ITEM METADATA RECORD
Title: On the binding of bilirubin and its structural analogues to hepatic microsomal bilirubin UDPglucuronyltransferase
Authors: Vanstapel, Florent ×
Blanckaert, Norbert #
Issue Date: Sep-1987
Series Title: Biochemistry vol:26 issue:19 pages:6074-82
Abstract: Hepatic glucuronidation of the asymmetrical natural bilirubin molecule results in formation of two different positional isomers, bilirubin C-8 monoglucuronide and bilirubin C-12 monoglucuronide. In view of the existence of multiple isoforms of UDPglucuronyltransferase, which is the microsomal enzyme system responsible for bilirubin esterification, we performed kinetic analysis of microsomal glucuronidation of bilirubin and a number of its structural congeners to determine whether synthesis of the two monoglucuronide isomers involved two distinct substrate-binding sites or reflected two different modes of binding to a single catalytic site. Both isomers were found in all tested species (man, rat, guinea pig, sheep), but there were marked species differences in the C-8/C-12 ratio of monoglucuronide found in bile or formed by liver microsomes. Correspondence between in vivo and in vitro results for such regioselectivity of glucuronidation was excellent in each species. On the basis of our results of kinetic analysis of bilirubin esterification at variable pigment substrate concentrations and inhibition studies with alternative substrates, we postulate that both natural monoglucuronide isomers are synthesized at a single binding site. Possible mechanisms responsible for the markedly regioselective esterification of bilirubin by rat and sheep liver were investigated by study of glucuronidation of selected structural analogues of the pigment. Our results do not support explanations of regioselectivity of bilirubin glucuronidation in terms of (i) preferential binding of either the C-8- or C-12-containing dipyrrolic half of the asymmetrical bilirubin molecule or (ii) enantioselective complexation of bilirubin UDPglucuronyltransferase to one of the two chirality enantiomers of intramolecularly hydrogen-bonded bilirubin.(ABSTRACT TRUNCATED AT 250 WORDS)
ISSN: 0006-2960
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Clinical Bacteriology and Mycology
Department of Imaging & Pathology - miscellaneous
Biomedical Quality Assurance Research Unit
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy

 




All items in Lirias are protected by copyright, with all rights reserved.

© Web of science