Action of Thrombin in the Clotting of Fibrinogen

Abstract

IN spite of much literature on the clotting of blood, the exact mechanism of the final event, the mode of transformation of soluble fibrinogen to insoluble fibrin by the action of thrombin, remains unknown. The concept of thrombin as a hydrolytic or proteolytic enzyme^1,2 has fallen into disfavour³, and in recent years other plausible but unproved mechanisms have been proposed^4–6. In a study⁷ of the proteins of the keratin–myosin–fibrinogen group by end-group assay with fluorodinitrobenzene⁸, only small amounts of terminal amino-groups could be detected in fibrinogen, although the amounts were not sufficiently small to conclude, as in the case of myosin and tropomyosin, that the molecule is constructed of cyclo-peptide units. The action of purified thrombin, however, results consistently in the appearance of amino-terminal residues of glycine, and whatever the ensuing mechanism, we believe that the fundamental enzymic step in the transformation of fibrinogen to fibrin is associated first with the appearance of these groups. This action of thrombin, which tentatively may be considered as a very specific proteolysis, was discovered independently in Cambridge and in Leeds, and for this reason the relevant observations are reported jointly.