Argikar, Upendra (2012) Unusual Glucuronides. Drug Metabolism and Disposition.

Abstract

Glucuronidation reaction is catalyzed by Uridine diphosphoglucuronosyl transferases (UGTs), enzymes present in mammalian species, by utilizing uridine diphosphoglucuronic acid (UDPGA) as a co-substrate. Conjugation of glucuronic acid to nucleophilic functional groups in chemical entities results in the formation of glucuronides. This metabolic process involves a nucleophilic attack by a given functional group of the substrate on C-O bond of UDPGA, ultimately resulting in cleavage of that bond along with the formation of a glucuronide and uridine diphosphate as a by-product. As anticipated, a number of nucleophilic functional groups such as hydroxyl, phenolic, acyl, primary secondary and tertiary amino, in a diverse set of chemical compounds are known to form the corresponding glucuronides. Glucuronides are believed to be the end products of metabolism. The objective of this review however, is to highlight unusual glucuronide conjugates. Furthermore, due to the mechanistic and chemical differences observed for two different types of diglucuronides reported so far, a classification is proposed. Overall, this commentary centers on uncommon glucuronides and also draws attention to glucuronides undergoing ensuing oxidative or conjugative metabolic transformations.

Item Type:	Article
Additional Information:	This is a review article that does not contain any proprietary, previously unpublished information.
Keywords:	glucuronides, UGTs
Date Deposited:	26 Apr 2016 23:46
Last Modified:	26 Apr 2016 23:46
URI:	https://oak.novartis.com/id/eprint/6754