Inherent specificities of purified cytochromes P-450 and P-448 toward biphenyl hydroxylation and ethoxyresorufin deethylation.
Liver microsomes from 3-methylcholanthrene-pretreated Long-Evans rats catalyzed the 2- and the 4-hydroxylation of biphenyl and the O-deethylation of ethoxyresorufin, sustained by either NADPH or cumene hydroperoxide. In contrast, the liver microsomes from corn oil- or phenobarbital-pretreated rats catalyzed the NADPH- or cumene hydroperoxide-sustained 4-hydroxylation of biphenyl, but the rates of 2-hydroxylation or ethoxyresorufin deethylation were negligible. A monooxygenase system reconstituted with partially purified NADPH-cytochrome  c reductase and cytochrome P-448 catalyzed NADPH-supported biphenyl 2- and 4-hydroxylation and ethoxyresorufin deethylation. A monooxygenase system reconstituted with the reductase and cytochrome P-450 catalyzed NADPH-supported biphenyl 4-hydroxylation but exhibited negligible 2-hydroxylation or ethoxyresorufin deethylation activites. Solubilized cytochrome P-448 catalyzed biphenyl 2- and 4-hydroxylation and ethoxyresorufin deethylation sustained by cumene hydroperoxide in the absence of both NADPH and NADPH-cytochrome c reductase, whereas solubilized cytochrome P-450, under the same conditions, catalyzed only biphenyl 4-hydroxylation. It is concluded that the patterns of biphenyl hydroxylation and ethoxyresorufin deethylation observed with live- microsomes from untreated or inducer-treated rats are due largely to the inherent enzymic specificities of their cytochromes P-450 and P-448.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001713:Biphenyl Compounds / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003580:Cytochromes / Q000378:metabolism*; D003640:Dealkylation; D005019:Ethyl Ethers / Q000378:metabolism; D006900:Hydroxylation; D066298:In Vitro Techniques; D008055:Lipids / Q000494:pharmacology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010078:Oxazines / Q000378:metabolism*; D011136:Polysorbates / Q000494:pharmacology; D051381:Rats
D001713:Biphenyl Compounds; D003580:Cytochromes; D005019:Ethyl Ethers; D008055:Lipids; D010078:Oxazines; D011136:Polysorbates; D008748:Methylcholanthrene; C007649:ethoxyresorufin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; D009251:NADPH-Ferrihemoprotein Reductase