Microsomal Ethanol Oxidation: Activity in Vitro and in Vivo

  • Mary K. Roach
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 56)


The oxidation of ethanol to acetaldehyde by components of the microsomal fraction of mammalian liver has been proposed as a route of alcohol metabolism ancillary to the alcohol dehydrogenase pathway (1, 2, 3, 4, 5). First reported by Orme-Johnson and Ziegler in 1965 (6), the in vitro reaction has since been examined in a number of laboratories. These studies have produced conflicting opinions of the enzymic mechanism, however. Initially, the reaction was thought to be mediated by the hepatic microsomal drug detoxification enzymes in a mechanism that did not involve either of the known alcohol oxidizing enzymes, alcohol dehydrogenase or catalase (1, 2, 6). The possibility of a mutual pathway for the metabolism of alcohol and other drugs stimulated great interest in this process. Later evidence indicated, however, that the reaction was hydrogen peroxide dependent, and it was suggested that catalase,as a contaminant of the microsomes, was the enzyme responsible for the conversion of ethanol to acetaldehyde (7, 8, 9, 10).


Ethanol Oxidation Ethanol Metabolism Mixed Function Oxidase Alcohol Metabolism Aldehyde Production 
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. 1.
    Lieber, C.S. and DeCarli, L.M.: Ethanol oxidation by hepatic microsomes: Adaptive increase after ethanol feeding. Science 162: 917–918, 1968PubMedCrossRefGoogle Scholar
  2. 2.
    Lieber, C.S. and DeCarli, L.M.: Hepatic microsomal ethanol-oxidizing system: In vitro characteristics and adaptive properties in vivo. J. Biol. Chem. 245: 2505–2512, 1970.PubMedGoogle Scholar
  3. 3.
    Lieber, C.S.: New pathway of ethanol metabolism in the liver. Gastroenterology 59: 930–937, 1970.PubMedGoogle Scholar
  4. 4.
    Rubin, E. and Lieber, C.S.: Alcoholism, alcohol and drugs. Science 172: 1097–1102, 1971.PubMedCrossRefGoogle Scholar
  5. 5.
    Lieber, C.S. and DeCarli, L.M.: The significance and characterization of hepatic microsomal ethanol oxidation in the liver. Drug Metab. Dis. 1: 428–440, 1973.Google Scholar
  6. 6.
    Orme-Johnson, W.H. and Ziegler, D.M.: Alcohol mixed function oxidase activity of mammalian liver microsomes. Biochem. Biophys. Res. Commun. 21: 78–82, 1965.PubMedCrossRefGoogle Scholar
  7. 7.
    Roach, M.K., Reese, W.N. and Creaven, P.J.: Ethanol oxidation in the microsomal fraction of rat liver. Biochem. Biophys. Res. Commun. 36: 596–602, 1969.PubMedCrossRefGoogle Scholar
  8. 8.
    Khanna, J.M., Kalant, H. and Lin. G.: Metabolism of ethanol by rat liver enzymes. Biochem. Pharmacol. 19: 2493–2499, 1970.Google Scholar
  9. 9.
    Isselbacher, K.J. and Carter, E.Â.: Ethanol oxidation by liver microsomes: Evidence against a separate and distinct enzyme system. Biochem. Biophys. Res. Commun. 39: 530–537, 1970.PubMedCrossRefGoogle Scholar
  10. 10.
    Thurman, R.G., Ley, H.G. and Scholz, R.: Hepatic microsomal ethanol oxidation: Hydrogen peroxide formation and the role of catalase. Eur. J. Biochem. 25: 420–430, 1972.PubMedCrossRefGoogle Scholar
  11. 11.
    Roach, M.K., Reese, W.N. and Creaven, P.J.: Microsomal ethanol metabolism in rat liver. Abstract, Fed. Proc. 28: 546, 1969.Google Scholar
  12. 12.
    Lieber, C.S. and DeCarli, L.M.: Effect of drug administration on the activity of the hepatic microsomal ethanol oxidizing system. Life Sci. 9: 267–276, 1970.CrossRefGoogle Scholar
  13. 13.
    Rubin, E., Hutterer, F. and Lieber, C.S.: Ethanol increases hepatic smooth endoplasmic reticulum and drug-metabolizing enzymes. Science 159: 1469–1470, 1968.PubMedCrossRefGoogle Scholar
