title: Metabolism of the herbicide chlortoluron by human cytochrome P450 3A4.
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 microM. 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.
authors.affiliation: Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, Sheffield University, UK.
authors.forename: Z
authors.initials: Z
authors.lastname: Mehmood
authors.forename: D E
authors.initials: DE
authors.lastname: Kelly
authors.forename: S L
authors.initials: SL
authors.lastname: Kelly
mesh_terms: D001345:Autoradiography; D001711:Biotransformation; D002248:Carbon Monoxide / Q000378:metabolism; D002384:Catalysis; D002855:Chromatography, Thin Layer; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D006540:Herbicides / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D008745:Methylation; D006899:Mixed Function Oxygenases / Q000096:biosynthesis* / Q000378:metabolism; D010671:Phenylurea Compounds / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D006540:Herbicides; D010671:Phenylurea Compounds; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C007033:chlortoluron