The kinetics of 4-nitrophenol conjugation by perfused livers and hepatic microsomes from streptozocin-induced diabetic rats

Author:

Morrison M H1,Barber H E2,Foschi P G3,Hawksworth G M12

Affiliation:

1. Departments of Therapeutics and Clinical Pharmacology, Foresterhill, Aberdeen AB9 2ZD

2. Department of Pharmacology, University Medical Buildings, Foresterhill, Aberdeen AB9 2ZD

3. Department of Geography, University of Aberdeen, St Mary's, High Street, Aberdeen, UK

Abstract

Abstract 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 snowed 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.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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