  14. 14.
    Rubin, E., Lieber, C.S., Alvares, A.P., Levin, W. and Kuntzman, R.: Ethanol binding to hepatic microsomes: Its increase by ethanol consumption. Biochem. Pharmacol. 20: 229231, 1971.Google Scholar
  15. 15.
    Rubin, E., Gang, H. and Lieber, C.S.: Interaction of ethanol and pyrazole with hepatic microsomes. Biochem. Biophys. Res. Commun. 42: 1–8, 1971.PubMedCrossRefGoogle Scholar
  16. 16.
    Gillette, J.R. and Gram, T.E.: Cytochrome P-450 reduction in liver microsomes and its relationship to drug metabolism. In: Microsomes and Drug Oxidations, Gillette. J.R., Conney, A.H., Cosmides, G.J., Estabrook, R.W., Fouts, J.R.and Mannering, G.J., (eds.) pp. 133–148 Academic Press, New York, 1969.Google Scholar
  17. 17.
    Roach, M.K., Khan, M., Knapp, M. and Reese, W.N.: Ethanol metabolism in vivo and the role of hepatic microsomal ethanol oxidation. Quart. J. Stud. Alcohol 33: 751–755, 1972.PubMedGoogle Scholar
  18. 18.
    Keilin, D. and Hartree, E.F.: Properties of catalase. Catalysis of coupled oxidation of alcohol. Biochem. J. 39: 293–301, 1945.Google Scholar
  19. 19.
    Gillette, J.R., Brodie, B.B. and LaDu, B.N.: The oxidation of drugs by liver microsomes: On the role of TPNH and oxygen. J. Pharmac, Exp. Ther. 119: 532–540, 1957Google Scholar
  20. 20.
    Lieber, C.S. and DeCarli, L.M.: Reduced nicotinamide-adenine dinucleotide phosphate oxidase: Activity enhanced by ethanol consumption. Science 170: 78–80, 1970.PubMedCrossRefGoogle Scholar
  21. 21.
    Thurman, R.G.: Induction of hepatic microsomal reduced nicotinamide-adenine dinucleotide phosphate-dependent production of hydrogen peroxide by chronic prior treatment with ethanol. Molec. Pharmacol. 9: 670–675, 1973.Google Scholar
  22. 22.
    Boveris, A., Oshino, N. and Chance, B.: The cellular production of hydrogen peroxide. Biochem. J. 128: 617–630, 1972.PubMedGoogle Scholar
  23. 23.
    Hrycay, E.G. and O’Brien, P.J.: Cytochrome P-450 as a microsomal peroxidase utilizing a lipid peroxide substrate. Arch. Biochem. Biophys. 147: 14–27, 1971.PubMedCrossRefGoogle Scholar
  24. 24.
    Mezey, E., Potter, J.J. and Reed, W.D.: Ethanol oxidation by a component of liver microsomes rich in cytochrome P-450. J. Biol. Chem. 248: 1183–1187, 1973.PubMedGoogle Scholar
  25. 25.
    Nicholls, P. and Schonbaum, G.R.: Catalases, In: The Enzymes. Boyer, P.D., Lardy, H. and Myrbach, K., (eds) pp. 147–225, Vol. 8 (2nd edition) Academic Press, New York, 1963.Google Scholar
  26. 26.
    Oshino, N., Oshino, R. and Chance, B.: The characteristics of the ‘peroxidatic’ reaction of catalase in ethanol oxidation. Biochem. J. 131: 555–567, 1973.PubMedGoogle Scholar
  27. 27.
    Feinstein, R.N.: Perborate as substrate in a new assay of catalase. J. Biol. Chem. 180: 1197–1202, 1949.PubMedGoogle Scholar
  28. 28.
    Goldstein, D.B.: A method for assay of catalase with the oxygen cathode. Anal. Biochem. 24: 431–437, 1968.PubMedCrossRefGoogle Scholar
  29. 29.
    Thurman, R.G. and Chance, B.: Inhibition of catalase in perfused rat liver by sodium azide. Ann. N.Y. Acad. Sci. 168: 348–353, 1969.PubMedCrossRefGoogle Scholar
  30. 30.
    Lin, G., Kalant, H. and Khanna, J.M.: Catalase involvement in microsomal ethanol-oxidizing system. Biochem. Pharmacol. 21: 3305–3308, 1972.PubMedCrossRefGoogle Scholar
  31. 31.
    Theorell, H. and Yonetani, T.: Liver alcohol dehydrogenase-DPN-pyrazole complex. Biochem. Z. 338: 537–553, 1963.PubMedGoogle Scholar
  32. 32.
