Metabolism of organochlorine pesticides: the role of human cytochrome P450 3A4.
Organochlorine compounds are widely used as pesticides and are substantial environmental pollutants and carcinogens due to their extensive environmental release. In the present study biotransformation of these pesticides was observed in the microsomal fractions and whole cells of Saccharomyces cerevisiae expressing human cytochrome P450 3A4. In both in vitro and in vivo studies, hexachlorobenzene and pentachlorobenzene were metabolised into pentachlorophenol which was further transformed into tetrachlorohydroquinone. Metabolites were identified by thin layer chromatography and 13C-NMR spectroscopy. The formation of products was observed only in the presence NADPH in microsomal fractions and no activity was observed in control microsomal fractions, or in whole cells.
Mehmood
Z
Z
Department of Molecular Biology and Biotechnology, Sheffield University, UK.
Williamson
M P
MP
Kelly
D E
DE
Kelly
S L
SL
D001189:Aryl Hydrocarbon Hydroxylases; D001711:Biotransformation; D002855:Chromatography, Thin Layer; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D006801:Humans; D006843:Hydrocarbons, Chlorinated; D007306:Insecticides / Q000493:pharmacokinetics*; D009682:Magnetic Resonance Spectroscopy; D008861:Microsomes / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
D006843:Hydrocarbons, Chlorinated; D007306:Insecticides; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating