BLOOD COAGULATION
Background
Involvement in blood coagulation is the classical role of vitamin K, and the major function of Gla-residues in the coagulation factors is that they facilitate the binding of these proteins to the negatively charged phospholipids on the surface of activated blood platelets.
Figure: simplified model for the binding of a Gla residue to negatively charged phospholipids
In this way the reaction rate of thrombin formation is accelerated several orders of magnitude. Gla-containing proteins involved in blood coagulation are prothrombin (FII), the factors VII, IX, and X, as well as the anticoagulant proteins C, S and Z. With the exception of protein S (which is produced in a variety of tissues) all the vitamin K-dependent coagulation factors are synthesized in the liver. Their Gla-content ranges between 10 (prothrombin) to 12 (factor IX) residues per molecule and the respective Gla-domains are essential for these proteins in their binding to negatively charged phospholipids such as those found in the outer membranes of activated blood platelets.
Recommended literature:
- Davie EW. Biochemical and molecular aspects of the coagulation cascade. >Thromb Haemost. 1995;74:1-6.
- Furie B, Bouchard BA, Furie BC. Vitamin K-dependent biosynthesis of gamma carboxyglutamic acid. Blood. 1999;93:1798-808.
- Vermeer C. Gamma-carboxyglutamate-containing proteins and the vitamin K-dependent carboxylase<. Biochem J
