Alcoholism pp 121-125 | Cite as

Class III Alcohol Dehydrogenases: Evidence for Their Identity with the Glutathione-Dependent Formaldehyde Dehydrogenases

  • Martti Koivusalo
  • Lasse Uotila
Part of the NATO ASI Series book series (NSSA, volume 206)


Alcohol dehydrogenases (EC from human (Vallee and Bazzone, 1983), rat (Julià et al., 1987b), mouse (Algar et al., 1983) and other mammalian species (Julià et al., 1987a) are divided into three classes, I, H and III, which are characterized by their specific, differing electrophoretic mobilities, reactivities with different alcohols and sensitivities to pyrazole and its derivatives. Class III alcohol dehydrogenases have anodic electrophoretic mobility at neutral to alkaline pH, and they are further distinguished by their insensitivity to pyrazole and poor use of ethanol and other short-chain alcohols as substrate. Long-chain alcohols like 1-octanol are, in contrast, used well as substrates by these enzymes (Vallee and Bazzone, 1983). The class III alcohol dehydrogenases occur in mammalian tissues much more widely than the enzymes from the other classes (Julià et al., 1987b). The class III enzymes have been purified from human liver (Wagner et al., 1984) and brain (Beisswenger et al., 1985), and from the livers of horse (Kaiser et al., 1989), rat (Julià et al., 1987b) and mouse (Algar et al., 1983) but the physiological significance of these enzymes has remained obscure although their involvement in the oxidation of long-chain fatty alcohols or ω-hydroxy fatty acids has been postulated (Giri et al., 1989).


