Effective NADH-dependent oxidation of 7beta-hydroxy-delta8-tetrahydrocannabinol to the corresponding ketone by Japanese monkey hepatic microsomes

Biological & Pharmaceutical Bulletin
Tamihide MatsunagaIkuo Yamamoto

Abstract

The NADH-dependent activity by hepatic microsomes of Japanese monkeys for 7-oxo-Delta(8)-tetrahydrocannabinol (7-oxo-Delta(8)-THC) formation from 7beta-hydroxy-Delta(8)-THC exhibited about 70% of the NADPH-dependent activity (100%) at the substrate concentration of 72.7 microM, although NADPH was an obligatory cofactor for maximal activity. Both NADH- and NADPH-dependent activities were significantly inhibited by the typical P450 inhibitors, such as SKF525-A and metyrapone. Both activities were almost completely inhibited by the NADPH-P450 reductase inhibitor diphenyliodonium chloride. The ratio of NADH- and NADPH-dependent activities varied significantly according to the substrate concentration. Interestingly, the NADH-dependent activity was higher than that of NADPH at low substrate concentrations of 13-50 microM. The ratio was also affected by the cofactor concentration. In the reconstituted system of CYP3A8 purified from hepatic microsomes of Japanese monkeys as a major enzyme responsible for the NADPH-dependent oxidation, NADH as well as NADPH could sustain the oxidation of 7beta-hydroxy-Delta(8)-THC to the corresponding ketone. The NADH-dependent oxidation of 7beta-hydroxy-Delta(8)-THC by monkey livers is mainly catalyzed...Continue Reading

References

Mar 1, 1976·Archives of Biochemistry and Biophysics·H ShigematsuH Yoshimura
Apr 1, 1977·Chemical & Pharmaceutical Bulletin·H ShigematsuH Yoshimura
Dec 15, 1985·Biochemical Pharmacology·S Kuwahara, G J Mannering
Nov 1, 1972·Journal of the American Chemical Society·R MechoulamY Grunfeld
Jul 1, 1997·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S YamanoS Toki

Related Concepts

7beta-hydroxy-delta8-tetrahydrocannabinol
Metazoa
Cytochrome P-450 Oxygenase
Hydrogen-Ion Concentration
Macaca
Microsomes, Liver
NADH
NADP
Oxidation-Reduction
Substrate Specificity

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