Inhibitory effect of Zn2+ on rabbit muscle pyruvate kinase and reactivation by histidine

Histidine was found to be an activator of rabbit muscle pyruvate kinase activity with a K1/2 value of 0.6 mM. Carnosine and anserine are also effective, but only at much higher concentrations. Hyperbolic kinetics with phosphoenolpyruvate of the enzyme were found in either the presence or absence of histidine. Of a number of divalent cations tested, only Zn2+ was found to be an effective inhibitor of enzyme activity at low concentrations. The kinetic data suggested that Zn2+ acted as inhibitor as well as activator for the enzyme activity; a high affinity binding site was associated with Ki of approximately 4.8 microM Zn2+ and a catalytic site was associated with Km of approximately 80 microM Zn2+ Zn2+, which is associated to a high affinity binding site of the enzyme, was removed by the addition of histidine with a K1/2 of approximately 0.6 mM. From these findings, histidine including anserine and carnosine in muscle may act as a chelating agent for the enzyme activity.