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.
D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D000815:Aniline Hydroxylase; D005037:Ethylmorphine-N-Demethylase; D009251:NADPH-Ferrihemoprotein Reductase