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National Institute of Environmental Health Sciences

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Publication Detail

Title: Ascorbic acid deficiency and hepatic UDP-glucuronyltransferase.

Authors: Neumann, C M; Zannoni, V G

Published In Drug Metab Dispos, (1988 Jul-Aug)

Abstract: The effect of dietary ascorbic acid on hepatic microsomal UDP-glucuronyltransferase (UDPGT) activity towards p-aminophenol, bilirubin, and acetaminophen was investigated. Ascorbate deficiency produced a 33% reduction in the specific activity of UDPGT towards p-aminophenol, whereas there was no difference between microsomes from ascorbate-deficient and supplemented guinea pigs in the activity towards bilirubin and acetaminophen. This suggests that the effect of the vitamin is on a specific isozyme. This reduction was correlated with the reduced quantity of hepatic microsomal cytochrome P-450, which has been previously reported for ascorbate-deficient guinea pigs. No difference was found in the apparent affinity for the substrate, p-aminophenol, or the cofactor, UDP-glucuronic acid. Differences in microsomal UDPGT activity towards p-aminophenol occurred between the two groups with membrane-perturbing processes such as sonication and Triton X-100. Sonication and magnesium chloride were found to increase activity 329% in ascorbate-supplemented animals and 138% in the ascorbate-deficient group. The addition of ascorbate acid in vitro, or its analog d-isoascorbic acid, could protect against the detrimental effects of excess substrate by maintaining a linear enzymatic rate over a 30-min time period; there was no significant effect on the initial rate of hepatic microsomal UDPGT activity in the ascorbate-supplemented animals whereas there was a significant increase in the ascorbate-deficient group. Glutathione was as effective as ascorbic acid in protecting against the detrimental effects of excess substrate whereas cysteine and dimethyltetrapteridine were only partially effective. Ascorbyl-2-sulfate and alpha-tocopherol had no significant effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PubMed ID: 2903022 Exiting the NIEHS site

MeSH Terms: Acetaminophen/metabolism; Aminophenols/metabolism; Animals; Ascorbic Acid Deficiency/enzymology*; Ascorbic Acid Deficiency/metabolism; Ascorbic Acid/administration & dosage; Bilirubin/metabolism; Cytochrome P-450 Enzyme System/metabolism; Diet; Glucuronosyltransferase/metabolism*; Guinea Pigs; Microsomes, Liver/enzymology*; Microsomes, Liver/metabolism; Models, Biological

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