title: A model for the reaction pathways of the K+-dependent phosphatase activity of the (Na+ + K+)-dependent ATPase.
abstract: (Na+ + K+)-dependent ATPase preparations from rat brain, dog kidney, and human red blood cells also catalyze a K+ -dependent phosphatase reaction. K+ activation and Na+ inhibition of this reaction are described quantitatively by a model featuring isomerization between E1 and E2 enzyme conformations with activity proportional to E2K concentration: (formula; see text) Differences between the three preparations in K0.5 for K+ activation can then be accounted for by differences in equilibria between E1K and E2K with dissociation constants identical. Similarly, reductions in K0.5 produced by dimethyl sulfoxide are attributable to shifts in equilibria toward E2 conformations. Na+ stimulation of K+ -dependent phosphatase activity of brain and red blood cell preparations, demonstrable with KCl under 1 mM, can be accounted for by including a supplementary pathway proportional to E1Na but dependent also on K+ activation through high-affinity sites. With inside-out red blood cell vesicles, K+ activation in the absence of Na+ is mediated through sites oriented toward the cytoplasm, while in the presence of Na+ high-affinity K+ -sites are oriented extracellularly, as are those of the (Na+ + K+)-dependent ATPase reaction. Dimethyl sulfoxide accentuated Na+ -stimulated K+ -dependent phosphatase activity in all three preparations, attributable to shifts from the E1P to E2P conformation, with the latter bearing the high-affinity, extracellularly oriented K+ -sites of the Na+ -stimulated pathway.
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D002712:Chlorides; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004285:Dogs; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D007668:Kidney / Q000201:enzymology; D008274:Magnesium / Q000494:pharmacology; D015636:Magnesium Chloride; D008345:Manganese / Q000494:pharmacology; D017895:Manganese Compounds; D009596:Nitrophenols / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D002712:Chlorides; D017895:Manganese Compounds; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D015636:Magnesium Chloride; C008644:nitrophenylphosphate; D008345:Manganese; D010744:Phosphoric Monoester Hydrolases; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium; C025340:manganese chloride; D011188:Potassium; D004121:Dimethyl Sulfoxide