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BIOMD0000000336 - Jones1994_BloodCoagulation

 

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Reference Publication
Publication ID: 8083242
Jones KC, Mann KG.
A model for the tissue factor pathway to thrombin. II. A mathematical simulation.
J. Biol. Chem. 1994 Sep; 269(37): 23367-23373
Department of Biochemistry, University of Vermont, College of Medicine, Burlington 05405-0068.  [more]
Model
Original Model: BIOMD0000000336.origin
Submitter: Michael Schubert
Submission ID: MODEL1106060000
Submission Date: 06 Jun 2011 16:56:03 UTC
Last Modification Date: 28 May 2014 13:03:08 UTC
Creation Date: 06 Jun 2011 17:21:19 UTC
Encoders:  Vijayalakshmi Chelliah
   Michael Schubert
set #1
bqbiol:hasTaxon Taxonomy Homo sapiens
set #2
bqbiol:isVersionOf Gene Ontology blood coagulation
Notes
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.

Model
Publication ID: 8083242 Submission Date: 06 Jun 2011 16:56:03 UTC Last Modification Date: 28 May 2014 13:03:08 UTC Creation Date: 06 Jun 2011 17:21:19 UTC
Mathematical expressions
Reactions
R1 R1b R2 R2b
R3 R3b R4 R5
R6 R7 R8 R9
R9b R10 R11 R12
R7_atn R8_atn R4_atn VIIIa_IXa_degradation
Rules
Assignment Rule (variable: IIa+1.2mIIa) Rate Rule (variable: I)    
Physical entities
Compartments Species
compartment_1 IX IX_TF_VIIa TF_VIIa
IXa X X_TF_VIIa
Xa VIIIa_IXa X_VIIIa_IXa
V Va VIII
VIIIa IIa II
II_Va_Xa Va_Xa mIIa
Global parameters
k1 k2 k3 k4
k5 k6 k7 k8
k9 k10 k11 k12
k13 k14 k15 k16
k17 k18 k19 k20
I IIa+1.2mIIa    
Reactions (20)
 
 R1 [IX] + [TF_VIIa] ↔ [IX_TF_VIIa];  
 
 R1b [IX_TF_VIIa] → [TF_VIIa] + [IXa];  
 
 R2 [X] + [TF_VIIa] ↔ [X_TF_VIIa];  
 
 R2b [X_TF_VIIa] → [TF_VIIa] + [Xa];  
 
 R3 [X] + [VIIIa_IXa] ↔ [X_VIIIa_IXa];  
 
 R3b [X_VIIIa_IXa] → [VIIIa_IXa] + [Xa];  
 
 R4 [IX] + [Xa] → [Xa] + [IXa];  
 
 R5 [V] + [Xa] → [Xa] + [Va];  
 
 R6 [VIII] + [Xa] → [Xa] + [VIIIa];  
 
 R7 [V] + [IIa] → [IIa] + [Va];  
 
 R8 [VIII] + [IIa] → [IIa] + [VIIIa];  
 
 R9 [II] + [Va_Xa] ↔ [II_Va_Xa];  
 
 R9b [II_Va_Xa] → [Va_Xa] + [mIIa];  
 
 R10 [mIIa] + [Va_Xa] → [Va_Xa] + [IIa];  
 
 R11 [VIIIa] + [IXa] ↔ [VIIIa_IXa];  
 
 R12 [Va] + [Xa] ↔ [Va_Xa];  
 
 R7_atn [V] + [mIIa] → [mIIa] + [Va];  
 
 R8_atn [VIII] + [mIIa] → [mIIa] + [VIIIa];  
 
 R4_atn [IX] + [Va_Xa] → [Va_Xa] + [IXa];  
 
 VIIIa_IXa_degradation [VIIIa_IXa] → ;   {VIIIa_IXa}
 
Rules (2)
 
 Assignment Rule (name: IIa_plus_1_2mIIa) IIa+1.2mIIa = IIa+1.2*mIIa
 
 Rate Rule (name: I) d [ I] / d t= ((-abs(I-VIIIa_IXa))+(I-VIIIa_IXa))*k20
 
Functions (1)
 
 function_4_VIIIa_IXa_degradation_2 lambda(I, VIIIa_IXa, compartment_1, (compartment_1*abs(I-VIIIa_IXa)+(I-VIIIa_IXa))/compartment_1)
 
   compartment_1 Spatial dimensions: 3.0  Compartment size: 1.0
 
 IX
Compartment: compartment_1
Initial concentration: 9.0E-8
 
 IX_TF_VIIa
Compartment: compartment_1
Initial concentration: 0.0
 
 TF_VIIa
Compartment: compartment_1
Initial concentration: 5.0E-9
 
 IXa
Compartment: compartment_1
Initial concentration: 0.0
 
 X
Compartment: compartment_1
Initial concentration: 1.7E-7
 
 X_TF_VIIa
Compartment: compartment_1
Initial concentration: 0.0
 
 Xa
Compartment: compartment_1
Initial concentration: 0.0
 
 VIIIa_IXa
Compartment: compartment_1
Initial concentration: 0.0
 
 X_VIIIa_IXa
Compartment: compartment_1
Initial concentration: 0.0
 
 V
Compartment: compartment_1
Initial concentration: 2.0E-8
 
 Va
Compartment: compartment_1
Initial concentration: 0.0
 
 VIII
Compartment: compartment_1
Initial concentration: 7.0E-10
 
 VIIIa
Compartment: compartment_1
Initial concentration: 0.0
 
 IIa
Compartment: compartment_1
Initial concentration: 0.0
 
 II
Compartment: compartment_1
Initial concentration: 1.4E-6
 
 II_Va_Xa
Compartment: compartment_1
Initial concentration: 0.0
 
 Va_Xa
Compartment: compartment_1
Initial concentration: 0.0
 
 mIIa
Compartment: compartment_1
Initial concentration: 0.0
 
Global Parameters (22)
 
 k1
Value: 2.0E7
Constant
 
 k2
Value: 2.0E7
Constant
 
 k3
Value: 1.0E7
Constant
 
 k4
Value: 2.0E7
Constant
 
 k5
Value: 1.0E7
Constant
 
 k6
Value: 1.0E8
Constant
 
 k7
Value: 1.0E7
Constant
 
   k8
Value: 4.0E8
Constant
 
 k9
Value: 0.005
Constant
 
 k10
Value: 0.4
Constant
 
 k11
Value: 0.3
Constant
 
 k12
Value: 1.15
Constant
 
 k13
Value: 8.2
Constant
 
 k14
Value: 32.0
Constant
 
 k15
Value: 100000.0
Constant
 
 k16
Value: 24.0
Constant
 
 k17
Value: 44.0
Constant
 
 k18
Value: 0.001
Constant
 
 k19
Value: 70.0
Constant
 
   k20
Value: 0.02
Constant
 
   I  
 
   IIa+1.2mIIa  
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000336

Curator's comment: (updated: 06 Jun 2011 18:03:39 BST)

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.

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