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Vol. 26, Issue 10, 1045-1047, October 1998

SHORT COMMUNICATION
Major Cytochrome P450 Enzyme Responsible for Oxidation of Secondary Alcohols to the Corresponding Ketones in Mouse Hepatic Microsomes
Oxidation of 7-Hydroxy-Delta 8-tetrahydrocannabinol to 7-Oxo-Delta 8-tetrahydrocannabinol

Tamihide Matsunaga, Nobuyuki Kishi, Hiroyuki Tanaka, Kazuhito Watanabe, Hidetoshi Yoshimura, and Ikuo Yamamoto

Department of Hygienic Chemistry
Faculty of Pharmaceutical Sciences
Hokuriku University
(T.M., N.K., H.T., K.W., I.Y.) and
Department of Food and Nutrition
Nakamura Gakuen University (H.Y.)

The oxidative activities of 7alpha - and 7beta -hydroxy-Delta 8-tetrahydrocannabinol (7alpha - and 7beta -hydroxy-Delta 8-THC) to 7-oxo-Delta 8-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 7alpha - and 7beta -hydroxy-Delta 8-THC were 2.55 and 4.92 nmol/min/nmol P450, respectively. The antibody against P450MDX-B almost completely inhibited the oxidative activities of 7alpha - and 7beta -hydroxy-Delta 8-THC in mice. These results indicate that P450MDX-B (CYP3A11) is a major enzyme responsible for the oxidation of 7alpha - and 7beta -hydroxy-Delta 8-THC to 7-oxo-Delta 8-THC in mouse liver.


Copyright © 1998 by The American Society for Pharmacology and Experimental Therapeutics



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T. Matsunaga, H. Tanaka, S. Higuchi, K. Shibayama, N. Kishi, K. Watanabe, and I. Yamamoto
Oxidation Mechanism of 7-Hydroxy-Delta 8-tetrahydrocannabinol and 8-Hydroxy-Delta 9-tetrahydrocannabinol to the Corresponding Ketones by CYP3A11
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Drug Metab. Dispos.Home page
T. Matsunaga, N. Kishi, S. Higuchi, K. Watanabe, T. Ohshima, and I. Yamamoto
CYP3A4 Is a Major Isoform Responsible for Oxidation of 7-Hydroxy-Delta 8-tetrahydrocannabinol to 7-Oxo-Delta 8-tetrahydrocannabinol in Human Liver Microsomes
Drug Metab. Dispos., November 1, 2000; 28(11): 1291 - 1296.
[Abstract] [Full Text]




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