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BIOMD0000000335 - Hockin2002_BloodCoagulation

 

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Reference Publication
Publication ID: 11893748
Hockin MF, Jones KC, Everse SJ, Mann KG.
A model for the stoichiometric regulation of blood coagulation.
J. Biol. Chem. 2002 May; 277(21): 18322-18333
Department of Biochemistry, College of Medicine, University of Vermont, Burlington, Vermont 05405, USA.  [more]
Model
Original Model: BIOMD0000000335.origin
Submitter: Michael Schubert
Submission ID: MODEL1106010000
Submission Date: 01 Jun 2011 14:29:34 UTC
Last Modification Date: 28 May 2014 13:55:22 UTC
Creation Date: 01 Jun 2011 14:22:14 UTC
Encoders:  Vijayalakshmi Chelliah
   Michael Schubert
set #1
bqmodel:isDerivedFrom BioModels Database Jones1994_BloodCoagulation
set #2
bqbiol:hasTaxon Taxonomy Homo sapiens
set #3
bqbiol:occursIn Brenda Tissue Ontology blood plasma
set #4
bqbiol:isVersionOf Gene Ontology blood coagulation
Notes

This model is from the article:
A model for the stoichiometric regulation of blood coagulation.
Hockin MF, Jones KC, Everse SJ, Mann KG. Journal of Biological ChemistryVolume 277, Issue 21, 24 May 2002, Pages 18322 -18333 11893748,
Abstract:
We have developed a model of the extrinsic blood coagulation system that includes the stoichiometric anticoagulants. The model accounts for the formation, expression, and propagation of the vitamin K-dependent procoagulant complexes and extends our previous model by including: (a) the tissue factor pathway inhibitor (TFPI)-mediated inactivation of tissue factor (TF).VIIa and its product complexes; (b) the antithrombin-III (AT-III)-mediated inactivation of IIa, mIIa, factor VIIa, factor IXa, and factor Xa; (c) the initial activation of factor V and factor VIII by thrombin generated by factor Xa-membrane; (d) factor VIIIa dissociation/activity loss; (e) the binding competition and kinetic activation steps that exist between TF and factors VII and VIIa; and (f) the activation of factor VII by IIa, factor Xa, and factor IXa. These additions to our earlier model generate a model consisting of 34 differential equations with 42 rate constants that together describe the 27 independent equilibrium expressions, which describe the fates of 34 species. Simulations are initiated by "exposing" picomolar concentrations of TF to an electronic milieu consisting of factors II, IX, X, VII, VIIa, V, and VIIII, and the anticoagulants TFPI and AT-III at concentrations found in normal plasma or associated with coagulation pathology. The reaction followed in terms of thrombin generation, proceeds through phases that can be operationally defined as initiation, propagation, and termination. The generation of thrombin displays a nonlinear dependence upon TF, AT-III, and TFPI and the combination of these latter inhibitors displays kinetic thresholds. At subthreshold TF, thrombin production/expression is suppressed by the combination of TFPI and AT-III; for concentrations above the TF threshold, the bolus of thrombin produced is quantitatively equivalent. A comparison of the model with empirical laboratory data illustrates that most experimentally observable parameters are captured, and the pathology that results in enhanced or deficient thrombin generation is accurately described.

Model
Publication ID: 11893748 Submission Date: 01 Jun 2011 14:29:34 UTC Last Modification Date: 28 May 2014 13:55:22 UTC Creation Date: 01 Jun 2011 14:22:14 UTC
Mathematical expressions
Reactions
R1 R2 R3 R4
R5 R6 R7 R8
R9 R10 R11 R12
R13 R14 R15 R16
R17 R18 R19 R20
R21 R22 R23 R24
R25 R26 R27 R6b
R8b R12b R18b  
Rules
Assignment Rule (variable: IIa+1.2mIIa)      
Physical entities
Compartments Species
compartment_1 TF TF_VII VII
TF_VIIa VIIa Xa
IIa TF_VIIa_X X
TF_VIIa_Xa IX TF_VIIa_IX
IXa II VIII
VIIIa IXa_VIIIa IXa_VIIIa_X
VIIIa1_L VIIIa2 V
Va Xa_Va Xa_Va_II
mIIa TFPI Xa_TFPI
TF_VIIa_Xa_TFPI ATIII Xa_ATIII
mIIa_ATIII IXa_ATIII IIa_ATIII
TF_VIIa_ATIII    
Global parameters
k1 k2 k3 k4
k5 k6 k7 k8
k9 k10 k11 k12
k13 k14 k15 k16
k17 k18 k19 k20
k21 k22 k23 k24
k25 k26 k27 k28
k29 k30 k31 k32
k33 k34 k35 k36
k37 k38 k39 k40
k41 k42 IIa+1.2mIIa  
Reactions (31)
 
