Blood-clotting factors, binding

First, phospholipid bilayers which mimic cellular membrane and platelet factor 3, on which several blood clotting factors bind in order to generate the more efficient cascade of enzymatic reactions (J ). They are the vitamin K-dependent proteins II, X and IX which are... 

There appears to be no reason to conclude, therefore, that phase separation occurs as a consequence of blood clotting factor binding, in contrast to the conclusion of Mayer and Nelsestuen (27,28) from similar experiments. The lack of phase separation in similar systems was recently confirmed by Lentz (26) describing the whole phase diagram of a PC-PG mixture. 

A conformational change induced in the protein antithrombin (AT) on binding a specific pentasaccharide S domain allows its interaction with Factor Xa, a blood clotting factor, preventing clotting. 

In the first part of this study, we focus on the binding of CTX to the two types of interface. Secondly, we discuss the binding and desorption of the 1 1 T-AT complex from the polymeric interfaces. Finally, we investigate the charge distribution within the plane of the membrane when blood clotting factors II and V are bound. 

The binding site for blood clotting factors can be enriched in negative lipids but, if domains of different composition compared to the bulk are formed, they must be very small in size and/or their composition must be very close to that of the initial mixture. 

In mammals and birds vitamin K] is an essential cofactor in the posttranslational carboxy lation reaction of glutamic acid residues (GLU) to y-carboxygiutamic acid residues (GLA) in a number of blood clotting factors (factors II, VII, IX, and X) and also in some other proteins, such as protein C, protein S and osteocalcin. These GLA residues provide the proteins with calcium-binding properties essential for the interaction with phospholipids and for their activation. Excellent articles and reviews on the biochemistry and on the physiological role of vitamin Kj in humans are given by Suttie (70), Friedman (71), and Friedrich (72). Besides vitamin K itself, ubiquinones and plastoquinones also occur in higher plants. Structures of vitamin Ki and of some of these related compounds are presented in Fig. 7. 

Blood-clotting factors and some other calcium-binding proteins... 

Heparin inhibits the formation of fibrin clots, inhibits the conversion of fibrinogen to fibrin, and inactivates several of the factors necessary for the clotting of blood. Heparin cannot be taken orally because it is inactivated by gastric acid in the stomach therefore, it must be given by injection. Heparin has no effect on clots that have already formed and aids only in preventing the formation of new blood clots (thrombi). The LMWHs act to inhibit clotting reactions by binding to antithrombin HI, which inhibits the synthesis of factor Xa and the formation of thrombin. 

Blood platelets are key players in the blood-clotting mechanism. These tiny fragments of cytoplasm are shed into the circulation from the surface of megakaryocytes located in the bone marrow. When the lining of a blood vessel is injured, activated platelets release clotting factors, adhere to each other and to damaged surfaces, and send out numerous filopodia. The shape changes that occur in activated platelets are the result of actin polymerization. Before activation, there are no microfilaments because profilin binds to G-actin and prevents its polymerization. After activation, profilin dissociates from G-actin, and bundles and networks of F-actin filaments rapidly appear within the platelet. 

Prothrombin and several other proteins of the blood clotting system (Factors VII, IX and X, and proteins C and S) each contain between four and six y-carboxygluta-mate residues which chelate calcium ions and so permit the binding of the blood clotting proteins to membranes. In vitamin K deficiency or in the presence of warfarin, an abnormal precursor of prothrombin (preprothrombin) containing little or no y-carboxyglutamate, and incapable of chelating calcium, is released into the circulation. 

Heparin is a carbohydrate-based (glycosaminoglycan) anticoagulant associated with many tissues, but mainly found stored intracellularly as granules in mast cells that line the endothelium of blood vessels. Upon release into the bloodstream, heparin binds to and thereby activates an additional plasma protein, namely antithrombin. The heparin-antithrombin complex then binds a number of activated clotting factors (including Ha, IXa, Xa, XIa and Xlla), thereby inactivating them. The heparin now disassociates from the complex and combines with another antithrombin molecule, thereby initiating another turn of this inhibitory cycle. 

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