Stortelder1997 - Thrombin Generation Amidolytic Activity

  public model
Model Identifier
BIOMD0000000358
Short description
Stortelder1997 - Thrombin Generation Amidolytic Activity

Mathematical modelling of a part of the blood coagulation mechanism.

This model is described in the article:

Stortelder W.J.H., Hemker P.W., Hemker, H.C.
CWI. Modelling, Analysis and Simulation, No. R 9720, p.1-11.

Abstract:

This paper describes the mathematical modelling of a part of the blood coagulation mechanism. The model includes the activation of factor X by a purified enzyme from Russel's Viper Venom (RVV), factor V and prothrombin, and also comprises the inactivation of the products formed. In this study we assume that in principle the mechanism of the process is known. However, the exact structure of the mechanism is unknown, and the process still can be described by different mathematical models. These models are put to test by measuring their capacity to explain the course of thrombin generation as observed in plasma after recalcification in presence of RVV. The mechanism studied is mathematically modelled as a system of differential-algebraic equations (DAEs). Each candidate model contains some freedom, which is expressed in the model equations by the presence of unknown parameters. For example, reaction constants or initial concentrations are unknown. The goal of parameter estimation is to determine these unknown parameters in such a way that the theoretical (i.e., computed) results fit the experimental data within measurement accuracy and to judge which modifications of the chemical reaction scheme allow the best fit. We present results on model discrimination and estimation of reaction constants, which are hard to obtain in another way.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Format
SBML (L2V4)
Related Publication
  • Mathematical modelling in blood coagulation ; Simulation and parameter estimation
  • Stortelder W.J.H., Hemker P.W., Hemker H.C.
  • CWI. Modelling, Analysis and Simulation [MAS], No. R 9720, p.1-11 1997 , Other Link (URL): http://www.narcis.nl/publication/RecordID/oai:cwi.nl:4725
  • This paper describes the mathematical modelling of a part of the blood coagulation mechanism. The model includes the activation of factor X by a purified enzyme from Russel's Viper Venom (RVV), factor V and prothrombin, and also comprises the inactivation of the products formed. In this study we assume that in principle the mechanism of the process is known. However, the exact structure of the mechanism is unknown, and the process still can be described by different mathematical models. These models are put to test by measuring their capacity to explain the course of thrombin generation as observed in plasma after recalcification in presence of RVV. The mechanism studied is mathematically modelled as a system of differential-algebraic equations (DAEs). Each candidate model contains some freedom, which is expressed in the model equations by the presence of unknown parameters. For example, reaction constants or initial concentrations are unknown. The goal of parameter estimation is to determine these unknown parameters in such a way that the theoretical (i.e., computed) results fit the experimental data within measurement accuracy and to judge which modifications of the chemical reaction scheme allow the best fit. We present results on model discrimination and estimation of reaction constants, which are hard to obtain in another way.
Contributors
Submitter of the first revision: Michael Schubert
Submitter of this revision: Michael Schubert
Modellers: Michael Schubert

Metadata information

is (3 statements)
BioModels Database MODEL1108260009
BioModels Database BIOMD0000000358
Gene Ontology blood coagulation

hasTaxon (1 statement)
Taxonomy Eukaryota

isDescribedBy (2 statements)

Curation status
Curated

Connected external resources

Name Description Size Actions

Model files

BIOMD0000000358_url.xml SBML L2V4 representation of Stortelder1997 - Thrombin Generation Amidolytic Activity 21.26 KB Preview | Download

Additional files

BIOMD0000000358-biopax2.owl Auto-generated BioPAX (Level 2) 14.17 KB Preview | Download
BIOMD0000000358-biopax3.owl Auto-generated BioPAX (Level 3) 22.05 KB Preview | Download
BIOMD0000000358.m Auto-generated Octave file 6.24 KB Preview | Download
BIOMD0000000358.pdf Auto-generated PDF file 187.97 KB Preview | Download
BIOMD0000000358.png Auto-generated Reaction graph (PNG) 54.52 KB Preview | Download
BIOMD0000000358.sci Auto-generated Scilab file 3.56 KB Preview | Download
BIOMD0000000358.svg Auto-generated Reaction graph (SVG) 23.21 KB Preview | Download
BIOMD0000000358.vcml Auto-generated VCML file 32.81 KB Preview | Download
BIOMD0000000358.xpp Auto-generated XPP file 4.03 KB Preview | Download
BIOMD0000000358_urn.xml Auto-generated SBML file with URNs 20.95 KB Preview | Download

  • Model originally submitted by : Michael Schubert
  • Submitted: Aug 26, 2011 5:19:20 PM
  • Last Modified: Oct 9, 2014 6:03:20 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Oct 9, 2014 6:03:20 PM
    • Submitted by: Michael Schubert
    • With comment: Current version of Stortelder1997 - Thrombin Generation Amidolytic Activity
  • Version: 1 public model Download this version
    • Submitted on: Aug 26, 2011 5:19:20 PM
    • Submitted by: Michael Schubert
    • With comment: Original import of Stortelder1997_ThrombinGeneration_AmidolyticActivity

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
PT 0.0 nmol
Va

Coagulation factor V
0.0 nmol
IIa

Prothrombin
0.0 nmol
V

Coagulation factor V
6.711998 nmol
Xa

Coagulation factor X
0.0 nmol
X

Coagulation factor X
81.24998 nmol
Xa ATIII

Antithrombin-III ; Coagulation factor X
0.0 nmol
II

Prothrombin
509.2998 nmol
IIa alpha2M

Alpha-2-macroglobulin ; Prothrombin
0.0 nmol
Reactions
Reactions Rate Parameters
Va + Xa + PL => PT compartment_1*(k_PT*Va*Xa*PL-k_PL*PT) k_PL = 801.4; k_PT = 122.9
V => Va; IIa compartment_1*kcat_V*IIa*V/(km_V+V) km_V = 149.7; kcat_V = 7.844
II => IIa; PT compartment_1*kcat_II*PT*II/(km_II+II) km_II = 62.25; kcat_II = 43.87
X => Xa; RVV compartment_1*kcat_X*RVV*X/(km_X+X) kcat_X = 239.1; km_X = 23.65
Xa => Xa_ATIII compartment_1*ki_Xa*Xa ki_Xa = 4.531
IIa => IIa_ATIII compartment_1*ki_IIaATIII*IIa ki_IIaATIII = 0.7859
IIa => IIa_alpha2M compartment_1*ki_IIaAlpha2M*IIa ki_IIaAlpha2M = 0.1762
II => IIa; Xa compartment_1*kcat_2*Xa*II/(km_2+II) kcat_2 = 12.4; km_2 = 0.06148
Curator's comment:
(added: 26 Aug 2011, 17:23:37, updated: 26 Aug 2011, 17:23:37)
Reproduction of figure 5 of the article. Model integrated using PySCeS and plotted with Matplotlib.