 R1 [TF] + [VII] ↔ [TF_VII];  
 
 R2 [TF] + [VIIa] ↔ [TF_VIIa];  
 
 R3 [TF_VIIa] + [VII] → [TF_VIIa] + [VIIa];  
 
 R4 [Xa] + [VII] → [Xa] + [VIIa];  
 
 R5 [IIa] + [VII] → [IIa] + [VIIa];  
 
 R6 [TF_VIIa] + [X] ↔ [TF_VIIa_X];  
 
 R7 [TF_VIIa] + [Xa] ↔ [TF_VIIa_Xa];  
 
 R8 [TF_VIIa] + [IX] ↔ [TF_VIIa_IX];  
 
 R9 [Xa] + [II] → [Xa] + [IIa];  
 
 R10 [IIa] + [VIII] → [IIa] + [VIIIa];  
 
 R11 [IXa] + [VIIIa] ↔ [IXa_VIIIa];  
 
 R12 [IXa_VIIIa] + [X] ↔ [IXa_VIIIa_X];  
 
 R13 [VIIIa] ↔ [VIIIa1_L] + [VIIIa2];  
 
 R14 [IXa_VIIIa_X] → [VIIIa1_L] + [VIIIa2] + [X] + [IXa];  
 
 R15 [IXa_VIIIa] → [VIIIa1_L] + [VIIIa2] + [IXa];  
 
 R16 [IIa] + [V] → [IIa] + [Va];  
 
 R17 [Xa] + [Va] ↔ [Xa_Va];  
 
 R18 [Xa_Va] + [II] ↔ [Xa_Va_II];  
 
 R19 [mIIa] + [Xa_Va] → [IIa] + [Xa_Va];  
 
 R20 [Xa] + [TFPI] ↔ [Xa_TFPI];  
 
 R21 [TF_VIIa_Xa] + [TFPI] ↔ [TF_VIIa_Xa_TFPI];  
 
 R22 [TF_VIIa] + [Xa_TFPI] → [TF_VIIa_Xa_TFPI];  
 
 R23 [Xa] + [ATIII] → [Xa_ATIII];  
 
 R24 [mIIa] + [ATIII] → [mIIa_ATIII];  
 
 R25 [IXa] + [ATIII] → [IXa_ATIII];  
 
 R26 [IIa] + [ATIII] → [IIa_ATIII];  
 
 R27 [TF_VIIa] + [ATIII] → [TF_VIIa_ATIII];  
 
 R6b [TF_VIIa_X] → [TF_VIIa_Xa];  
 
 R8b [TF_VIIa_IX] → [TF_VIIa] + [IXa];  
 
 R12b [IXa_VIIIa_X] → [IXa_VIIIa] + [Xa];  
 
 R18b [Xa_Va_II] → [Xa_Va] + [mIIa];  
 
Rules (1)
 
