The Mechanism of the Reductive Dehalogenation of Polyhalogenated Compounds by Microsomal Cytochrome P450

  • Wolfgang Nastainczyk
  • Hansjürgen Ahr
  • Volker Ulrich
Part of the Advances in Experimental Medicine and Biology book series (AEMB)


Polyhalogenated ethanes are metabolized by reductive dehalogenation under anaerobic and also hypoxic conditions in vitro in the presence of NADPH and hepatic microsomal cytochrome P450. The cytochrome P450 dependence was shown by induction and inhibition experiments using microsomal fractions from livers of rats receiving Various pretreatments. The main products of the in vitro metabolism of hexa- and pentachloroethane were tetra- and trichloroethene, respectively. Minor products were penta- (0.5%) and (4%). The stoichiometry of NADPH-oxidation and product formation was 1:1. From these results and earlier investigations on polyhalogenated methanes, a reaction scheme is proposed. The reductive dehalogenation probably proceeds by two sequential one electron reductions forming first a radical and then a carbanion. The carbanion may undergo protonation, α-, or β-elimination forming a monodehalogenated haloalkane, an olefin or a carbene, respectively.


Carbon Tetrachloride Liver Microsome NADPH Oxidation Microsomal Cytochrome Carbene Complex 
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. Ahr, J.H., King, L.J., Nastainczyk, W., Ullrich, V.1980, The mech-anism of chloroform and carbon monoxide formation from carbon tetrachloride by microsomal cytochrome P450, Biochem. Pharmacol. in press.Google Scholar
  2. Bartlet, A.L., 1976, Actions of carbon tetrachloride, hexachloroethane and the products of their metabolism in sheep on fasciola hepatica, Br. J. Pharmac. 58: 395.CrossRefGoogle Scholar
  3. Booth, J., Hewer, A., Keysal l, G.R., Sims, R., 1975, Enzymatic reduction of aromatic hydrocarbon epoxides by the microsomal fraction of rat liver, Xenobiotica, 5: 197Google Scholar
  4. Fronmer, U., Ullrich, V. and Staudinger, H., 1970, Hydroxylation of aliphatic compounds by liver microsomes, Hoppe-Seyler’s Z. Physiol. Chem. 351: 903.CrossRefGoogle Scholar
  5. Gillette, J.R., Kamm, J.J. and Sasame, H.A., 1968, Mechanism of pnitrobenzoate reduction in liver: The possible role of cytochrome P450 in liver microsomes, Mol. Pharmacol., 4: 541.PubMedGoogle Scholar
  6. Gornall, A.G., Bardawill, C.J. and David, M.M., 1949, Determination of serum protein by means of the biuret reaction, J. Biol. Chem., 177: 751Google Scholar
  7. Harada, N. and Omura, T., 1979, Participation of cytochrome P450 in the reduction of nitro compounds by rat liver microsomes, J. Biochem., 87: 1539.Google Scholar
  8. Hernandez, P.H., Mazel, P. and Gillette, J.R., 1967, Studies on the mechanism of action of mammalian hepatic azoreductase-II, Biochem. Pharmacol., 16: 1877Google Scholar
  9. Jondorf, W.R. Parke, D.V. and Williams, R.T., 1957, The metabolism of (’4C) hexachloroethane, Biochem. J., 65, No. 2: 14 p.Google Scholar
  10. McLean, A.E.M. and McLean, E.K., 1966, The effect of diet and 1.1. 1-trichloro-2.2-bis-(p-chlorophenyl)ethane (DDT) on microsomal hydroxylating enzymes and on sensitivity of rats to CC14 poisoning, Biochem. J., 100: 564.PubMedGoogle Scholar
  11. Nastainczyk, W., Ullrich, V. and Sies, H., 1978, Effect of oxygen concentration on the reaction of halothane with cytochrome P450 in liver microsomes and isolated perfused rat liver, Biochem. Pharmacol., 17: 387Google Scholar
  12. Omura, T. and Sato, R., 1964, The carbon monoxide-binding pigment of liver microsomes, J. Biol. Chem. 239: 2370.PubMedGoogle Scholar
  13. Poyer, J.L., Floyd, R.A., McCay, P.B., Janzen, E.G., Davis, E.P., 1978, Spin-trapping of the trichloromethyl radical produced during enzymic NADPH oxidation in the presence of carbon tetrachloride or bromotrichloromethane, Biochim. Biophys. Acta, 539: 402.PubMedCrossRefGoogle Scholar
  14. Ullrich, V., 1972, Enzymatic hydroxylations with molecular oxygen Angew. Chem. Intern. edit., 11: 701.Google Scholar
  15. Wolf, R., Mansuy, D., Nastainczyk, W., Deutschmann, G., Ullrich, V., 1977, The reduction of polyhalogenated methanes by liver microsomal cytochrome P450, Mol. Pharmacol., 13: 698Google Scholar

Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • Wolfgang Nastainczyk
    • 1
  • Hansjürgen Ahr
    • 1
  • Volker Ulrich
    • 1
  1. 1.Department of Physiological ChemistryUniversity of Saarland665 Homburg-SaarFederal Republic of Germany

Personalised recommendations