Skip to main content

Microsomal Ethanol Oxidation: Activity in Vitro and in Vivo

  • Chapter
Biochemical Pharmacology of Ethanol

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 56))

Abstract

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).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Lieber, C.S. and DeCarli, L.M.: Ethanol oxidation by hepatic microsomes: Adaptive increase after ethanol feeding. Science 162: 917–918, 1968

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  3. Lieber, C.S.: New pathway of ethanol metabolism in the liver. Gastroenterology 59: 930–937, 1970.

    PubMed  CAS  Google Scholar 

  4. Rubin, E. and Lieber, C.S.: Alcoholism, alcohol and drugs. Science 172: 1097–1102, 1971.

    Article  PubMed  CAS  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    Article  CAS  Google Scholar 

  13. Rubin, E., Hutterer, F. and Lieber, C.S.: Ethanol increases hepatic smooth endoplasmic reticulum and drug-metabolizing enzymes. Science 159: 1469–1470, 1968.

    Article  PubMed  CAS  Google Scholar 

  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. Rubin, E., Gang, H. and Lieber, C.S.: Interaction of ethanol and pyrazole with hepatic microsomes. Biochem. Biophys. Res. Commun. 42: 1–8, 1971.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    PubMed  CAS  Google Scholar 

  18. Keilin, D. and Hartree, E.F.: Properties of catalase. Catalysis of coupled oxidation of alcohol. Biochem. J. 39: 293–301, 1945.

    CAS  Google Scholar 

  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, 1957

    CAS  Google Scholar 

  20. Lieber, C.S. and DeCarli, L.M.: Reduced nicotinamide-adenine dinucleotide phosphate oxidase: Activity enhanced by ethanol consumption. Science 170: 78–80, 1970.

    Article  PubMed  CAS  Google Scholar 

  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.

    CAS  Google Scholar 

  22. Boveris, A., Oshino, N. and Chance, B.: The cellular production of hydrogen peroxide. Biochem. J. 128: 617–630, 1972.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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. Oshino, N., Oshino, R. and Chance, B.: The characteristics of the ‘peroxidatic’ reaction of catalase in ethanol oxidation. Biochem. J. 131: 555–567, 1973.

    PubMed  CAS  Google Scholar 

  27. Feinstein, R.N.: Perborate as substrate in a new assay of catalase. J. Biol. Chem. 180: 1197–1202, 1949.

    PubMed  CAS  Google Scholar 

  28. Goldstein, D.B.: A method for assay of catalase with the oxygen cathode. Anal. Biochem. 24: 431–437, 1968.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  30. Lin, G., Kalant, H. and Khanna, J.M.: Catalase involvement in microsomal ethanol-oxidizing system. Biochem. Pharmacol. 21: 3305–3308, 1972.

    Article  PubMed  CAS  Google Scholar 

  31. Theorell, H. and Yonetani, T.: Liver alcohol dehydrogenase-DPN-pyrazole complex. Biochem. Z. 338: 537–553, 1963.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    CAS  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  38. Lieber, C.S. and DeCarli, L.M.: Role of hepatic microsomal ethanol metabolism. Chem.-Biol. Interactions 3: 292–293, 1971.

    CAS  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  42. Klaassen, C.D.: Ethanol metabolism in rats after microsomal metabolizing enzyme induction. Proc. Soc. Exp. Biol. Med. 132: 1099–1102, 1969.

    PubMed  CAS  Google Scholar 

  43. Tephly, T.R., Tinelli, F. and Watkins, W.D.: Alcohol metabolism: Role of microsomal oxidation in vivo. Science 166: 627–628, 1969.

    Article  PubMed  CAS  Google Scholar 

  44. Mezey, E.: Effect of phenobarbital administration on ethanol oxidizing enzymes and on rates of ethanol degradation. Biochem. Pharmacol. 20: 508–510, 1971.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1975 Plenum Press, New York

About this chapter

Cite this chapter

Roach, M.K. (1975). Microsomal Ethanol Oxidation: Activity in Vitro and in Vivo . In: Majchrowicz, E. (eds) Biochemical Pharmacology of Ethanol. Advances in Experimental Medicine and Biology, vol 56. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-7529-6_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-7529-6_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-7531-9

  • Online ISBN: 978-1-4684-7529-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics