Fibrinóxeno: Diferenzas entre revisións
Nova páxina: "{{entradución}} {{cleanup-reorganize|date=February 2012}} {{proteína | Name = Cadea alfa do fibrinóxeno | caption = Estrutura cristalográfica dun fragmento de fibrina ..." |
(Sen diferenzas.)
|
Revisión como estaba o 28 de agosto de 2012 ás 17:02
Este artigo está a ser traducido ao galego por un usuario desta Wikipedia; por favor, non o edite. O usuario Miguelferig (conversa · contribucións) realizou a última edición na páxina hai 11 anos. Se o usuario non publica a tradución nun prazo de trinta días, procederase ó seu borrado rápido. |
| |
| Estrutura cristalográfica dun fragmento de fibrina humana. [1] | |
Fibrinóxeno
| |
| Identificadores | |
| Símbolo | ? |
| Entrez | 2243 |
| HUGO | 3661 |
| OMIM | |
| RefSeq | NM_000508 |
| UniProt | P02671 |
| Outros datos | |
Fibrinóxeno
| |
| Identificadores | |
| Símbolo | ? |
| Entrez | 2244 |
| HUGO | 3662 |
| OMIM | |
| RefSeq | NM_005141 |
| UniProt | P02675 |
| Outros datos | |
Fibrinóxeno
| |
| Identificadores | |
| Símbolo | ? |
| Entrez | 2266 |
| HUGO | 3694 |
| OMIM | |
| RefSeq | NM_021870 |
| UniProt | P02679 |
| Outros datos | |
Modelo:Infobox protein family Modelo:Infobox protein family Modelo:Infobox protein family O fibrinóxeno (ou factor I de coagulación) é unha glicoproteína do plasma soluble, sintetizada no fígado, que se converte en fibrina pola acción da trombina durante a coagulación do sangue.
Esta transformación ten lugar na cascada de coagulación que activa a protrombina (un cimóxeno) en trombina (unha serina protease), que é responsable de converter o fibrinóxeno en fibrina. A fibrina establece despois enlaces cruzados co factor XIII para formar o coágulo. O FXIIIa estabiliza a fibrina ademais pola incorporación dos inhibidores da fibrinólise alfa-2-antiplasmina e TAFI (inhibidor da fibrinólise activable pola trombina, procarboxipeptidase B), e unindo diversas proteínas adhesivas de varias células. [2] Tanto a activación do factor XIII pola trombina coma o activador do plasminóxeno (t-PA) son catalizadas pola fibrina. [2] A fibrina únese especificamente aos factores de coagulación activados factor Xa e á trombina e atrápaos na rede de fibras, funcionando así como un inhibidor temporal destes encimas, que permanecen activos e poden liberarse durante a fibrinólise. [3] Investigacións recentes mostraron que a fibrina pode intervir na resposta inflamatoria e no desenvolvemento da artrite reumatoide.[4]
Deficiencia de fibrinóxeno
Congenital deficiency (afibrinogenemia) or disturbed function of fibrinogen has been described in a few cases.[5]
It can lead to either bleeding or thromboembolic complications, or is clinically without pathological findings. More common are acquired deficiency stages that can be detected by laboratory tests in blood plasma or in whole blood by means of thrombelastometry.[6] Acquired deficiency is found after hemodilution, blood losses and/or consumption such as in trauma patients, during some phases of disseminated intravascular coagulation (DIC), and also in sepsis. In patients with fibrinogen deficiency, the correction of bleeding is possible by infusion of fresh frozen plasma (FFP), cryoprecipitate (a fibrinogen-rich plasma fraction) or by fibrinogen concentrates. There is increasing evidence that correction of fibrinogen deficiency or fibrinogen polymerization disorders is very important in patients with bleeding.[7]
Uso para o diagnóstico
Fibrinogen levels can be measured in venous blood. Normal levels are about 1.5-3 g/L, depending on the method used. In typical circumstances, fibrinogen is measured in citrated plasma samples in the laboratory, however the analysis of whole-blood samples by use of thrombelastometry (platelet function is inhibited with cytochalasin D) is also possible.[6] Higher levels are, amongst others, associated with cardiovascular disease (>3.43 g/L). It may be elevated in any form of inflammation, as it is an acute-phase protein; for example, it is especially apparent in human gingival tissue during the initial phase of periodontal disease.[8] Fibrinogen levels increase in pregnancy to an average of 4.5 g/l, compared to an average of 3 g/l in non-pregnant people.[9]
