TY - JOUR T1 - Catalytic Activity and Stereoselectivity of Purified Forms of Rabbit Liver Microsomal Cytochrome P-450 in the Oxygenation of the (-) and (+) Enantiomers of <em>trans</em>-7,8-Dihydroxy-7,8-Dihydrobenzo[α]Pyrene JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1011 LP - 1018 VL - 16 IS - 3 AU - J. DEUTSCH AU - K. P. VATSIS AU - M. J. COON AU - J. C. LEUTZ AU - H. V. GELBOIN Y1 - 1979/11/01 UR - http://molpharm.aspetjournals.org/content/16/3/1011.abstract N2 - Purified forms of rabbit liver microsomal cytochrome P-450 (phenobarbital-inducible P-450LM2 and β-naphthoflavone-inducible P-450LMLM4), were examined for catalytic activity in the conversion of the (-) and (+) enantiomers of trans-7,8-dihydroxy-7,8-dihydrobenzo-[a]pyrene to stereoisomeric, highly reactive and mutagenic 7,8-dlhydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[α]pyrenes. In the reconstituted enzyme system, P-450LMLM4 from both phenobarbital- and β-naphthoflavone-induced animals has much higher catalytic activity than P-450LMLM2 with either enantiomer of the trans-7,8-diol. Both forms of the cytochrome exhibit greater activity toward the (-) than the (+) isomer of the substrate, but this is more striking with P-450LMLM4. The relative amounts of diol-epoxides formed from either enantiomer of the substrate differ markedly with the form of the cytochrome used. P-450LMLM2 gives somewhat more diol-epoxide I than diol-epoxide II with both substrates. In contrast, P-450LMLM4 gives almost exclusively diol-epoxide I from the (-)trans-7,8-diol and more diol-epoxide II than diol-epoxide I from the (+)trans-7,8-diol. Thus, P-450LMLM4 is highly stereospecific in oxygenating at the 9,10 double bond, regardless of the absolute configuration of the hydroxyl groups at the 7 and 8 positions of the substrate. ACKNOWLEDGMENTS The authors wish to thank Sylvia B. Dahl for purifying cytochrome P-450 and Barbara M. Michniewicz for purifying the reductase. ER -