Streptokinase-plasmin

Since plasmin in free form (not bound to fibrin) is extremely and rapidly inactivated by the inhibitor system (Fig. 4), plasminogen activators are used for treatment of thrombosis. Under such a condition, if plasmin is formed by the activators (especially by tPA) at the site of fibrin, the bound form can degrade fibrin because it is protected against the inhibitor system. In the medical practice, mainly two endogenous plasminogen activators, tPA and uPA, and one exogenous, the streptokinase (SK) are used [1,4]. 

Co-enzyme obtained from cultures of various strains of Streptococcus haemolyticus and capable of changing plasminogen into plasmin (complex enzyme mixture of streptokinase, streptodornase and streptolysin 0"). From fermentation liquors of hemolytic streptococci species Streptococcus haemolyticus), e. g. H 46 A. 

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. 

Fibrin is dissolved by plasmin. Plasmin exists as an inactive precursor, plasminogen, which can be activated by tissue plasminogen activator (t-PA). Both t-PA and streptokinase are widely used to treat early thrombosis in the coronary arteries. 

Mammahan blood will clot spontaneously if allowed to stand however, on further standing, this clot may dissolve as a result of the action of a proteolytic enzyme called plasmin. Plasmin is normally present as its inactive precnrsor, plasminogen. Certain strains of streptococci were fonnd to produce a substance which was capable of activating plasminogen (Fig. 25.3), a phenomenon that suggested a potential use in liquefying clots. This snbstance was isolated, found to be an enzyme and called streptokinase. 

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. 

The role of the fibrinolytic system is to dissolve any clots that are formed within the intact vascular system and so restrict clot formation to the site of injury. The digestion of the fibrin and hence its lysis is catalysed by the proteolytic enzyme, plasmin, another serine proteinase. Plasmin is formed from the inactive precursor, plasminogen, by the activity of yet other proteolytic enzymes, urokinase, streptokinase and tissue plasminogen activator (tPA) which are also serine proteinases. These enzymes only hydrolyse plasminogen that is bound to the fibrin. Any plasmin that escapes into the general circulation is inactivated by binding to a serpin (Box 17.2). 

Urokinase Urokinase is an enzyme that is extracted from human urine or kidney cells [46-55], which directly cleaves specific peptide bonds, in particular the Arg-560-Val-561 bond in the plasminogen molecule, thus transforming it into plasmin. It is used for the same indications as streptokinase. Synonyms of this drug are abbokinase and others. 

Plasminogen, an inactive precursor, is activated to plasmin which as a protease is able to break down fibrin clots. The thrombolytic agents in use promote the conversion of plasminogen to plasmin at the site of a thrombus. Indications include post-myocardial infarction treatment. The thrombolytic must be administered within 6 hours for an optimal effect. Other indications are treatment of acute pulmonary thromboembolism, deep-vein thrombosis, acute arterial thrombosis and thromboembolism, as well as in the clearance of arteriovenous catheters and can-nulae. Agents are streptokinase, anistreplase, urokinase, alteplase, reteplase and tenecteplase. 

Streptokinase Trypsin Uiicase Urokinase Plasminogen- plasmin Protein hydrolysis Urate+02->allantoin Plasminogen->plasmm Blood clots Inflammation Gout Blood clots... 

On the other hand, tPA and the variant TNKase (tenecteplase) catalyze the plasminogen to plasmin conversion only in a fibrin-dependent manner, thereby, in theory, reducing nonfibrin-dependent systemic lytic states. Clinical studies, however, comparing streptokinase with alteplase... 

Anistreplase (streptokinase- plasminogen complex) streptococci protein streptococci plaminogen, which is then cleaved to form plasmin. Plasmin mediate fibrinolysis. Systemic lytic state and immunogenicity may limit its use. Because antistreplase is aheadly lined to plaminogen, the onset of fibrinolytic is faster. These enzymes are not fibrin-specific. 

Complex of the catalytic domain of human plasmin and streptokinase PDB ID IBML... 

Schematic representation of the fibrinolytic system. Plasmin is the active fibrinolytic enzyme. Several clinically useful activators are shown on the left in bold. Anistreplase is a combination of streptokinase and the proactivator plasminogen. Aminocaproic acid (right) inhibits the activation of plasminogen to plasmin and is useful in some bleeding disorders. t-PA, tissue plasminogen activator.

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. 

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