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Fibrin
Fibrin (also called '''Factor Ia''') is a fibrous protein involved in the clotting of blood, and is non globular. It is a fibrillar protein that is Polymerization|polymerised to form a "mesh" that forms a hemostasis|hemostatic plug or clot (in conjunction with platelets) over a wound site.
Fibrin is made from '''fibrinogen''', a soluble blood plasma|plasma glycoprotein that is synthesised by the liver. Processes in the coagulation cascade activate the zymogen prothrombin to the serine protease thrombin, which is responsible for converting fibrinogen into fibrin. Fibrin is then cross linked by factor XIII to form a clot. Recent research has shown that fibrin plays a key role in the inflammatory response and development of rheumatoid arthritis.
Fibrin is involved in the following biological processes: signal transduction, blood coagulation, platelet activation, and protein polymerization.
Role in disease
Excessive generation of fibrin due to activation of the coagulation cascade leads to thrombosis, while ineffective generation predisposes to hemorrhage.
Dysfunction or disease of the liver can lead to a decrease in fibrinogen production or the production of abnormal fibrinogen molecules with reduced activity (dysfibrinogenaemia). Hereditary abnormalities of fibrinogen (the gene is carried on chromosome 4) are of both quantitative and qualitative in nature and include; afibrinogenaemia, hypofibrinogenaemia, dysfibrinogenaemia, and hypodysfibrinogenaemia.
Diagnostic use
Fibrinogen levels can be measured in vein|venous blood. Normal levels are about 1.5-3.0 g/L. Higher levels are, amongst others, associated with cardiovascular disease (>4.6 g/L). It may be elevated in any form of inflammation, as it is an acute phase protein.
It is used in veterinary medicine as an inflammatory marker: in horses a level above the normal range of 1.0-4.0 g/L suggests some degree of systemic inflammatory response.
Low levels of fibrinogen can indicate a systemic activation of the clotting system, with consumption of clotting factors faster than synthesis. This excessive clotting factor consumption condition is known as Disseminated Intravascular Coagulation or "DIC." DIC can be difficult to diagnose, but a strong clue is low fibrinogen levels in the setting of prolonged clotting times (PT or PTT), in the context of acute critical illness such as sepsis or trauma.
Physiology
Fibrinogen (also called factor I) is a 340 KDa glycoprotein synthesised in the liver by hepatocytes and megakaryocytes. The concentration in blood plasma is 1.5-4.0 g/L (normally measured using the Clauss method) or about 7 µM. In its natural form, fibrinogen can form bridges between platelets, by binding to their GpIIb/IIIa surface membrane proteins; however its major function is as the precursor to fibrin.
Fibrinogen, the principal protein of vertebrate blood clotting is a hexamer containing two sets of three different chains (α, β, and γ), linked to each other by disulfide bonds. The N-terminal sections of these three chains contain the cysteines that participate in the cross-linking of the chains. The C-terminal parts of the α, β and γ chains contain a domain of about 225 amino-acid residues, which can function as a molecular recognition unit. In fibrinogen as well as in angiopoietin this domain is implicated in protein-protein interactions. In lectins, such as mammalian ficolins and invertebrate tachylectin 5A, the fibrinogen C-terminal domain binds carbohydrates. On the fibrinogen α and β chains, there is a small peptide sequence (called a fibrinopeptide). It is these small peptides that prevent fibrinogen spontaneously forming polymers with itself. [http://www.expasy.org/prosite/PDOC00445 Fibrinogen C-terminal domain in PROSITE]
Image
The image at right is a crystal structure of the double-d fragment from human fibrin with two bound ligands. The experimental method used to obtain the image was X-ray diffraction, and it has a resolution of 2.30 A. The structure is mainly made up of single alpha helices shown in red and beta sheets shown in yellow. The two blue structures are the bound ligands. The chemical structures of the ligands are Ca+2 ion, alpha-D-mannose (C6H1206), and D-glcosamine (C8H15NO6).
See also
- Fibrinogen alpha chain
- Fibrinogen beta chain
- Fibrinogen gamma chain
- Fibrinolysis
- D-dimer
References
External links
- Defibrinated blood harvested from sheep video
Category:Coagulation system
Category:Blood proteins
Category:Acute phase proteins
Related Images- right
Sources: StartLearningNow, Wikipedia | Usage license: GNU FDL
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