Explain the Vitamin K dependent proteins?
The four vitamin K-dependent procoagulants (factor II or prothrombin, and factors VII, IX, and X), about which we studied above, are serine proteases that are synthesized in the liver and then secreted into the circulation as inactive forms (zymogens). Their biological activity depends on their normal complement of Gla residues, which are efficient chelators of calcium ions. In the presence of Gla residues and calcium ions, these proteins bind to the surface membrane phospholipids of platelets and endothelial cells where, together with other cofactors, they form membrane-bound enzyme complexes. When coagulation is initiated, the zymogens of the four vitamin K-dependent clotting factors are cleaved to yield the active protease clotting factors.
Two other vitamin K-dependent proteins, protein C and protein S, play a regulatory role in the inhibition of coagulation. The function of protein C is to degrade phospholipid- bound activated factors V and VIII in the presence of calcium. Protein S acts as a synergistic cofactor to protein C by enhancing the binding of activated protein C to negatively charged phospholipids. There is evidence that protein S is synthesized by several tissues including the blood vessel wall and bone and may have other functions besides its well-established role as a coagulation inhibitor. Yet another vitamin K-dependent plasma protein (protein 2) is suspected to have a haemostatic role but its function is currently unknown.
Apart from the coagulation proteins, several other vitamin K-dependent proteins have been isolated from bone, cartilage, kidney, lungs and other tissues. Only two, osteocalcin and nlatrix Gla protein (MGP), have been well characterized. Both are found in bone but MGP also occurs in cartilage, blood vessel walls, and other soft tissues. One function of MGP is to inhibit mineralization. Thus far, no clear biological role for osteocalcin has been established despite its being the major noncollagenous bone protein synthesized by osteoblasts. Nephrocalcin has been isolated from kidney and urine. Atherocalcin, plaque Gla protein proline rich Gla proteins have been identified from atheromatous plaques, spinal and thyroid tissues.