Formation of a Protein-Acetaldehyde Adduct in Liver during Chronic Alcohol Exposure

  • Renee C. Lin
  • Lawrence Lumeng
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)


Acetaldehyde is an intermediary metabolite of ethanol oxidation that forms in the liver during alcohol ingestion. Formation of acetaldehyde is mediated by two alcohol metabolizing systems: alcohol dehydrogenase (ADH) (Li, 1977) and the microsomal ethanol oxidizing system (MEOS or cytP450IIE1) (Lieber et al., 1970). In individuals who do not abuse alcohol, ADH is the most important enzyme responsible for the conversion of ethanol to acetaldehyde. However, MEOS is inducible by chronic alcohol consumption (Lieber, et al., 1972), therefore its contribution to the elimination of alcohol becomes more significant in chronic alcoholics.


Alcohol Dehydrogenase Liquid Diet 37KD Protein Ethanol Oxidation Acetaldehyde Concentration 
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. Baroana, E., Leo, M.A., Borowsky, S.A. and Lieber, C.S. (1975). Alcoholic hepatomegaly: accumulation of protein in the liver. Science 190, 794–795.CrossRefGoogle Scholar
  2. Barry, R.E., Williams, A.J.K. and McGivan, J.D. (1987). The detection of acetaldehyde/liver plasma membrane protein adduct formed in vivo by alcohol feeding. Liver 7, 364–368.PubMedGoogle Scholar
  3. Behrens, U.J., Hoerner, M., Lasker, J.M. and Lieber, C.S. (1988). Formation of acetaldehyde adducts with ethanol-inducible P450IIE1 in vivo. Biochem. Biophys. Res. Commun. 154, 584–590.CrossRefPubMedGoogle Scholar
  4. Crabb, D.W. and Li, T.-K. (1985). Expression of alcohol dehydrogenase in primary monolayer cultures of rat hepatocytes. Biochem. Biophys. Res. Commun. 128, 12–17.CrossRefPubMedGoogle Scholar
  5. DeMaster, E.G., Shirota, F.N., Redfern, B., Nagasawa, H.T. (1989). Identification of nitroxyl (HN=O) as a product of cyanamide-oxidation catalyzed by bovine liver catalase in vitro. FASEB 3, A432.Google Scholar
  6. Donohue, T.M., Tuma, D.J. and Sorrell, M.F. (1983). Acetaldehyde adducts with proteins: binding of 14C-acetaldehyde to serum albumin. Arch. Biochem. Biophys. 220, 239–246.CrossRefPubMedGoogle Scholar
  7. Enat, R., Jefferson, D.M., and Ruiz-Opazo, N. (1984). Hepatocytes proliferation in vitro: its dependence on the use of serum-free hormonally defined medium and substrata of extracellular matrix. PNAS, USA 81, 1411–1415.CrossRefGoogle Scholar
  8. Gaines, K.C., Salhany, J.M., Tuma, D.J. and Sorrell, M.F. (1977). Reactions of acetaldehyde with human erythrocyte membrane proteins. FEBS 75, 115–119.CrossRefGoogle Scholar
  9. Goldberg, L. and Rydberg, U. (1969). Inhibition of ethanol metabolism in vivo by administration of pyrazole. Biochem. Pharmacol. 18, 1749–1762.CrossRefPubMedGoogle Scholar
  10. Hoerner, M., Behrens, U.J., Worner, T. and Lieber, C.S. (1986). Humoral immune response to acetaldehyde adducts in alcoholic patients. Res. Commun. Chem. Pathol. Pharm. 54, 3–12.Google Scholar
  11. Israel, Y., Hurwitz, E., Niemela, O. and Ornon, R. (1986). Monoclonal and polyclonal antibodies against acetaldehyde-containing epitopes in acetaldehyde-protein adducts. Proc. Nati. Acad. Sci. USA 83, 7923–7927.CrossRefGoogle Scholar
  12. Jennett, R.B., Tuma, D.J. and Sorrell, M.F. (1980). Effect of ethanol and its metabolites. Pharmacology 21, 363–368.CrossRefPubMedGoogle Scholar
  13. Jennett, R.B., Johnson, E.L. and Sorrell, M.F. (1985). Covalent binding of acetaldehyde to tubulin is associated with impaired polymerization. Hepatology 5, 1055.Google Scholar
  14. Krikun, G., Feierman, D.E. and Cederbaum, A.I. (1986). Rat liver microsomal induction of the oxidation of drug and alcohols, and sodium dodecyl sulfate-gel profiles after in vivo treatment with pyrazole or 4-methylpyrazole. J. Pharmacol. Exp. Ther. 237, 1012–1019.PubMedGoogle Scholar
  15. Li, T.-K. and Theorell, H. (1969). Human liver alcohol dehydrogenase: inhibition by pyrazole and pyrazole analogs. Acta Chem. Scand. 23, 892–902.CrossRefPubMedGoogle Scholar
  16. Li, T.-K. (1977). Enzymology of human alcohol metabolism. In: Advances in Enzymology ( A. Meister, Ed.) Vol. 45, pp. 427–483, John Wiley & Sons, Inc., New York.Google Scholar
  17. Lieber, C.S. and DeCarli, L.M. (1970). Hepatic microsomal ethanol-oxidizing system. in vitro characteristics and adaptive properties in vivo. J. Biol. Chem. 245, 2505–2512.PubMedGoogle Scholar
  18. Lieber, C.S. and DeCarli, L.M. (1972). The role of the hepatic microsomal ethanol oxidizing sytem (MEOS) for ethanol metabolism in vivo. J. Pharmacol. Exp. Ther. 181, 279–287.PubMedGoogle Scholar
