Fibrinogen-fibrin conversion inhibitors

As indicated in Chapter III, step 1 of the fibrinogen-fibrin conversion is an example of a limited proteolytic reaction in which hydrolysis does not go to completion. Side-chain hydrogen bonding may stabilize the peptide bond in the manner indicated in Chapter III. We shall therefore discuss the reversibility of step 1 and the thermodynamic parameters for the equilibrium (Laskowski et al., 1960b). As in the case of the kinetic experiments discussed in Section 5b, the medium used was 1 molar NaBr at pH 5.3 to prevent polymerization of fibrin monomer, and the analysis for f was carried out using TAMe as a thrombin inhibitor, as already mentioned The equilibrium position was approached from both directions. 

Finally, the common pathway involves thrombin in a number of functions. Its primary role is the conversion of fibrinogen to fibrin, the building block of a haemostatic plug. In addition, it activates factors VIII and V and their inhibitor protein C (in the presence of thrombomoduhn), and it activates factor XIII, which cross-links the fibrin polymers. 

Blocking the action of thrombin prevents conversion of fibrinogen to fibrin (52). Thrombin inhibitors are produced by the salivary glands of Ixodes holocyclus 61), Ixodes ricinus 62), A. americanum 63), and 0. savignyi 64). Dermacentor andersoni salivary glands contain inhibitors of factor V, an integral part of the complex with Xa that converts prothrombin to thrombin, and factor Vn, a component of the extrinsic pathway 65). Omithodoros moubata produces inhibitor of the intrinsic pathway component,... 

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