Oxidation of 7-Hydroxy-Δ8-tetrahydrocannabinol to 7-Oxo-Δ8-tetrahydrocannabinol
Abstract
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.
Footnotes
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Send reprint requests to: Dr. Ikuo Yamamoto, Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa 920-1181, Japan.
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This work was partially supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan, and by the Special Research Fund of Hokuriku University.
- Abbreviations used are::
- THC
- tetrahydrocannabinol
- MALCO
- microsomal alcohol oxygenase
- P450
- cytochrome P450
- HPLC
- high-performance liquid chromatography
- Received January 27, 1998.
- Accepted May 27, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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