Guinea pig hepatic enzyme, microsomal alcohol oxygenase, was able to oxidize both 7α- and 7β-hydroxy-Δ8-tetrahydrocannabinol (7α- and 7β- hydroxy-Δ8-THC) to 7-oxo-Δ8-THC. A cytochrome P450, named P450GPF-B, which mediates this oxidative metabolism was purified from hepatic microsomes of untreated female guinea pigs. The purified enzyme showed a single protein band of molecular mass 50,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The NH2-terminal amino acid sequence of P450GPF-B is highly homologous with those of several cytochrome P450s belonging to the CYP3A subfamily. 18O derived from atmospheric oxygen was incorporated into 31 and 6%, respectively, of 7-oxo-Δ8-THC formed from 7α- and 7β-hydroxy-Δ8- THC when the substrates were incubated with P450GPF-B under 18O2. The antibody against P450GPF-B significantly suppressed the oxidative activities of 7α- and 7β-hydroxy-Δ8-THC to 7-oxo-Δ8-THC in hepatic microsomes of guinea pig. These results indicate that P450GPF-B is a major enzyme responsible for the hepatic microsomal alcohol oxygenase activities in the guinea pig.
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