AJP - Gastrointestinal and Liver Physiology, Vol 244, Issue 1 3-12, Copyright © 1983 by American Physiological Society
Mechanism of Ca2+ transport by Ca2+-Mg2+-ATPase pump: analysis of major states and pathways
D. H. Haynes
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.
