Summary
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 1.1.2.2.-tetrachloroethane (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.
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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.
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.
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: 197
Fronmer, U., Ullrich, V. and Staudinger, H., 1970, Hydroxylation of aliphatic compounds by liver microsomes, Hoppe-Seyler’s Z. Physiol. Chem. 351: 903.
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.
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: 751
Harada, N. and Omura, T., 1979, Participation of cytochrome P450 in the reduction of nitro compounds by rat liver microsomes, J. Biochem., 87: 1539.
Hernandez, P.H., Mazel, P. and Gillette, J.R., 1967, Studies on the mechanism of action of mammalian hepatic azoreductase-II, Biochem. Pharmacol., 16: 1877
Jondorf, W.R. Parke, D.V. and Williams, R.T., 1957, The metabolism of (’4C) hexachloroethane, Biochem. J., 65, No. 2: 14 p.
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.
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: 387
Omura, T. and Sato, R., 1964, The carbon monoxide-binding pigment of liver microsomes, J. Biol. Chem. 239: 2370.
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.
Ullrich, V., 1972, Enzymatic hydroxylations with molecular oxygen Angew. Chem. Intern. edit., 11: 701.
Wolf, R., Mansuy, D., Nastainczyk, W., Deutschmann, G., Ullrich, V., 1977, The reduction of polyhalogenated methanes by liver microsomal cytochrome P450, Mol. Pharmacol., 13: 698
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Nastainczyk, W., Ahr, H., Ulrich, V. (1982). The Mechanism of the Reductive Dehalogenation of Polyhalogenated Compounds by Microsomal Cytochrome P450. In: Snyder, R., et al. Biological Reactive Intermediates—II. Advances in Experimental Medicine and Biology, vol 136. Springer, New York, NY. https://doi.org/10.1007/978-1-4757-0674-1_62
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DOI: https://doi.org/10.1007/978-1-4757-0674-1_62
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