Calcium metal is present in great abundance in the body, being mostly distributed in bones and teeth. A very small amount is present in the body fluids. Its concentration is more in the extracellular fluid than in the intracellular fluid.
Ca2+ ion is stored in the sarcoplasmic reticulum membrane on calcium binding proteins especially Calsequestrin. This protein has such a high affinity for Calcium that it binds about 43 Ca2+ ions per molecule. Ca2+ also binds to several other proteins such as troponin, parvalbumin, calmodulin, concavalin A and staphylococcal nuclease. Ca2+ plays an important role in several biological processes.
Calcium in bones and teeth:
About 99% of an adults calcium (~ 1.2 kg) is in bones and teeth. It is present as basic calcium phosphate (hydroxyapatite) reinforced by the protein collagen.
In teeth enamel the protein keratin is present instead of collagen. When there is deficiency of calcium in blood some of the calcium from bones dissolves to maintain the calcium level in blood.
Ca2+ in blood clotting:
Coagulation of blood occurs to prevent excess bleeding when tissues are damaged. The overall mechanism is complex and involves a cascade process many steps of which are dependent on Ca2+. Clot formation involves activation of certain proteins to form fibrin, the molecules of which are then cross-linked.
Ca2+ in muscle contraction:
Ca2+ plays an important role in the regulation of muscle contraction. Skeletal muscle contains an intricate network of membrane bound tubules and vesicles. This membrane system is called sarcoplasmic reticulum (SR) regulates the Ca2+ concentration surrounding the contractile fibers of the muscles. At rest Ca2+ is pumped into the SR so that the concentration of Ca2+ around the muscle fibers is very low. Excitation of the SR membrane by a nerve impulse leads to a sudden release of large amounts of Ca2+ which triggers muscle contraction. In other words, Ca2+ is the intermediary between nerve impulse and muscle contraction.
The major constituents of the muscle fibre are the proteins myosin and actin, plus the regulatory proteins troponin and tropomysin. Each muscle fibre is made up of some of 1000 fibrils. Myosin and actin are organized in the fibril in the form of two filaments, one thick and one thin. Muscle contraction and relaxation results from the sliding of one filaments over the other. The interaction of myosin and actin is inhibited by troponin and tropomysin in the absence of Ca2+. Nerve excitation triggers the release of Ca2+ by SR. The released calcium binds to troponin and causes conformational changes that are transmitted to actin through tropomysin. These conformational changes enables actin to interact with myosin resulting in muscle contraction and ATP hydrolysis which persists till Ca2+ is removed.
Ca2+ as a messenger:
A primary messenger is an extracellular agent which responds to an extracellular stimulus. The signal is transmitted via a secondary messenger> Ca2+ acts as a secondary messenger intracellularly because its concentration can change rapidly in response to external stimuli. Ca2+ ion binds to several proteins and in which it is catalytically most reactive. Thus Ca2+ initiates the activation or deactivation of a large number of proteins and enzymes.
The versatility of Ca2+ in inducing a variety of intracellular processes probably arises because there are many ways in which a polypeptide can fold around it. One of the Ca2+ binding proteins of note is calmodulin whose function is triggered by a change of Ca2+ ion concentration.
The calmodulins are small proteins with glutamate and aspartate residue which bind Ca2+ ions. The protein confirmation is changed on metal ion binding so that it can now reorganize, bind and activate an enzyme.
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