A kinetic model, based on published studies of thrombin neutralization, is used to examine factors that limit spread of free thrombin in a simple plasma. It employs equations with presently available rate parameters which describe the courses of the major thrombin-binding reactions at 37°C in buffered saline solutions approximating plasma ultrafiltrate. Thrombin is bound reversibly by fibrinogen and fibrin-1 polymers as enzyme-substrate complexes (1) and by “fibrin” at a non-proteolyt ic site (2), and essentially irreversibly by antithrombins (3). These bindings reduce free thrombin levels and so limit spread of activity. The model equations with parameters from (1) and (3) show that thrombin neutralization by thrombin-substrate complexes is very brief and thrombin-antithrombin reactions are much too slow for early reduction of thrombin activity. However, parameters from (2) show that rapid reversible binding of thrombin by “fibrin” much reduces level of free thrombin and the level continues to fall as the thrombin is passed to the antithrombins. The model shows that a rapidly-acting antithrombin (e.g. heparin-ATIII) could reduce free thrombin fast enough to inhibit slower thrombin activations (e.g. of FXIII), and that a sufficient concentration of a reversible binder can govern the level of free thrombin. This suggests that a non-toxic reversible binder, with suitable Kd and half-life, would be valuable in treating thrombosis. Verification and extension of the model findings require better experimental definition of the parameters.(1) Lewis, S.D. et al. J. Biol. Chem. 260, 10192-10199, 1985.(2) Liu, C.Y. et al. J. Biol. Chem. 254, 10421-10425, 1979.(3) Jordan, R. et al. J. Biol. Chem. 254, 2902-2913, 1979. (Supported by grants from the Colorado Heart Foundation)
Photocatalytic degradation kinetics of Orange G dye over ZnO and Ag/ZnO thin film catalysts
