title: Cytochrome P450 3A4 mediated metabolism of 2,4-dichlorophenol.
abstract: The metabolism of the environmental pollutant and hepatocarcinogen 2,4-dichlorophenol (2,4-DCP) was studied using microsomal fractions and whole-cells of Saccharomyces cerevisiae containing human cytochrome P450 3A4. 2,4-DCP exhibited a typical type I substrate binding spectrum with a K, of 75 microM. 2,4-DCP was metabolised into two major metabolites identified as 2-chloro-1,4-hydroxyquinone and 2-chloro-1,4-benzoquinone in microsomal fractions and whole cells of yeast expressing human cytochrome P450 3A4. A further metabolite, 1,2,4-hydroxybenzene, was also detected during biotransformation by whole cells, but was not observed in microsomal fractions. 2,4-DCP metabolism was dependent on NADPH in microsomal fractions and no activity was observed in microsomal fractions or whole cells of control transformants. Metabolites were identified by TLC followed by GC-MS.
authors.affiliation: Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, 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: D000871:Anthelmintics / Q000378:metabolism*; D016227:Benzoquinones / Q000032:analysis / Q000378:metabolism; D001665:Binding Sites; D001711:Biotransformation; D002733:Chlorophenols / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D003470:Culture Media; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004785:Environmental Pollutants / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006873:Hydroquinones / Q000032:analysis / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000254:growth & development
chemical_list: D000871:Anthelmintics; D016227:Benzoquinones; D002733:Chlorophenols; D003470:Culture Media; D004785:Environmental Pollutants; D006873:Hydroquinones; D011994:Recombinant Proteins; D009249:NADP; C107220:2-chloro-1,4-hydroxyquinone; C107221:2-chloro-1,4-benzoquinone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C004762:2,4-dichlorophenol