RGD Reference Report - Defective function of a microsomal UDP-glucuronyltransferase in Gunn rats. - Rat Genome Database

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Defective function of a microsomal UDP-glucuronyltransferase in Gunn rats.

Authors: Nakata, D  Zakim, D  Vessey, DA 
Citation: Nakata D, etal., Proc Natl Acad Sci U S A 1976 Feb;73(2):289-92.
RGD ID: 1354703
Pubmed: PMID:813224   (View Abstract at PubMed)
PMCID: PMC335892   (View Article at PubMed Central)

The kinetic parameters of the p-nitrophenol-metabolizing form of UDP-glucuronyltransferase [-UDPglucuronosyltransferase; UDPglucuronate beta-glucuronosyltransferase (acceptor-unspecific), EC] have been compared in liver microsomes from the Gunn strain of rat and from normal; Wistar rats. The abnormally low rate of glucuronidation of p-nitrophenol in the Gunn rats, as compared with Wistar rats, is due to decreased affinity of UDP-glucuronyltransferase for UDP-glucuronic acid. Activities at Vmax and the Michaelis constant for p-nitrophenol, KPNP, of UDP-glucuronyltransferase are the same for enzyme from either strain of rat. Studies of the kinetic parameters of the reverse reaction catalyzed by UDP-glucuronyltransferase indicate that the enzyme from Gunn rats also has decreased affinity for UDP. Calculated values of deltaG degrees for the binding of the UDP portion of UDP-glucuronic acid suggest that the defect of UDP-glucuronyltransferase of Gunn rats appears limited to abnormal interactions between the enzyme and the UDP portion of UDP-glucuronic acid. Studies of the extent of UDP-induced inhibition of the forward reaction support this idea. Diethylnitrosamine, added to microsomes in vitro, enhances the affinity of UDP-glucuronyltransferase for the UDP portion of UDP-glucuronic acid. Despite the defective conformation of the UDP-glucuronic acid binding site of UDP-glucuronyltransferase from Gunn rats this enzyme is activated in the normal way by UDP-N-acetylglucosamine, which is a K-type effector with regard to UDP-glucuronic acid.

Objects referenced in this article
Strain Gunn-Ugt1a1j/BluHsd Gunn rat Rattus norvegicus

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