Aldolase-catalysed inactivation of glyceraldehyde-3-phosphate dehydrogenase

Abstract

ALDOLASE is known to catalyse its own inactivation in the presence of substrate and electron acceptors¹. The underlying mechanism is that in the presence of electron acceptors aldolase catalyses the oxidation of dihydroxyacetone phosphate to hydroxypyruvaldehyde phosphate^2,3 and this highly reactive nascent α-dicarbonyl reacts in situ with an active-centre residue⁴. Inactivation of aldolase is entirely due to reaction in situ of nascent hydroxypyruvaldehyde phosphate, for hydration and dilution of released hydroxypyruvaldehyde phosphate practically abolishes its contribution to inactivation⁴. As the inactivating agent loses reactivity on diffusion into solvent⁴, its action is restricted to the enzyme molecule that has produced it; other molecules of aldolase or other enzymes (transaldolase, transketolase) are not inactivated by aldolase-generated reagent¹. We report here that oxidative cycles of aldolase cause the inactivation of glyceraldehyde-3-phosphate dehydrogenase (GAPD), suggesting a direct transfer of the inactivating agent between the two enzymes. Kinetic evidence for an interaction between aldolase and GAPD has been presented⁵.