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 trans-7,8-dihydroxy-7,8-dihydrobenzo[α]pyrene
AU - Deutsch, J.
AU - Vatsis, K. P.
AU - Coon, M. J.
AU - Leutz, J. C.
AU - Gelboin, H. V.
PY - 1979
Y1 - 1979
N2 - Purified forms of rabbit liver microsomal cytochrome P-450 (phenobarbital-inducible P-450(LM) 2 and β-naphthoflavone-inducible P-450(LM) 4) were examined for catalytic activity in the conversion of the (-) and (+) enantiomers of trans-7,8-dihydroxy-7,8-dihydrobenzo-[α]pyrene to stereoisomeric, highly reactive and mutagenic 7,8-dihydroxy-9,10-oxy 7,8,9,10-tetrahydrobenzo[α]pyrenes. In the reconstituted enzyme system, P-450(LM) 4 from both phenobarbital- and β-naphthoflavone-induced animals has much higher catalytic activity than P-450(LM) 2 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-450(LM) 4. The relative amounts of diol-epoxides formed from either enantiomer of the substrate differ markedly with the form of the cytochrome used. P-450(LM) 2 gives somewhat more diol-epoxide I than diol-epoxide II with both substrates. In contrast, P-450(LM) 4 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-450(LM) 4 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.
AB - Purified forms of rabbit liver microsomal cytochrome P-450 (phenobarbital-inducible P-450(LM) 2 and β-naphthoflavone-inducible P-450(LM) 4) were examined for catalytic activity in the conversion of the (-) and (+) enantiomers of trans-7,8-dihydroxy-7,8-dihydrobenzo-[α]pyrene to stereoisomeric, highly reactive and mutagenic 7,8-dihydroxy-9,10-oxy 7,8,9,10-tetrahydrobenzo[α]pyrenes. In the reconstituted enzyme system, P-450(LM) 4 from both phenobarbital- and β-naphthoflavone-induced animals has much higher catalytic activity than P-450(LM) 2 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-450(LM) 4. The relative amounts of diol-epoxides formed from either enantiomer of the substrate differ markedly with the form of the cytochrome used. P-450(LM) 2 gives somewhat more diol-epoxide I than diol-epoxide II with both substrates. In contrast, P-450(LM) 4 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-450(LM) 4 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.
UR - http://www.scopus.com/inward/record.url?scp=0018599252&partnerID=8YFLogxK
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C2 - 119154
AN - SCOPUS:0018599252
SN - 0026-895X
VL - 16
SP - 1011
EP - 1018
JO - Molecular Pharmacology
JF - Molecular Pharmacology
IS - 3
ER -