Complexation with plasmin

One of the most efficient plasmin inhibitor is a2-PI (70 kDa), which is synthesized by the liver, secreted into the blood circulation, where its concentration is 1 pM. It rapidly forms equimolar complex with plasmin, and in this complex, the active site of the enzyme is irreversibly blocked. The complex, thereafter, is removed by the liver. It is remarkable that when plasmin is bound to its substrate (fibrin), it is protected against its primarily inhibitor, a2-PI the rate of inactivation decreases by 400-fold (Fig. 4) [3]. 

The a2-plasmin inhibitor, a single-chain glycoprotein (70 kDa), forms rapidly an equimolar complex with plasmin, where the enzyme loses its activity. It is synthesized by the liver and secreted into the blood circulation, where its concentration is 1 pM. 

Circulahng plasmin is rapidly neutralized by aj-an-tiplasmin, a physiological serine protease inhibitor that forms an inert complex with plasmin. In contrast, hbrin-bound plasmin is resistant to inactivation by 2-an-tiplasmin. Under normal circumstances plasma t-PA is inactive because it is inhibited by PAI-1, while t-PA that is bound to hbrin is unaffected by PAI-1. In addition, plasma t-PA has a very rapid turnover in blood (half-life 5 to 8 minutes). For these reasons, hbrinolysis is normally restricted to the thrombus. 

Figure 51-7. Scheme of sites of action of streptokinase, tissue plasminogen activator (t-PA), urokinase, plasminogen activator inhibitor, and Kj-antiplasmin (the last two proteins exert inhibitory actions). Streptokinase forms a complex with plasminogen, which exhibits proteolytic activity this cleaves some plasminogen to plasmin, initiating fibrinolysis. 

An exogenous plasminogen activator that has been used in clinical trials as a fibrinolytic agent is the 53-kDa single-chain polypeptide called streptokinase (SK). It forms a complex with plasminogen on an equimolar basis. The resulting 156-kDa streptokinase-plasminogen complex (plg-SK) converts Glu-plasmino-gen to Glu-plasmin (41). 

The measurement of plasminogen activator inhibitor-1 (PAI-1), which complexes with tissue plasminogen activator (t-PA) and thus affects the ability of the latter to activate fibrinolysis, is useful in the assessment of fibrinolytic disorders (93). The complex formed by the fibrinolytic enzyme plasmin with its inhibitor... 

The answer is b. (Hardman, p 1352.) Streptokinase forms a stable complex with plasminogen. The resulting conformational change allows for formation of free plasmin, the active fibrinolytic enzyme. 

Mechanism of Action An enzyme that activates the fibrinolytic system by converting plasminogen to plasmin, an enzyme that degrades fibrin clots. Acts indirectlybyform ing a complex with plasminogen, which converts plasminogen to plasmin. Action oc-curs within the thrombus, on its surface, and in circulating blood. Therapeutic Effect Destroys thrombi. 

It acts by forming a complex with circulating plasminogen that binds loosely to fibrin and it converts plasminogen to plasmin. It has no intrinsic activity. It is given by parenteral route and has a short plasma half life. 

The kinetics of the lytic effect displayed by the complexes of immobilized heparin with thrombin and fibrinogen, in distinction from those with plasmin, are described by their saturation curves. The observed slowing down of the dissolution of unstabilized fibrin is probably due to the inhibiton of the lytic activity of the complexes by the soluble products of the reaction. In fact, as it was shown in Ref. 106, further addition of immobilized heparin-protein complex to partially hydrolyzed fibrin results in a complete recovery of the dissolution rate. 

Streptokinase is a protein derived from p-haemolytic streptococci it forms a complex with plasminogen (bound loosely to fibrin) where it converts plasminogen to plasmin. Too rapid administration causes abrupt fall in blood pressure. The is 20 min. 

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