Hypothesis: control of intracellular calcium level.
It is proposed that cells store calcium in the hydrogen belt of their membranes, on the cytoplasmic side, with the Ca2+ ion captive in cages formed by the phosphate and carbonyl oxygens of two acidic phospholipid molecules; for instance, phosphatidylinositol and phosphatidylserine. Evidence for the existence of such Ca-cages is adduced from the properties of the [Ca(phosphatidate)2] complex. Cytoplasmic Ca2+ concentration, approx. 10(-7) M, corresponds to the calcium cage dissociation constant. The high stability of the cages is the result of multiple hydrogen bonds between inositol and serine, or inositol and inositol. Phosphorylation of the inositol in position 4 and 5 opens the calcium cage by breaking the inter-headgroup hydrogen bonds and by introducing electrostatic and steric hindrance. This allows the escape of Ca2+ into the cytosol. The mono in equilibrium with di in equilibrium with triphosphoinositide shuttle serves as a regulator of Ca2+ concentration in the cytoplasm: phosphorylation of the lipids will raise, dephosphorylation lower the level of free Ca2+. The inositide shuttle may be linked to a stimulus-induced inositide cycle in which inositol triphosphate is generated, and to Ca(phosphatidate)2 cross-membrane transport.
D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006706:Homeostasis; D008051:Lipid Bilayers; D008563:Membrane Lipids / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D008968:Molecular Conformation
D008051:Lipid Bilayers; D008563:Membrane Lipids; D002118:Calcium