Vitamin K is a substrate for the enzyme catalyzing the carboxylation of specific glutamyl residues to y-carboxyglutamy1 residues in hepatic precursors of a limited number of plasma proteins, including prothrombin. The y-carboxylation of these proteins can be blocked by the anticoagulant warfarin; and in the bovine and human, warfarin treatment results in the secretion of under-y-carboxylated fo...

S TUDIES of the chemical nature of prothrombin have indicated a glycoprotein structure.2 Data obtained on purified bovine prothrombin have shown the reducing sugar content to be approximately 5 per cent, based on a reference standard of galactose and mannose.35 Laki et al.5 reported a value of 6.5 per cent in terms of glucose, and 1.6 to 1.7 per cent hexosamine. Alexander6 and colleagues observ...

The mechanism by which thrombin and prothrombin control neurite retraction was studied in Ad12E1HER10 human neuroepithelial cells. Morphological changes in differentiated cells were apparent within minutes of the addition of very low concentrations of thrombin (3 pM). Higher concentrations (2 nM) of prothrombin were required to elicit a similar response. Doses of thrombin and prothrombin suffic...

The amino acid sequence of the nonthrombin half of human prothrombin is presented. Prothrombin fragment 1 has 155 amino acid residues as compared with 156 for the bovine equivalent. Ten gamma-carboxyglutamic acid residues are at the same location in each species. Human prothrombin fragment 2 contains 118 amino acid residues, as does the similar bovine fragment. Comparing bovine and human prothr...

Mannan-binding lectin-associated serine protease-1 (MASP-1), a protein of the complement lectin pathway, resembles thrombin in terms of structural features and substrate specificity. Due to its interplay with several coagulation factors, it has the ability to induce fibrin clot formation independent of the usual coagulation activation pathways. We have recently shown that MASP-1 activates proth...

Long-standing dogma proposes a profound contribution of membrane binding by prothrombin in determining the rate at which it is converted to thrombin by prothrombinase. We have examined the action of prothrombinase on full-length prothrombin variants lacking γ-carboxyglutamate modifications (desGla) with impaired membrane binding. We show an unexpectedly modest decrease in the rate of thrombin f...

Regulation of vascular homeostasis depends upon collaboration between cells of the vessel wall and blood coagulation system. A direct interaction between integrin alphaVbeta3 on endothelial cells and smooth muscle cells and prothrombin, the pivotal proenzyme of the blood coagulation system, is demonstrated and activation of the integrin is required for receptor engagement. Evidence that prothro...

Attention has recently been focused on the consumption of prothrombin during blood coagulation. Studies of the velocity of prothrombin conversion to thrombin have yielded important information concerning the clotting defect in various hemorrhagic disorders. Thrombin evolution is retarded in the coagulation of hemophilic blood (1-5), thrombocytopenic blood (3, 4, 6, 7) and blood exposed to silic...

By RICHARD WARREN, M.D. AND JOHN S. BELKO, M.S. A PRACTICAL CLINICAL METHOD for determining the activity in plasma of the accelerators of prothrombin conversion has not been so rapidly forthcoming as have been descriptions of their properties and reactions. Those methods which have been described have employed two general principles. The first. of these is the ability of the unknow’n plasma to ...

S TUDIES of the chemical nature of prothrombin have indicated a glycoprotein structure.2 Data obtained on purified bovine prothrombin have shown the reducing sugar content to be approximately 5 per cent, based on a reference standard of galactose and mannose.35 Laki et al.5 reported a value of 6.5 per cent in terms of glucose, and 1.6 to 1.7 per cent hexosamine. Alexander6 and colleagues observ...