Plasmin streptokinase-activator complex

Plasmin-streptokinase-activator complex Plasminogen activation Thrombolysis 23-25... 

Animal experiments corroborated that, compared with the nonacylated complex, a smaller quantity of the acylated plasmin-streptokinase-activator complex (APSAC) was required to obtain thrombolysis [35]. 

Anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC), is the plasminogen-streptokinase complex (above) in which the enzyme centre that converts plasminogen to plasmin is protected from deactivation, so prolonging its action. 

Streptokinase forms an activator complex with plasminogen, which results in the cleavage of the Arg-Val bond in plasminogen, and conversion of plasminogen to plasmin. The activator complex also diffuses into the clot and activates preplasmin-2, a mediator that also lyses fibrin. 

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 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. 

Streptokinase induces its thrombolytic effect by binding specifically and tightly to plasminogen. This induces a conformational change in the plasminogen molecule that renders it proteolytically active. In this way, the streptokinase-plasminogen complex catalyses the proteolytic conversion of plasminogen to active plasmin. 

Streptokinase is a protein (but not an enzyme in itself) synthesized by streptococci that combines with the proactivator plasminogen. This enzymatic complex catalyzes the conversion of inactive plasminogen to active plasmin. Urokinase is a human enzyme synthesized by the kidney that directly converts plasminogen to active plasmin. Plasmin itself cannot be used because naturally occurring inhibitors in plasma prevent its effects. However, the absence of inhibitors for urokinase and the streptokinase-proactivator complex permits their use clinically. Plasmin formed inside a thrombus by these activators is protected from plasma antiplasmins, which allows it to lyse the thrombus from within. 

STREPTOKINASE Streptokinase (streptase) is a 47,000 Da protein produced by /3-hemolytic streptococci. It forms a stable, noncovalent 1 1 complex with plasminogen, producing a conformational change that exposes the active site on plasminogen that cleaves Arg 560 on free plasminogen to form free plasmin. Streptokinase is rarely used clinically for fibrinolysis since the advent of newer agents. 

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. 

Streptokinase and plasminogen form a complex having the characteristics of a plasminogen activator and activating plasminogen molecules not yet combined with streptokinase to plasmin. The concept of acylation of fibrinolytic enzymes... 

Figure 34—3. Diagram of the fibrinolytic system. The useful thrombolytic drugs are shown on the left in bold type. These drugs increase the formation of plasmin, the major fibrinolytic enzyme. The activator shown in the shaded box is a complex of streptokinase and plasminogen. Aminocaproic acid, a useful inhibitor of fibrinolysis, is shown on the right. (Reproduced, with permission, from Katzung BG [editor] Basic Clinical Pharmacology, 8th ed. McGraw-Hill. 2001.)...

Streptokinase, an extracellular protein (415 aa, Mr 47 kDa) produced by various strains of /3-hemolytic streptococci. Streptokinase is not generally considered to be a proteolytic enzyme, but is one of the most potent exogenous activators of human plasminogen. Complexes of streptokinase with human plasminogen can hydrolytically activate other plasminogen molecules to plasmin which then dissolves blood clots alone [L. A. Schick, F. J. Castellino, Biochem. Biophys. Res. Commun. 1974, 57, 47 K. W. Jackson, J. Tang, Biochemistry 1982, 21, 6620]. 

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