phosphomutases

Phosphomutases are enzymes that catalyze intramolecular transfer of a phosphate group within a molecule, typically moving a phosphate from one carbon to another in sugar phosphates. This rearrangement converts isomeric phosphate esters, such as glucose-1-phosphate and glucose-6-phosphate, or mannose-6-phosphate and mannose-1-phosphate, and thereby supports pathways in carbohydrate metabolism and nucleotide-sugar biosynthesis.

Phosphomutases are widespread in bacteria, archaea, plants and animals, and play essential roles in glycogen and nucleotide-sugar production. They are generally classified into two mechanistic groups. Cofactor-dependent phosphomutases, including phosphoglucomutase and phosphomannomutase, operate via a covalently bound phospho-enzyme intermediate that shuttles a phosphate to the substrate and back to the enzyme. Cofactor-independent phosphomutases (the iPGM family) use metal ions to facilitate the transfer without a covalent enzyme intermediate. Although their sequences and structures differ, both classes achieve the same overall chemistry: intramolecular phosphate migration.

Representative examples include phosphoglucomutase (glucose-1-phosphate ⇄ glucose-6-phosphate), important in glycogen metabolism, and phosphomannomutase (mannose-6-phosphate ⇄ mannose-1-phosphate), which feeds into GDP-mannose production for glycan biosynthesis. In humans, mutations in phosphomutase family members, notably PMM2 and PGM1, underlie certain congenital disorders of glycosylation, illustrating their medical relevance.

The enzymes typically function in the cytosol and often as homodimers or multiprotein complexes, with conserved active-site residues positioned to mediate phosphate transfer. They are subject to regulation by cellular energy status and substrate availability, reflecting their central role in carbohydrate metabolism.