Abstract
Thrombin, a key enzyme in the blood coagulation cascade, hydrolyzes fibrinogen into fibrin, which specifically associates into the fibers that build up a thrombus scaffold. The assembly of fibrin involves a set of stepwise reactions, for which a complete and detailed kinetic portrait is needed. Existing kinetic models focus on particular parts of the process, for example the mechanism of enzyme action itself or the kinetics of formation of fibrin assemblies. The current study considers a thorough model of the process from fibrinogen hydrolysis to the assembly of fibrin. Composing the model requires taking into account several reaction intermediates, stepwise removal of fibrinopeptides, and association of partially hydrolyzed fibrin, in particular desAA fibrin. The model is versatile enough to adopt new data both on fibrinogen hydrolysis and fibrin association. In addition, the model could be considered as an example of a kinetic description of other complex enzyme systems having several intermediates and feedbacks, such as the blood coagulation cascade and signal transduction.
Published Version
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