The Fibrinogen-Fibrin Conversion1

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The thrombin-induced conversion of fibrinogen to fibrin that is the primary subject of this review is essentially the final stage in the complex series of processes involved in blood coagulation. Fibrinogen exists in normal blood, while thrombin is present as its precursor prothrombin. The coagulation process consists of the conversion of prothrombin to thrombin and of the subsequent action of thrombin on fibrinogen to produce fibrin. In the fibrinogen-fibrin conversion fibrinogen, already a high polymer of many amino acids is converted to an even higher polymeric form or coagulum, the fibrin clot. Prothrombin can be converted to thrombin in a series of highly complex, and as yet not well understood, reactions. The chapter explores four of the processes by which the conversion of prothrombin to thrombin takes place. These are (1) activation by citrate, (2) activation by calcium ions, Ac-globulin and thromboplastin, (3) activation by calcium ions, platelets and thromboplastin, and (4) activation by trypsin. The chapter concludes by addressing the various problems of current interest in protein chemistry, which appear in the study of the fibrinogen-fibrin conversion. The first step is an example of a limited proteolysis by a protease of curious specificity. This proteolysis may turn out to be one of the first illustrations of the existence of “strong” peptide bonds in proteins. Further, it offers a nice illustration of the phenomenon of unmasking or activation in biological systems. The second step involves protein-protein associations with unequal association constants. The last step may involve gel formation or crystallization.

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    1

    Part of this review was written while one of us (H.A.S.) was at the Carlsberg Laboratorium, Copenhagen, Denmark, as a Fulbright Research Scholar and John Simon Guggenheim Memorial Foundation Fellow.

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