Journal of Biomedical Science

, Volume 8, Issue 1, pp 71–76 | Cite as

Mammalian alcohol dehydrogenase — Functional and structural implications

  • Jan-Olov Höög
  • Jesper J. Hedberg
  • Patrik Strömberg
  • Stefan Svensson
Original Paper


Mammalian alcohol dehydrogenase (ADH) constitutes a complex system with different forms and extensive multiplicity (ADH1–ADH6) that catalyze the oxidation and reduction of a wide variety of alcohols and aldehydes. The ADH1 enzymes, the classical liver forms, are involved in several metabolic pathways beside the oxidation of ethanol, e.g. norepinephrine, dopamine, serotonin and bile acid metabolism. This class is also able to further oxidize aldehydes into the corresponding carboxylic acids, i.e. dismutation. ADH2, can be divided into two subgroups, one group consisting of the human enzyme together with a rabbit form and another consisting of the rodent forms. The rodent enzymes almost lack ethanol-oxidizing capacity in contrast to the human form, indicating that rodents are poor model systems for human ethanol metabolism. ADH3 (identical to glutathione-dependent formaldehyde dehydrogenase) is clearly the ancestral ADH form and S-hydroxymethylglutathione is the main physiological substrate, but the enzyme can still oxidize ethanol at high concentrations. ADH4 is solely extrahepatically expressed and is probably involved in first pass metabolism of ethanol beside its role in retinol metabolism. The higher classes, ADH5 and ADH6, have been poorly investigated and their substrate repertoire is unknown. The entire ADH system can be seen as a general detoxifying system for alcohols and aldehydes without generating toxic radicals in contrast to the cytochrome P450 system.

Key words

Alcohol dehydrogenase Enzyme kinetics Protein expression 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Borràs E, Coutelle C, Rosell A, Fernández-Muixi F, Broch M, Crosas B, Hjelmqvist L, Lorenzo A, Gutiérrez C, Santos M, Szczepanek M, Heilig M, Quattrocchi P, Farrés J, Vidal F, Richart C, Mach T, Bogdal J, Jörnvall H, Seitz HK, Couzigou P, Parés X. Genetic polymorphism of alcohol dehydrogenase in Europeans: The ADH2*2 allele decreases the risk for alcoholism and is associated with ADH3*1. Hepatology 31:984–989;2000.CrossRefPubMedGoogle Scholar
  2. 2.
    Cronholm T. Effect of ethanol on the redox state of the coenzyme bound to alcohol dehydrogenase studied in isolated hepatocytes. Biochem J 248:567–572;1987.PubMedGoogle Scholar
  3. 3.
    Duester G. Families of retinoid dehydrogenases regulating vitamin A function — Production of visual pigment and retinoic acid. Eur J Biochem 267:4315–4324;2000.PubMedGoogle Scholar
  4. 4.
    Duester G, Farrés J, Felder MR, Holmes R, Höög J-O, Parés X, Plapp BV, Yin S-J, Jörnvall H. Recommended nomenclature for the vertebrate alcohol dehydrogenase gene family. Biochem Pharm 58:389–395;1999.CrossRefPubMedGoogle Scholar
  5. 5.
    Edenberg HJ, Bosron WF. Alcohol dehydrogenase. In: Guengerich, FP. Comprehensive Toxicology, vol. 3. New York. Pergamon Press, 119–131;1997.Google Scholar
  6. 6.
    Eklund H, Nordström B, Zeppezauer E, Söderlund G, Ohlsson I, Boiwe T, Söderberg B-O, Tapia O, Brändén C-I, Åkeson Å. Three-dimensional structure of horse liver alcohol dehydrogenase at 2.4 Å resolution. J Mol Biol 102:27–59;1976.PubMedGoogle Scholar
  7. 7.
    Hedberg JJ, Höög J-O, Nilsson JA, Zheng X, Elfwing Å, Grafström RC. Expression of alcohol dehydrogenase 3 (ADH3) in tissue and cultured cells from human oral mucosa. Am J Pathol 157:1745–1755;2000.PubMedGoogle Scholar
  8. 8.
    Jensen DE, Belka GK, Du Bois GC. S-nitrosoglutathione is a substrate for rat alcohol dehydrogenase class III isoenzyme. Biochem J 331:659–68;1998.PubMedGoogle Scholar
  9. 9.
    Jörnvall H, Höög J-O. Nomenclature of alcohol dehydrogenases. Alcohol Alcohol 30:153–161;1995.PubMedGoogle Scholar
  10. 10.
    Jörnvall H, Höög J-O, Persson B. SDR and MDR: Completed genome sequences show these protein families to be large, of old origin, and of complex nature. FEBS Lett 445:261–264;1999.CrossRefGoogle Scholar
  11. 11.
    Li T-K, Bosron WF, Dafeldecker WP, Lange LG, Vallee BL. Isolation of Π-alcohol dehydrogenase of human liver: Is it a determinant of alcoholism? Proc Natl Acad Sci USA 74:4378–4381;1997.Google Scholar
  12. 12.
    Marschall H-U, Opperman UCT, Svensson S, Nordling E, Persson B, Höög J-O, Jörnvall H. Human liver class I alcohol dehydrogenase γγ isozyme: The sole cytosolic 3β-hydroxysteroid dehydrogenase of iso-bile acids. Hepatology 31:990–996;2000.PubMedGoogle Scholar
  13. 13.
    Persson B, Zigler JS Jr, Jörnvall H. A superfamily of medium-chain dehydrogenases/reductases (MDR): Sub-lines including ζ-crystallin, alcohol and polyol dehydrogenases, quinone oxidoreductases, enoyl reductases, VAT-1 and other proteins. Eur J Biochem 226:15–22;1994.PubMedGoogle Scholar
  14. 14.
    Popescu G, Napoli JL. Analysis of rat cytosolic 9-cis-retinol dehydrogenase activity and enzymatic characterization of rat ADHII. Biochim Biophys Acta 1476:43–52;2000.PubMedGoogle Scholar
  15. 15.
    Svensson S, Höög J-O, Schneider G, Sandalova T. Crystal structures of mouse class II alcohol dehydrogenase reveal determinants of substrate specificity and efficiency. J Mol Biol 302:441–453;2000.PubMedGoogle Scholar
  16. 16.
    Svensson S, Lundsjö A, Cronholm T, Höög J-O. Aldehyde dismutase activity of human liver alcohol dehydrogenase. FEBS Lett 394:217–220;1996.CrossRefPubMedGoogle Scholar
  17. 17.
    Svensson S, Some M, Lundsjö A, Helander A, Cronholm T, Höög J-O. Activities of human alcohol dehydrogenases in the metabolic pathways of ethanol and serotonin. Eur J Biochem 262:324–329;1999.CrossRefPubMedGoogle Scholar
  18. 18.
    Svensson S, Strömberg P, Höög J-O. A novel subtype of class II alcohol dehydrogenase in rodents: Unique Pro47 and Ser182 modulates hydride transfer. J Biol Chem 274:29712–29719;1999.PubMedGoogle Scholar
  19. 19.
    Yasunami M, Chen C-S, Yoshida A. A human alcohol dehydrogenase gene(ADH6) encoding an additional class of isozyme. Proc Natl Acad Sci USA 88:7610–7614;1991.Google Scholar

Copyright information

© National Science Council 2001

Authors and Affiliations

  • Jan-Olov Höög
    • 1
  • Jesper J. Hedberg
    • 1
  • Patrik Strömberg
    • 1
  • Stefan Svensson
    • 1
  1. 1.Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSweden

Personalised recommendations