THE KINETICS OF 4-NITROPHENOL CONJUGATION BY PERFUSED LIVERS AND HEPATIC MICROSOMES FROM STREPTOZOCIN-INDUCED DIABETIC RATS

The formation of both glucuronide and sulphate conjugates of 4-nitrophenol is deficient in perfused livers from male diabetic rats. Experiments with ''native'' hepatic microsomes demonstrated that the defect in glucuronidation is due to a decrease in the maximal velocity of the reaction. There is no alteration in the affinity of the glucuronyltransferase for 4-nitrophenol. Non-linear regression analysis of the 4-nitrophenol liver perfusate concentrations showed that the elimination follows saturable Michaelis-Menten kinetics. Clearance values in ''native'' microsomal preparations and in perfused livers were calculated and found to be similar in both systems. This provides evidence that glucuronyltransferase is ''native'' in the intact liver.