title: Effects of choline on Na(+)- and K(+)-interactions with the Na+/K(+)-ATPase.
abstract: Choline chloride, 100 mM, stimulates Na+/K(+)-ATPase activity of a purified dog kidney enzyme preparation when Na+ is suboptimal (9 mM Na+ and 10 mM K+) and inhibits when K+ is suboptimal (90 mM Na+ and 1 mM K+), but has a negligible effect at optimal concentrations of both (90 mM Na+ and 10 mM K+). Stimulation occurs at low Na+ to K+ ratios, but not at those same ratios when the actual Na+ concentration is high (90 mM). Stimulation decreases or disappears when incubation pH or temperature is increased or when Li+ is substituted for K+ or Rb+. Choline+ also reduces the Km for MgATP at the low ratio of Na+ to K+ but not at the optimal ratio. In the absence of K+, however, choline+ does not stimulate at low Na+ concentrations: either in the Na(+)-ATPase reaction or in the E1 to E2P conformational transition. Together, these observations indicate that choline+ accelerates the rate-limiting step in the Na+/K(+)-ATPase reaction cycle, K(+)-deocclusion; consequently, optimal Na+ concentrations reflect Na+ accelerating that step also. Thus, the observed K0.5 for Na+ includes high-affinity activation of enzyme phosphorylation and low-affinity acceleration of K(+)-deocclusion. Inhibition of Na+/K(+)-ATPase and K(+)-nitrophenylphosphatase reactions by choline+ increases as the K(+)-concentration is decreased; the competition between choline+ and K+ may represent a similar antagonism between conformations selected by choline+ and by K+.
authors.affiliation: Department of Pharmacology, State University of New York, Health Science Center, Syracuse 13210.
authors.forename: J D
authors.initials: JD
authors.lastname: Robinson
authors.forename: P R
authors.initials: PR
authors.lastname: Pratap
mesh_terms: D009597:4-Nitrophenylphosphatase / Q000187:drug effects; D000818:Animals; D001667:Binding, Competitive; D002794:Choline / Q000494:pharmacology*; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D007679:Kidney Medulla / Q000201:enzymology; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism*; D011487:Protein Conformation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D012964:Sodium; D009597:4-Nitrophenylphosphatase; D000254:Sodium-Potassium-Exchanging ATPase; D002794:Choline; D011188:Potassium