title: Mouse hepatic microsomal enzyme that catalyzes oxidation of 11-oxo-delta 8-tetrahydrocannabinol to delta 8-tetrahydrocannabinol-11-oic acid.
abstract: Mouse hepatic microsomes oxidized 11-oxo-delta 8-tetrahydrocannabinol (11-oxo-delta 8-THC, aldehyde) to delta 8-THC-11-oic-acid (carboxylic acid). The reaction required NADPH and molecular oxygen and showed an optimal pH around 7.5. The activity of NADPH-dependent carboxylic acid formation was mainly localized in microsomes. The reaction was inhibited by various inhibitors of cytochrome P-450-dependent oxidation such as SKF 525-A, alpha-naphthoflavone, and metyrapone. Disulfiram and menadione also inhibited the microsomal oxidation of the aldehyde to the carboxylic acid, but pyrazole did not inhibit the reaction. The pretreatment of mice with phenobarbital significantly increased the oxidation activity on the basis of microsomal protein, but did not affect it on the basis of cytochrome P-450 content. The mechanism for the oxidation of the aldehyde to the carboxylic acid was confirmed to be oxygenation, since oxygen-18 was incorporated into delta 8-THC-11-oic acid from molecular oxygen during the hepatic microsomal oxidation of 11-oxo-delta 8-THC.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: N
authors.initials: N
authors.lastname: Hirahashi
authors.forename: S
authors.initials: S
authors.lastname: Narimatsu
authors.forename: I
authors.initials: I
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008297:Male; D013058:Mass Spectrometry; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000201:enzymology*; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D011506:Proteins; C016780:11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid; C020443:11-oxo-delta(8)-tetrahydrocannabinol; D008748:Methylcholanthrene; D013759:Dronabinol; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital