Hirudin is a naturally occurring peptide in the salivary glands of medicinal leeches (Hirudo medicinalis) that has a blood anticoagulant property. This is fundamental for the leeches’ alimentary habit of hematophagy, since it keeps the blood flowing after the initial phlebotomy performed by the worm on the host’s skin. Peptides (from the Greek πεπτος, digestible), are the family of short molecules formed from the linking, in a defined order, of various α-amino acids. ... The salivary glands produce saliva, which keeps the mouth and other parts of the digestive system moist. ... Orders Arhynchobdellida or Rhynchobdellida There is some dispute as to whether Hirudinea should be a class itself, or a subclass of the Clitellata. ... An anticoagulant is a substance that prevents coagulation; that is, it stops blood from clotting. ... An Anopheles stephensi mosquito obtaining a blood meal from a human host through its pointed proboscis. ... Bloodletting (or blood-letting, in modern medicine referred to as phlebotomy) was a popular medical practice from antiquity up to the late 19th century, involving the withdrawal of often considerable quantities of blood from a patient in the belief that this would cure or prevent illness and disease. ...

Structure

In 1884, the British physiologist John Berry Haycraft discovered that the leech secreted a powerful anticoagulant, which he named hirudin, though it was not isolated until the 1950s, nor its structure fully determined until 1976. Full length, hirudin is made up of 65 amino acids. These amino acids are organised into a compact N-terminal domain containing three disulfide bonds and a C-terminal domain which is completely disordered, when the protein is un-complexed in solution.^[1][2] Natural hirudin contains a mixture of various isoforms of the protein. However, recombinant techniques can be used to produce homogeneous preparations of hirudin.^[3] A disulfide bond (SS-bond), also called a disulfide bridge, is a strong covalent bond between two sulfhydryl groups. ... A protein complex is a group of two or more associated proteins formed by protein-protein interaction that is stable over time. ... In biology, a protein isoform is a version of a protein with some small differences, usually a splice variant or the product of some posttranslational modification. ... Recombinant proteins are proteins that are produced by different genetically modified organisms following insertion of the relevant DNA into their genome. ... Look up Homogeneous in Wiktionary, the free dictionary. ...

Biological activity

A key event in the final stages of blood coagulation is the convertion of fibrinogen into fibrin by the serine protease enzyme thrombin.^[4] Thrombin is produced from prothrombin, by the action of an enzyme, prothrombinase, in the final states of coagulation. Fibrin is then cross linked by factor XIII to form a blood clot. The principal inhibitor of thrombin in normal blood circulation is antithrombin III.^[3] Similar to antithrombin III, the anticoagulatant activity of hirudin is based on its ability to inhibit the pro-coagulant activity of thrombin. Coagulation is the thickening or congealing of any liquid into solid clots. ... Fibrin is a protein involved in the clotting of blood. ... Fibrin is a protein involved in the clotting of blood. ... Crystal structure of Trypsin, a typical serine protease. ... Thrombin (activated Factor II) is a coagulation protein that has many effects in the coagulation cascade. ... Thrombin (activated Factor II) is a coagulation protein that has many effects in the coagulation cascade. ... A thrombus is the final product of blood coagulation, through the aggregation of platelets and the activation of the humoral coagulation system. ... HIV protease in a complex with the protease inhibitor ritonavir. ... Thrombin (activated Factor II) is a coagulation protein that has many effects in the coagulation cascade. ... Antithrombin is a small molecule that inactivates several enzymes of the coagulation system. ... Antithrombin is a small molecule that inactivates several enzymes of the coagulation system. ... Thrombin (activated Factor II) is a coagulation protein that has many effects in the coagulation cascade. ...

Hirudin is the most potent natural inhibitor of thrombin. Unlike antithrombin III hirudin binds to and inhibits only the activity of thrombin forms with a specific activity on fibrinogen.^[3] Therefore, hirudin prevents or dissolves the formation of clots and thrombi (i.e. it has a thrombolytic activity), and has therapeutic value in blood coagulation disorders, in the treatment of skin hematomas and of superficial varicose veins, either as an injectable or a topical application cream. In some aspects, hirudin has advantages over more commonly used anticoagulants and thrombolytics, such as heparin, as it does not interfere with the biological activity of other serum proteins and can also act on complexed thrombin. Antithrombin is a small molecule that inactivates several enzymes of the coagulation system. ... Blood clot diagram. ... Thrombolysis is the breakdown (lysis) by pharmacological means, of blood clots. ... Blood diseases affect the production of blood and its components, such as blood cells, hemoglobin, blood proteins, the mechanism of coagulation, etc. ... It has been suggested that this article or section be merged with Epidermis (skin). ... Hematoma on an elbow, nine days after a blood sample was taken Hematoma on a forearm, one day after repeated shocks A hematoma, or haematoma, is a collection of blood, generally the result of hemorrhage. ... Varicose veins are veins on the leg which are large, twisted, and ropelike, and can cause pain, swelling, or itching. ... Heparin is a highly sulfated glycosaminoglycan widely used as an injectable anticoagulant. ... A protein complex is a group of two or more associated proteins formed by protein-protein interaction that is stable over time. ...

It is difficult to extract large amounts of hirudin from natural sources, so a method for producing and purifying this protein using recombinant biotechnology has been developed. This has lead to the development and marketing of a number of hirudin based anticoagulant pharmaceutical products such as Refludan® (lepirudin) and Revasc/Iprivask® (Desirudin). Several other direct thrombin inhibitors are derived chemically from hirudin. Recombinant proteins are proteins that are produced by different genetically modified organisms following insertion of the relevant DNA into their genome. ... The structure of insulin Biotechnology is technology based on biology, especially when used in agriculture, food science, and medicine. ... Direct thrombin inhibitors (DTIs) are a class of medication that act as anticoagulants (delaying blood clotting) by directly inhibiting the enzyme thrombin. ...

References

1. ^ Folkers PJM, Clore GM. et al. (1989). "Solution structure of recombinant hirudin and the Lys-47-Glu mutant: a nuclear magnetic resonance and hybrid distance geometry-dynamical simulated annealing study". Biochemistry 28 (6): 2601-2617. PMID 2567183. 
2. ^ Haruyama H. and Wuthrich K. (1989). "Conformation of recombinant desulfatohirudin in aqueous solution determined by nuclear magnetic resonance". Biochemistry 28 (10): 4301-4312. PMID 2765488. 
3. ^ ^{a b c} Rydell TJ, Tulinsky A. et al. (1991). "Refined structure of the Hirudin-Thrombin complex". J. Mol. Biol. 221 (2): 583-601. PMID 1920434. 
4. ^ Fenton JW 2nd, Ofosu SA et al. (1998). "Thrombin and antithrombotics". Semin Thromb Hemost 24 (2): 87-91. PMID 9579630. 

See also

• Hirudotherapy