PGAM

PGAM, or phosphoglycerate mutase, is a glycolytic enzyme that catalyzes the reversible interconversion of 3-phosphoglycerate and 2-phosphoglycerate, a step that connects the early triose-phosphate pool to the later stages of glycolysis and gluconeogenesis.

Two major classes exist: cofactor-dependent PGAM (dPGM) and cofactor-independent PGAM (iPGM). dPGM enzymes operate via a phosphohistidine intermediate and, in many species, participate in a cycle involving 2,3-bisphosphoglycerate; iPGM enzymes are metallophosphoesterases that catalyze the same overall reaction without a histidine intermediate. Structurally, dPGM commonly forms a dimer and is typically cytosolic, while iPGM is usually monomeric and metal-dependent.

In humans, the best-characterized enzyme is dPGM, encoded by PGAM1 and PGAM2. The enzyme is typically a cytosolic homodimer and contributes to glycolytic flux in tissues with high energy demand, including red blood cells where glycolysis interfaces with the 2,3-BPG pathway that modulates hemoglobin oxygen affinity.

iPGM occurs in many bacteria, plants, fungi, and some parasites and is absent in humans. Because of this distribution, iPGM has been explored as a potential antimicrobial or antiparasitic drug target, whereas dPGM is of interest in cancer metabolism and other aspects of human physiology.

Genomic and evolutionary notes: the two PGAM classes represent distinct evolutionary lineages that arrived at the same catalytic outcome. The enzyme activities are conserved, but regulatory properties and tissue distribution differ across organisms.