Skip to main content
SpringerLink
Log in

Genetics of Human Alcohol and Aldehyde Dehydrogenases

  • Chapter
Advances in Human Genetics 15

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Adinolfi, A., and Hopkinson, D. A., 1979, Affinity characteristics of human alcohol dehydrogenase (ADH) isozymes, Ann. Hum. Genet. 43:109–119.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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 

  • Blair, A. H., and Vallee, B. L., 1966, Some catalytic properties of human liver alcohol dehydrogenase isoenzymes, Biochemistry 5:2026–2034.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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 

  • Castle, S. L., and Board, P. G., 1982, Electrophoretic investigation of formaldehyde dehydrogenase in human tissues, Hum. Hered. 32:222–224.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Duester, G., Hatfield, G. W., and Smith, M., 1985a, Molecular genetic analysis of human alcohol dehydrogenase, Alcohol, 2:53–56.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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 

  • Fukui, M., and Wakasugi, C., 1972, Liver alcohol dehydrogenase in a Japanese population, Jpn. J. Legal Med. 26:46–51.

    CAS  Google Scholar 

  • Goedde, H. W., Harada, S., and Agarwal, D. P., 1979a, Racial differences in alcohol sensitivity: A new hypothesis, Hum. Genet. 51:331–334.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Harada, S., Agarwal, D. P., and Goedde, H. W., 1978, Human liver alcohol dehydrogenase isoenzyme variations, Hum. Genet. 40:215–220.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Hsu, L. C., Mohandas, T., Yoshida, A. 1985a, Chromosomal assignment of ALDH1 and ALDH2 genes, Cytogenet. Cell Genet. 41:(in press).

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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.

    PubMed  CAS  Google Scholar 

  • Jenkins, W. J., and Peters, T. J., 1983, The sub-cellular localisation of acetaldehyde dehydrogenase in human liver, Cell Biochem. Function 1:37–40.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Lange, L. G. and Vallee, B. L., 1976, Double ternary complex affinity chromatography: Preparation of alcohol dehydrogenases, Biochemistry 15:4681–4686.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Maniatis, T., Sambrook, J., and Fritsch, E., 1982, Handbook of Molecular Cloning Techniques, Cold Spring Harbor Laboratories, Cold Spring Harbor, New York.

    Google Scholar 

  • Maroni, G., and Aulberg, C. C. L., 1983, Genetic control of ADH expression in Drosophila melanogaster, Genetics 105:921–933.

    CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Pares, X., and Vallee, B. L., 1981, New human liver alcohol dehydrogenase forms with unique kinetic characteristics, Biochem. Biophys. Res. Commun. 98:122–130.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • Smith, M., 1972, Studies on the Developmental Changes and Polymorphism of Human Alcohol Dehydrogenase, Ph D Thesis, University of London.

    Google Scholar 

  • Smith, M., Hopkinson, D. A., and Harris, H., 1971, Developmental changes and polymorphism in human alcohol dehydrogenase, Ann. Hum. Genet. 34:251–271.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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 

  • 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 

  • 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 

  • 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 

  • 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 

  • Southern, E., 1975, Detecting of specific sequences among DNA fragments separated by gel electrophoresis, J. Mol. Biol. 98:503–517.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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 

  • Von Bahr-Lindstrom, H., and Joravall, J., 1985, Isolation of cDNA clones for class IADH genes, EMBO J. (in press).

    Google Scholar 

  • 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 

  • Von Wartburg, J. P., and Schurch, P. M., 1968, Atypical human alcohol dehydrogenase, Ann. N. Y. Acad. Sci. 151:936–944.

    Google Scholar 

  • Von Wartburg, J. P., and Bühler, R., 1984, Biology of disease alcoholism and aldehydism: New biomedical concepts, Lab. Invest. 50:5–15.

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Woods, K. R., and Wang, K. T., 1967, Biochim. Biophys. Acta 133:369–370.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Yoshida, A., Wang, G., and Dave, V., 1983, Determinations of genotypes of human aldehyde dehydrogenase ALDH2 locus, Am. J. Hum. Genet. 35:1107–1116.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of California at Irvine, Irvine, California, 92717, USA

    Moyra Smith

Authors
  1. Moyra Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Pennsylvania, Philadelphia, USA

    Harry Harris (Harnwell Professor of Human Genetics) (Harnwell Professor of Human Genetics)

  2. Mount Sinai School of Medicine, The City University of New York, USA

    Kurt Hirschhorn (Herbert H. Lehman Professor and Chairman of Pediatrics) (Herbert H. Lehman Professor and Chairman of Pediatrics)

Rights and permissions

Reprints and permissions

Copyright information

© 1986 Plenum Press, New York

About this chapter

Cite this chapter

Smith, M. (1986). Genetics of Human Alcohol and Aldehyde Dehydrogenases. In: Harris, H., Hirschhorn, K. (eds) Advances in Human Genetics 15. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-8356-1_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-8356-1_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4615-8358-5

  • Online ISBN: 978-1-4615-8356-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation