ADP-glucose Pyrophosphorylase Allosteric Regulation Involves Changes in Substrate Specificity

A.C. EBRECHT; L. SOLAMEN; K.B. OLSEN; M.A. BALLICORA; A.A. IGLESIAS

Rosario

Congreso; 50th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2014

SAIB

ADP-glucose pyrophosphorylase (ADP-Glc PPase) is the enzyme that catalyzes synthesis of ADP-Glc and PPi from ATP and Glc-1P, through a reaction that requires a divalent metal ion (physiologically Mg2+). Several studies established that this is the regulatory step in the synthesis of glycogen and starch in bacteria and plants, respectively. Within the family of PPases, the ADP-Glc PPase is the only that is allosterically regulated. In particular the enzyme from Escherichia coli is mainly activated by fructose-1,6-bisP (FBP). We observed that the E. coli ADP-Glc PPase exhibits a degree of promiscuity toward substrates and the essential cofactor. Such a promiscuous behavior was found affected by FBP, which markedly increased the affinity of the enzyme toward ATP as well the catalytic efficiencywhen using Glc-1P. Co2+ and Mn2+ also behaved as cofactors of the enzyme in reactions with both ATP and UTP. Although only with ATP the FBP increased the catalytic efficiency for divalent cation. Results support the view that the allosteric regulator would play a critical role in determining the specific use of ATP as a substrate. The action of the activator in a mechanism to increase the specificity of the enzyme is a new view. It opens perspectives for understanding device procedures for allosteric regulation of ADP-Glc PPases (and other enzymes?) in the context of the metabolic scenario.