Inhibition of human red cell Nak-ATPase by magnesium and potassium.

The inhibition of NaK-ATPase (EC 3.6.1.3) from human red cells by Mg²⁺ is markedly dependent on the relative concentrations of Na⁺ and K⁺. Inhibition increases with increasing K⁺ and decreases with increasing Na⁺. The inhibition appears to be a combined effect of Mg²⁺ and K⁺ at sites distinct from the sites at which these cations activate the enzyme. The kinetics of activation of the enzyme by Na⁺ with inhibitory levels of Mg²⁺ and K⁺ are biphasic, indicating both low and high affinity Na⁺ sites. At noninhibitory levels of Mg²⁺ and K⁺ only high affinity Na⁺ sites are seen. The results are inconsistent with any model in which Mg²⁺ and K⁺ compete with Na⁺ at a single site. A kinetic model is proposed to explain the mechanism of inhibition by Mg²⁺ and K⁺.