RT Journal Article
SR Electronic
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
FD American Society for Pharmacology and Experimental Therapeutics
SP 1045
OP 1047
VO 26
IS 10
A1 Tamihide Matsunaga
A1 Nobuyuki Kishi
A1 Hiroyuki Tanaka
A1 Kazuhito Watanabe
A1 Hidetoshi Yoshimura
A1 Ikuo Yamamoto
YR 1998
UL http://dmd.aspetjournals.org/content/26/10/1045.abstract
AB 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