Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Mechanism of Inhibition of Rat Liver Bilirubin UDP-Glucuronosyltransferase by Triphenylalkyl Derivatives
Journal of Biochemical and Molecular Toxicology, Volume 12, No. 1, Year 1998
Notification
URL copied to clipboard!
Description
A series of potent and competitive inhibitors of UDP-glucuronosyltransferase derived from 7,7,7-triphenylheptanoic acid has been synthesized in order to probe the active site of the isozyme involved in the glucuronidation of the endogenous toxic compound, bilirubin IXα. Like triphenylalkylcarboxylic acids, triphenyl alcohols were found to be very effective competitive inhibitors of the reaction (Ki12 to 180 μM). Superimposition of the best inhibitors with bilirubin by computer modeling showed a marked spatial similarity, which accounts for the observed competitive-type inhibition. The bulky triphenylmethyl moiety of the inhibitor superimposed well on the part of the bilirubin molecule containing three of the four pyrrole rings. In agreement, substitution of the triphenylmethyl moiety by planar structures such as fluorenyl or indenyl rings completely suppressed the inhibition. In addition, the weak inhibition exerted by the shortest carboxylic acids could be related to the higher acidity of these molecules. The inhibition potency depended on the acidity of the molecules; the more acidic, the less inhibitory, suggesting that the presence of a negative charge on the inhibitor molecule prevents bilirubin glucuronidation. Based on these results, a reaction mechanism for bilirubin glucuronidation is postulated. © 1997 John Wiley & Sons, Inc.
Authors & Co-Authors
Said, Mourad
Morocco, Oujda
Université Mohammed Premier Oujda
Battaglia, Eric
France, Paris
Cnrs Centre National de la Recherche Scientifique
Elass, Abdelaziz
France, Paris
Inserm
Cano, Virginie
France, Nancy
Laboratoire Cnrs Centre du Médicament, Nancy
Ziegler, Jean Marie
France, Nancy
Laboratoire Cnrs Centre du Médicament, Nancy
Cartier, Alain
France, Vandoeouvre-les-nancy
Laboratoire Lorrain de Chimie Moléculaire
Livertoux, Marie Hélène
France, Nancy
Laboratoire Cnrs Centre du Médicament, Nancy
Vergoten, Gérard
France, Paris
Inserm
Fournel-Gigleux, Sylvie
France, Paris
Cnrs Centre National de la Recherche Scientifique
Magdalou, Jacques
France, Paris
Cnrs Centre National de la Recherche Scientifique
Statistics
Citations: 10
Authors: 10
Affiliations: 5
Identifiers
Doi:
10.1002/(SICI)1099-0461(1998)12:1<19::AID-JBT4>3.0.CO;2-S
Research Areas
Environmental