Sex differences in the kinetic constants of ethylmorphine demethylation and type I binding to hepatic microsomal cytochrome P-450 in mice. The influence of castration and testosterone.
1. In the CPB-SE mouse strain sex differences were observed in the Km and Vmax of ethylmorphine demethylation and in the deltaAmax of its type I binding to cytochrome P-450. In the CPB-V strain a small sex difference in the Vmax of the demethylation was found, whereas Ks and deltaAmax of type I binding differed considerably. 2. Testosterone pre-treatment of female CPB-SE mice abolished all sex differences, as did castration of males, except in Vmax, which was partially decreased. In the CPB-V strain testosterone pre-treatment of females abolished sex differences in type I binding, but had no effect on ethylmorphine demethylation. 3. Km values exceeded the corresponding Ks in all cases and sex differences in deltaAmax far exceeded those in Vmax. It is concluded that the Km is determined not only by the Ks of type I binding and the reduction rate of the type I complex between ethylmorphine and cytochrome P-450. The larger sex differences in deltaAmax as compared with Vmax may be attributable to type I binding of ethylmorphine to cytochrome P-450 subspecies not involved in its demethylation.
D000818:Animals; D002369:Castration; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003640:Dealkylation; D005036:Ethylmorphine / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009022:Morphine Derivatives / Q000378:metabolism*; D011485:Protein Binding; D012737:Sex Factors; D013739:Testosterone / Q000494:pharmacology*
D009022:Morphine Derivatives; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System; D005036:Ethylmorphine