Phosphomannose

Phosphomannose refers to sugar phosphates derived from the sugar mannose, most notably mannose-6-phosphate (M6P) and mannose-1-phosphate (M1P). These phosphorylated forms function as important metabolic intermediates and, in the case of M6P, as targeting signals for lysosomal enzymes.

Formation and metabolism. Mannose taken up by cells is phosphorylated to M6P by hexokinase activity. The enzyme phosphomannomutase converts M6P to M1P, which can then be converted to GDP-mannose by GDP-mannose pyrophosphorylase. GDP-mannose serves as a donor in the biosynthesis of glycoproteins, including N-glycans, O-mlycosylation, and glycosylphosphatidylinositol (GPI) anchors, as well as for dolichol phosphate–mannose production. Separately, M6P is the signal recognized by mannose-6-phosphate receptors that direct lysosomal hydrolases to lysosomes.

Roles in biology. M6P acts as a key lysosomal targeting tag, guiding hydrolytic enzymes to lysosomes where they participate in macromolecule degradation. M1P and GDP-mannose are central to the assembly of N-linked glycans and other mannose-containing glycoconjugates, essential for protein folding, stability, and trafficking. The pathway linking M6P to M1P and GDP-mannose operates in the cytosol and endoplasmic reticulum, feeding glycosylation processes in the secretory pathway.

Clinical significance. Defects in related enzymes can cause congenital disorders of glycosylation; for example, deficiency of phosphomannomutase (PMM2) or phosphomannose isomerase (MPI) disrupts glycan assembly and sugar metabolism. MPI deficiency (CDG-Ib) can be treated with oral mannose supplementation, highlighting the clinical relevance of phosphomannose metabolism to human health.

See also. Phosphomannomutase, phosphomannose isomerase, glycosylation, N-glycans, lysosomal targeting.