TY - JOUR T1 - Major Cytochrome P450 Enzyme Responsible for Oxidation of Secondary Alcohols to the Corresponding Ketones in Mouse Hepatic Microsomes JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1045 LP - 1047 VL - 26 IS - 10 AU - Tamihide Matsunaga AU - Nobuyuki Kishi AU - Hiroyuki Tanaka AU - Kazuhito Watanabe AU - Hidetoshi Yoshimura AU - Ikuo Yamamoto Y1 - 1998/10/01 UR - http://dmd.aspetjournals.org/content/26/10/1045.abstract N2 - The oxidative activities of 7α- and 7β-hydroxy-Δ8-tetrahydrocannabinol (7α- and 7β-hydroxy-Δ8-THC) to 7-oxo-Δ8-THC in hepatic microsomes of mice were significantly increased by the treatment of mice with dexamethasone or phenobarbital. A cytochrome P450 enzyme, named P450MDX-B, was purified from hepatic microsomes of dexamethasone-treated mice, and its apparent molecular mass was estimated to be 51,000. The NH2-terminal amino acid sequence of P450MDX-B was the same as that of CYP3A11. The oxidative activities of 7α- and 7β-hydroxy-Δ8-THC were 2.55 and 4.92 nmol/min/nmol P450, respectively. The antibody against P450MDX-B almost completely inhibited the oxidative activities of 7α- and 7β-hydroxy-Δ8-THC in mice. These results indicate that P450MDX-B (CYP3A11) is a major enzyme responsible for the oxidation of 7α- and 7β-hydroxy-Δ8-THC to 7-oxo-Δ8-THC in mouse liver. The American Society for Pharmacology and Experimental Therapeutics ER -