GDPmannose

GDP-mannose, or GDP-mannose, is guanosine diphosphate mannose, a nucleotide sugar that serves as an activated donor of the sugar mannose in glycosylation pathways. It is synthesized in the cytosol from mannose-1-phosphate and GTP by GDP-mannose pyrophosphorylase, an enzyme sometimes described as mannose-1-phosphate guanylyltransferase. Once formed, GDP-mannose is used by a range of glycosyltransferases in the endoplasmic reticulum and Golgi to assemble N-linked and O-linked glycans on proteins, and to form dolichol-linked intermediates such as dolichol phosphate mannose (Dol-P-Man), which donate mannose in early steps of N-glycosylation and in GPI-anchor biosynthesis.

In bacteria, GDP-mannose also functions as a sugar donor for the biosynthesis of surface polysaccharides, capsule formation, and certain glycoproteins, contributing to cell surface characteristics and virulence in some species. The pathway is conserved across domains of life, though specific roles and regulatory mechanisms can differ.

Clinical relevance centers on the essential role of GDP-mannose in protein glycosylation. Defects in GDP-mannose metabolism or in enzymes that utilize it—such as GMPPB, a subunit of the GDP-mannose pyrophosphorylase complex—can lead to congenital disorders of glycosylation and related dystroglycanopathies, which can present with muscular, neurological, and developmental abnormalities.