Reactome: A Curated Pathway Database

Dissolution of Fibrin Clot (R-HSA-75205)

Species Homo sapiens


The crosslinked fibrin multimers in a clot are broken down to soluble polypeptides by plasmin, a serine protease. Plasmin can be generated from its inactive precursor plasminogen and recruited to the site of a fibrin clot in two ways, by interaction with tissue plasminogen activator at the surface of a fibrin clot, and by interaction with urokinase plasminogen activator at a cell surface. The first mechanism appears to be the major one responsible for the dissolution of clots within blood vessels. The second, although capable of mediating clot dissolution, may normally play a major role in tissue remodeling, cell migration, and inflammation (Chapman 1997; Lijnen 2001). These other functions of urokinase plasminogen activator will be annotated in future versions of Reactome.
Clot dissolution is regulated in two ways. First, efficient plasmin activation and fibrinolysis occur only in complexes formed at the clot surface or on a cell membrane - proteins free in the blood are inefficient catalysts and are rapidly inactivated. Second, both plasminogen activators and plasmin itself are inactivated by specific serpins, proteins that bind to serine proteases to form stable, enzymatically inactive complexes (Kohler and Grant 2000).
These events are outlined in the drawing: black arrows connect the substrates (inputs) and products (outputs) of individual reactions, and blue lines connect output activated enzymes to the other reactions that they catalyze.

Locations in the PathwayBrowser
Additional Information
GO Biological Process fibrinolysis (0042730)
Literature References
pubMedId Title Journal Year
11460480 Elements of the fibrinolytic system Ann N Y Acad Sci 2001
9330876 Plasminogen activators, integrins, and the coordinated regulation of cell adhesion and migration Curr Opin Cell Biol 1997
10853003 Plasminogen-activator inhibitor type 1 and coronary artery disease N Engl J Med 2000