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Metabolism of the herbicide chlortoluron by human cytochrome P450 3A4
Authors:Zahid Mehmood  Diane E Kelly  Steven L Kelly
Abstract:Studies were carried out to investigate the metabolism of herbicide chlortoluron in the microsomal fractions and whole cells of Saccharomyces cerevisiae expressing human cytochrome P450 3A4. Both whole cells and microsomal fractions of yeast expressing human cytochrome P450 3A4 exhibited a typical dithionite-reduced, CO-difference absorbance spectrum with maximum absorbance at 448 nm. Chlortoluron produced a type I binding spectrum with cytochrome P450 3A4 with a Ks value of 200 μM. Chlortoluron was metabolised into four metabolites; hydroxylated-N-monodemethylated, hydroxylated ring methylated, N-didemethylated and N-monodemethylated products. Chlortoluron metabolism was absolutely dependent on NADPH and no metabolism was observed in control transformants.
Keywords:Cytochrome P450 3A4  yeast expression  chlortoluron  biotransformation
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