Sodium + potassium-activated ATPase of mammalian brain. Regulation of phosphatase activity.
1. The K+-nitrophenylphosphatase activity associated with mammalian brain (Na+ + K+)-ATPase displays K+ activation curves that have intermediary plateaus and maxima in the presence of less than saturating concentrations of Na+. Zero Na+ and saturating Na+ produce sigmoid K+-activation curves with low and high K+ affinities respectively. 2. ATP inhibits K+-activated nitrophenylphosphatase through both competitive and non-competitive mechanisms. ATP is synergistic with Na+ in the mechanism which converts the enzyme from low to high K+ affinity. 3. The Na+ and K+ interactions can be accounted for by equations which describe a model with separate regulatory sites for Na+ and K+ and with K+- requiring catalytic site which is only accessible in one of the two principal conformational stages of the enzyme. 4. The effects of ATP can be accounted for by the same model through interactions at a single nucleotide binding site. Inhibition which is competitive with K+ and non-competitive with substrate arises from stabilization of the inactive enzyme conformation. Inhibition which is non-competitive with K+ and competitive with substrate results from interactions with the active enzyme conformation. The synergism between Na+ and ATP appears to arise as a consequence of the formation of phosphoryl enzyme. 5. A model for (Na+ + K+)-ATPase is discussed which involves in-phase coupling of subunit interactions as suggested by these studies.
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002417:Cattle; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006168:Guinea Pigs; D007700:Kinetics; D008433:Mathematics; D008861:Microsomes / Q000201:enzymology; D008954:Models, Biological; D009596:Nitrophenols; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology*
D009596:Nitrophenols; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D012964:Sodium; D010744:Phosphoric Monoester Hydrolases; D000251:Adenosine Triphosphatases; D011188:Potassium; D004121:Dimethyl Sulfoxide