Butenas2004_BloodCoagulation

  public model
Model Identifier
BIOMD0000000362
Short description

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
For more information see the terms of use.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Format
SBML (L2V4)
Related Publication
  • The significance of circulating factor IXa in blood.
  • Butenas S, Orfeo T, Gissel MT, Brummel KE, Mann KG
  • The Journal of biological chemistry , 5/ 2004 , Volume 279 , pages: 22875-22882 , PubMed ID: 15039440
  • Department of Biochemistry, University of Vermont, Burlington, Vermont 05405-0068, USA.
  • The presence of activation peptides (AP) of the vitamin K-dependent proteins in the phlebotomy blood of human subjects suggests that active serine proteases may circulate in blood as well. The goal of the current study was to evaluate the influence of trace amounts of key coagulation proteases on tissue factor-independent thrombin generation using three models of coagulation. With procoagulants and select coagulation inhibitors at mean physiological concentrations, concentrations of factor IXa, factor Xa, and thrombin were set either equal to those of their AP or to values that would result based upon the rates of AP/enzyme generation and steady state enzyme inhibition. In the latter case, numerical simulation predicts that sufficient thrombin to produce a solid clot would be generated in approximately 2 min. Empirical data from the synthetic plasma suggest clotting times of 3-5 min, which are similar to that observed in contact pathway-inhibited whole blood (4.3 min) initiated with the same concentrations of factors IXa and Xa and thrombin. Numerical simulations performed with the concentrations of two of the enzymes held constant and one varied suggest that the presence of any pair of enzymes is sufficient to yield rapid clot formation. Modeling of states (numerical simulation and whole blood) where only one circulating protease is present at steady state concentration shows significant thrombin generation only for factor IXa. The addition of factor Xa and thrombin has little effect (if any) on thrombin generation induced by factor IXa alone. These data indicate that 1) concentrations of active coagulation enzymes circulating in vivo are significantly lower than can be predicted from the concentrations of their AP, and 2) expected trace amounts of factor IXa can trigger thrombin generation in the absence of tissue factor.
Contributors
Submitter of the first revision: Michael Schubert
Submitter of this revision: Michael Schubert
Modellers: Michael Schubert

Metadata information

is (2 statements)
BioModels Database MODEL1108260005
BioModels Database BIOMD0000000362

isDescribedBy (1 statement)
PubMed 15039440

isDerivedFrom (2 statements)
PubMed 8083241
PubMed 9020158

hasTaxon (1 statement)
Taxonomy Eukaryota

isVersionOf (1 statement)
Gene Ontology blood coagulation

Curation status
Curated
Tags

Connected external resources

SBGN view in Newt Editor

Name Description Size Actions

Model files
BIOMD0000000362_url.xml SBML L2V4 representation of Butenas2004_BloodCoagulation 61.63 KB Preview | Download

Additional files
BIOMD0000000362-biopax2.owl Auto-generated BioPAX (Level 2) 58.45 KB Preview | Download
BIOMD0000000362-biopax3.owl Auto-generated BioPAX (Level 3) 101.41 KB Preview | Download
BIOMD0000000362.m Auto-generated Octave file 15.14 KB Preview | Download
BIOMD0000000362.pdf Auto-generated PDF file 308.77 KB Preview | Download
BIOMD0000000362.png Auto-generated Reaction graph (PNG) 430.99 KB Preview | Download
BIOMD0000000362.sci Auto-generated Scilab file 13.44 KB Preview | Download
BIOMD0000000362.svg Auto-generated Reaction graph (SVG) 93.13 KB Preview | Download
BIOMD0000000362.vcml Auto-generated VCML file 87.96 KB Preview | Download
BIOMD0000000362.xpp Auto-generated XPP file 11.07 KB Preview | Download
BIOMD0000000362_urn.xml Auto-generated SBML file with URNs 60.43 KB Preview | Download

  • Model originally submitted by : Michael Schubert
  • Submitted: Aug 26, 2011 5:15:02 PM
  • Last Modified: Oct 9, 2014 6:08:33 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Oct 9, 2014 6:08:33 PM
    • Submitted by: Michael Schubert
    • With comment: Current version of Butenas2004_BloodCoagulation
  • Version: 1 public model Download this version
    • Submitted on: Aug 26, 2011 5:15:02 PM
    • Submitted by: Michael Schubert
    • With comment: Original import of Butenas2004_BloodCoagulation

(*) 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

Coagulation factor VII ; Tissue factor 		0.0 mol
TF VIIa Xa

Coagulation factor X ; Coagulation factor VII ; Tissue factor 		0.0 mol
TF VIIa IX

Coagulation factor IX ; Coagulation factor VII ; Tissue factor 		0.0 mol
Va

Coagulation factor V 		0.0 mol
mIIa

Prothrombin 		0.0 mol
VII

Coagulation factor VII 		1.0E-8 mol
VIIa

Coagulation factor VII 		1.0E-10 mol
Reactions
Reactions Rate Parameters
TF_VIIa + Xa => TF_VIIa_Xa compartment_1*(k12*TF_VIIa*Xa-k11*TF_VIIa_Xa) k12 = 2.2E7; k11 = 19.0
TF_VIIa + ATIII => TF_VIIa_ATIII compartment_1*k42*TF_VIIa*ATIII k42 = 230.0
TF_VIIa_X => TF_VIIa_Xa compartment_1*k10*TF_VIIa_X k10 = 6.0
TF_VIIa_IX => TF_VIIa + IXa compartment_1*k15*TF_VIIa_IX k15 = 1.8
mIIa + V => mIIa + Va compartment_1*k44*mIIa*V k44 = 3000000.0
mIIa + ATIII => mIIa_ATIII compartment_1*k39*mIIa*ATIII k39 = 7100.0
TF + VII => TF_VII compartment_1*(k2*TF*VII-k1*TF_VII) k2 = 3200000.0; k1 = 0.0031
Xa + VII => Xa + VIIa compartment_1*k6*Xa*VII k6 = 1.3E7
TF + VIIa => TF_VIIa compartment_1*(k4*TF*VIIa-k3*TF_VIIa) k4 = 2.3E7; k3 = 0.0031
TF_VIIa_Xa + TFPI => TF_VIIa_Xa_TFPI compartment_1*(k36*TF_VIIa_Xa*TFPI-k35*TF_VIIa_Xa_TFPI) k35 = 1.1E-4; k36 = 3.2E8
Curator's comment:
(added: 26 Aug 2011, 17:26:19, updated: 26 Aug 2011, 17:26:19)
Reproduction of figure 1 of the article. Model integrated using PySCeS and plotted with Matplotlib.