Activation of human erythrocyte pyruvate kinase by hexose-bisphosphates

Abstract

Summary Human erythrocyte pyruvate kinase (E.C. 2.7.1.40, ATP-pyruvate phosphotransferase) is activated by hexose-1,6-bisphosphates in the order: fructose- > mannose- > glucose-bisphosphate. These activators promote substantial reductions (7 to 10 fold) in the K M for the substrate phosphoenolpyruvate but do not effect the maximum velocity. The ability of mannose- and glucose-1,6-bisphosphate to function as activators of both human erythrocyte phosphofructokinase (Rose, I.A. and Warms, J.V.B. (1974), Biochem. Biophys. Acta 156, 231–239) and pyruvate kinase may account for the presence of these metabolites in red cells at relatively high levels. Fructose-1,6-bisphosphate also induces slight increases in the K M values for the active substrate, Mg·ADP, at sub-saturating levels of phosphoenolpyruvate but is without effect at saturating levels of phosphoenolpyruvate. A possible role for these activators in maintaining a balance in the flux through the pyruvate kinase reaction is proposed.