UDPglycosyltransferases

UDP-glycosyltransferases (UGTs) are a widespread family of enzymes that catalyze the transfer of sugar moieties from uridine diphosphate (UDP)-activated sugars to diverse acceptors, forming glycosides. This reaction generally increases solubility and can alter activity, localization, and storage of the substrates, aiding detoxification and metabolism.

In plants, UDP-glycosyltransferases typically use UDP-glucose or other UDP-sugars to attach sugars to phenolics, flavonoids, and related secondary metabolites. Plant UGTs contribute to the formation of glycosides that influence pigment, flavor, and defense. A hallmark of many plant UGTs is the conserved PSPG motif near the C-terminus, which recognizes UDP-sugar donors. The common structural framework is the GT-B fold, comprising two Rossmann-like domains that create the active site for glycosyl transfer.

In animals and other organisms, UDP-glucuronosyltransferases (UGTs) reside in the endoplasmic reticulum membrane and primarily use UDP-glucuronic acid to attach glucuronic acid to lipophilic drugs, hormones, bilirubin, and other endogenous compounds. This glucuronidation enhances excretion and is a major pathway for phase II metabolism.

Substrate ranges among UGTs are broad and often overlapping, leading to significant roles in drug metabolism, toxin clearance, hormone regulation, and biosynthesis of natural products. Gene families encode multiple isoforms with tissue-specific and inducible expression, contributing to interindividual variability in pharmacokinetics and responses. Dysregulation or inhibition of UGTs can affect drug efficacy and safety, making these enzymes central to pharmacology and toxicology.