Role of Hydroxyl Radicals in Microsomal Oxidation of Alcohols

  • Arthur I. Cederbaum
  • Elisa Dicker
  • Gerald Cohen


A series of hydroxyl radical (•0H) scavenging agents competitively inhibited microsomal oxidation of ethanol and 1-butanol. The inhibition by the scavengers was specific since these agents had no effect on catalase-dependent oxidation of ethanol, microsomal drug metabolism or microsomal electron transfer. Chemical evidence for production of •OH during microsomal electron transfer was provided by the generation of appropriate products from •OH scavenging agents. H2O2 was shown to play a role as a precursor of •OH. Fe-EDTA increased microsomal oxidation of ethanol without affecting drug metabolism. A role for cytochrome P-450 in catalyzing •OH generation remains to be evaluated. These results suggest that the molecular mechanism underlying the oxidation of ethanol by liver microsomes reflects the ability of ethanol to interact with •OH generated from microsomal electron transfer.


Liver Microsome Ethanol Oxidation Chemical Evidence Aniline Hydroxylase Microsomal Oxidation 
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. Anbar, M., and Neta, P., 1967, A compilation of specific bimolecular rate constants for the reactions of hydrated electrons, hydrogen atoms and hydroxyl radicals with inorganic and organic compounds in aqueous solution, Int. J. Appl. Radiat. Isot., 18: 493.CrossRefGoogle Scholar
  2. Beauchamp, C., and Fridovich, I., 1970, A mechanism for the production of ethylene from methional. The generation of the hydroxyl radical by xanthine oxidase, J. Biol. Chem., 245: 4641.PubMedGoogle Scholar
  3. Brownlee, N.R., J.J. Huttner, R.V. Panganamala, and D.G. Cornwell, 1977, Role of vitamin E in glutathione-induced oxidant stress: Methemoglobin, lipid peroxidation, and hemolysis, J. Lipid Res., 18: 365.Google Scholar
  4. Cederbaum, A.I., E. Dicker, E. Rubin, and G. Cohen, 1977, The effect of dimethylsulfoxide and other hydroxy radical scavengers on the oxidation of ethanol by rat liver microsomes, Biochem. Biophys. Res. Comm., 78: 1254.PubMedCrossRefGoogle Scholar
  5. Cederbaum, A.I., E. Dicker,.arid G. Cohen, 1978, Effect of hydroxyl radical scavengers on microsomal oxidation of alcohols and on associated microsomal reactions, Biochem., 17: 3058CrossRefGoogle Scholar
  6. Cederbaum, A.I., E. Dicker, E. Rubin, and G. Cohen, 1979Google Scholar
  7. Effect on thiourea on microsomal oxidation of alcohols and associated microsomal functions, Biochem., 18:1187.Google Scholar
  8. Cederbaum, A.I., E. Dicker, and G. Cohen, 1980, (submitted for publication).Google Scholar
  9. Cohen, G., and R.E. Heikkila, 1974, The generation of hydrogen peroxide, superoxide radical, and hydroxyl radical by 6hydroxydopamine, dialuric acid, and related cytotoxic agents, J. Biol. Chem., 249: 2447.PubMedGoogle Scholar
  10. Cohen, G., and A.I. Cederbaum, 1979, Chemical evidence for production of hydroxyl radicals during microsomal electron transfer, Science, 204: 66.PubMedCrossRefGoogle Scholar
  11. Cohen, G., and A.I. Cederbaum, 1980, Microsomal metabolism of hydroxyl radical scavenging agents: Relationship to the microsomal oxidation of alcohols, Arch. Biochem. Biophys., 199: 438.PubMedCrossRefGoogle Scholar
  12. Haber, F., and J. Weiss, 1934, The catalytic decomposition of hydrogen peroxide by iron salts, Proc. R. Soc. London, Ser. A., 147: 332.CrossRefGoogle Scholar
  13. Halliwell, B., 1978, Superoxide-dependent formation of hydroxyl radicals in the presence of iron chelates: Is it a mechanism for hydroxyl radical production in biochemical systems?, FEBS Lett., 92; 321.PubMedCrossRefGoogle Scholar
  14. Joly, J.G., J.P. Villeneuve, and P. Mavier, 1977, Chronic ethanol administration induces a form of cytochrome P-450 with specific spectral and catalytic properties, Alcoholism: Clin. Exp. Res., 1: 17.CrossRefGoogle Scholar
  15. Lieber, C.S., and L.M. DeCarli, 1970, Hepatic microsomal ethanol oxidizing system. In vitro characteristics and adaptive properties in vivo, J. Biol. Chem., 245: 2505.PubMedGoogle Scholar
  16. Lieber, C.S., and DeCarli, L.M., 1972, The role of the hepatic microsomal ethanol oxidizing system ( MEOS) for ethanol metabolism in vivo, J. Pharmacol. Exp. Ther., 181: 279.PubMedGoogle Scholar
  17. McCord, J. M., and Day, E. D., 1978, Superoxide dependent production of hydroxyl radical catalyzed by iron-EDTA complex, FEBS Lett., 86: 139.PubMedCrossRefGoogle Scholar
  18. McLune, G. J., and Fee, J. A., 1976, Stopped flow spectrophotometric observation of superoxide dismutation in aqueous solution, FEBS Lett., 67: 294.CrossRefGoogle Scholar
  19. Miwa, G. T., Levin, W., Thomas, P. E., and Lu, A. Y. H., 1978, The direct oxidation of ethanol by a catalase-and alcohol dehydrogenase-free reconstituted system containing cytochrome P-450, Arch. Biochem. Biophys., 187: 464.CrossRefGoogle Scholar
  20. Ohnishi, K., and Lieber, C. S., 1977, Reconstitution of the microsomal ethanol oxidizing system. Qualitative and quantitative changes of cytochrome P-450 after chronic ethanol consumption, J. Biol. Chem., 252: 7124.PubMedGoogle Scholar
  21. Rigo, A., Stevanato, R., Finazzi-Agro, A., and Rotilio, G., 1977, An attempt to evaluate the rate of the Haber-Weiss reaction by using SOH radical scavengers, FEBS Lett., 80: 130.PubMedCrossRefGoogle Scholar
  22. Tauber, A. I., and Babior, B. M., 1977, Evidence for hydroxyl radical production by human neutrophiles, J. Clin. Invest., 60: 374.PubMedCrossRefGoogle Scholar
  23. Teschke, R., Matsuzaki, S., Ohnishi, K., DeCarli, L. M., andGoogle Scholar
  24. Lieber, C. S., 1977, Microsomal ethanol oxidizing system (MEOS): current status of its characterization and its role, Alcoholism: Clin. Exp. Res., 1: 7.CrossRefGoogle Scholar
  25. Walling, C., 1975, Fentons reagent revisited, Acc. Chem. Res., 8: 125.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1980

Authors and Affiliations

  • Arthur I. Cederbaum
    • 1
  • Elisa Dicker
    • 1
  • Gerald Cohen
    • 1
  1. 1.Departments of Biochemistry and Neurology and Alcohol Research CenterMount Sinai School of Medicine, CUNYNew YorkUSA

Personalised recommendations