[Tetraprotomeric hypothesis of Na/K-ATPase]

Since the discovery of Na/K-ATPase by Skou, the mechanism of Na/K-dependent ATP hydrolysis and Na and K transport has been extensively studied. The hydrolysis appears to occur sequentially via the Na-Enzyme-ATP complex (NaE1ATP), ADP-sensitive phosphoenzyme (NaE1P), the K-sensitive phosphoenzyme (E2P) and the K-occluded enzyme (KE2), known the Post-Albers mechanism, in a protomer or diprotomer that consists of alpha- and beta-chains. The tetrameric nature of the enzyme such as a quarter, half, third to fourth and full site reactivity and the visualization by electron microscopy show direct biochemical evidence for the presence of a tetraprotomer structure of Na/K-ATPase during ATP hydrolysis. ATP binding is followed by two parallel paths, which occur at each of the two half sites for phosphorylation-dephosphorylation, and direct ATP hydrolysis via (NaE1P : E.ATP)2, (E2P : E.ATP : E2P : E.ADP/Pi) and (KE2 : E.ADP/Pi)2, respectively. The sequential formation of E2P from NaE1P and KE2 from E2P is accompanied by, respectively, hydrolysis of half of the TCA-labile bound ATP to ADP/Pi and of another half of the bound ATP to ADP/Pi. All reaction intermediates detectable in the Post-Albers scheme bind ATP and/or ADP/Pi.