Characterization of microsomal alcohol oxygenase catalyzing the oxidation of 7-hydroxy-delta 8-tetrahydrocannabinol to 7-oxo-delta 8-tetrahydrocannabinol in rat liver.
The formation of 7-oxo-delta8-tetrahydrocannabinol (7-oxo-delta8-THC) from 7beta-hydroxy-delta8-THC was found in hepatic microsomes of rats. The activity was stereoselective and about 3-fold higher than that from 7alpha-hydroxy-delta8-THC. The oxidative activity of 7alpha- and 7beta-hydroxy-delta8-THC to 7-oxo-delta8-THC was significantly higher in male than in female, and significantly enhanced by both dexamethasone and phenobarbital, and then inhibited up to about 20% of the control value by antibody against P450GPF-B, presumably a member of the 3A subfamily, a major enzyme responsible for the formation of 7-oxo-delta8-THC in guinea pigs. This antibody also inhibited the formation of 7alpha- and 7beta-hydroxy-delta8-THC, and 7-oxo-delta8-THC from delta8-THC by hepatic microsomes of rats. These results indicate that there is a sex-related difference in the oxidation of 7-hydroxy-delta8-THC to 7-oxo-delta8-THC and the reaction is mainly catalyzed by P450 enzyme(s) belonging to the 3A subfamily as major enzyme(s) of microsomal alcohol oxygenase in rats.
Matsunaga
T
T
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Shibayama
K
K
Higuchi
S
S
Tanaka
H
H
Watanabe
K
K
Yamamoto
I
I
D000818:Animals; D002384:Catalysis; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000276:immunology / Q000378:metabolism*; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007074:Immunoglobulin G / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013379:Substrate Specificity
C109363:7-hydroxy-delta(8)-tetrahydrocannabinol; C109364:7-oxo-delta(8)-tetrahydrocannabinol; D065607:Cytochrome P-450 Enzyme Inhibitors; D007074:Immunoglobulin G; D013759:Dronabinol; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; C109362:cytochrome P450GPF-B