Summary
Various investigators have separated the coagulation products formed when fibrinogen
is clotted with thrombin and identified fibrinopeptides A and B. Two other peaks are
observed in the chromatogram of the products of coagulation, but these have mostly
been dismissed by other workers. They have been identified by us as amino acids, smaller
peptides and amorphous material (37). We have re-chromatographed these peaks and identified
several amino acids. In a closed system of fibrinogen and thrombin, the only reaction
products should be fibrin and peptide A and peptide B. This reasoning has come about
because thrombin has been reported to be specific for the glycyl-arginyl peptide bond.
It is suggested that thrombin also breaks other peptide linkages and the Peptide A
and Peptide B are attacked by thrombin to yield proteolytic products. Thrombin is
therefore probably not specific for the glycyl-arginyl bond but will react on other
linkages as well.
If the aforementioned is correct then the fibrinopeptides A and B would cause an inhibition
with the coagulation mechanism itself. We have shown that an inhibition does occur.
We suggest that there is an autoinhibition to the clotting mechanism that might be
a control mechanism in the human body.
The experiment was designed for coagulation to occur under controlled conditions of
temperature and time. Purified reactants were used. We assembled an apparatus to record
visually the speed of the initial reaction, the rate of the reaction, and the density
of the final clot formed after a specific time.
The figures we derived made available to us data whereby we could calculate and plot
the information to show the mechanism and suggest that such an inhibition does exist
and also further suggest that it might be competitive.
In order to prove true competitive inhibition it is necessary to fulfill the criteria
of the Lineweaver-Burk plot. This has been done. We have also satisfied other criteria
of Dixon (29) and Bergman (31) that suggest true competitive inhibition.
