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BIOMD0000000436 - Gupta2009 - Eicosanoid Metabolism

 

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Reference Publication
Publication ID: 19486676
Gupta S, Maurya MR, Stephens DL, Dennis EA, Subramaniam S.
An integrated model of eicosanoid metabolism and signaling based on lipidomics flux analysis.
Biophys. J. 2009 Jun; 96(11): 4542-4551
Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.  [more]
Model
Original Model: BIOMD0000000436.origin
Submitter: Byrnes Robert
Submission ID: MODEL1204240001
Submission Date: 24 Apr 2012 23:56:54 UTC
Last Modification Date: 14 Dec 2012 14:13:40 UTC
Creation Date: 22 Jan 2010 22:59:01 UTC
Encoders:  Byrnes Robert
   Shakti Gupta
   Mano Ram Maurya
   Daren L. Stephens
   Edward A. Dennis
   Shankar Subramaniam
set #1
bqbiol:isVersionOf Gene Ontology icosanoid metabolic process
Pathway Ontology eicosanoids signaling pathway
set #2
bqbiol:occursIn Taxonomy Mammalia
Notes
Gupta2009 - Eicosanoid Metabolism

Integrated model of eicosanoid metabolism and signaling based on lipidomics flux analysis.

This model is described in the article:

Gupta S, Maurya MR, Stephens DL, Dennis EA, Subramaniam S.
Biophys. J. 2009 Jun; 96(11):4542-51.

Abstract:

There is increasing evidence for a major and critical involvement of lipids in signal transduction and cellular trafficking, and this has motivated large-scale studies on lipid pathways. The Lipid Metabolites and Pathways Strategy consortium is actively investigating lipid metabolism in mammalian cells and has made available time-course data on various lipids in response to treatment with KDO(2)-lipid A (a lipopolysaccharide analog) of macrophage RAW 264.7 cells. The lipids known as eicosanoids play an important role in inflammation. We have reconstructed an integrated network of eicosanoid metabolism and signaling based on the KEGG pathway database and the literature and have developed a kinetic model. A matrix-based approach was used to estimate the rate constants from experimental data and these were further refined using generalized constrained nonlinear optimization. The resulting model fits the experimental data well for all species, and simulated enzyme activities were similar to their literature values. The quantitative model for eicosanoid metabolism that we have developed can be used to design experimental studies utilizing genetic and pharmacological perturbations to probe fluxes in lipid pathways.

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: 19486676 Submission Date: 24 Apr 2012 23:56:54 UTC Last Modification Date: 14 Dec 2012 14:13:40 UTC Creation Date: 22 Jan 2010 22:59:01 UTC
Mathematical expressions
Reactions
r2 r3 r7 r5
r11 r10 r8 r4
r9 r13 r14 r15
r16 r17 r18 r19
r20 r21 r22 r1
r6 r12    
Rules
Assignment Rule (variable: timevalue) Assignment Rule (variable: LPSactivity) Assignment Rule (variable: DGactivity) Assignment Rule (variable: GPChoratio)
Events
       
       
Physical entities
Compartments Species
c1 FA HETE PGH2
PGE2 PGF2a PGD2
PGJ2 dPGJ2 Arachidonic acid
LPS DG GPCho
dPGD2    
Global parameters
k1 k2 k3 k4
k5 k6 k7 k8
k9 k10 k11 k12
k13 k14 k15 k16
k17 k18 k19 k20
k21 k22 DNA DGperDNA
onepmol t0 t1 t2
t3 t4 t5 t6
timevalue zero LPSactivity LPSslope
LPSint LPSslopezero LPSslope1 LPSslope3
LPSintzero LPSint1 LPSint3 DGactivity
DGint DGslope DGslopezero DGslope1
DGslope2 DGslope3 DGslope4 DGslope5
DGslope6 DGintzero DGint1 DGint2
DGint3 DGint4 DGint5 DGint6
GPChoratio GPChoint GPChoslope GPChoslopezero
GPChoslope1 GPChoslope2 GPChoslope3 GPChoslope4
GPChoslope5 GPChoslope6 GPChointzero GPChoint1
GPChoint2 GPChoint3 GPChoint4 GPChoint5
GPChoint6      
Reactions (22)
 
 r2 [FA] → [Arachidonic acid];  
 
 r3 [DG] → [Arachidonic acid];  
 
 r7 [GPCho] → [Arachidonic acid];  
 
 r5 [GPCho] → [Arachidonic acid];   {DG}
 
 r11 [Arachidonic acid] → [PGH2];   {LPS}
 
 r10 [Arachidonic acid] → [PGH2];   {DG}
 
 r8 [Arachidonic acid] → [HETE];  
 
 r4 [Arachidonic acid] → ;  
 
 r9 [HETE] → ;  
 
 r13 [PGH2] → [PGE2];  
 
 r14 [PGE2] → ;  
 
 r15 [PGH2] → [PGF2a];  
 
 r16 [PGF2a] → ;  
 
 r17 [PGH2] → [PGD2];  
 
 r18 [PGD2] → [PGJ2];  
 
 r19 [PGD2] → [dPGD2];  
 
 r20 [dPGD2] → ;  
 
 r21 [PGJ2] → [dPGJ2];  
 
 r22 [dPGJ2] → ;  
 
 r1 [FA] → [Arachidonic acid];   {LPS}
 
 r6 [GPCho] → [Arachidonic acid];   {LPS}
 
 r12 [Arachidonic acid] → [PGH2];  
 
