(Na+ + K+)-ATPase: on the number of the ATP sites of the functional unit.

Questions concerning the number of the ATP sites of the functional unit of (Na+ + K+)-ATPase (i.e., the sodium pump) have been at the center of the controversies on the mechanisms of the catalytic and transport functions of the enzyme. When the available data pertaining to the number of these sites are examined without any assumptions regarding the reaction mechanism, it is evident that although some relevant observations may be explained either by a single site or by multiple ATP sites, the remaining data dictate the existence of multiple sites on the functional unit. Also, while from much of the data it is clear that the multiple sites of the unit enzyme represent the interacting catalytic sites of an oligomer, it is not possible to rule out the existence of a distinct regulatory site for ATP in addition to the interacting catalytic sites. Regardless of the ultimate fate of the regulatory site, any realistic approach to the resolution of the kinetic mechanism of the sodium pump should include the consideration of the established site-site interactions of the oligomer.