UDPGlcA

UDP-glucuronic acid (UDP-GlcA) is a nucleotide sugar that serves as an activated donor of glucuronic acid in diverse biosynthetic pathways. It is produced in the cytosol by the NAD+-dependent oxidation of UDP-glucose, Catalyzed by UDP-glucose dehydrogenase (UGDH), yielding UDP-glucuronate that can be used in further reactions.

One major role of UDP-GlcA is as a substrate for UDP-glucuronosyltransferases (UGTs) in phase II detoxification. These enzymes transfer the glucuronyl moiety to a wide range of substrates, including bilirubin, steroid hormones, drugs, and other xenobiotics, forming glucuronides that are more water-soluble and more readily excreted.

UDP-GlcA is also a key precursor in the biosynthesis of glycosaminoglycans (GAGs). It provides the glucuronic acid residues required for the formation of hyaluronan and sulfated proteoglycans such as chondroitin sulfate, dermatan sulfate, and heparan sulfate, which are major components of the extracellular matrix.

In bacteria, UDP-GlcA is used for capsule and cell wall polysaccharide biosynthesis, contributing to surface polysaccharide diversity and, in some cases, virulence. The pool of UDP-GlcA is interconnected with other nucleotide sugars through interconversion pathways, linking its availability to broader aspects of metabolism and glycobiology.

Overall, UDP-glucuronic acid is a central activated sugar in both detoxification pathways and structural glycoconjugate biosynthesis, with broad relevance across organisms.