Regulation of Pyruvate Dehydrogenase from Escherichia coli INTERACTIONS OF ADENYLATE ENERGY CHARGE AND OTHER REGULATORY PARAMETERS

Abstract Activity of the pyruvate dehydrogenase complex (pyruvate + DPN+ + HSCoA → acetyl-SCoA + DPNH + CO2 + H+) of Escherichia coli is stimulated by glycolytic intermediates. Fructose-di-P is the most effective modifier, and activity is enhanced also by fructose-6-P, glyceraldehyde-3-P, phosphoenolpyruvate, dihydroxyacetone-P, and glucose-6-P. These effects are exerted on the pyruvate decarboxylase component of the complex. Fructose-di-P overcomes the inhibition resulting from a high value of the adenylate energy charge. The activity of the complex is modulated also by the oxidation level of the DPN+-DPNH pool, increasing steeply with increase in the DPN+ mole fraction in the physiological range around 0.8. The responses to the adenylate energy charge, the DPN+ mole fraction, and the acetyl coenzyme A concentration are in the right direction, and the interactions are of the right type, to suggest that modulation of pyruvate dehydrogenase activity contributes to the stabilization of these parameters in vivo.