DIFFERENTIAL CATALYTIC PROPERTIES IN METABOLISM OF ENDOGENOUS AND EXOGENOUS SUBSTRATES AMONG CYP3A ENZYMES EXPRESSED IN COS-7 CELLS

The catalytic properties of CYP3A7 in the metabolism of endogenous and exogenous substrates were compared with those of CYP3A4 and CYP3A5 us ing COS-7 expressing enzymes. The highest activities of dehydroepiandr osterone (DHEA) and dehydroepiandrosterone 3-sulfate (DHEA-S) 16 alpha -hydroxylase were observed in COS-7 cells expressing CYP3A7. In contra st, the activity of testosterone 6 beta-hydroxylase of CYP3A7 expresse d in COS-7 cells was much less than that of CYP3A4 expressed in COS-7 cells. The rate of carbamazepine 10,11-epoxidation was the greatest in COS-7 cells expressing CYP3A4, followed by CYP3A5 and CYP3A7. On the other hand, the formation of reductive metabolite of zonisamide was th e highest in COS-7 cells expressing CYP3A4, followed by CYP3A7 and CYP 3A5. Furthermore, the addition of triazolam resulted in a decrease in GP-hydroxylation catalyzed by CYP3A7, but not by CYP3A4, whereas the p retreatment of microsomes with triacetyloleandomycin (TAO) resulted in a decrease in the reaction catalyzed by CYP3A4, but not by CYP3A7. To gether with these results, it was suggested that CYP3A7 exerts differe ntial catalytic properties not only in metabolism of endogenous substr ates but also in drug metabolism compared to CYP3A4 and CYP3A5. (C) 19 98 Elsevier Science B.V.