STUDIES ON MECHANISM OF SEX DIFFERENCE IN DRUG-OXIDIZING ACTIVITY OF LIVER MICROSOMES

Abstract

The main pathway of drug inactivation occurs in liver microsomes by mixed function oxygenation in the presence of NADPH and oxygen (1). The participation in these reactions of a carbon monoxide-binding hemoprotein called P-450 as the oxygen activating component has been established (1-6). One of characteristics of the drug-oxidizing enzymes of liver microsomes is to have marked sex difference in the activity of rats (7-12). In previous paper, we reported that the magnitude of the sex difference in the drug-oxidizing activity in rats was markedly different according to the substrate used (11, 12). On the other hand, it has been observed that there are no clear sex difference in the activities of microsomal drug-oxidizing enzymes of other species of animals (8, 13). More recently, it was observed in our laboratory that the activity of microsomal NADPH-linked electron transport system, such as, the activity of NADPH oxidase, NADPH-cytochrome c reductase and NADPH-neotetrazolium reductase and the content of P-450 were higher in male rats than in female rats (14, 15). Therefore, it is of interest to establish the relationship between the activities of microsomal NADPH-linked electron transport system and drug-oxidizing enzymes in connection with the sex difference and to investigate whether the such sex difference in the activity of microsomal NADPH- or NADH-linked electron transport system is observed in other species of animals.