Abstract
Calcium ion inhibits (Na+ + K+)-ATPase (EC 3.6.1.3) primarily by reducing the rate of the phosphorylation step. Inhibition of this step is competitive with respect to Na+ and noncompetitive with respect to Mg++. Although Ca++ acts to reduce the rate of the phosphorylation step, high concentrations are required to reduce the steady-state levels of phospho-enzyme, and Ca++ alone stimulates a slow phosphorylation of the enzyme. In the presence of Ca++ and Mg++ the phospho-enzyme formed is sensitive to K+ and ouabain, and its steady-state levels are low when K+ is present. If the concentration of Mg++ is low, of the phosphoenzyme formed in the presence of Ca++ is insensitive to K+ and ouabain, and reacts readily with ADP. The reactivity of the Ca++-dependent phospho-enzyme with ADP is reduced by the addition of Mg++; conversely, the reactivity of the Mg++-dependent phospho-enzyme with ADP is increased by high concentrations of Na+. Ca++ also inhibits the Mg++- and P[unknown]-dependent pathway of [3H]ouabain binding. The identification of an ADP-sensitive intermediate in the reaction cycle of this enzyme is reported. Its transformation to a K+-sensitive intermediate is influenced by Na+, Mg++, and Ca++ in a manner consistent with proposed reaction mechanisms for this enzyme.
ACKNOWLEDGMENTS The authors would like to thank Mrs. Annie Han for excellent technical assistance, and Mr. Ralph Evans, who assisted as a summer student.
- Copyright ©, 1973, by Academic Press, Inc.
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|