Mechanism of Ca2+ transport by Ca2+-Mg2+-ATPase pump: analysis of major states and pathways

Am J Physiol. 1983 Jan;244(1):G3-12. doi: 10.1152/ajpgi.1983.244.1.G3.


Mechanistic studies of Ca2+ transport by the Ca2+-Mg2+-ATPase of skeletal sarcoplasmic reticulum are reviewed, and a unifying model is proposed. The significant steps in the transport cycle are modeled in terms of occupation and disposition of three binding sites on the enzyme: a) two translocation sites capable of binding to Ca2+ or a charge-stoichiometric amount of alkali cation (M+) or H+, b) an ATP-ADP-binding site, and c) a phosphorylation or phosphate-binding site. The normal transport cycle is characterized as the following sequence of steps: a) binding of two Ca2+ and Mg-ATP to external sites with high affinity and random order, b) enzyme phosphorylation, c) inward translocation of the Ca2+-laden sites, d) Ca2+ release to the sarcoplasmic reticulum lumen and ADP release to the external medium (random order), e) binding of Mg2+ or a charge-stoichiometric amount of K+ plus H+ to the translocators, f) dephosphorylation, g) the return of the K+- and H+-laden translocators to the outside, and h) dissociation of K+ and H+ from the translocator and completion of the cycle with step a. The enzyme is characterized as a Ca2+-K+ plus H+ countertransporter. The K+ plus H+ remove Ca2+ from the inwardly oriented translocator, thereby relieving a product inhibition and increasing the rate of enzyme dephosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Adenosine Triphosphate / metabolism
  • Animals
  • Binding Sites
  • Binding, Competitive
  • Biological Transport, Active
  • Ca(2+) Mg(2+)-ATPase
  • Calcium / metabolism*
  • Calcium-Transporting ATPases / metabolism*
  • Cations, Monovalent
  • Enzyme Activation
  • Hydrogen-Ion Concentration
  • Ion Channels / metabolism*
  • Kinetics
  • Magnesium / metabolism
  • Models, Biological
  • Phosphorus Radioisotopes
  • Phosphorylation
  • Potassium / metabolism
  • Potassium / pharmacology
  • Protons
  • Rabbits
  • Rats
  • Sarcoplasmic Reticulum / enzymology


  • Cations, Monovalent
  • Ion Channels
  • Phosphorus Radioisotopes
  • Protons
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Ca(2+) Mg(2+)-ATPase
  • Calcium-Transporting ATPases
  • Magnesium
  • Potassium
  • Calcium