Alpha 2 Plasmin Inhibitor and Fibrinolysis: The primary physiological inhibitor of plasmin is Alpha 2 Plasmin Inhibitor. The binding of Alpha 2 Plasmin Inhibitor to plasmin (ogen) plays a critical role in fibrinolysis. The binding of circulating free plasmin (ogen) by Alpha 2 Plasmin Inhibitor prevents both zymogen and enzyme from binding to fibrin and ultimately initiating fibrinolysis. Alpha 2 Plasmin Inhibitor already crosslinked to fibrin prevents plasmin catalytic action on local sites of fibrin deposition as well as impeding subsequent activation of plasminogen via plasminogen activator. Human Alpha 2 Plasmin Inhibitor (a2-PI) is a single-chain glycoprotein and is one of the major serine proteinase inhibitors circulating in plasma. Physiologically, it is the predominant inhibitor of plasmin and it therefore plays a significant role in the specific inhibition of fibrinolysis. The role of a2-PI in fibrinolysis is three fold: covalent inhibition of plasmin, interference with the binding of plasminogen to fibrin, and factor XIIIa catalyzed cross-linking of a2-PI to fibrin (1). Rapid inactivation of plasmin proteolytic activity occurs through a two-step process. The inhibitor first forms a reversible complex with plasmin which is sub-sequently followed by the formation of a covalent, enzymatically inactive, complex with the catalytic site in plasmin (2,3). a2-PI also functions by interfering with the binding of plasminogen to fibrin, effectively slowing the activation of plasminogen by fibrin-bound plasminogen activator (4). The interference in binding ultimately delays the initiation of fibrinolysis. Covalent cross-linking of a2-PI to the a-chains of fibrin which is mediated by factor XIIIa, protects crosslinked fibrin clots from plasmin degradation and thereby markedly stabilizes the fibrin clot against fibrinolysis (5). Failure to protect the fibrin clot from rapid dissolution before injured vessels can be restored results in a bleeding tendency described in patients with a deficiency in a2-PI or factor XIII (6,7). The structure of a2-PI consists of three functionally important regions. A reactive site is located at Arg-364 that forms a covalent bond with the plasmin active site (8). A high affinity plasminogen-binding site located within the last 20 COOH-terminal amino acids is responsible for binding the NH2 -terminal kringle structures of plasmin(ogen) (4). An endogenous partially degraded form (non-plasminogen-binding form) of a2-PI lacking this COOH-terminal region makes up about 30% of the circulating a2-PI found in normal plasma (9). Lastly, the cross-linking site in a2-PI is located in the NH2 -terminal part of the molecule at Gln-2 (10). Extinction Coefficient: E1%1cm, 280nm=7.03 Specific Activity: ~0.8M/M human plasmin Storage and Stability: Aliquot to avoid repeated freezing and thawing and store at -70C. Aliquots are stable for 6 months after receipt. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.
Reinheit:
95% by SDS-PAGE. Alpha 2 Plasmin Inhibitor is prepared from fresh frozen plasma by a combination of ion exchange, affinity, and gel filtration chromatography steps. Our purification selects exclusively for the native plasmin-ogen-binding form. Purity is assessed by SDS-PAGE analysis and plasmin inhibition assay.
Formulierung:
Supplied as a liquid in 50mM potassium phosphate, 7.5mM KCl, 0.075mM EDTA, pH 7.4.
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