UDPglucuronic

UDP-glucuronic acid, also known as UDP-glucuronate, is a nucleotide sugar that serves as an activated donor of glucuronic acid in two major biological contexts: the biosynthesis of glycosaminoglycans and the detoxification of xenobiotics through glucuronidation. It is formed in the cytosol by oxidation of UDP-glucose via the enzyme UDP-glucose dehydrogenase (UGDH), a reaction that uses NAD+ as a cofactor and yields UDP-glucuronate along with NADH. The UDP-glucuronate pool is maintained by cellular metabolism and is transported into the lumen of the endoplasmic reticulum and Golgi apparatus by specific nucleotide sugar transporters.

In glycosaminoglycan biosynthesis, UDP-glucuronate provides glucuronic acid residues that are incorporated into proteoglycans such as hyaluronic acid, dermatan sulfate, chondroitin sulfate, and heparan sulfate by various glycosyltransferases. This pathway is essential for the formation of extracellular matrix components and for proper cell signaling and tissue organization.

In detoxification, UDP-glucuronate is transferred from UDP-glucuronic acid to a wide range of lipophilic substrates by UDP-glucuronosyltransferases (UGTs). This glucuronidation increases substrate water solubility and promotes renal or biliary excretion. UGT enzymes are primarily located in the endoplasmic reticulum of hepatocytes and other tissues, reflecting the broad role of glucuronidation in drug metabolism, bilirubin clearance, steroid inactivation, and elimination of various xenobiotics.

Clinical and physiological relevance: impaired UDP-glucuronate synthesis or glucuronidation can affect drug clearance and bilirubin metabolism, contributing to jaundice and altered pharmacokinetics. UDP-glucuronic acid thus occupies a central role at the interface of metabolism, detoxification, and extracellular matrix production.