Cytochrome P-450-catalyzed stereoselective epoxidation at the K region of benz[a]anthracene and benzo[a]pyrene.
The enantiomers of K-region benz[a]anthracene (BA) 5,6-epoxide and benzo[a]pyrene (BP) 4,5-epoxide were resolved by chiral stationary-phase high-performance liquid chromatography (CSP-HPLC). The K-region epoxides formed in the metabolism of BA by liver microsomes from untreated (control), phenobarbital (PB)-treated, and 3-methylcholanthrene (MC)-treated male Sprague-Dawley rats were determined by CSP-HPLC to have a 5R,6S/5S,6R enantiomer ratio of 25:75, 21:79, and 4:96, respectively. The K-region 4,5-epoxide formed in the metabolism of BP by the same rat liver microsomal preparations contained a 4R,5S/4S,5R enantiomer ratio of 48:52 (control), 40:60 (PB), and 5:95 (MC), respectively. The results indicate that various cytochrome P-450 isozymes of rat liver exhibit different stereoselective properties in catalyzing the epoxidation reactions at the K region of BA and of BP.
D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D001564:Benzo(a)pyrene / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004852:Epoxy Compounds / Q000378:metabolism*; D004988:Ethers, Cyclic / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008433:Mathematics; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology; D009249:NADP / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D001551:Benz(a)Anthracenes; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D007527:Isoenzymes; D001564:Benzo(a)pyrene; D009249:NADP; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; C030935:benz(a)anthracene; D010634:Phenobarbital