Fibrin Conversion

The Fibrinogen-Fibrin Conversion Harold A. Scheraga and Michael Laskowski, Jr. 

Structural Aspects of the Fibrinogen to Fibrin Conversion R. F. Doolittle... 

The clotting factors are protein molecules. Activation mostly means proteolysis (cleavage of protein fragments) and, with the exception of fibrin, conversion into protein-hydrolyzing enzymes (proteases). Some activated factors require the presence of phospholipids (PL) and Ca + for their proteolytic activity. Conceivably, Ca + ions cause the adhesion of factor to a phospholipid surface, as depicted in C. Phospholipids are contained in platelet factor 3 (PF3), which is released from ag-Lullmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of license. 

Doolittle, R. F. (1973). Structural aspects of the fibrinogen to fibrin conversion. Adv. Protein Chem. 27, 1-109. 

Limited Proteolysis and Aggregation in the Fibrinogen-Fibrin Conversion... 

Essentially all the experiments on the fibrinogen-fibrin conversion to be discussed here were carried out with the less pure preparations of Seegers and Alkjaersig (1956) before the introduction of the Rasmussen (1955) procedure for the purification of thrombin. It is hoped that the traces of impurities thereby introduced do not vitiate any of the conclusions derived from these experiments. Further discussion of the earlier work on thrombin will be found in the reviews of Seegers (1955) and Scheraga and Laskowski (1957). 

We may thus summarize the reaction scheme for the fibrinogen-fibrin conversion in terms of the following steps, each of which is thought to be reversible (Laskowski et al, 1952). 

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. 

Fig. 83. Sedimentation patterns of protein species involved in the fibrinogen-fibrin conversion. The solvent in all cases is 1 Af NaBr. A fibrinogen, F, at pH 6.3 B Fibrin monomer, f, at pH 5.3 (the same pattern is obtained either for a solution of fibrin at pH 6.3 or for a mixture of thrombin and fibrinogen at pH 5.3) C fast and slow peak pattern in a system of intermediate polymers (the same pattern is obtained either for a solution of fibrin at pH 6.1 or for a mixture of thrombin and fibrinogen at pH 6.1) (Donnelly et al., 1955).

In conclusion, the fibrinogen-fibrin conversion provides an excellent example of a set of reactions which illustrate the role of side-chain hydrogen bonding in limited proteolysis and in protein association. Further work on step 3 may indicate to what extent the ideas of Chapter IV may be applicable. Finally, the key role which side-chain hydrogen bonding can play, not only in denaturation, but also in the modification of pK s, in limited proteolysis, and in protein association, should be noted. 

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