Hirudin
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Overview
Hirudin is a naturally occurring peptide in the salivary glands of medicinal leeches (such as 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.
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]
Biological activity
A key event in the final stages of blood coagulation is the conversion 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.
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.
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 led to the development and marketing of a number of hirudin based anticoagulant pharmaceutical products such as lepirudin (Refludan®) and Desirudin (Revasc/Iprivask®). Several other direct thrombin inhibitors are derived chemically from hirudin.
References
- ↑ 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.
- ↑ 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.
- ↑ 3.0 3.1 3.2 Rydell TJ, Tulinsky A. et al. (1991). "Refined structure of the Hirudin-Thrombin complex". J. Mol. Biol. 221 (2): 583-601. PMID 1920434.
- ↑ Fenton JW 2nd, Ofosu SA et al. (1998). "Thrombin and antithrombotics". Semin Thromb Hemost 24 (2): 87-91. PMID 9579630.
See also
WikiDoc Research Resources for Hirudin | |
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| Articles on Hirudin | Most recent articles on Hirudin • Most cited articles on Hirudin • Review articles on Hirudin • Articles on Hirudin in N Eng J Med, Lancet, BMJ |
| Media (Slides, Video, Images, MP3) on Hirudin | Powerpoint slides on Hirudin • Images of Hirudin • Photos of Hirudin • Podcasts & MP3s on Hirudin • Videos on Hirudin |
| Evidence Based Medicine Regarding Hirudin | Cochrane Collaboration on Hirudin • Bandolier on Hirudin • TRIP on Hirudin |
| Cost Effectiveness of Hirudin | Cost Effectiveness of Hirudin |
| Clinical Trials Involving Hirudin | Ongoing Trials on Hirudin at Clinical Trials.gov • Trial results on Hirudin • Clinical Trials on Hirudin at Google |
| Guidelines / Policies / Government Resources (FDA/CDC) Regarding Hirudin | US National Guidelines Clearinghouse on Hirudin • NICE Guidance on Hirudin • NHS PRODIGY Guidance • FDA on Hirudin • CDC on Hirudin |
| Textbook Information on Hirudin | Books and Textbook Information on Hirudin |
| Pharmacology Resources on Hirudin | Dosing of Hirudin • Drug interactions with Hirudin • Side effects of Hirudin • Allergic reactions to Hirudin • Overdose information on Hirudin • Carcinogenicity information on Hirudin • Hirudin in pregnancy • Pharmacokinetics of Hirudin • |
| Genetics, Pharmacogenomics, and Proteinomics of Hirudin | Genetics of Hirudin • Pharmacogenomics of Hirudin • Proteomics of Hirudin |
| Newstories on Hirudin | Hirudin in the news • Be alerted to news on Hirudin • News trends on Hirudin |
| Commentary on Hirudin | Blogs on Hirudin |
| Patient Resources on Hirudin | Patient resources on Hirudin • Discussion groups on Hirudin • Patient Handouts on Hirudin • Directions to Hospitals Treating Hirudin • Risk calculators and risk factors for Hirudin |
| Healthcare Provider Resources on Hirudin | Symptoms of Hirudin • Causes & Risk Factors for Hirudin • Diagnostic studies for Hirudin • Treatment of Hirudin |
| Continuing Medical Education (CME) Programs on Hirudin | CME Programs on Hirudin |
| International Resources on Hirudin | Hirudin en Espanol • Hirudin en Francais |
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Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
