Streptokinase fibrinolytic enzymes

Fibrinolytic enzymes Streptokinase No enzymic activity, until it Streptococcus Treatment of venous... 

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. 

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 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... 

A study in coronary patients has shown that fibrinogen levels are Increased over normal controls ° and that fibrinolytic activity is also decreased in these patients.The rate of degradation of fibrinogen is inhibited in rats fed an atherogenic diet. It would seem reasonable then that some control over the clinical outcome of atherosclerosis could be had by the use of fibrinolytic agents. The enzymes streptokinase and urokinase continue to be evaluated with some benefits reported in the therapy of acute Thromboembolism.Phenformin is still the only drug of interest as a fibrinolytic agent other than the enzymes and CPIB mentioned earlier. 

Thrombosis is one of the most common and devastating diseases. Fibrinolytic enzymes are effectively in treating thrombosis. A variety of fibrinolytic enzymes, such as UK, streptokinase (SK), recombinant tissue-type plasminogen activator (rt-PA), staphylokinase (SAK) and recombinant prourokinase (pro-UK), have been studied as thrombolytic agents [67,68]. In general, these agents are administered via intravenous injection, and their limitations include fast clearance, lack of resistance to re-occlusion, bleeding complications and other adverse effects [67]. 

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.)...

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). 

Although most of the enzyme-based drugs are inhibitors of enzymes, a number of enzyme preparations have also been developed as drugs for the treatment of a number of diseases. The development of enzymes as therapeutics has been made easier due to the advances in biotechnology. Most successful example of enzyme therapy includes various preparations of plasminogen activators (thrombolytic or fibrinolytic agents) such as a bacterial protein streptokinase and two plasminogen activators... 

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. 

Varidase = 10 000 lU streptokinase and 2500 lU streptodornase. Streptokinase is a protein, an enzyme produced by beta-hemolytic streptococci. It has indirect fibrinolytic properties by binding with plasminogen. It is a fibrin non-specific thrombolytic. 

Streptokinase (SK), in spite of its name (-ase suffix), is a nonenzyme protein (mol. wt. 47,000). It is a catabolic product of group C 3-hemolytic streptococci. Unlike the real enzymes to be considered, it activates the fibrinolytic system indirectly. More recent research has shown that necessary steps require a prior formation of a 1 1 complex with plasminogen. This alters its conformation, thereby exposing an active site in the modified proenzyme. It is this modified complex that becomes the actual PA. SK is still a widely used thrombolytic agent, primarily because it is the least costly, is easy to obtain and had been in use for years before other PAs became available. 

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