Substrate inhibition of the (Na+, K+)-ATPase in the presence of excess Mg2+.

1. High concentrations of ATP inhibit completely the activity of (Na+, K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) prepared from sheep brain. 2. The inhibition depends on the concentration of total ATP, i.e. complexed ATP+ free ATP. 3. The inhibition by high ATP concentrations persists in the absence of K+, and is then independent of the Na+ concentration between 2 and 140 mM Na+. 4. Raising the K+ concentration at 20 mM Na+ increases the ATP concentration required for the maximal hydrolysis rate. 5. The Hill number for the inhibition process is about three. 6. The inhibition by ATP is temperature-dependent, in that as the temperature is increased, higher ATP concentrations are required for inhibition.