Drug metabolism in a reconstituted system by diabetes-dependent hepatic cytochrome P-450.

Previous studies have shown that diabetes induces a unique 52,000 molecular weight cytochrome P-450 in rat hepatic microsomes. In the present study, the catalytic properties of the two major purified diabetic P-450s were contrasted to those of the major normal purified P-450 in a reconstituted drug metabolizing system. the greatest rate of aniline hydroxylation was catalyzed by the 52,000 molecular weight diabetic P-450 (7-fold greater than normal). This same diabetic P-450 also catalyzed a slower rate of ethylmorphine N-demethylation compared to the major normal and the other diabetic P-450. These results indicate that the catalytic properties of this diabetes-dependent P-450 are responsible for the substrate-specific alterations in drug metabolism observed in both liver microsomes and isolated perfused liver from diabetic rats.