Phosphomannomutase 1 (PMM1)

Phosphomannomutase 1 is a cytosolic enzyme encoded by the *PMM1* gene on human chromosome 22. It catalyzes the reversible conversion of mannose 6-phosphate to mannose 1-phosphate, a vital step in the synthesis of GDP-mannose and dolichol-phosphate-mannose. These compounds are essential donors in protein N-glycosylation and GPI-anchor pathways, which are crucial for the synthesis and function of glycoproteins and cell surface proteins. PMM1 also exhibits phosphatase activity in the presence of inosine monophosphate (IMP), allowing it to contribute to glucose 6-phosphate salvage and brain energy homeostasis during ischemic conditions. Loss-of-function mutations impact glycoprotein biosynthesis and have been linked to rare, congenital disorders of glycosylation with neurological manifestations. PMM1 is part of the hexose-phosphate mutase enzyme family, and although closely related to phosphomannomutase 2 (PMM2), their physiological roles are distinct[3][4][6][9].

Other names

PMM1Mannose phosphomutase 1Phosphomannomutase, isozyme 1(Gene symbol: PMM1)

Mutation or depletion disrupts GDP-mannose biosynthesis, impairing glycoprotein maturation and function IMP binding allosterically converts PMM1 from a mutase to phosphatase, hydrolyzing glucose 1,6-bisphosphate to rescue glycolysis during brain ischemia Potential pharmacological targeting would aim to modulate its mutase or phosphatase activity for therapeutic benefit