Abstract
A cytochrome P450 (designated P450 MUT-2) which catalyses the oxidation of 11-oxo- Δ 8-tetrahydrocannabinol (11-oxo- Δ 8-THC) to Δ 8-THC-11-oic acid has been purified from hepatic microsomes of untreated male mice. Analysis of NH 2-terminal sequence suggests that the isozyme is a member of the P450 2C gene subfamily. P450 MUT-2 exhibited aldehyde oxygenase activity for 11-oxo- Δ 8-TH, 11-oxo- Δ 9-THC, 11-oxo-cannabinol (11-oxo-CBN) and 9-anthraldehyde together with high activity for the hydroxylation of cannabinoids at the 11-position. Antibody against P450 MUT-2 significantly inhibited the microsomal formation of Δ 8-THC-11-oic acid from 11-oxo- Δ 8-THC, but not that of 9-anthracene carboxylic acid from 9-anthraldehyde. Major metabolic reactions of Δ 8-THC, Δ 9-THC and CBN with mouse hepatic microsomes were the 11-hydroxylation (all cannabinoids), 7α-( Δ 8-THC) or 8 α-hydroxylation ( Δ 9-THC) and epoxide formation ( Δ 8- and Δ 9-THC). All these reactions except for 7 α-hydroxylation of Δ 8-THC and α-epoxide formation from Δ 9-THC were also markedly inhibited by the antibody. These results indicate that P450 MUT-2 is a major enzyme for metabolizing cannabinoids by mouse hepatic microsomes.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
