Description of Antithrombin

Antithrombin, also known as Antithrombin III (ATIII), is a member of the SERPIN family of proteinase inhibitors and the primary inhibitor of thrombin in plasma. It is produced in the liver and circulates in plasma at ~200 μg/ml (~3.5 μM). Antithrombin inhibits a broad spectrum of serine proteases including thrombin, activated forms of factor X, factor IX, factor XI, factor XII, as well as kallikrein, plasmin and urokinase. Enzyme inhibition by antithrombin occurs through proteolytic cleavage at Arg385-Ser386 and subsequent rapid formation of a stable, inactive 1:1 enzyme-antithrombin complex. Heparin has a profound accelerating effect on the inhibitory activity of antithrombin towards some enzymes. For example, the rate of inhibition of thrombin and activated factor X is increased 1000-fold in the presence of optimal concentrations of heparin, whereas heparin has relatively little effect on the inhibition rate of activated factor XI, activated factor XII and kallikrein. Antithrombin is a single chain molecule with a molecular weight of 59 kDa. Interaction with thrombin results in an SDS-stable thrombin-antithrombin complex of 96 kDa^1-3.

References and Reviews

1. Damus PS, Rosenberg RD; Antithrombin – Heparin Cofactor; Methods in Enzymology 45, pp 653-669, 1976.
2. Harpel PC; Blood Proteolytic Enzyme Inhibitors: Their Role in Modulating Blood Coagulation and Fibrinolytic Enzyme Pathways; in Hemostasis and Thrombosis, eds. RW Colman, J Hirsh, VJ Marder and EW Salzman, pp. 738-747, J.B. Lippincott Co., Philadelphia PA, USA, 1982.
3. Griffith MJ, Noyes CM, Church FC; Reactive Site Peptide Structural Similarity between Heparin Cofactor II and Antithrombin III; JBC:260, pp 2218-2225, 1985.