Plasmina

A plasmina é un importante encima (EC 3.4.21.7) presente no sangue que degrada moitas proteínas do plasma sanguíneo, principalmente a fibrina dos coágulos sanguíneos, polo que participa na fibrinólise. A plasmina orixínase a partir do plasminóxeno codificado polo xene PLG do cromosoma 6.^[1] A deficiencia en plasmina pode orixinar tromboses.

Función e activación[editar | editar a fonte]

Fibrinólise (simplificada). As frechas azuis significan estimulación e as vermellas inhibición.

A plasmina é unha serina protease que actúa disolvendo os coáguloos sanguíneos de fibrina. Ademais da fibrinólise, a plasmina proteoliza proteínas noutros varios sistemas: activa colaxenases, a algúns mediadores do sistema de complemento e debilita a parede do folículo de Graaf (o que orixinará a ovulación). Cliva a fibrina, fibronectina, trombospondina, laminina, e o factor de von Willebrand.

A plasmina orixínase a partir dunha proteína precursora ou cimóxeno chamado plasminóxeno, que se libera do fígado á circulación sistémica. Na circulación, o plasminóxeno adopta unha conformación pechada resistente á activación. Sobre os coágulos ou sobre a superficie celular, o plasminóxeno adopta unha forma aberta que pode ser convertida en plasmina activa por diversos encimas, como o activador do plasminóxeno tisular (tPA), activador do plasminóxeno uroquinase (uPA), calicreína, e o factor XII (factor de Hageman). A fibrina é un cofactor da activación do plasminóxeno polo activador do plasminóxeno tisular. O receptor do activador do plasminóxeno uroquinase (uPAR) é un cofactor para a activación do plasminóxeno polo activador do plasminóxeno uroquinase. A conversión do plasminóxeno en plasmina implica a clivaxe do enlace peptídico entre a Arg-561 e a Val-562.^[1]^[2]^[3]^[4]

A clivaxe da plasmina, á súa vez, produce anxiostatina.^[5]

Interaccións[editar | editar a fonte]

A plasmina interacciona coa trombospondina 1,^[6]^[7] a alfa 2-antiplasmina^[8]^[9] e a proteína que se une ao factor de crecemento similar á insulina 3 (IGFBP3).^[10]

Notas[editar | editar a fonte]

↑ ^1,0 ^1,1 "Entrez Gene: plasminogen".
↑ Miyata T, Iwanaga S, Sakata Y, Aoki N (1982). "Plasminogen Tochigi: inactive plasmin resulting from replacement of alanine-600 by threonine in the active site". Proc. Natl. Acad. Sci. U.S.A. 79 (20): 6132–6. PMC 347073. PMID 6216475. doi:10.1073/pnas.79.20.6132.
↑ Forsgren M, Råden B, Israelsson M, Larsson K, Hedén LO (1987). "Molecular cloning and characterization of a full-length cDNA clone for human plasminogen". FEBS Lett. 213 (2): 254–60. PMID 3030813. doi:10.1016/0014-5793(87)81501-6.
↑ Law RHP, Caradoc-Davies T, Cowieson N, Horvath AJ, Quek AJ, Encarnacao JA, Steer D, Cowan A, Zhang Q, Lu BGC, Pike RN, Smith AI, Coughlin PB, Whisstock JC (2012). "The X-ray Crystal Structure of Full-Length Human Plasminogen". Cell Reports 1 (3): 185. doi:10.1016/j.celrep.2012.02.012.
↑ Paul Stathakis, Melinda Fitzgerald, Lisa J. Matthias, Colin N. Chesterman and Philip J. Hogg. Generation of Angiostatin by Reduction and Proteolysis of Plasmin Catalysis by a Plasmin Reductase Secreted by Cultures Cells. The Journal of Biological Chemistry. [1]
↑ Silverstein, R L; Leung L L, Harpel P C, Nachman R L (1984). "Complex formation of platelet thrombospondin with plasminogen. Modulation of activation by tissue activator". J. Clin. Invest. (UNITED STATES) 74 (5): 1625–33. ISSN 0021-9738. PMC 425339. PMID 6438154. doi:10.1172/JCI111578.
↑ DePoli, P; Bacon-Baguley T, Kendra-Franczak S, Cederholm M T, Walz D A (1989). "Thrombospondin interaction with plasminogen. Evidence for binding to a specific region of the kringle structure of plasminogen". Blood (UNITED STATES) 73 (4): 976–82. ISSN 0006-4971. PMID 2522013.
↑ Wiman, B; Collen D (1979). "On the mechanism of the reaction between human alpha 2-antiplasmin and plasmin". J. Biol. Chem. (UNITED STATES) 254 (18): 9291–7. ISSN 0021-9258. PMID 158022.
↑ Shieh, B H; Travis J (1987). "The reactive site of human alpha 2-antiplasmin". J. Biol. Chem. (UNITED STATES) 262 (13): 6055–9. ISSN 0021-9258. PMID 2437112.
↑ Campbell, P G; Durham S K, Suwanichkul A, Hayes J D, Powell D R (1998). "Plasminogen binds the heparin-binding domain of insulin-like growth factor-binding protein-3". Am. J. Physiol. (UNITED STATES) 275 (2 Pt 1): E321–31. ISSN 0002-9513. PMID 9688635.

