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Antithrombin III (AT III), also known simply as antithrombin or AT, is a plasma glycoprotein and a member of the serpin (serine protease inhibitor) superfamily. It plays a critical role in regulating blood coagulation by inhibiting several enzymes in the coagulation cascade. Its inhibitory activity is significantly enhanced by heparin; thus, heparin’s anticoagulant effect depends on sufficient levels of functional antithrombin. Deficiency or dysfunction leads to increased risk for venous thromboembolism and related complications.
Antithrombin III neutralizes target serine proteases by forming an irreversible covalent complex with them. The interaction involves the active site serine residue on thrombin or other target proteases binding to an arginine residue within AT’s reactive center loop. This results in rapid inhibition of clotting enzyme activity—especially when catalyzed by heparin.
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