Triosephosphate Isomerase: Isotope Studies on the Mechanistic Pathway

Triosephosphate isomerase (E.C. 5.3.1.1), “TIM,” is responsible for the rapid interconversion of triosephosphates in glycolysis. Although the equilibrium is well over (96%) on the side of dihydroxyacetone phosphate (DHAP), the flux of material in vivo is overwhelmingly through d-glyceraldehyde 3-phosphate (GAP) to pyruvate. The triosephosphate equilibrium (and the aldolase equilibrium that precedes it, which is strongly in favor of hexose) is driven in the required direction of hexose diphosphate → phosphoglycerate, by the exergonic phosphorylation of ADP by 1,3-diphosphoglycerate.