The functional significance of vitamin K action. Difference in phospholipid binding between normal and abnormal...

In comparison to normal prothrombin, the abnormal prothrombin produced in response to vitamin K antagonists has been found to bind much less tightly, if at all, to phospholipid surfaces. As a consequence, the activation of abnormal prothrombin by Factor Xa and Ca2+ is not accelerated by the addition of phospholipid to the mixture while the activation of normal prothrombin under these conditions is greatly accelerated by phospholipid addition. In the absence of phospholipid, however, the rate of activation of abnormal prothrombin by Factor Xa and Ca2+ in both the presence and absence of Factor Va is indistinguishable from that of normal prothrombin. The distribution of the partial proteolysis products during activation by Factors Xa, Va, and Ca2+ also appears to be the same for both prothrombins. These observations provide an explanation for the function in prothrombin activation of the gamma-carboxyglutamate residues formed in the vitamin K-dependent carboxylation of prothrombin.