[Mechanisms of activation of tissue-type plasminogen activator]

Tissue-type plasminogen activator (t-PA) is an important component of the fibrinolytic system. t-PA is released into the circulation as a one-chain peptide with little enzyme activity. There exist several mechanisms which enhance plasminogen activation rate by t-PA: 1. activation of enzyme activity of one-chain t-PA by fibrin binding; 2. activation of enzyme activity by transforming one-chain to two-chain t-PA by plasmin; 3. stimulation of plasminogen activation by forming a ternary complex of t-PA, plasminogen and fibrin; 4. stimulation of plasminogen activation by forming Lys-plasminogen, which has a higher affinity to fibrin and is a better substrate for t-PA than Glu-plasminogen; 5. enhancement of ternary complex concentration after initiation of fibrinolysis due to tighter binding of t-PA and plasminogen to partially degraded fibrin.