 Assignment Rule (name: IIa_plus_1_2mIIa) IIa+1.2mIIa = IIa+1.2*mIIa
 
   compartment_1 Spatial dimensions: 3.0  Compartment size: 1.0
 
 TF
Compartment: compartment_1
Initial concentration: 2.5E-11
 
 TF_VII
Compartment: compartment_1
Initial concentration: 0.0
 
 VII
Compartment: compartment_1
Initial concentration: 1.0E-8
 
 TF_VIIa
Compartment: compartment_1
Initial concentration: 0.0
 
 VIIa
Compartment: compartment_1
Initial concentration: 1.0E-10
 
 Xa
Compartment: compartment_1
Initial concentration: 0.0
 
 IIa
Compartment: compartment_1
Initial concentration: 0.0
 
 TF_VIIa_X
Compartment: compartment_1
Initial concentration: 0.0
 
 X
Compartment: compartment_1
Initial concentration: 1.6E-7
 
 TF_VIIa_Xa
Compartment: compartment_1
Initial concentration: 0.0
 
 IX
Compartment: compartment_1
Initial concentration: 9.0E-8
 
 TF_VIIa_IX
Compartment: compartment_1
Initial concentration: 0.0
 
 IXa
Compartment: compartment_1
Initial concentration: 0.0
 
 II
Compartment: compartment_1
Initial concentration: 1.4E-6
 
 VIII
Compartment: compartment_1
Initial concentration: 7.0E-10
 
 VIIIa
Compartment: compartment_1
Initial concentration: 0.0
 
 IXa_VIIIa
Compartment: compartment_1
Initial concentration: 0.0
 
 IXa_VIIIa_X
Compartment: compartment_1
Initial concentration: 0.0
 
 VIIIa1_L
Compartment: compartment_1
Initial concentration: 0.0
 
 VIIIa2
Compartment: compartment_1
Initial concentration: 0.0
 
 V
Compartment: compartment_1
Initial concentration: 2.0E-8
 
 Va
Compartment: compartment_1
Initial concentration: 0.0
 
 Xa_Va
Compartment: compartment_1
Initial concentration: 0.0
 
 Xa_Va_II
Compartment: compartment_1
Initial concentration: 0.0
 
 mIIa
Compartment: compartment_1
Initial concentration: 0.0
 
 TFPI
Compartment: compartment_1
Initial concentration: 2.5E-9
 
 Xa_TFPI
Compartment: compartment_1
Initial concentration: 0.0
 
 TF_VIIa_Xa_TFPI
Compartment: compartment_1
Initial concentration: 0.0
 
 ATIII
Compartment: compartment_1
Initial concentration: 3.4E-6
 
 Xa_ATIII
Compartment: compartment_1
Initial concentration: 0.0
 
 mIIa_ATIII
Compartment: compartment_1
Initial concentration: 0.0
 
 IXa_ATIII
Compartment: compartment_1
Initial concentration: 0.0
 
 IIa_ATIII
Compartment: compartment_1
Initial concentration: 0.0
 
 TF_VIIa_ATIII
Compartment: compartment_1
Initial concentration: 0.0
 
Global Parameters (43)
 
 k1
Value: 0.0031
Constant
 
 k2
Value: 3200000.0
Constant
 
 k3
Value: 0.0031
Constant
 
 k4
Value: 2.3E7
Constant
 
 k5
Value: 440000.0
Constant
 
 k6
Value: 1.3E7
Constant
 
 k7
Value: 23000.0
Constant
 
 k8
Value: 1.05
Constant
 
 k9
Value: 2.5E7
Constant
 
 k10
Value: 6.0
Constant
 
 k11
Value: 19.0
Constant
 
 k12
Value: 2.2E7
Constant
 
 k13
Value: 2.4
Constant
 
 k14
Value: 1.0E7
Constant
 
 k15
Value: 1.8
Constant
 
 k16
Value: 7500.0
Constant
 
 k17
Value: 2.0E7
Constant
 
 k18
Value: 0.0050
Constant
 
 k19
Value: 1.0E7
Constant
 
 k20
Value: 0.0010
Constant
 
 k21
Value: 1.0E8
Constant
 
 k22
Value: 8.2
Constant
 
 k23
Value: 22000.0
Constant
 
 k24
Value: 0.0060
Constant
 
 k25
Value: 0.0010
Constant
 
 k26
Value: 2.0E7
Constant
 
 k27
Value: 0.2
Constant
 
 k28
Value: 4.0E8
Constant
 
 k29
Value: 103.0
Constant
 
 k30
Value: 1.0E8
Constant
 
 k31
Value: 63.5
Constant
 
 k32
Value: 1.5E7
Constant
 
 k33
Value: 3.6E-4
Constant
 
 k34
Value: 900000.0
Constant
 
 k35
Value: 1.1E-4
Constant
 
 k36
Value: 3.2E8
Constant
 
 k37
Value: 5.0E7
Constant
 
 k38
Value: 1500.0
Constant
 
 k39
Value: 7100.0
Constant
 
 k40
Value: 490.0
Constant
 
 k41
Value: 7100.0
Constant
 
 k42
Value: 230.0
Constant
 
   IIa+1.2mIIa  
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000335

Curator's comment: (updated: 01 Jun 2011 15:34:56 BST)

Thrombin generation model by Hockin et al, 2002. Factors are denoted by their roman numberals. Initial concentration of Tissue Factor (TF) was varied from 25pM (in model file) to values seen in the plot.

Simulation using Copasi (LSODE) and rendering using Matplotlib.

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