Dual role of Zn2+ as inhibitor and activator of fructose 1,6-bisphosphatase of rat liver.
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+, and the kinetic data suggest that the enzyme possesses a distinct high-affinity binding site for Zn2+, with Ki of approximately 0.3 muM. 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 two equivalents of Zn2+ per subunit; one equivalent is partially displaced by Mg2+ and is presumably bound to the site for activating cations. A second equivalent binds to the high-affinity site, presumably identical to the inhibitory 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.
D000818:Animals; D001665:Binding Sites; D003035:Cobalt / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D006597:Fructose-Bisphosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006639:Histidine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008274:Magnesium / Q000494:pharmacology; D051381:Rats; D015032:Zinc / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*
D003035:Cobalt; D006639:Histidine; D004492:Edetic Acid; D006597:Fructose-Bisphosphatase; D008274:Magnesium; D015032:Zinc