RT Journal Article
SR Electronic
T1 INHERENT SPECIFICITIES OF PURIFIED CYTOCHROMES P-450 AND P-448 TOWARD BIPHENYL HYDROXYLATION AND ETHOXYRESORUFIN DEETHYLATION
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 245
OP 253
VO 3
IS 4
A1 M. DANNY BURKE
A1 RICHARD T. MAYER
YR 1975
UL http://dmd.aspetjournals.org/content/3/4/245.abstract
AB 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 liver microsomes from untreated or inducer-treated rats are due largely to the inherent enzymic specificities of their cytochromes P-450 and P-448. Copyright © 1975 by The American Society for Pharmacology and Experimental Therapeutics