Dual Role of Zn2+as Inhibitor and Activator of Fructose 1,6-bisphosphatase of Rat Liver

• Published in: Proceedings of the National Academy of Sciences - PNAS 1976-08, Vol.73 (8), p.2692-2695
• Main Authors: Tejwani, Gopi A., Pedrosa, Fabio O., Pontremoli, S., Horecker, B. L.
• Format: Article
• Language: English
• Subjects: Animals; Binding Sites; Biochemistry; Citrates; Cobalt - pharmacology; Edetic Acid - pharmacology; Enzymes; Fructose-Bisphosphatase - antagonists & inhibitors; Fructose-Bisphosphatase - metabolism; Heavy metals; Histidine - pharmacology; Hydrogen-Ion Concentration; Kinetics; Legends; Liver; Liver - enzymology; Magnesium - pharmacology; Metal ions; Rats; Zinc - antagonists & inhibitors; Zinc - metabolism; Zinc - pharmacology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.73.8.2692

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 Kiof approximately 0.3 μ M. At higher concentrations (about 10-5M) 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.