What enzyme does tenecteplase inhibit that physiologically inhibits fibrinolysis by tPA?

Tenecteplase is a genetically modified tissue plasminogen activator (tPA) that is primarily used in the treatment of acute myocardial infarction. It functions by promoting the conversion of plasminogen to plasmin, which is essential for fibrinolysis. However, the physiological regulation of fibrinolysis involves various inhibitors, one of which is Plasminogen Activator Inhibitor 1 (PAI-1).

PAI-1 plays a crucial role in inhibiting the activity of tPA and thus limiting the fibrinolytic process. When tPA is inhibited by PAI-1, the conversion of plasminogen to plasmin is reduced, leading to decreased fibrin breakdown. By inhibiting PAI-1, tenecteplase effectively promotes fibrinolysis, allowing for the breakdown of thrombi that cause vascular occlusion.

Understanding this relationship is key to appreciating the pharmacodynamics of tenecteplase and other thrombolytics, as the balance between fibrinolysis and its inhibition is critical for effective therapeutic outcomes in conditions like myocardial infarction.