Dual role of Zn2+ as inhibitor and activator of fructose 1,6-bisphosphatase of rat liver.

Publisher Website
Google Scholar
Abstract
At neutral pH, Zn2+ is a potent and specific inhibitor of rat liver fructose 1,6-bisphosphatase (EC 3.1.3.11; D-fructose-1,6-bisphosphate 1-phosphohydrolase). Inhibition by Zn2+ is uncompetitive with respect to the activating cations Mg2+ and Mn2+. The kinetic data suggest that the enzyme possesses a distinct high-affinity binding site for Zn2+, with Ki of approximately 0.3 .mu.M. At higher concentrations (about 10-5 M) Zn2+, and to a lesser extent Co2+, function as activating cations. Binding studies show that the enzyme binds 2 equivalents of Zn2+ per subunit; 1 equivalent is partially displaced by Mg2+ and is presumably bound to the site for activating cations. A 2nd equivalent binds to the high-affinity site, presumably identical to the inhibitor site. The results suggest that Zn2+ functions as an allosteric regulator, and that the commonly observed activation of fructose 1,6-bisphosphatase at neutral pH by EDTA, histidine and other chelators is due to removal of endogenous Zn2+ by these agents.