Kininogen
Biochemistry
| Synonym | Fitzgerald factor |
|---|---|
| Molecular weight | 122.000 Da |
| Half-life | 144 hours |
| Plasma-concentration | 74 - 84 μg/ml |
| Normal range | 70 - 130 % |
High molecular weight kininogen (HMWK or Fitzgerald factor) is a cofactor for the activation of prekallikrein, factor XII and factor XI. HMWK has its own enzyme activity.
HMWK has a multi-domain structure and numerous functions, inhibition of cystein proteases of the type of papain, participation in inflammatory processes and increase of the vessel permeability. By the cleavage of HMWK by kallikrein bradykinin is released. This causes an improvement of the microcirculation by vasodilatation.
Clinical significance
The rare hereditary HMWK-deficiency is seen from an extremely prolonged aPTT. Risk of bleeding or thrombosis is, however, not present.
Indication
Suspected hereditary HMWK-deficiency, unexplained prolongation of the aPTT.
Literature
- Dotsenko VL, Neshkova EA, Rugnes E, Johansen H, Blokhina TB, Iarovaia GA. The effect of leukocyte elastase on high molecular weight kininogen from human plasma in the presence of alpha-1 protease inhibitor. Analysis of proteolytic degradation. Vopr Med Khim 47, 55-71, 2007.
- Sharma JN et al. Role of tissue kallikrein-kininogen-kinin pathways in the cardiovascular system. Arch Med Res 37, 299, 2006.
- Davis AE. The pathophysiology of hereditary angioedema. Clin Immunol 114, 3, 2005.
- Joseph K et al. Formation of bradykinin: a major contributor to the innate inflammatory response. Adv Immunol 86, 159-208, 2005.
- Sugi T et al. Antiphospholipid antibodies and kininogens in pathologic pregnancies: a review. Am J Reprod Immunol 47, 283, 2002.
- Imamura T, Tanase S, Hayashi I, Potempa J, Kozik A, Travis J. Release of a new vascular permeability enhancing peptide from kininogens by human neutrophil elastase. Biochem Biophys Res Commun 294, 423-428, 2002.
- Weber N, Wendel HP, Ziemer G. Quality assessment of heparin coatings by their binding capacities of coagulation and complement enzymes. J Biomater Appl 15, 8-22, 2000.
- Bouma BN, Vlooswijk RA, Griffin JH. Immunologic studies of human coagulation factor XI and its complex with high molecu-lar weight kininogen. Blood 62, 1123-1131, 1983.
- Schmaier AH, Silver L, Adams AL, Fischer GC, Munoz PC, Vroman L, Colman RW. The effect of high molecular weight kinino-gen on surface-adsorbed fibrinogen. Thromb Res 33, 51-67, 1984.
- Maier M, Austen KF, Spragg J. Characterization of the procoagulant chain derived from human high molecular weight kinin-ogen (Fitzgerald factor) by human tissue kallikrein. Blood 62, 457-463, 1983.
- Bochenska O, Rapala-Kozik M, Wolak N, Kamysz W, Grzywacz D, Aoki W, Ueda M, Kozik A. Inactivation of human kininogen-derived antimicrobial peptides by secreted aspartic proteases produced by the pathogenic yeast Candida albicans. Biol Chem. Dec 396(12), 1369-75, 2015.
- Langhauser F, Göb E, Kraft P, Geis C, Schmitt J, Brede M, Göbel K, Helluy X, Pham M, Bendszus M, Jakob P, Stoll G, Meuth SG, Nieswandt B, McCrae KR, Kleinschnitz. Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation. Blood. Nov 8, 120(19), 4082-92, 2012.