Mammalian Class II Alcohol Dehydrogenase: Species and Class Comparisons at Genomic and Protein Levels

  • Jan-Olov Höög
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 284)


Human class II alcohol dehydrogenase is formed of the it-subunit to an active dimer, and the enzyme belongs to the family of long-chain zinc-containing alcohol dehydrogenases (Jörnvall et al., 1987a). Including in the family is the two other mammalian alcohol dehydrogenases (ADH), class I and class III (Vallee and Bazzone, 1983) as the related sorbitol dehydrogenase (Jörnvall et al., 1987b). Class I ADH is the classical ADH that is responsible for the main metabolism of ethanol and the class III ADH has recently been shown to be identical to glutathione-dependent formaldehyde dehydrogenase (Koivusalo et al., 1989). The class II ADH, the least studied form of the different ADHs, shows a much higher Km for ethanol than the class I isozymes, 34 mM compared to 50 µM for the ββ isozyme of class I (Bosron et al., 1979). The ππ enzyme is also active towards norepinephrine metabolites (Mårdh et al., 1986). The class II ADH is encoded by its own gene, ADH4, that have been mapped to locus 4q22 in the human genome (McPhearson et el., 1989). This is in the same region where the other human ADH genes, ADH1-3 and ADH5, have been localized (Smith, 1986). The rat class II ADH, designated ADH-1, has been ascribed retinol dehydrogenase activity and this enzyme is also more anodic than the human class II form (Julià et al., 1986). This gives the class II enzyme other properties compared to the class I and III of mammalian ADH.


