Thrombin

  • OMIM: 176930
  • UniProt: P00734
  • MGI: 88380
  • CAS Number: 9002-04-4

Thrombin ( factor IIa ) is the main enzyme of the blood coagulation in vertebrates and one of the blood clotting factors. Thrombin is one of the serine proteases and cleaves fibrinogen to fibrin and fibrinopeptides. Moreover, it enables the blood coagulation factors V, VII, VIII, XIII and, together with thrombomodulin protein C. It has functions for inflammation and wound healing. Thrombin is formed in the liver and is found as a precursor ( prothrombin) continuously in the blood plasma. Defects in the F2 gene are the cause of Dysprothrombinämie and can increase susceptibility to stroke.

Occurrence

Prothrombin is the factor II coagulation. It is produced in the liver and is continuously released into the blood. Prothrombin is detectable in blood plasma. In the blood, there are only slight traces of free thrombin, which is normally formed when breaching of tissue from the prothrombin in place. A Thrombinämie, the presence of free thrombin and thus the coagulation of blood in uninjured vessels is prevented by endogenous Antithrombins.

Biosynthesis

In humans, the F2 gene is located on chromosome 11 and extends over 20,300 base pairs and 14 exons. After transcription, the 1997 bases long mRNA is translated into a 622 amino acid protein and is produced by post-translational modification of prothrombin with 579 amino acids.

Biological Function

The action of thrombin based on its protease activity, and relates to a proteolytic activation of dissolved in the blood plasma proteins ( coagulation factors and fibrin) and, secondly, the effect signal to vascular cells.

The injury to a blood vessel dissolves in the blood plasma of a proteolytic cascade reaction, the release of thrombin from prothrombin is at the end. The FIIa generation is done in the prothrombinase complex ( coagulation factors II, Va and Xa, calcium ions may be associated with membranous phospholipids ). The liberated thrombin cleaves dissolved in the blood plasma present fibrinogen to fibrin, which assembles to insoluble fibrin polymers. At the same time, thrombin promotes the activation of the coagulation factors V, VII and VIII and thus - through a positive feedback loop - his own release.

In addition to the effect of thrombin on the plasma protein signal its effect is on cells of the vascular system. The mediation of this effect signal via protease - activated receptors (PAR ) on the surface, among others of platelets and smooth muscle cells. In platelets, thrombin triggers platelet activation in vascular smooth muscle cells proliferation and migration processes, which are also for atherosclerotic processes of importance.

Pharmacology, diagnostic

Thrombin can be inhibited by various compounds, such as:

  • Antithrombins
  • Heparin
  • Low molecular weight heparins
  • Pentasaccharide
  • Orgaran
  • Hirudin
  • Rhodniin
  • Ornithodorin
  • Dabigatran etexilate

The function of thrombin can be estimated using various coagulation tests: prothrombin, thromboplastin time ( Quick's value ), partial thromboplastin time, thrombin generation.

Applications in the food industry

Thrombin from the domestic pig (Sus scrofa), is used by the food industry in the production of food, such as sausages. An application as an adhesive to produce artificially large pieces of meat such as ham, the European Parliament rejected in May 2010 by a narrow margin from.

See also: Meat Glue

History

Thrombin was first described in 1892 by Schmidt in his work to the blood doctrine:

" The fiber coagulation has a series of reactions in the circulating blood for its remote condition and consists essentially (...) in three consecutive files and interdependent, namely:

Human Genome Organisation Mouse Genome Informatics CAS registry number Anatomical Therapeutic Chemical Classification System MEROPS Hydrolysis Euteleostomi Hemostasis Tissue (biology) Transglutaminase Alexander Schmidt (physiologist) Tissue factor Kallikrein
325526
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