Thrombin anticoagulant enzyme

These last reactions are considered the cause of the reperfusion damage (7-9). Both reactions need 02to be completed. Since during ischemia the availability of 02 is extremely low, the tendency is to accumulate hypoxantine, locally When suddenly the 02 becomes available a massive OS is developed. Unfortunately, the antiproteases (anticoagulant enzymes) are much more sensitive to the oxidation than proteases (10,1 I) such as thrombin, and the consequence is the formation of a thrombus. OS facilitates the precipitation of acute ischemic episodes and antioxidants may limit the damage/incidence of an acute episode (165,167,168) for the prevention of acute episodes. 

Marlar RA, Kleiss AJ, Griffin JH. Mechanism of action of human activated protein C, a thrombin-dependent anticoagulant enzyme. Blood 1982 59(5) 1067-72. 

The other mechanism relies on thrombin binding to thrombomodulin, resulting in an imusual substrate specificity switch from its circulating substrate fibrinogen to protein-C, which in turn deactivates cofactors Va and Vin (48). The net result is the conversion of thrombin from coagulant to anticoagulant enzyme. 

Anticoagulant thrombin-like enzyme found in venom of Malayan pit viper, Agkistrodon rhodostoma. 

D. Thrombin-Like Enzymes. Ancrod (arvin), a very specific snake venom component, has been investigated extensively for its anticoagulant action. Ancrod is a very specific protease whose action has some similarity to that of thrombin and occurs in the terminal sequence of a complex blood coagulation mechanism. Ancrod hydrolyzes only the Aa chain of fibrinogen and produces a polymer of the type (a Bp y)n rather than the (aPy)n type normal fibrin clot. The microclot produced by ancrod from fibrinogen is readily hydrolyzed by plasmin that was activated from tissue plasminogen. This results in a defibrination effect. This property is extensively used in the treatment of a patient who has suffered from myocardial infarction. 

Thrombin and Factor Xa are both serine proteases involved in the blood coagulation cascade. Inhibition of these two enzymes is providing novel anticoagulants (157-159). 

Heparin acts as a catalyst for antithrombin III (AT III), increasing its activity by approximately a thousand times. Antithrombin III is a plasma enzyme that inactivates certain activated serine proteases of the coagulation cascade, most importantly activated factors II (thrombin) and X. The larger heparin species (found in unfractionated heparin) catalyzes the inactivation of activated factors II and X. In contrast, LMWH chiefly inactivates activated factor X. The final effect of both is systemic anticoagulation. Heparin also possesses inherent platelet-aggregating properties and may also induce the production of platelet-aggregating antibodies. Heparin can inhibit aldosterone synthesis. 

Enzyme assays employed in the diagnosis of diseases are one of the most frequently used clinical laboratory procedures. The most commonly used body fluid for this purpose is serum, the fluid that appears after the blood has clotted. The liquid portion of unclotted blood is called plasma. Serum is used for many enzyme assays because the preparation of plasma requires addition of anticoagulants (e.g., chelating agents) that interfere with some assays. Enzymes in circulating plasma are either plasma-specific or nonplasma-specific. Plasma-specific enzymes are normally present in plasma, perform their primary function in blood, and have levels of activity that are usually higher in plasma than in tissue cells. Examples are those enzymes involved in blood clotting (e.g., thrombin), fibrinolysis (e.g., plas-min), and complement activation, as well as cholinesterase... 

As noted previously, for heparin to exert its anticoagulant effect, a plasma cofactor, antithrombin III, is needed. It has been proposed that heparin acts as a catalyst to cause a marked increase in the rate of interaction between AT-III and serine proteases like thrombin and Factor Xa (B4). Some uncertainty still exists as to whether the binding of heparin to the inhibitor or the enzyme or to both is the key step (P6). 

Antithrombin-III (11) and only a portion of this, probably only one or two chains, converts Antithrombin-III into an immediate inhibitor of the enzyme thrombin (14). The chains optimal for this do not appear to be identical to those optimal for USP anticoagulant activity or to those optimal for production of inhibitor activity against other important plasma serine proteases (coagulation Factor Xa, etc.). 

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