Human Liver Alcohol Dehydrogenase Alcohol Dehydrogenase Activity Formaldehyde Dehydrogenase Substrate Competition 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Algar, E. M., Seeley, T-L., and Holmes, R. S., 1983, Purification and molecular properties of mouse alcohol dehydrogenase isozymes, Eur.J.Biochem., 137: 139–147.PubMedCrossRefGoogle Scholar
  2. Beisswenger, T. B., Holmquist, B., and Vallee, B. L., 1985, x-ADH is the sole alcohol dehydrogenase isozyme of mammalian brains: Implications and inferences, Proc.Natl.Acad.Sci.USA, 82: 8369–8373.PubMedCrossRefGoogle Scholar
  3. Carlock, L., Hiroshige, S., Wasmuth, J., and Smith, M., 1985, Assignment of the ADH5 gene coding for class III ADH to human chromosome 4: 4q21–4q25, Cytogenet.Cell Genet., 40: 598.Google Scholar
  4. Giri, P. R., Linnoila, M., O’Neill, J. B., and Goldman, D., 1989, Distribution and possible metabolic role of class III alcohol dehydrogenase in the human brain, Brain Res., 481: 131–141.PubMedCrossRefGoogle Scholar
  5. Hiroshige, S., Carlock, L., Wasmuth, J., and Smith, M., 1985, Regional assignment of human formaldehyde dehydrogenase (1–1DH) to the region 4q21–4q25, Cytogenet.Cell Genet., 40: 651–652.Google Scholar
  6. Julià, P., Boleda, M. D., Farrés, J., and Parés, X., 1987a, Mammalian alcohol dehydrogenase: characteristics of class III isoenzymes, Alcohol & Alcoholism, Suppl. 1: 169–173.Google Scholar
  7. Julià, P., Farrés, J., and Pares, X., 1987b, Characterization of three isoenzymes of rat alcohol dehydrogenase. Tissue distribution and physical and enzymatic properties, Eur.J.Biochem., 162: 179–189.PubMedCrossRefGoogle Scholar
  8. Julià, P., Parés, X., and Jömvall, H., 1988, Rat liver alcohol dehydrogenase of class III. Primary structure, functional consequences and relationships to other alcohol dehydrogenases, Eur.J.Biochem., 172: 73–83.PubMedCrossRefGoogle Scholar
  9. Kaiser, R., Holmquist, B., Hempel, J., Vallee, B. L., and Jömvall, H., 1988, Class III human liver alcohol dehydrogenase: a novel structural type equidistantly related to the class I and class II enzymes, Biochemistry 27: 1132–1140.PubMedCrossRefGoogle Scholar
  10. Kaiser, R., Holmquist, B., Vallee, B. L., and Jömvall, H., 1989, Characteristics of mammalian class III alcohol dehydrogenases, an enzyme less variable than the traditional liver enzyme of class I, Biochemistry 28: 8432–8438.PubMedCrossRefGoogle Scholar
  11. Koivusalo, M., Baumann, M., and Uotila, L., 1989, Evidence for the identity of glutathione-dependent formaldehyde dehydrogenase and class III alcohol dehydrogenase, FEBS Lett., 257: 105–109.PubMedCrossRefGoogle Scholar
  12. Koivusalo, M., Koivula, T., and Uotila, L., 1982, Oxidation of formaldehyde by nicotinamide nucleotide-dependent dehydrogenases, in “Enzymology of Carbonyl Metabolism: Aldehyde Dehydrogenase and Aldo/Keto Reductase”, H. Weiner and B. Vermuth, eds., pp. 155–168, Alan R. Liss, Inc., New York.Google Scholar
  13. Koivusalo, M., and Uotila, L., 1974, Enzymic method for the quantitative determination of reduced glutathione, Anal.Biochem., 59: 34–45.PubMedCrossRefGoogle Scholar
  14. Uotila, L., 1989, Glutathione thiol esterases, in: “Coenzymes and Cofactors, vol. III, Glutathione. Chemical, Biochemical and Medical Aspects”, part A, D. Dolphin, R. Poulson and O. Avramovic, eds., pp. 767–804, John Wiley & Sons, Inc., NewYork.Google Scholar
  15. Uotila, L., and Koivusalo, M., 1974a, Formaldehyde dehydrogenase from human liver. Purification, properties and evidence for the formation of glutathione thiol esters by the enzyme, J.Biol.Chem., 249: 7653–7663.PubMedGoogle Scholar
  16. Uotila, L., and Koivusalo, M., 1974b, Purification and properties of S-formylglutathione hydrolase from human liver, J.Biol.Chem., 249: 7664–7672.PubMedGoogle Scholar
  17. Uotila, L. , and Koivusalo, M. , 1983, Formaldehyde dehydrogenase, in: “Functions of Glutathione. Biochemical, Physiological, Toxicological and Clinical Aspects”, A. Larsson, S. Orrenius, A. Holmgren, and B. Mannervik, eds. , pp. 175–186, Raven Press, New York.Google Scholar
  18. Uotila, L., and Koivusalo, M., 1987, Multiple forms of formaldehyde dehydrogenase in human red blood cells, Human Heredity, 37: 102–106.PubMedCrossRefGoogle Scholar
  19. Uotila, L., and Koivusalo, M., 1989, Glutathione-dependent oxidoreductases: Formaldehyde dehydrogenase, in “Coenzymes and Cofactors, vol. III, Glutathione. Chemical, Biochemical and Medical Aspects”, part A, D. Dolphin, R. Poulson, and O. Avramovic, eds., pp. 517–551, John Wiley & Sons, Inc., New York.Google Scholar
  20. Uotila, L., and Mannervik, B., 1979, A steady-state kinetic model for formaldehyde dehydrogenase from human liver. A mechanism involving NAD+ and the hemimercaptal adduct of glutathione and formaldehyde as substrates and free glutathione as an allosteric activator of the enzyme, Biochem.J., 177, 869–878.PubMedGoogle Scholar
  21. Vallee, B. L. , and Bazzone, T. J. , 1983, Isozymes of human liver alcohol dehydrogenase, in: “Isozymes: Current Topics in Biological and Medical Research”, vol. 8, M. C. Rattazi, J. C. Scandalios, and G. S. Whitt, eds. , pp. 219–244, Alan R. Liss, Inc., New York.Google Scholar
  22. Wagner, F. W., Parés, X., Holmquist, B., and Vallee, B. L., 1984, Physical and enzymatic properties of a class III isozyme of human liver alcohol dehydrogenase: xADH, Biochemistry, 23: 2193–2199.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Martti Koivusalo
    • 1
  • Lasse Uotila
    • 1
  1. 1.Department of Medical ChemistryUniversity of HelsinkiHelsinkiFinland

Personalised recommendations