Principles of Biochemistry

9.2.3.3. Calcium mediated hormone action

Ionized calcium of cytosol is the important signal for hormone action than cAMP. The extra cellular calcium (Ca⁺⁺⁾ concentration is about 5mmol/L and the intracellular concentration of this free ion is much lower 0.1-10 µmol.

The hormones that bind cell membrane receptor enhance membrane permeability to Ca ⁺⁺ thereby increase Ca ⁺⁺ influx. This is probably accomplished by a Na⁺ /Ca⁺⁺ exchange mechanic that has a high capacity but a low affinity for Ca++. There is a Ca ⁺⁺ ATPase dependent pump that extrudes Ca ⁺⁺ in exchange for H⁺. This has a high affinity for Ca²⁺ but a low capacity.

Cell surface receptors such as those for acetylcholine, ADH, when occupied by their respective ligands, activate phospholipase C. Receptor binding and activation phospholipase C are coupled by G protein. The phosphplipase C catalysis the hydrolysis phosphotidyl inositol 4,5-bisphosphate (PIP2) to inositol triphosphates (IP3) and 1,2 diacylglycerol (DG).

The diacylglycerol is itself capable of activation of protein kinase with free Ca⁺⁺ions as activator.

Inositol triphosphate (IP3) is an effective releaser of calcium from intracellular storage sites such as endoplasmic reticulum and mitochondria.

Thus the hydrolysis of PIP2 leads to activation of protein kinase C and promotes an increase of cytoplasmic calcium ion concentration. A regulatory protein called Calmodulin has 4Ca⁺⁺ binding cites. Ca⁺⁺ ­. Calmodulin complex can activate specific kinases.

These activated protein kinase C can phosphorylate specific substrates and alter physiologic functions for which Ca⁺⁺ is needed.