title: Cytochrome P4502D isozymes catalyze the 4-hydroxylation of methamphetamine enantiomers.
abstract: The 4-hydroxylation of S(+)- and R(-)-methamphetamine by rat liver microsomes was examined in Sprague-Dawley and Dark Agouti strains to determine the role of cytochrome P4502D (CYP2D) subfamily isozymes in catalyzing the reaction. In the study, anti-P450-BTL IgG, bufuralol, and quinine, a substrate and inhibitors of CYP2D isozymes, respectively, were found to block approximately 90% of the reaction as catalyzed by microsomes from Sprague-Dawley rats. Reconstituted systems of CYP2D isozymes purified from rat liver microsomes also mediated the reaction. These observations and the minimal activity found in microsomes from Dark Agouti rats support the notion that methamphetamine, like other phenylisopropylamine compounds, is oxidized on the 4-position of the aromatic ring by CYP2D isozymes.
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California Los Angeles School of Medicine 90095-1735, USA.
authors.forename: L Y
authors.initials: LY
authors.lastname: Lin
authors.forename: Y
authors.initials: Y
authors.lastname: Kumagai
authors.forename: A
authors.initials: A
authors.lastname: Hiratsuka
authors.forename: S
authors.initials: S
authors.lastname: Narimatsu
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Funae
authors.forename: E W
authors.initials: EW
authors.lastname: Distefano
authors.forename: A K
authors.initials: AK
authors.lastname: Cho
mesh_terms: D000818:Animals; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008694:Methamphetamine / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013237:Stereoisomerism
chemical_list: D007527:Isoenzymes; D008694:Methamphetamine; D003577:Cytochrome P-450 Enzyme System