Véxase tamén[editar | editar a fonte]

Bibliografía[editar | editar a fonte]

Shanmukhappa K, Mourya R, Sabla GE, Degen JL, Bezerra JA (2005). "Hepatic to pancreatic switch defines a role for hemostatic factors in cellular plasticity in mice". Proc. Natl. Acad. Sci. U.S.A. 102 (29): 10182–7. PMC 1177369. PMID 16006527. doi:10.1073/pnas.0501691102.
Anglés-Cano E, Rojas G (2003). "Apolipoprotein(a): structure-function relationship at the lysine-binding site and plasminogen activator cleavage site". Biol. Chem. 383 (1): 93–9. PMID 11928826. doi:10.1515/BC.2002.009.
Ranson M, Andronicos NM (2004). "Plasminogen binding and cancer: promises and pitfalls". Front. Biosci. 8: s294–304. PMID 12700073. doi:10.2741/1044.

Outros artigos[editar | editar a fonte]

Ligazóns externas[editar | editar a fonte]

The MEROPS online database for peptidases and their inhibitors: S01.233 Arquivado 13 de setembro de 2019 en Wayback Machine.
MeshName - Plasmin [2]

[entrez-1] 1,0 ^1,1 "Entrez Gene: plasminogen".

[pmid6216475-2] Miyata T, Iwanaga S, Sakata Y, Aoki N (1982). "Plasminogen Tochigi: inactive plasmin resulting from replacement of alanine-600 by threonine in the active site". Proc. Natl. Acad. Sci. U.S.A. 79 (20): 6132–6. PMC 347073. PMID 6216475. doi:10.1073/pnas.79.20.6132.

[pmid-3] Forsgren M, Råden B, Israelsson M, Larsson K, Hedén LO (1987). "Molecular cloning and characterization of a full-length cDNA clone for human plasminogen". FEBS Lett. 213 (2): 254–60. PMID 3030813. doi:10.1016/0014-5793(87)81501-6.

[Law_2012-4] Law RHP, Caradoc-Davies T, Cowieson N, Horvath AJ, Quek AJ, Encarnacao JA, Steer D, Cowan A, Zhang Q, Lu BGC, Pike RN, Smith AI, Coughlin PB, Whisstock JC (2012). "The X-ray Crystal Structure of Full-Length Human Plasminogen". Cell Reports 1 (3): 185. doi:10.1016/j.celrep.2012.02.012.

[5] Paul Stathakis, Melinda Fitzgerald, Lisa J. Matthias, Colin N. Chesterman and Philip J. Hogg. Generation of Angiostatin by Reduction and Proteolysis of Plasmin Catalysis by a Plasmin Reductase Secreted by Cultures Cells. The Journal of Biological Chemistry. [1]

[pmid6438154-6] Silverstein, R L; Leung L L, Harpel P C, Nachman R L (1984). "Complex formation of platelet thrombospondin with plasminogen. Modulation of activation by tissue activator". J. Clin. Invest. (UNITED STATES) 74 (5): 1625–33. ISSN 0021-9738. PMC 425339. PMID 6438154. doi:10.1172/JCI111578.

[pmid2522013-7] DePoli, P; Bacon-Baguley T, Kendra-Franczak S, Cederholm M T, Walz D A (1989). "Thrombospondin interaction with plasminogen. Evidence for binding to a specific region of the kringle structure of plasminogen". Blood (UNITED STATES) 73 (4): 976–82. ISSN 0006-4971. PMID 2522013.

[pmid158022-8] Wiman, B; Collen D (1979). "On the mechanism of the reaction between human alpha 2-antiplasmin and plasmin". J. Biol. Chem. (UNITED STATES) 254 (18): 9291–7. ISSN 0021-9258. PMID 158022.

[pmid2437112-9] Shieh, B H; Travis J (1987). "The reactive site of human alpha 2-antiplasmin". J. Biol. Chem. (UNITED STATES) 262 (13): 6055–9. ISSN 0021-9258. PMID 2437112.

[pmid9688635-10] Campbell, P G; Durham S K, Suwanichkul A, Hayes J D, Powell D R (1998). "Plasminogen binds the heparin-binding domain of insulin-like growth factor-binding protein-3". Am. J. Physiol. (UNITED STATES) 275 (2 Pt 1): E321–31. ISSN 0002-9513. PMID 9688635.

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