Abstract
Crude or crystalline trypsin in proper concentration coagulates human, dog, rabbit, guinea pig and horse plasma or whole blood. It does not clot fibrinogen directly, but reacts with prothrombin to form thrombin. This activation is independent of the presence of either calcium or platelets. It follows that neither of these is necessarily an intrinsic part of thrombin. Trypsin also coagulates blood in vivo, which suggests that circulating blood contains free and reactive prothrombin, rather than an inactive hypothetical complex from which prothrombin is liberated only after blood is shed.
An excess of trypsin digests fibrinogen, prothrombin and thrombin; and too little trypsin has no effect. The activation of prothrombin therefore takes place within a relatively narrow zone of enzyme concentration, which varies directly with the amount of protein present. At this optimum zone, there is a dynamic equilibrium between the activation of prothrombin to thrombin and the destruction of both reagents by the enzyme.
Since trypsin, in activating prothrombin, has qualitatively the same effect as the physiological system calcium plus platelets (or calcium plus tissue extracts), it is tentatively suggested that these systems contain a proteolytic enzyme similar to trypsin which reacts with prothrombin to form thrombin.
It has been further found that the proteolytic enzyme papain, freed of calcium, nevertheless coagulates whole blood, plasma, or fibrinogen. In this case, the enzyme does not activate prothrombin, but acts directly on fibrinogen to form a soft fibrillar gel resembling fibrin, with a marked tendency to resolution. If one admits this clot to be fibrin, this constitutes strong evidence that the physiological coagulant thrombin is also a proteolytic enzyme with a specific reactivity for fibrinogen.
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