Plasmin protease inhibitor

Serine protease inhibitor that inhibits trypsin, chymotrypsin, kallikrein, and plasmin Binding is reversible, with most aprotinin-protease complexes dissociating at pH>10or <3 Peptidase inhibitor... 

Cyanobacteria -Microcystis aeruginosa Micropeptins 478-A and -B -peptide-based plasmin inhibitors Cyanopeptolins A-D -protease inhibitors Cyanopeptolin 963A-chymotrypsin inhibitor 120 6, 262 263... 

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. 

Cardiopulmonary bypass, with extracorporeal circulation during cardiac artery bypass graft or heart valve replacement surgery, causes transient hemostatic defects in blood cells and perioperative bleeding. The protease inhibitor aprotinin (Trasylol) inhibits kalhkrein (coagulation phase) and plasmin (hbrinolysis) and protects platelets from mechanical injury. The overall effect after infusion is a decrease in bleeding. 

Markland W, Charles Ley A, Lee SW, Charles Ladner R, Iterative optimization of high-affinity protease inhibitors using phage display, Plasmin Biochemistry, 35 8045-8057, 1996. 

Plasmin is soluble but it remains active in the location of a clot. As it diffuses into the blood with clot fragments, the plasmin binds to a2-antiplasmin, a serine protease inhibitor (see next section). In addition to inhibiting plasmin in the blood (Fig. 11.10b), a2-antiplas-min inhibits various other serine proteases, especially activated protein C (APC) (next section) and elastase (Sect. 6.2.1). Plasmin action is inhibited where fibrin is cross-linked to fibronectin, but the large fibrin fragments tend to promote healing. The fragments of fibrin are named as shown in Fig. 11.10c and d. Factors that activate or inhibit fibrinolysis are summarized in Table 11.2. 

Oj-antitrypsin is a nonspecific serine protease inhibitor with a broad spectrum of inhibitor activities. It is present in plasma at the highest concentration of any other serine protease inhibitor. While the protein has not been identified as a major inhibitor of the enzymes involved in coagulation and fibrinolysis, it is known to inactivate thrombin, plasmin, kallikrein, and Factor Xla. A deficiency in the circulating levels of this inhibitor has been strongly associated with the development of pulmonary disease. Several manual and automated synthetic substrate procedures for Oj-antitrypsin have been published using the first-generation substrate, BAPNA (M6). 

Tobacco-produced recombinant research-grade bovine aprotinin (Apronexin NP) [238] is also available from Sigma Aldrich. Aprotinin is a protease inhibitor which is used as a research reagent in biomanufacturing for several therapeutic applications. It has been traditionally extracted from bovine lung tissue. Aprotinin is a single, 58 amino-acid polypeptide with three disulfide bonds, and inhibits several serine proteases such as trypsin, chymotrypsin, plasmin, and kallikrein. 

Antithrombin III (AT-III), a single-chain glycoprotein of 58 kDa and 480 amino acids, is synthesized in the liver. It is a serine protease inhibitor, and acts as the most important inhibitor in the coagulation cascade to avoid blood clot formation. AT-III inhibits a wide spectram of serine proteases induding thrombin, factors IXa, Xa and XIa, kaUikrein, plasmin, urokinase, Cl-esterase, and trypsin. AT-III interacts with heparin by binding to specific sul-fated and non-sulfated monosaccharide units on heparin. The binding of AT-III to heparin enhances the inhibition of factors IXa, Xa, and thrombin. 

Antithrombin (AT) is a serine protease inhibitor that inhibits thrombin, factor Xa, IXa, XIa, Xlla, tPA, urokinase, trypsin, plasmin, and kallikrein (Lahiri et al. 1976 Travis and Salvesen, 1983 Menache, 1991 Menache et al. 1992). Human Antithrombin of molecular weight equal approximately to 58,000 Da, contains 432 amino acids, three disulfide bridges, and four carbohydrate side chains, which account for 15% of the total mass (Magnusson, 1979 Franzen et al. 1980). Human antithrombin is synthesized in the liver and present in plasma at levels of 14 to 20mg/dl (Murano et al. 1980 Rosenberg et al. 1986). One cause of decreased level of antithrombin is pathological conditions. 

Operative procedures, such as heart valve replacement, frequently have effects on platelet function and endogenous coagulation factors (137). These effects may result in significant peri- or postoperative bleeding. Aprotinin is a serine protease inhibitor that blocks kallikrein and plasmin and provides some protection to platelets from mechanical injury. The inhibition of fibrinolysis results in profound antihemorrhagic effects (137). Side effects of aprotinin therapy usually are minor, but anaphylaxis has possibly been implicated in a small population (<0.5%). For this reason. 

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