel, J., Vallee, B. L., Bosron, W. F., and Li, T. K., 1984, Human liver alcohol dehydrogenase: Amino acid substitution in the beta 2 beta 2 Oriental enzyme explains functional properties, establishes an active site structure and parallels mutational exchanges in the yeast enzyme, Proc. Natl. Acad. Sci. USA 81:3024–3028.PubMedCrossRefGoogle Scholar
  43. Julia, P., Farres, J., and Pares, X., 1983, Purification and partial characterization of a rat retina alcohol dehydrogenase active with ethanol and retinol, Biochem. J. 213:547–550.PubMedGoogle Scholar
  44. Lange, L. G. and Vallee, B. L., 1976, Double ternary complex affinity chromatography: Preparation of alcohol dehydrogenases, Biochemistry 15:4681–4686.PubMedCrossRefGoogle Scholar
  45. Li, T. K., and Magnes, L. J., 1975, Identification of a distinct molecular form of alcohol dehydrogenase in human livers with high activity, Biochem. Biophys. Res. Commun. 63:202–208.PubMedCrossRefGoogle Scholar
  46. Maniatis, T., Sambrook, J., and Fritsch, E., 1982, Handbook of Molecular Cloning Techniques, Cold Spring Harbor Laboratories, Cold Spring Harbor, New York.Google Scholar
  47. Maroni, G., and Aulberg, C. C. L., 1983, Genetic control of ADH expression in Drosophila melanogaster, Genetics 105:921–933.Google Scholar
  48. Meera Khan, P., Wynen, L. M. M., Hagemeier, A., and Pearson, P., 1984, Human formaldehyde dehydrogenase (FDH) and its assignment to chromosome 4, Cytogenet. Cell Genet. 38:112–115.PubMedCrossRefGoogle Scholar
  49. Pares, X., and Vallee, B. L., 1981, New human liver alcohol dehydrogenase forms with unique kinetic characteristics, Biochem. Biophys. Res. Commun. 98:122–130.PubMedCrossRefGoogle Scholar
  50. Pietruszko, R., 1983, Aldehyde dehydrogenase isozymes, in: Isozyme: Current Topics in Biological and Medical Research (M. C. Rattazi, J. G. Scandalios, G. S. Whitt, eds.), Vol 8, pp. 195–217, Alan R. Liss, New York.Google Scholar
  51. Rex, D. K., Smialek, J. E., Bosron, W. F., and Li, T. K., 1985, Alcohol and aldehyde dehydrogenase isozenzymes in a North American Indian population, Alcohol, in press.Google Scholar
  52. Ricciardi, B. R., Saunders, J. B., William, R., and Hopkinson, D. A., 1983, Hepatic ADH and ALDH isoenzymes in different racial groups and in chronic alcoholism, Pharmacol. Biochem. Behav. 18(Suppl. 1):61–65.PubMedCrossRefGoogle Scholar
  53. Santisteban, I., Povey, S., West, L. F., Parrington, J. M., and Hopkinson, D. A., 1985, Chromosome assignment, biochemical and immunological studies on a human aldehyde dehydrogenase (ALDH3), Ann. Hum. Genet., 49:87–100.PubMedCrossRefGoogle Scholar
  54. Schwartz, M., O’Donnell, J., and Sofer, W., 1979, Origin of multiple forms of alcohol dehydrogenase from Drosophila melanogaster, Arch. Biochem. Biophys. 194:365–378.CrossRefGoogle Scholar
  55. Smith, M., 1972, Studies on the Developmental Changes and Polymorphism of Human Alcohol Dehydrogenase, Ph D Thesis, University of London.Google Scholar
  56. Smith, M., Hopkinson, D. A., and Harris, H., 1971, Developmental changes and polymorphism in human alcohol dehydrogenase, Ann. Hum. Genet. 34:251–271.PubMedCrossRefGoogle Scholar
  57. Smith, M., Hopkinson, D. A., and Harris, H., 1972, Alcohol dehydrogenase isozymes in stomach and liver: Evidence for activity of the ADH3 locus, Ann. Hum. Genet. 35:243–253.PubMedCrossRefGoogle Scholar
  58. Smith, M., Hopkinson, D. A., and Harris, H., 1973a, Studies on the properties of the human alcohol dehydrogenase isozymes determined by the different loci ADH1, ADH2, ADH3, Ann. Hum. Genet. 37:49–67.CrossRefGoogle Scholar
  59. Smith, M., Hopkinson, D. A., and Harris, H., 1973b, Studies on the sub-unit structure and molecular size of the human alcohol dehydrogenase isozymes determined by the different loci ADH1, ADH2, ADH3, Ann. Hum. Genet. 36:401–414.CrossRefGoogle Scholar
  60. Smith, M., Duester, G., Bilanchone, V., Carlock, L., and Hatfield, G. W., 1984a, Derivation of probes for molecular genetic analysis of human class I alcohol dehydrogenase (ADH), a polymorphic gene family on human chromosome 4, Am. J. Hum. Genet. 36:153s.Google Scholar
