The Fibrinogen-Fibrin Conversion

The Fibrinogen Molecule: Its Size, Shape, and Mode of Polymerization

“…It is almost certain that the nodules represented in outline contain incompletely resolved substructure• No evidence has been obtained or would be expected from this electron microscope study of small peptides which might be split off in the activation by thrombin. The central nodule is certainly much too big to represent such low molecular weight products as have been observed (1). The absence of dimers and higher order polymers in fibrinogen preparations is to be noted and probably indicates a strong repulsion between the molecules.…”

“…The extensive literature dealing with the fibrinogen molecule and its conversion to fibrin has been reviewed at length by Scheraga and Laskowski (1) and in a briefer discussion by Waugh (2). The molecular weight of fibrinogen is well established from physical chemical data at 330,000 to 340,000 (3).…”

Pathogenesis of the Coagulation Defect Developing During Pathological Plasma Proteolytic (“Fibrinolytic”) States. Ii. The Significance, Mechanism and Consequences of Defective Fibrin Polymerization*

“…Fibrin formation, involving the full complexity of fibrinogen-fibrin conversion, has necessarily had to serve as the prime measure and sole indicator of each of a long series of interrelated reactions; yet recent evidence (14,15) has demonstrated that fibrinogenfibrin conversion is itself a complex of multiphasic reactions, each of which is susceptible to influence by altered reaction conditions. The present evidence demonstrates that such altered reaction conditions arising clinically (1) may themselves inhibit fibrinogen-fibrin conversion in a striking fashion.…”

Protein structure and function, from a colloidal to a molecular view

“…Further, ifionizable donor and/or acceptor groups are involved in the (intermolecular) hydrogen bonds, then the enthalpy of reaction will depend (in a predictable manner) on pH. Such a pH-dependent exothermicity has been demonstrated for the association of fibrin monomer (355), and the donor and acceptor groups have been identified as tyrosyl and histidyl, respectively (324,355). Exothermicity is a rare occurrence in protein association, and the example of fibrin monomer polymerization is almost a unique one.…”

“…In fact, the acquired stabilization can be sufficiently great so that, for example, a proteolytic enzyme can lead to synthesis rather than hydrolysis ofa peptidebond. The reversibility of such processes has been demonstrated (by approaching equilibrium from both directions) in the thrombin-fibrinogen reaction (154,321,324), and in other proteolytic reactions involving, e.g., the action of trypsin on soybean trypsin inhibitor (146) and hemoglobin (207). It has also been used for peptide synthesis with proteolytic enzymes (26).…”