UDPgalactose

UDP-galactose, or uridine diphosphate galactose, is a nucleotide sugar that serves as an activated donor of the sugar galactose in a variety of biosynthetic processes. It participates in glycosylation, where galactose residues are transferred to proteins, lipids, and oligosaccharides by galactosyltransferases. UDP-galactose is also a substrate in the synthesis of lactose in mammary glands, where it contributes the galactose moiety to glucose to form lactose.

Biochemistry and metabolism: In humans, UDP-galactose is formed and maintained by the interconversion of UDP-glucose and UDP-galactose, primarily through the action of UDP-glucose 4-epimerase (GALE). In the broader context of galactose metabolism, the Leloir pathway converts dietary galactose to UDP-galactose via galactokinase and galactose-1-phosphate uridylyltransferase, with GALE balancing the UDP-sugar pools to meet cellular glycosylation demands. The availability of UDP-galactose is thus linked to both galactose intake and the intracellular UDP-sugar balance.

Biological roles: UDP-galactose provides galactose units for N- and O-glycosylation, glycosphingolipid biosynthesis, and proteoglycan assembly. It is essential for proper formation of complex glycans in the Golgi apparatus and for the synthesis of glycan structures that influence protein folding, stability, and cell signaling. In lactose production, UDP-galactose is used by lactose synthase to generate lactose in milk.

Clinical significance: Defects in GALE can cause epimerase-deficiency galactosemia, a rare metabolic disorder with variable presentation and severity. Patients may exhibit issues related to galactose metabolism and glycosylation. Management focuses on dietary modification and monitoring of galactose-associated metabolites, with prognosis depending on residual enzyme activity and early detection.