Mannose1phosphate

Mannose-1-phosphate is the phosphorylated form of the hexose sugar mannose, with the phosphate attached to the anomeric carbon. It is a key metabolic intermediate in the biosynthesis of GDP-mannose, a donor of mannose for glycosylation reactions in cells. Its chemical formula is C6H13O9P, and it is the product of mannose-6-phosphate via a phosphomutase reaction.

Biosynthesis and pathway role

In many organisms, mannose-6-phosphate is converted to mannose-1-phosphate by phosphomannomutase. Mannose-1-phosphate is then converted to GDP-mannose by GDP-mannose pyrophosphorylase (also called mannose-1-phosphate guanylyltransferase) using GTP as the energy source. GDP-mannose serves as a donor for various mannosyltransferases that build glycan structures on proteins and lipids; it also feeds into the synthesis of dolichol phosphate mannose, a carrier used in N- and O-linked glycosylation pathways in eukaryotes.

Occurrence and significance

Mannose-1-phosphate is found across bacteria, archaea, and eukaryotes as part of the pathway to generate GDP-mannose. In bacteria, GDP-mannose can be used for the production of capsular polysaccharides and glycoconjugates. In eukaryotes, GDP-mannose-derived donors are essential for proper glycosylation, which affects protein folding, stability, and trafficking.

Clinical relevance

Disruptions in enzymes upstream of mannose-1-phosphate, such as phosphomannomutase, can lead to congenital disorders of glycosylation in humans. The most common is PMM2-CDG, caused by deficiency in phosphomannomutase 2, highlighting the pathway’s importance for normal cellular glycosylation.