Plasminogen activators are serine proteases that catalyze the activation of plasmin via proteolytic cleavage of its zymogen form plasminogen. Plasmin is an important factor in fibrinolysis, the breakdown of fibrin polymers formed during blood clotting. There are two main plasminogen activators: urokinase (uPA) and tissue plasminogen activator (tPA). Tissue plasminogen activators are used to treat medical conditions related to blood clotting including embolic or thrombotic stroke, myocardial infarction, and pulmonary embolism. Plasminogen activators are inhibited by plasminogen activator inhibitor-1, plasminogen activator inhibitor-2, and protein C inhibitor. Function Produced mainly in the liver, plasminogen is the inactive zymogen form of plasmin, and circulates in plasma in a closed conformation that cannot be activated. Binding clots or cell surface causes its conformation to change, allowing it to be activated by plasminogen activators. Plasminogen activators do so by cleaving the R561/V562 peptide bond, producing the active protein plasmin, which catalyzes the degradation of fibrin polymers that make up the structure of blood clots. Inhibition The main inhibitor of tissue plasminogen activator and urokinase is plasminogen activator inhibitor-1 (PAI-1). Plasminogen activator inhibitor-1 is a serine protease, synthesized by endothelial cells, that specifically inhibits tissue plasminogen activator (tPA) and urokinase (uPA). Tissue plasminogen activator and urokinase are the activators of plasminogen and results in the breakdown of blood clots (fibrinolysis). PAI-1 levels has also been studied in patients and how they influence certain diseases. Elevated serum levels of PAI-1 have been found in obese individuals. Elevated levels of PAI-1 also seem to increase the risk of atherothrombotic events and may also promote vascular disease. Plasminogen activator inhibitor-2 (PAI-2) is also a serine protease that inactivates tPA and uPA. PAI-2 is produced by the placenta and only found in high quantities in the blood during pregnancy. Factors Factor XIa and XIIa are two main factors involved in the plasminogen activator. Factor XI (FXI) is a serine protase produced by the liver and circulates in its inactive form. Deficiency in factor XI is known to cause hemophilia C. Factor XIIa is another plasma protein that is involved in the activation of zymogen factor is activated into factor XIa. This activation is important to the coagulation cascade. Applications Due to its contribution to fibrinolysis, tissue plasminogen activator is used medically to treat blood clot-related disorders including thrombotic or embolic stroke, myocardial infarction, and pulmonary embolism. It is manufactured using recombinant techniques and is sold as alteplase, reteplase, and