Inhibition of fibrin assembly by fragment D and its dimer derived from fibrinogen and stabilized fibrin. Evidence for the two-step type of inhibition

Platonova, T.N.; Musialkovskaia, A.A.; Tolstykh, V.M.; Belitser, V.A.

Biokhimiia 45(10): 1780-1787

1980


ISSN/ISBN: 0320-9725
PMID: 7236767
Document Number: 164111
The influence of purified fragments D and DD on fibrin monomer polymerization has been studied. When applied separately, DD is less strong an inhibitor than D. An addition of small amounts of DD to the reaction mixtures containing D does not change the inhibitory effect, when the concentration of the latter fragment is low. At high concentrations of D the contribution of DD becomes more pronounced. Small amounts of D added to DD-containing systems strongly enhances the inhibition. These properties of the D--DD mixtures are unpredictable and puzzling; they contradict the generally accepted view that the specific inhibitors of fibrin polymerization, to which D and DD belong, act in a simple competitive way. The whole incomprehensible situation may be clarified in terms of a hypothesis on a two-step mechanism of inhibition. It is assumed that at the first (preliminary) step of the inhibitor effect DD is less competent than D, whereas at the second step DD possessing a high affinity for the fibrin monomer, functions as the most effective competitive inhibitor.

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