UDPsugars

UDP-sugars, or uridine diphosphate sugars, are a family of activated sugar donors used by glycosyltransferases to assemble glycans on proteins, lipids, and other carbohydrates. The activated sugar is transferred from UDP-sugar to an acceptor molecule in a reaction that often releases UDP, enabling a wide range of glycosylation processes essential for cell-surface features and secreted molecules.

Biosynthesis and diversity: UDP-sugars are synthesized in the cytosol from simple carbohydrate precursors. The most common member is UDP-glucose, formed from glucose-1-phosphate and UTP by UDP-glucose pyrophosphorylase; UDP-glucose can be converted to UDP-galactose by UDP-glucose 4-epimerase. UDP-glucuronic acid is produced from UDP-glucose via oxidation, and UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylgalactosamine (UDP-GalNAc) arise through dedicated pathways starting from metabolic intermediates such as fructose-6-phosphate. Other UDP-sugars include UDP-xylose and related derivatives. In bacteria, UDP-sugars contribute to capsule and cell wall biosynthesis and other glycan structures, highlighting their central role across domains of life.

Function and cellular context: UDP-sugars serve as donor substrates for glycosyltransferases located in the endoplasmic reticulum and Golgi apparatus in eukaryotes, and in various cytosolic or membrane-associated steps in microbes. N-linked and O-linked glycosylation, as well as proteoglycan and glycolipid biosynthesis, rely on appropriate pools of UDP-sugars. Nucleotide-sugar transporters shuttle UDP-sugars into organelles where glycosylation reactions occur, linking cytosolic metabolism to extracellular glycan structures.

Clinical and research relevance: Defects in UDP-sugar biosynthesis, transport, or glycosyltransferase activity can cause congenital disorders of glycosylation. In bacteria, UDP-sugars are explored as targets for antibiotics and as determinants of virulence and immune evasion.