PathwayStep733 PathwayStep734 PathwayStep735 PathwayStep736 PathwayStep737 PathwayStep738 PathwayStep739 PathwayStep749 PathwayStep748 PathwayStep747 PathwayStep746 PathwayStep745 PathwayStep744 PathwayStep743 PathwayStep742 PathwayStep741 PathwayStep740 PathwayStep750 PathwayStep751 crosslinked fibrin multimer:tissue plasminogen activator (one-chain):plasminogen -> crosslinked fibrin multimer:tissue plasminogen activator (one-chain) + plasmin histidine-rich glycoprotein:plasminogen <-> histidine-rich glycoprotein + plasminogen histidine-rich glycoprotein + plasminogen <-> histidine-rich glycoprotein:plasminogen crosslinked fibrin multimer:tissue plasminogen activator (one-chain) + plasminogen -> crosslinked fibrin multimer:tissue plasminogen activator (one-chain):plasminogen crosslinked fibrin multimer + tissue plasminogen activator (one-chain) -> crosslinked fibrin multimer:tissue plasminogen activator (one-chain) plasminogen:histidine-rich glycoprotein -> plasmin + histidine-rich glycoprotein (uPA [one-chain] catalyst) plasminogen + histidine-rich glycoprotein -> plasminogen:histidine-rich glycoprotein urokinase plasminogen activator + urokinase plasminogen activator receptor (uPAR) -> urokinase plasminogen activator:uPAR alpha-2-antiplasmin + plasmin -> alpha-2-antiplasmin:plasmin fibrin multimer, crosslinked:tissue plasminogen activator (one-chain) + plasminogen activator inhibitor 1 -> fibrin multimer, crosslinked:tissue plasminogen activator (one-chain):plasminogen activator inhibitor 1 fibrin multimer, crosslinked:tissue plasminogen activator (two-chain) + plasminogen activator inhibitor 1 -> fibrin multimer, crosslinked:tissue plasminogen activator (two-chain):plasminogen activator inhibitor 1 crosslinked fibrin multimer:tissue plasminogen activator (two-chain):plasminogen -> crosslinked fibrin multimer:tissue plasminogen activator (two-chain) + plasmin crosslinked fibrin multimer:tissue plasminogen activator (two-chain) + plasminogen -> crosslinked fibrin multimer:tissue plasminogen activator (two-chain):plasminogen crosslinked fibrin multimer:tissue plasminogen activator (one-chain) -> crosslinked fibrin multimer:tissue plasminogen activator (two-chain) fibrin multimer, crosslinked -> fibrin digestion products (plasmin) Dissolution of Fibrin Clot Edited: D'Eustachio, P, 0000-00-00 00:00:00 GENE ONTOLOGYGO:0042730 Pubmed10853003 Pubmed11460480 Pubmed9330876 Reactome Database ID Release 4375205 Reactome, http://www.reactome.org ReactomeREACT_641 Reviewed: Rush, MG, 2008-01-11 00:00:00 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.<br>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).<br>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. plasminogen:histidine-rich glycoprotein -> plasmin + histidine-rich glycoprotein (uPA [two-chain] catalyst) urokinase plasminogen activator (one-chain):uPAR -> urokinase plasminogen activator (two-chain):uPAR urokinase plasminogen activator (two-chain):uPAR + plasminogen activator inhibitor 2 (PAI-2) -> PAI-2:urokinase plasminogen activator (two-chain):uPAR urokinase plasminogen activator (two-chain):uPAR + plasminogen activator inhibitor 1 (PAI-1) -> PAI-1:urokinase plasminogen activator (two-chain):uPAR