A2-Plasmin Inhibitor

Fibrinolytics. Figure 2 Various fibrin structures for plasmin. Fibrinogen (Fg) is converted to fibrin (F) by thrombin (T), and thrombin can also convert factor XIII (XIII) to activated factor XIII (Xllla). The latter produces crosslinks between fibrins (FxxF) and also may crosslink fibrin with a2-plasmin inhibitor (FxxFxxPI). The efficiency of digestion of these plasmin substrates by plasmin, resulting in the soluble fibrin degradation products (FDP), is different. The amount of FDP formed in time is expressed in arbitrary units. 

Fibrinolytics. Figure 4 Inactivation of plasmin by a2-plasmin inhibitor Effect of fibrin. The inactivation rate of free plasmin is very rapid (the second order rate constant k 430 104M-1s-1), while of fibrin bound plasmin is slow (the second order rate constant k 1 104M"1s"1). Inactivation of plasmin in the figure is shown in arbitrary units. Abbreviations plasmin (P), fibrin (F). 

The a2-plasmin inhibitor, a single-chain glycoprotein (70 kDa), forms rapidly an equimolar complex with plasmin, where the enzyme loses its activity. It is synthesized by the liver and secreted into the blood circulation, where its concentration is 1 pM. 

Sakata, Y., and Aoki, N. (1980). Cross-linking of a2-plasmin inhibitor to fibrin by fibrin-stabilizing factor./. Clin. Invest. 65, 290-297. 

Chung, D. H., Ohashi, K., Watanabe, M., Miyasaka, N., and Hirosawa, S. (2000). Mannose trimming targets mutant a2-plasmin inhibitor for degradation by the proteasome. J. Biol. Chem. 275, 4981-4987. 

For example, the protease sensitive factor Xllla substrate sequence of a2-plasmin inhibitor (a2Plj g, NQEQVSPL (TG, transglutaminase substrate)) has been fused... 

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