  61. Smith, M., Duester, G., and Hatfield, G. W., 1985a, Development of DNA probes to investigate genetic variations of human alcohol metabolizing enzymes, in: NIDA/NIAAA Technical Review Genetic and Biological Markers of Drug Abuse and Alcoholism, NIDA Research Monograph, Government Printing Press, Washington.Google Scholar
  62. Smith, M., Duester, G., Carlock, L., and Wasmuth, J., 1985b, Assignment of alpha, beta and gamma ADH encoding genes to human chromosome 4q21–4q25, Cytogenet. Cell Genet. 41:(in press).Google Scholar
  63. Smith, M., Duester, G., Hiroshige, S., Anderson, K. A., and Murray, J., 1985c, DNA polymorphism in three class I ADH genes, Am. J. Hum. Genet. (submitted).Google Scholar
  64. Smith, M. Hiroshige, S., Saxon, P., Wasmuth. J., 1985d, Assignment of the gene encoding mitochondrial aldehyde dehydrogenase (ALDH2) to chromosome 12, Cytogenet. Cell Genet. 41:(in press).Google Scholar
  65. Southern, E., 1975, Detecting of specific sequences among DNA fragments separated by gel electrophoresis, J. Mol. Biol. 98:503–517.PubMedCrossRefGoogle Scholar
  66. Stamatoyannopoulos, G., Chen, S.-H., and Fukui, M., 1975, Liver alcohol dehydrogenase in Japanese: High frequency of atypical form and its role in alcohol sensitivity, Am. J. Hum. Genet. 27:789–796.PubMedGoogle Scholar
  67. Strydom, D. J., and Vallee, B. J., 1982, Characterization of human alcohol dehydrogenase isoenzymes by high performance liquid chromatographic peptide mapping, Anal. Biochem. 123:422–429.PubMedCrossRefGoogle Scholar
  68. Teng, Y. S., Jehan, S., and Lie-Ijo, L. E., 1979, Human alcohol dehydrogenase ADH2 and ADH3 polymorphisms in ethnic Chinese and Indians of West Malaysia, Hum. Genet. 53:87–90.PubMedCrossRefGoogle Scholar
  69. Vaisanen, P., Bilanchone, V., and Smith, M., 1984, Development of monoclonal antibodies to determine relationships of different alcohol dehydrogenase isozymes, Am. J. Hum. Genet. 36:131s.Google Scholar
  70. Vallee, B. L., and Bazzone, T. J., 1983, Isozymes of human liver alcohol dehydrogenase, in: Isozymes: Gurrent Topics in Biological and Medical Research, Vol. 8, pp. 219–244, Liss, New York.Google Scholar
  71. Von Bahr-Lindstrom, H., and Joravall, J., 1985, Isolation of cDNA clones for class IADH genes, EMBO J. (in press).Google Scholar
  72. Von Bahr-Lindstrom, H., Jornvall, J., and Vallee, B. L., 1985, Amino acid sequence of human ADH1 (alpha) polypeptide, EMBO J. (in press).Google Scholar
  73. Von Wartburg, J. P., and Schurch, P. M., 1968, Atypical human alcohol dehydrogenase, Ann. N. Y. Acad. Sci. 151:936–944.Google Scholar
  74. Von Wartburg, J. P., and Bühler, R., 1984, Biology of disease alcoholism and aldehydism: New biomedical concepts, Lab. Invest. 50:5–15.Google Scholar
  75. Wagner, F. W., Burger, A. R., and Vallee, B. L., 1983, Kinetic properties of human Over alcohol dehydrogenase: Oxidation of alcohols by class I isoenzymes, Biochemistry 22:1857–1863.PubMedCrossRefGoogle Scholar
  76. Woods, K. R., and Wang, K. T., 1967, Biochim. Biophys. Acta 133:369–370.PubMedGoogle Scholar
  77. Woods, D. E., Markham, A. F., Ricker, R. T., Goldberger, G., Colten, H. R., 1982, Isolation of cDNA clones for the human complement protein Factor B, a Class III major histocompatibility complex gene product, Proc. Nat. Acad. Sci. 79:5661–5665.PubMedCrossRefGoogle Scholar
  78. Yin, S. J., Bosron, W. F., Li, T. K., Ohnishi, K., Okuda, K., Ishii, H., and Tsuchiya, M., 1984, Polymorphism of human liver alcohol dehydrogenase: Identification of ADH2 2–1 and ADH2 2–2 phenotypes in the Japanese by isoelectric focusing, Biochem. Genet. 22:169–180.PubMedCrossRefGoogle Scholar
  79. Yoshida, A., Wang, G., and Dave, V., 1983, Determinations of genotypes of human aldehyde dehydrogenase ALDH2 locus, Am. J. Hum. Genet. 35:1107–1116.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Moyra Smith
    • 1
  1. 1.Department of PediatricsUniversity of California at IrvineIrvineUSA

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