Alcohol Dehydrogenase ADH4 Gene Positional Identity Human Class Alcohol Dehydrogenase Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. von Bahr-Lindström, H., Jörnvall, H., & Höög, J.-O. (199O) Molecular cloning and characterization of the human ADH4 gene. Nucl. Acids Res. in press.Google Scholar
  2. Bosron, W.F., Li, T.-K., Dafeldecker, W.P., & Vallee, B.L. (1979) Human liver &#96O;-alcohol dehydrogenase: Kinetic and molecular properties. Biochemisty 18, 11O1&#x2O13;11O5.CrossRefGoogle Scholar
  3. Crabb, D.W., Stein, P.M., Dipple, K.M., Hittle, J.B., Sidhu, R., Qulali, M., Zhang, K., & Edenberg, H.J. (1989) Structure and expression of the rat class I alcohol dehydrogenase gene. Genomics 5, 9O6&#x2O13;914.CrossRefGoogle Scholar
  4. Dong, Y., Poellinger, L., Okret, S., Höög, J.-O., von Bahr-Lindström, H., Jörnvall, H., & Gustafsson, J.-A. (1988) Regulation of gene expression of class I alcohol dehydrogenase by glucocorticoids. Proc. Natl. Acad. Sci. USA 85, 767&#x2O13;771.PubMedCrossRefGoogle Scholar
  5. Duester, G., Smith, M., Bilanchone, V., & Hatfield, G.W. (1986) Molecular analysis of the human class I alcohol dehydrogenase gene family and nucleotide sequence of the gene encoding the ß subunit. J. Biol. Chem. 261, 2O27&#x2O13;2O33.Google Scholar
  6. Duester, G., Winter, L., Stewart, M., Dong, Y., Poellinger, L., Okret, S., & Gustafsson, J.-A. (199O) Tandem glucooorticoid responsive elements mediate induction of the human ß alcohol dehydrogenase gene by glucocorticoids. Mol. Cell Biol., in press.Google Scholar
  7. Duley, J.A., Harris, O., & Holmes, R. (1985) Analysis of human alcohol-and aldehyde-metabolizing isozymes by electrophoresis and isoelectric focusing. Alcohol. Clin. Exp. Res. 9, 263&#x2O13;271.PubMedCrossRefGoogle Scholar
  8. Eklund, H., Müller-Wille, P., Horjales, E., Futer, O., Holmquist, B., Vallee, B.L., Höög, J.-O., Kaiser, R., & Jörnvall, H. (199O) Comparison of three classes of human liver alcohol dehydrogenase. Emphasis on different substrate binding pockets. Eur. J. Biochem., in press.Google Scholar
  9. Frezza, M., di Padova, C., Pozzato, G., Terpin, M., Baraona, E. & Lieber, C.S. (199O) High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. New Engl. J. Med. 332, 95&#x2O13;99.Google Scholar
  10. Höög, J.-O., von Bahr-Lindström, H., Hedén, L.-O., Holmquist, B., Larsson, K., Hempel, J., Vallee, B.L., & Jörnvall, H. (1987) Structure of the class II enzyme of human liver alcohol dehydrogenase: Combined cDNA and protein sequence determination of the &#96O; subunit. Biochemistry 26, 1926&#x2O13;1932.PubMedCrossRefGoogle Scholar
  11. Julià, P., Farrés, J., & Parés, X. (1986) Ocular alcohol dehydrogenase in the rat: Regional distribution and kinetics of the ADH-1 isoenzyme with retinol and retinal. Exp. Eye Res. 42, 3O5&#x2O13;314.CrossRefGoogle Scholar
  12. Julià, P., Farrés, J., & Parés, X. (1987) Characterization of three isoenzymes of rat alcohol dehydrogenase. Tissue distribution and physical and enzymatic properties. Eur. J. Biochem. 162, 179&#x2O13;189.Google Scholar
  13. Jörnvall, H., Höög, J.-O., von Bahr-Lindström, H., & Vallee, B.L. (1987a) Mammalian alcohol dehydrogenases of separate classes: Intermediates between different enzymes and intraclass isozymes. Proc. Natl. Acad. Sci. USA 84, 258O&#x2O13;2584.CrossRefGoogle Scholar
  14. Jörnvall, H., Persson, B., & Jeffery, J. (1987b) Characteristics of alcohol/polyol dehydrogenases. The zinc-containng long-chain alchol dehydrogenases. Eur. J. Biochem. 167, 195&#x2O13;2O1.Google Scholar
  15. Jörnvall, H., von Bahr-Lindström, H., & Höög, J.-O. (1989) Alcohol dehydrogenases -Structure. In: Human Metabolism of Alcohol vol. II (eds. Batt, R.D. & Crow, K.E.) CRC press, pp. 43&#x2O13;64.Google Scholar
  16. Kaiser, R. Holmquist, B., Vallee, B.L., & Jörnvall, H. (1989) Characteristics of mammalian class III alcohol dehydrogenases, an enzyme less variable than the traditional liver enzyme of class I. Biochemistry 28, 8432&#x2O13;8438.PubMedCrossRefGoogle Scholar
  17. Kaiser, R., Nussrallah, B., Dam, R., Wagner, F.W., & Jörnvall, H. (199O) Avian alcohol dehydrogenase. Characterization of the quail enzyme, functional interpretations, and relationships to the different classes of mammalian alcohol dehydrogenases. Biochemistry, in press.Google Scholar
  18. Koivusalo, M., Baumann, M., & Uotila, L. (1989) Evidence for the identity of glutathione-dependent formaldehyde dehydrogenase and class III alcohol dehydrogenase. FEBS Lett. 257, 1O5&#x2O13;1O9.CrossRefGoogle Scholar
  19. Lawn, R.M., Fritsch, E.F., Parker, R.C., Blake, G., & Maniatis, T. (1978) The isolation and characterization of linked δ-and ß-globin genes from a cloned library of human DNA. Cell 15, 1157&#x2O13;1174.PubMedCrossRefGoogle Scholar
  20. Maniatis, T., Fritsch, E.F., & Sambrook, J. (1982) Molecular Cloning. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.Google Scholar
  21. McPhearson, J.D., Smith, M., Wagner, C., Wasmuth, J., & Höög, J.-O. (1989) Mapping of the class II alcohol dehydrogenase gene locus to 4q22. Cytogenet. Cell Genet. 51, 1O43.Google Scholar
  22. Matsuo, Y., & Yokoyama, S. (199O) Cloning and sequencing of a processed pseudogene derived from a human class III alcohol dehydrogenase gene. Am. J. Hum. Genet. 46, 85–91.PubMedGoogle Scholar
  23. Moreno, A., Boleda, M.D., Peralba, J.M., & Parés, X. (1989) Purification and characterization of a new alcohol dehydrogenase form from human stomach. Alcohol Alcoholism 24, 383.Google Scholar
  24. Mount, S.M. (1982) A catalogue of splice junction signals. Nucl. Acids Res. 1O, 459–472.CrossRefGoogle Scholar
  25. Mårdh, G., Dingley, A.L., Auld, D.S., & Vallee, B.L. (1986) Human class II (&#96O;) alcohol dehydrogenase has a redox-specific function in norepinephrine metabolism. Proc. Natl. Acad. Sci. USA 83, 89O8–8912.CrossRefGoogle Scholar
  26. Sanger, F., Nicklen, S., & Coulson, A.R. (1977) DNA sequencing with chain termination inhibitors. Proc. Natl. Acad. Sci. USA 74, 5463–5467.PubMedCrossRefGoogle Scholar
  27. Smith, M. (1986) Genetics of human alcohol and aldehyde dehydro-genases. Adv. Hum. Genet. 15, 249–29O.PubMedCrossRefGoogle Scholar
  28. Vallee, B.L. & Bazzone, T.J. (1983) Isozymes of human liver alcohol dehydrogenase. Isozymes 8, 219–244.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Jan-Olov Höög
    • 1
  1. 1.Department of Chemistry IKarolinska InstitutetStockholmSweden

Personalised recommendations