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 aPTT), in the context of acute critical illness such as sepsis or trauma. Besides low fibrinogen level, fibrin polymerization disorders that can be induced by several factors, including plasma expanders, can also lead to severe bleeding problems.[6] Fibrin polymerization disorders can be detected by viscoelastic methods such as thrombelastometry.[6]
Fixioloxía
Fibrinogen is a 340 kDa glycoprotein synthesised in the liver by hepatocytes. 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). These small peptides are what prevent fibrinogen from spontaneously forming polymers with itself.[10]
The conversion of fibrinogen to fibrin occurs in several steps. First, thrombin cleaves the N-terminus of the fibrinogen alpha and beta chains to fibrinopeptide A and B respectively.[11] The resulting fibrin monomers polymerize end to end to from protofibrils, which in turn associate laterally to form fibrin fibers.[12] In a final step, the fibrin fibers associate to form the fibrin gel.[13]
Notas
- ↑ PDB 1FZC; Everse SJ, Spraggon G, Veerapandian L, Riley M, Doolittle RF (1998). "Crystal structure of fragment double-D from human fibrin with two different bound ligands". Biochemistry 37 (24): 8637–42. PMID 9628725. doi:10.1021/bi9804129. Parámetro descoñecido
|month=ignorado (Axuda) - ↑ 2,0 2,1 Muszbek L, Bagoly Z, Bereczky Z, Katona E (2008). "The involvement of blood coagulation factor XIII in fibrinolysis and thrombosis". Cardiovascular & Hematological Agents in Medicinal Chemistry 6 (3): 190–205. PMID 18673233. doi:10.2174/187152508784871990. Parámetro descoñecido
|month=ignorado (Axuda) - ↑ Kaiser B (2003). "DX-9065a, a direct inhibitor of factor Xa". Cardiovascular Drug Reviews 21 (2): 91–104. PMID 12847561. doi:10.1111/j.1527-3466.2003.tb00108.x.
- ↑ Gilliam BE; Reed, Melinda R; Chauhan, Anil K; Dehlendorf, Amanda B; Moore, Terry L (2011). "Evidence of Fibrinogen as a Target of Citrullination in IgM Rheumatoid Factor-Positive Polyarticular Juvenile Idiopathic Arthritis". Pediatric Rheumatology 9 (8): xx–xx. ISSN 1546-0096. PMC 3071779. PMID 21439056. doi:10.1186/1546-0096-9-8.
- ↑ Acharya SS, Dimichele DM (2008). "Rare inherited disorders of fibrinogen". Haemophilia : the Official Journal of the World Federation of Hemophilia 14 (6): 1151–8. PMID 19141154. doi:10.1111/j.1365-2516.2008.01831.x. Parámetro descoñecido
|month=ignorado (Axuda) - ↑ 6,0 6,1 6,2 6,3 Lang T, Johanning K, Metzler H, Piepenbrock S, Solomon C, Rahe-Meyer N, Tanaka KA (2009). "The effects of fibrinogen levels on thromboelastometric variables in the presence of thrombocytopenia". Anesthesia and Analgesia 108 (3): 751–8. PMID 19224779. doi:10.1213/ane.0b013e3181966675. Parámetro descoñecido
|month=ignorado (Axuda) - ↑ Fries D, Innerhofer P, Schobersberger W (2009). "Time for changing coagulation management in trauma-related massive bleeding". Current Opinion in Anaesthesiology 22 (2): 267–74. PMID 19390253. doi:10.1097/ACO.0b013e32832678d9. Parámetro descoñecido
|month=ignorado (Axuda) - ↑ Page RC, Schroeder HE (1976). "Pathogenesis of inflammatory periodontal disease. A summary of current work". Lab. Invest. 34 (3): 235–49. PMID 765622. Parámetro descoñecido
|month=ignorado (Axuda) - ↑ Page 5 in: Title: Medical and Surgical Diagnostic Disorders in Pregnancy. Author: Salvi. Publisher: Jaypee Brothers Publishers, 2003. ISBN: 818061090X, 9788180610905
- ↑ PDOC00445 Fibrinogen C-terminal domain in PROSITE
- ↑ Blombäck B, Hessel B, Hogg D, Therkildsen L (1978). "A two-step fibrinogen--fibrin transition in blood coagulation". Nature 275 (5680): 501–5. PMID 692730. doi:10.1038/275501a0. Parámetro descoñecido
|month=ignorado (Axuda) - ↑ Hermans J, McDonagh J (1982). "Fibrin: structure and interactions". Semin. Thromb. Hemost. 8 (1): 11–24. PMID 7036348. doi:10.1055/s-2007-1005039. Parámetro descoñecido
|month=ignorado (Axuda) - ↑ Lorand L, Credo RB (1977). "hrombin and fibrin stabilization". En Mann KG, Lundblad RL, Fenton J. Chemistry and Biology of Thrombin. Ann Arbor, Mich: Ann Arbor Science Publishers. pp. 311–323. ISBN 0-250-40160-6.
Véxase tamén
Ligazóns externas
- Jennifer McDowall/Interpro: Protein Of The Month: Fibrinogen.
- D'Eustachio/reactome: fibrinogen → fibrin monomer + 2 fibrinopeptide A + 2 fibrinopeptide B