  19. Lieber, C.S. and DeCarli, L.M. (1982). The feeding of alcohol in liquid diets: two decades of applications and 1982 update. Alcoholism: Clin. Exp. Res. 6, 523–531.CrossRefGoogle Scholar
  20. Lieber, C.S., DeCarli, L.M. and Sorrell, M.F. (1989). Experimental methods of ethanol administration. Hepatology 10, 501–510.CrossRefPubMedGoogle Scholar
  21. Lin, R.C. and Snodgrass, P.J. (1975). Primary culture of normal adult rat liver cells which maintain stable urea cycle enzymes. Biochem. Biophys. Res. Commun. 64, 725–734.CrossRefPubMedGoogle Scholar
  22. Lin, R.C., Smith, R.S. and Lumeng L. (1988a). Detection of a protein-acetaldehyde adduct in the liver of rats fed alcohol chronically. J. Clin. Invest. 81, 615–619.CrossRefPubMedGoogle Scholar
  23. Lin, R.C., Lumeng, L, Kelly, T. and Pound, D. (1988b). Protein-acetaldehyde adducts in serum of alcoholic patients. In: Biomedical and Social Aspects of Alcohol and Alcoholism ( Kuriyama, K., Takada, A. and Ishii, H., Eds.), pp. 541–544, Excerpta Medica International Congress Series, Amsterdam.Google Scholar
  24. Lin, R.C. and Lumeng, L. (1989). Further studies on the 37KD liver protein-acetaldehyde adduct that forms in vivo during chronic alcohol ingestion. Hepatology 10, 807–814.CrossRefPubMedGoogle Scholar
  25. Lin, R.C., Fillenwarth, M.J., Minter, R. and Lumeng, L. (1990). Formation of the 37KDa protein-acetaldehyde adduct in primary cultured rat hepatocytes exposed to alcohol. Hepatology (in press).Google Scholar
  26. Lumeng, L., Minter, R.G. and Li, T.-K. (1982). Distribution of stable acetaldehyde adducts in blood under physiological conditions. Fed. Proc. 41, 765.Google Scholar
  27. Lumeng, L. and Minter, R.G. (1985). Formation of acetaldehyde-hemoglobin adducts in vitro and in vivo demonstrated by high performance liquid chromatography. Alcoholism: Clin. Exp. Res. 9, 209.Google Scholar
  28. Mauch, T.J., Donohue, T.M., Zetterman, R.K. and Sorrell, M.F. (1985). Covalent binding of acetaldehyde to lysine-dependent enzymes can inhibit catalytic activity. Hepatology 5, 1056.Google Scholar
  29. McFarlane, I.G. (1984). Autoimmunity in liver disease. Clin. Sci. 67, 569–578.PubMedGoogle Scholar
  30. Medina, V.A., Donohue, T.M., Sorrell, M.F. and Tuma, D.J. (1985). Covalent binding of acetaldehyde to hepatic proteins during ethanol oxidation. J. Lab. Clin. Med. 105, 5–10.PubMedGoogle Scholar
  31. Neuberger, J., Crossley, I.R., Saunders, J., Davis, M., Portmann, B., Eddleston, A.L.W.F. and Williams, R. (1984). Antibodies to alcohol-altered liver cell determinants in patients with alcohol liver disease. Gut 25, 300–304.CrossRefPubMedGoogle Scholar
  32. Niemela, O. and Israel, Y. (1987a). Immunological detection of acetaldehyde containing epitopes (ACES) in human hemoglobin: a new test in alcoholism (abstract). Alcoholism: Clin. Exp. Res. 11, 203.Google Scholar
  33. Niemela, O., Klajner, F., Orrego, H., Vidins, E., Blendis, L. and Israel, Y. (1987b). Antibodies against acetaldehyde-modified protein epitopes in human alcoholics. Hepatology 7, 1210–1214.CrossRefPubMedGoogle Scholar
  34. Nomura, F. and Lieber, C.S. (1981). Binding of acetaldehyde to rat liver microsomes: enhancement after chronic alcohol consumption. Biochem. Biophys. Res. Commun. 100, 131–137.CrossRefPubMedGoogle Scholar
  35. Peachey, J.E. and Sellers, E.M. (1981). The disulfiram and calcium carbimide acetaldehyde-mediated ethanol reactions. Pharmacol. Ther. 15, 89–97.CrossRefPubMedGoogle Scholar
  36. Reynier, M. (1969). Pyrazole inhibition and kinetic studies of ethanol and retinol oxidation catalyzed by rat liver alcohol dehydrogenase. Acta Chem. Scand. 23, 1119–1129.CrossRefPubMedGoogle Scholar
  37. Ritchie, J.M. (1985). The aliphatic alcohols. In: The Pharmacological Basis of Therapeutics ( Gilman, A.G., Goodman, L.S, Gilman, A., Eds.) 7th Ed., pp. 372–386, McMillan, New York.Google Scholar
  38. Salaspuro, M. and Lindros, K. (1985). Metabolism and toxicity of acetaldehyde. In: Alcohol Related Diseases in Gastroenterology ( Seitz, H.K., Kommerell, B., Eds), pp. 105–123, Springer-Verlag, Berlin.Google Scholar
  39. Stevens, V.J., Fantl, W.J., Newman, C.B., Sims, R.V., Cerami, A. and Peterson, C.M. (1981). Acetaldehyde adducts with hemoglobin. J. Clin. Invest. 67, 361–369.CrossRefPubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Renee C. Lin
    • 1
  • Lawrence Lumeng
    • 1
  1. 1.Departments of Medicine and BiochemistryIndiana University School of Medicine, and the Veterans Affairs Medical CenterIndianapolisUSA

Personalised recommendations