Factor X activation

McGee M. P., Li L. C. Functional difference between intrinsic and extrinsic coagulation pathways. Kinetics of factor X activation on human monocytes and alveolar macrophages. J Biol Chem 1991 266,8079-85. 

Activated factor XII leads to the activation of factor XI in turn, activated factor XI, along with Ca++ ions and factor IV, leads to activation of factor IX. Activated factor IX, along with Ca++ ions, factor VIII, and PF3, leads to the activation of factor X. From the point of factor X activation, the extrinsic and intrinsic mechanisms follow the same pathway to fibrin formation. 

Extrinsic pathway This pathway has fewer steps than the intrinsic pathway and occurs rapidly, within a matter of seconds if the trauma is severe. It is called the extrinsic pathway because a protein tissue factor, also called thromboplastin or coagulation factor III, takes into the blood stream from outside and initiates the formation of prothrombinase. Tissue factor is released from the surface of the damaged cells. It activates factor VII. Factor VII combines with factor X, activating it. Factor X in the presence of Ca combines with factor V to give active enzyme prothrombinase. 

Viperidae endopeptidase, factor X activator, fibrinogenase, kininogenase, metalloproteinase, prothrombin activator, serine protease, thrombin-like enzyme... 

The first complex to form is almost certainly the extrinsic factor X activation complex. Factor Vila binds to tissue factor, an integral membrane protein that is exposed upon injury of the blood vessel. The phospholipid bilayer surface is provided by the damaged cell membranes. In vivo, Ca + is always present in the blood. ... 

Takeya, H., Nishida, S., Miyata, T., Kawada, S., Saisaka, Y., Morita, T., and Iwanaga, S. (1992). Coagulation factor X activating enzyme from Russells viper venom (RVV-X). J. Biol Chem. 267 14109-14117. 

Since both these proteins are cofactors and not proteases, the assay system for synthetic substrates involves a complicated method that requires the availability of purified coagulation factors. For Factor VIII, the assay is based on the rate of Factor X activation, and the conditions must be chosen so as to make the test proportional only to the Factor VIII, activity. In 1979, Segat-chian reported on a two-stage test method that utilized the chromogenic substrate S-2222 (S12). In this assay the inhibitor hirudin is added to block thrombin s activity so the generation of Factor Xa is the critical parameter. Recently Rosen has reported on a modified assay (R4). 

Intact platelets do not show procoagulant phospholipids on their exterior. These phospholipids are located on the inside leaf of the bilayer membrane (H6). They become accessible when the platelets are disrupted or by a process initiated by small amounts of collagen and thrombin that shifts these procoagulant agents from the inside to the outside. Both in prothrombin and intrinsic Factor X activation, phospholipids cause a sharp decrease in the for prothrombin and Factor X, respectively (T2). The procoagulant activity of the platelets is usually called platelet factor 3 (PF3). In the circulating blood... 

Al. Aiach, M, Schreiber, N., Nussas, C., Michaud, A., Leon, M. and Leclerc, M., An automated amidolytic assay for testing Factor X activity. Thromb. Res. 21, 317-320... 

The effect of deglycosylation of bovine factor XI has been investigated with factor-X-activating enzyme from Russell s viper venom or extrinsic Xase (factor Vlla/tissue factor/phospholipid) by examining the activation rates of derivatives of factor X prepared using O-glycanase, sialidase, and/or N-glycanase [52]. The removal of 0-linked carbohydrate resulted in a decrease in the rate of activation. 

Sites associated with FVIII activation and cofactor activity are marked by arrows. Thrombin, the main physiological activator of FVIII, cleaves at amino acids 372, 740, and 1689 FIXa complexes with FVIIIa at amino acids 558-565, 698-710, and 1811-1818 during assembly of the Factor X-activating complex and phospholipids (PL) of the membrane surface during complex assembly bind FVIII at the carboxy-terminal of the light chain, von Will-... 

The extrinsic and intrinsic pathways merge with activation of factor X. Activation of factor X by factor IX of the intrinsic pathway requires factor VIII (antihemophilic factor). 

Anticoagulant large polymeric molecule with antithrombin and anti-factor X activity. Rapid onset, in vitro and in vivo anticoagulation. Antidote protamine. See also Enoxaparin. 

McNeely T, Griffith M. The anticoagulant mechanism of action of heparin in contact-activated plasma inhibition of factor X activation. Blood 1985 65 1226-31. 

HDL inhibits monocyte chemotaxis, inhibits the adhesion of monocyte and blood cell to vascular endothelium, inhibits endothelial dysfunction and apoptosis, inhibits LDL oxidation, inhibits complement activation, reduces platelet aggregability and coagulation, inhibits platelet activation, and inhibits factor X activation. HDL helps maintain endothelial integrity, facilitate vascular relaxation, stimulates the proliferation of EC and SMC, stimulates the synthesis of prostacyclin and natriuretic peptide C in EC, stimulates protein C and S activation, and may favor fibrinolysis. These functions are exerted by different components of HDL, this complexity emphasizes that changes in HDL functioning rather than plasma HDL-C levels determine the anti-atherogenicity of therapeutic alterations of HDL metabolism (reviewed in refs. 499 and 500). 

The sensitivity of the early ELISA methods (51) was in the same range as previous in vitro methods, but increased greatly with the incorporation of amplifier systems (58,64). Specificity has also improved with the preparation of antitoxins against highly purified toxins and use of monoclonal antibodies (64). The reports on the ELCA method describe meticulous preparation of high quality reagents and an exceptionally effective amplification which utilizes the Russell s viper venom factor X activator to initiate the clotting cascade (9,10). Its sensitivity appears to equal or exceed that of the mouse. 

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