Abstract

Representative examples of drug metabolites containing a carboxylic acid group conjugated to glucuronic acid are shown to be active chemical electrophiles, which acylate albumin in vitro through transesterification reactions. Based on these and other observations, we propose that this acylating reactivity is characteristic of 1-O-acyl glucuronides as a class, and that albumin is representative of many susceptible biopolymers. The hypothesis is advanced that this reaction can occur in vivo as well, and that it may offer a molecular mechanism for the physiological activity or toxicity of some xenobiotic and lipophilic compounds.