UDPGalNAc

UDP-N-acetylgalactosamine (UDP-GalNAc) is a nucleotide sugar used as a donor substrate by glycosyltransferases in the biosynthesis of glycoconjugates. It consists of the uridine diphosphate moiety linked to N-acetylgalactosamine.

Biosynthesis and availability of UDP-GalNAc are typically governed by the cellular pools of UDP-N-acetylglucosamine (UDP-GlcNAc) and the enzyme UDP-GlcNAc 4-epimerase (GALE), which catalyzes reversible interconversion between UDP-GlcNAc and UDP-GalNAc. This epimerase helps maintain balanced levels of both nucleotide sugars for glycosylation reactions. In some organisms and tissues, UDP-GalNAc can also be formed via salvage pathways that start from GalNAc-1-phosphate and UTP, though this route is less prominent in humans.

Biological roles of UDP-GalNAc include serving as the sugar donor for polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts), which initiate mucin-type O-glycosylation by transferring GalNAc to serine or threonine residues on proteins, often leading to the Tn antigen before further elaboration. UDP-GalNAc is also used in the biosynthesis of glycosaminoglycans, such as chondroitin sulfate and dermatan sulfate, where GalNAc residues are incorporated into the repeating disaccharide units of proteoglycans.

Clinical and research notes: Alterations in UDP-GalNAc metabolism or GALE activity can disrupt glycan structures and have been associated with congenital galactosemia variants and disorders of glycosylation. UDP-GalNAc remains a focus in glycoengineering and cancer glycomics because of its central role in mucin-type O-glycosylation.