Major cytochrome P450 enzyme responsible for oxidation of secondary alcohols to the corresponding ketones in mouse hepatic microsomes. Oxidation of 7-hydroxy-delta8-tetrahydrocannabinol to 7-oxo-delta8-tetrahydrocannabinol.
The oxidative activities of 7alpha- and 7beta-hydroxy-Delta8-tetrahydrocannabinol (7alpha- and 7beta-hydroxy-Delta8-THC) to 7-oxo-Delta8-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 7alpha- and 7beta-hydroxy-Delta8-THC were 2.55 and 4.92 nmol/min/nmol P450, respectively. The antibody against P450MDX-B almost completely inhibited the oxidative activities of 7alpha- and 7beta-hydroxy-Delta8-THC in mice. These results indicate that P450MDX-B (CYP3A11) is a major enzyme responsible for the oxidation of 7alpha- and 7beta-hydroxy-Delta8-THC to 7-oxo-Delta8-THC in mouse liver.
Department of Hygienic Chemistry Faculty of Pharmaceutical Sciences Hokuriku University, Kanazawa, Japan.
T
T
Matsunaga
N
N
Kishi
H
H
Tanaka
K
K
Watanabe
H
H
Yoshimura
I
I
Yamamoto
D000438:Alcohols / Q000378:metabolism*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000378:metabolism; D007659:Ketones / Q000378:metabolism*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology*; D010084:Oxidation-Reduction
C109363:7-hydroxy-delta(8)-tetrahydrocannabinol; C109364:7-oxo-delta(8)-tetrahydrocannabinol; D000438:Alcohols; D007659:Ketones; D013759:Dronabinol; D003577:Cytochrome P-450 Enzyme System