    Teschke, R., Hasumura, Y., Joly, J.-G, Ishii, H. and Lieber, Lieber, C.S.: Microsomal ethanol-oxidizing system (MEOS): Purification and properties of a rat liver system free of catalase and alcohol dehydrogenase. Biochem. Biophys. Res.Commun. 49: 1187–1193, 1972.PubMedCrossRefGoogle Scholar
  33. 33.
    Teschke, R., Hasumura, Y.and Lieber, C.S.: Hepatic microsomal ethanol oxidizing system (MEOS): Solubilization, isolation and characterization. Arch. Biochem. Biophys., In Press.Google Scholar
  34. 34.
    Thurman, R.G. and Scholz, R.: The role of hydrogen peroxide and catalase in hepatic microsomal ethanol oxidation. Drug Metab. Dispos. 1: 441–448, 1973.Google Scholar
  35. 35.
    Thurman, R.G., Hesse, S. and Scholz, R.: The role of NADPHdependent hydrogen peroxide formation and catalase in hepatic microsomal ethanol oxidation. In: Alcohol and aldehyde metabolizing systems, Thurman, R.G., Yonetani, T., Williamson, J.R. and Chance, B., (eds.) pp. 257–269, Academic Press, 1974.Google Scholar
  36. 36.
    Vatsis, K.P. and Schulman, M.P.: Absence of ethanol metabolism in ‘acatalatic’ hepatic microsomes that oxidize drugs. Biochem. Biophys. Res. Commun. 52: 588–594, 1973.PubMedCrossRefGoogle Scholar
  37. 37.
    Feinstein, R.N., Savol, R. and Howard, J.B.: Conversion of catalatic to peroxidatic activity of normal and acatalasemic mice. Enzymologia 41: 345–358, 1971.PubMedGoogle Scholar
  38. 38.
    Lieber, C.S. and DeCarli, L.M.: Role of hepatic microsomal ethanol metabolism. Chem.-Biol. Interactions 3: 292–293, 1971.Google Scholar
  39. 39.
    Lieber, C.S. and DeCarli, L.M.: The role of the hepatic microsomal ethanol oxidizing system (MEOS) for ethanol metabolism in vivo. J. Pharmac. Exp. Ther. 181: 279–287, 1972.Google Scholar
  40. 40.
    Khanna, J.M. and Kalant, H.: Effect of inhibitors and inducers of drug metabolism on ethanol metabolism in vivo. Biochem. Pharmacol. 19: 2033–2041, 1970.PubMedCrossRefGoogle Scholar
  41. 41.
    Khanna, J.M., Kalant, H. and Lin G.: Significance in vivo of the increase in microsomal ethanol-oxidizing system after chronic administration of ethanol, phenobarbital and chlorcyclizine. Biochem. Pharmacol. 21: 2215–2226, 1972.PubMedCrossRefGoogle Scholar
  42. 42.
    Klaassen, C.D.: Ethanol metabolism in rats after microsomal metabolizing enzyme induction. Proc. Soc. Exp. Biol. Med. 132: 1099–1102, 1969.PubMedGoogle Scholar
  43. 43.
    Tephly, T.R., Tinelli, F. and Watkins, W.D.: Alcohol metabolism: Role of microsomal oxidation in vivo. Science 166: 627–628, 1969.PubMedCrossRefGoogle Scholar
  44. 44.
    Mezey, E.: Effect of phenobarbital administration on ethanol oxidizing enzymes and on rates of ethanol degradation. Biochem. Pharmacol. 20: 508–510, 1971.PubMedCrossRefGoogle Scholar
  45. 45.
    Khanna, J.M. Kalant, H., Lin, G. and Bustos, G.O.: Effect of carbon tetrachloride treatment on ethanol metabolism. Biochem. Pharmacol. 20: 3269–3279, 1971.PubMedCrossRefGoogle Scholar
  46. 46.
    Mezey, E.: Duration of the enhanced activity of the microsomal ethanol-oxidizing enzyme system and rate of ethanol degradation in ethanol-fed rats after withdrawal. Biochem. Pharmacol. 21: 137–142, 1972.PubMedCrossRefGoogle Scholar
  47. 47.
    Mezey, E. and Tobon, F.: Rates of ethanol clearance and activities of the ethanol-oxidizing enzymes in chronic alcoholic patients. Gastroenterology 61: 707–715, 1971.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1975

Authors and Affiliations

  • Mary K. Roach
    • 1
  1. 1.Section of BiochemistryTexas Research Institute of Mental Sciences Texas Medical CenterHoustonUSA

Personalised recommendations