Sglucuronides

S-glucuronides are a subset of glucuronide conjugates formed when a glucuronic acid moiety is attached to a substrate via a sulfur atom. In phase II metabolism, UDP-glucuronosyltransferases transfer the glucuronyl group from UDP-glucuronic acid to nucleophilic sites on xenobiotics or endogenous compounds. When the nucleophile is a thiol, the product is an S-glucuronide, characterized by a thio-glycosidic bond between the sulfur atom of the substrate and the anomeric carbon of the glucuronic acid.

Substrates for S-glucuronidation are typically small-molecule thiols or sulfhydryl groups present in drugs, dietary constituents, or endogenous molecules. Although O- and N-glucuronidation are more common, S-glucuronidation has been observed in humans and other mammals and contributes to the overall detoxification and elimination of thiol-containing compounds. The resulting metabolite generally increases hydrophilicity and facilitates renal or biliary excretion; however, the stability of S-glucuronides can vary with pH and structural context.

Analytical and clinical relevance: S-glucuronides can be detected in biological samples by chromatographic methods coupled with mass spectrometry. They may be enzymatically cleaved by glucuronidases under certain conditions, which can be exploited to study total glucuronidation. In pharmacology and toxicology, identifying S-glucuronides aids in understanding metabolic pathways for sulfur-containing drugs and endogenous thiols and can inform assessments of exposure and detoxification capacity.