Jones1994_BloodCoagulation

  public model
Model Identifier
BIOMD0000000336
Short description
Jones1994_BloodCoagulation
This model is built based on the experimental findings described in Lawson et al., 1994 (PMID:8083241)

This model is described in the article:

Jones KC, Mann KG.
J. Biol. Chem. 1994 Sep; 269(37): 23367-23373

Abstract:

A mathematical simulation of the tissue factor pathway to the generation of thrombin has been developed using a combination of empirical, estimated, and deduced rate constants for reactions involving the activation of factor IX, X, V, and VIII, in the formation of thrombin, as well as rate constants for the assembly of the coagulation enzyme complexes which involve factor VIIIa-factor IXa (intrinsic tenase) and factor Va-Xa (prothrombinase) assembled on phospholipid membrane. Differential equations describing the fate of each species in the reaction were developed and solved using an interactive procedure based upon the Runge-Kutta technique. In addition to the theoretical considerations involving the reactions of the tissue factor pathway, a physical constraint associated with the stability of the factor VIIIa-factor IXa complex has been incorporated into the model based upon the empirical observations associated with the stability of this complex. The model system provides a realistic accounting of the fates of each of the proteins in the coagulation reaction through a range of initiator (factor VIIa-tissue factor) concentrations ranging from 5 pM to 5 nM. The model is responsive to alterations in the concentrations of factor VIII, factor V, and their respective activated species, factor VIIIa and factor Va, and overall provides a reasonable approximation of empirical data. The computer model permits the assessment of the reaction over a broad range of conditions and provides a useful tool for the development and management of reaction studies.

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
  • A model for the tissue factor pathway to thrombin. II. A mathematical simulation.
  • Jones KC, Mann KG
  • The Journal of biological chemistry , 9/ 1994 , Volume 269 , pages: 23367-23373 , PubMed ID: 8083242
  • Department of Biochemistry, University of Vermont, College of Medicine, Burlington 05405-0068.
  • A mathematical simulation of the tissue factor pathway to the generation of thrombin has been developed using a combination of empirical, estimated, and deduced rate constants for reactions involving the activation of factor IX, X, V, and VIII, in the formation of thrombin, as well as rate constants for the assembly of the coagulation enzyme complexes which involve factor VIIIa-factor IXa (intrinsic tenase) and factor Va-Xa (prothrombinase) assembled on phospholipid membrane. Differential equations describing the fate of each species in the reaction were developed and solved using an interactive procedure based upon the Runge-Kutta technique. In addition to the theoretical considerations involving the reactions of the tissue factor pathway, a physical constraint associated with the stability of the factor VIIIa-factor IXa complex has been incorporated into the model based upon the empirical observations associated with the stability of this complex. The model system provides a realistic accounting of the fates of each of the proteins in the coagulation reaction through a range of initiator (factor VIIa-tissue factor) concentrations ranging from 5 pM to 5 nM. The model is responsive to alterations in the concentrations of factor VIII, factor V, and their respective activated species, factor VIIIa and factor Va, and overall provides a reasonable approximation of empirical data. The computer model permits the assessment of the reaction over a broad range of conditions and provides a useful tool for the development and management of reaction studies.
Contributors
Michael Schubert

Metadata information

is
BioModels Database MODEL1106060000
BioModels Database BIOMD0000000336
isDescribedBy
PubMed 8083242
hasTaxon
Taxonomy Homo sapiens
isVersionOf
Gene Ontology blood coagulation

Curation status
Curated

Tags

Connected external resources
Name Description Size Actions

Model files

BIOMD0000000336_url.xml SBML L2V4 representation of Jones1994_BloodCoagulation 38.32 KB Preview | Download

Additional files

BIOMD0000000336-biopax2.owl Auto-generated BioPAX (Level 2) 35.93 KB Preview | Download
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BIOMD0000000336_urn.xml Auto-generated SBML file with URNs 37.72 KB Preview | Download
BIOMD0000000336-biopax3.owl Auto-generated BioPAX (Level 3) 61.41 KB Preview | Download
BIOMD0000000336.m Auto-generated Octave file 8.98 KB Preview | Download
BIOMD0000000336.svg Auto-generated Reaction graph (SVG) 55.51 KB Preview | Download
BIOMD0000000336.xpp Auto-generated XPP file 6.52 KB Preview | Download
BIOMD0000000336.png Auto-generated Reaction graph (PNG) 222.86 KB Preview | Download
BIOMD0000000336.sci Auto-generated Scilab file 159.00 Bytes Preview | Download

  • Model originally submitted by : Michael Schubert
  • Submitted: Jun 6, 2011 5:56:03 PM
  • Last Modified: May 28, 2014 2:03:08 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: May 28, 2014 2:03:08 PM
    • Submitted by: Michael Schubert
    • With comment: Current version of Jones1994_BloodCoagulation
  • Version: 1 public model Download this version
    • Submitted on: Jun 6, 2011 5:56:03 PM
    • Submitted by: Michael Schubert
    • With comment: Original import of Jones1994

(*) 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
TF VIIa

Tissue factor
5.0E-9 mol
IXa

Coagulation factor IX
0.0 mol
X

Coagulation factor X
1.7E-7 mol
X TF VIIa

Tissue factor ; Coagulation factor X
0.0 mol
Xa

Coagulation factor X
0.0 mol
Reactions
Reactions Rate Parameters
X + TF_VIIa => X_TF_VIIa compartment_1*(k6*X*TF_VIIa-k17*X_TF_VIIa) k17 = 44.0; k6 = 1.0E8
X_TF_VIIa => TF_VIIa + Xa compartment_1*k12*X_TF_VIIa k12 = 1.15
IX_TF_VIIa => TF_VIIa + IXa compartment_1*k11*IX_TF_VIIa k11 = 0.3
IX + Xa => Xa + IXa compartment_1*k15*IX*Xa k15 = 100000.0
VIIIa + IXa => VIIIa_IXa compartment_1*(k7*VIIIa*IXa-k9*VIIIa_IXa) k7 = 1.0E7; k9 = 0.005
IX + Va_Xa => Va_Xa + IXa compartment_1*k15*IX*Va_Xa k15 = 100000.0
X + VIIIa_IXa => X_VIIIa_IXa compartment_1*(k6*X*VIIIa_IXa-k18*X_VIIIa_IXa) k18 = 0.001; k6 = 1.0E8
X_VIIIa_IXa => VIIIa_IXa + Xa compartment_1*k13*X_VIIIa_IXa k13 = 8.2
V + Xa => Xa + Va compartment_1*k1*V*Xa k1 = 2.0E7
VIII + Xa => Xa + VIIIa compartment_1*k3*VIII*Xa k3 = 1.0E7
Curator's comment:
(added: 06 Jun 2011, 18:03:39, updated: 06 Jun 2011, 18:03:39)
Thrombin generation model by Jones & Mann, 1994. Factors are denoted by their roman numberals. Initial concentration of Tissue Factor (TF) was varied from 5pM (as in model file) to values seen in the plot. Simulation using Copasi (LSODE) and rendering using Matplotlib to reproduce figure 4 of the article. Note: Va-Xa complex binding uses k6 as in the article ODEs. In the article rate constants table, it should use k8 but that does not reproduce the figure.