Terentyeva2015 - Mechanisms of XII activation

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Mathematical model of the mechanism and kinetics of blood coagulation factor XII.
Related Publication
  • Kinetics and mechanisms of surface-dependent coagulation factor XII activation.
  • Terentyeva VA, Sveshnikova AN, Panteleev MA
  • Journal of theoretical biology , 10/ 2015 , Volume 382 , pages: 235-243 , PubMed ID: 26187095
  • Faculty of Physics, M.V. Lomonosov Moscow State University, Moscow, Russia; Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
  • Surface-induced activation of factor XII is critical part of the intrinsic pathway of blood coagulation. The mechanism of this process remains unclear: in particular, it is not known whether the initial amounts of factor XIIa, an active form of factor XII, are produced purely by factor XII contacting a surface or if traces of factor XIIa pre-exist. Furthermore, it is not known whether factor XII first has to bind to a surface before it can interact with the surface-bound factor XIIa in a two-dimensional process to become activated ("bound-substrate model") or if surface-bound factor XIIa activates a fluid-delivered form of factor XII ("free-substrate model"). To investigate these possibilities, we used mathematical modeling to implement various hypotheses. Time courses of factor XII production were generated under different initial conditions and matched with experimental data. We established that only the "bound-substrate model" fits with the majority of experimental data, whereas the "free-substrate model" does not. We also addressed the question of spontaneous activation and found that measurable differences between the models with and without spontaneous activation appear only under limiting conditions (deficit or excess of surface). As there are insufficient data regarding the system's behavior upon such variations of surface concentration in the literature, we designed new experiments to answer this question.
Submitter of the first revision: Matthew Roberts
Submitter of this revision: Matthew Roberts
Modellers: Matthew Roberts

Metadata information

isDescribedBy (1 statement)
PubMed 26187095

isPartOf (1 statement)
Gene Ontology blood coagulation

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Terentyeva2015.xml SBML L2V4 representation of Terentyeva2015 - Mechanisms of XII activation 18.91 KB Preview | Download

Additional files

Terentyeva2015.cps Noncurated model COPASI file. Kinetic constant values from second last column in Table 1 used. Initial conditions unknown - some species' IC guessed from Fig. 2. XIIa_frag ODE lists an elimination rate that is not dependent on XIIa_frag so conc. can be less than zero - one of the XIIa terms was changed to XIIa_frag to avoid this. XII_f not explicitly defined ('minor forms that don't have procoagulant activity') so XII_amidolytic may be improperly defined. 48.13 KB Preview | Download

  • Model originally submitted by : Matthew Roberts
  • Submitted: Aug 16, 2018 10:16:20 AM
  • Last Modified: Aug 16, 2018 10:16:20 AM
  • Version: 2 public model Download this version
    • Submitted on: Aug 16, 2018 10:16:20 AM
    • Submitted by: Matthew Roberts
    • With comment: Edited model metadata online.