The mechanism of the modifying effect of ATP on Na(+)-K+ ATPase.

On the basis of a review of the literature and a study of the molecular and kinetic properties of Na(+)-K+ ATPase, a model is proposed that explains the regulation of the activity of the enzyme by ATP in terms of an acceleration of the E2----E1 transition. It is presumed that the transition occurs via a short-lived oligomer whose formation is accelerated by ATP. In the context of this model, the non-Michaelis-Menton kinetics of the enzyme can be explained by interprotomer interactions. After solubilization of the enzyme with octaethylene glycol dodecyl ether, the hydrolysis of ATP follows ordinary Michaelis-Menton kinetics. The validity of the model is also supported by radiation-inactivation experiments with a nucleotide (GTP) which does not accelerate the E2----E1 transition, as well as by experiments with a low concentration of ATP. In both situations, the size of the molecular target corresponds to the monomeric form of the enzyme.