Rules (4)
 
 Assignment Rule (name: timevalue) timevalue = t+t0
 
 Assignment Rule (name: LPSactivity) LPSactivity = activitycalc(timevalue, LPSslope, LPSint)
 
 Assignment Rule (name: DGactivity) DGactivity = activitycalc(timevalue, DGslope, DGint)
 
 Assignment Rule (name: GPChoratio) GPChoratio = activitycalc(timevalue, GPChoslope, GPChoint)/GPChointzero
 
Events (7)
 
  
LPSint = LPSintzero
LPSslope = LPSslopezero
DGint = DGintzero
DGslope = DGslopezero
GPChoint = GPChointzero
GPChoslope = GPChoslopezero
 
  
LPSint = LPSint1
LPSslope = LPSslope1
DGint = DGint1
DGslope = DGslope1
GPChoint = GPChoint1
GPChoslope = GPChoslope1
 
  
DGint = DGint2
DGslope = DGslope2
GPChoint = GPChoint2
GPChoslope = GPChoslope2
 
  
LPSint = LPSint3
LPSslope = LPSslope3
DGint = DGint3
DGslope = DGslope3
GPChoint = GPChoint3
GPChoslope = GPChoslope3
 
  
DGint = DGint4
DGslope = DGslope4
GPChoint = GPChoint4
GPChoslope = GPChoslope4
 
  
DGint = DGint5
DGslope = DGslope5
GPChoint = GPChoint5
GPChoslope = GPChoslope5
 
  
DGint = DGint6
DGslope = DGslope6
GPChoint = GPChoint6
GPChoslope = GPChoslope6
 
Functions (1)
 
 activitycalc lambda(x, slopea, yintercepta, yintercepta+x*slopea)
 
  Spatial dimensions: 3.0  Compartment size: 1.0  (Units: litre)
 
 FA
Compartment: c1
Initial amount: 1.0  (Units: pmol)
Constant
 
 HETE
Compartment: c1
Initial amount: 0.0  (Units: pmol)
 
 PGH2
Compartment: c1
Initial amount: 0.0  (Units: pmol)
 
 PGE2
Compartment: c1
Initial amount: 0.0  (Units: pmol)
 
 PGF2a
Compartment: c1
Initial amount: 0.0  (Units: pmol)
 
 PGD2
Compartment: c1
Initial amount: 0.0
 
 PGJ2
Compartment: c1
Initial amount: 0.0  (Units: pmol)
 
 dPGJ2
Compartment: c1
Initial amount: 0.0  (Units: pmol)
 
 Arachidonic acid
Compartment: c1
Initial amount: 25.0  (Units: pmol)
 
 LPS
Compartment: c1
Initial amount: 0.5  (Units: dimensionless)
 
 DG
Compartment: c1
Initial amount: 0.0  (Units: dimensionless)
 
 GPCho
Compartment: c1
Initial amount: 1.0  (Units: pmol)
 
 dPGD2
Compartment: c1
Initial amount: 0.0  (Units: pmol)
 
Global Parameters (77)
 
 k1
Value: 355.637   (Units: perh)
Constant
 
 k2
Value: 1.0E-15   (Units: perh)
Constant
 
 k3
Value: 1.0E-15   (Units: perh)
Constant
 
 k4
Value: 1.0E-15   (Units: perh)
Constant
 
 k5
Value: 1.0E-15   (Units: ugDNAperh)
Constant
 
 k6
Value: 0.33   (Units: perh)
Constant
 
 k7
Value: 1.0E-15   (Units: perh)
Constant
 
 k8
Value: 0.0070   (Units: perh)
Constant
 
 k9
Value: 0.187   (Units: perh)
Constant
 
 k10
Value: 0.024   (Units: ugDNAperh)
Constant
 
 k11
Value: 0.111   (Units: perh)
Constant
 
 k12
Value: 0.098   (Units: perh)
Constant
 
 k13
Value: 0.204   (Units: perh)
Constant
 
 k14
Value: 1.0E-15   (Units: perh)
Constant
 
 k15
Value: 0.061   (Units: perh)
Constant
 
 k16
Value: 1.0E-15   (Units: perh)
Constant
 
 k17
Value: 3.116   (Units: perh)
Constant
 
 k18
Value: 0.054   (Units: perh)
Constant
 
 k19
Value: 0.029   (Units: perh)
Constant
 
 k20
Value: 0.014   (Units: perh)
Constant
 
 k21
Value: 0.034   (Units: perh)
Constant
 
 k22
Value: 0.116   (Units: perh)
Constant
 
 DNA
Value: 1.0   (Units: ug)
Constant
 
 DGperDNA
Value: 1.0   (Units: pmolperugDNA)
 
   onepmol
Value: 1.0   (Units: pmol)
Constant
 
   t0
Constant
 
   t1
Value: 0.5   (Units: time)
Constant
 
   t2
Value: 1.0   (Units: time)
Constant
 
   t3
Value: 2.0   (Units: time)
Constant
 
   t4
Value: 4.0   (Units: time)
Constant
 
   t5
Value: 8.0   (Units: time)
Constant
 
   t6
Value: 12.0   (Units: time)
Constant
 
   timevalue  
 
   zero
Constant
 
   LPSactivity  
 
   LPSslope  
 
   LPSint  
 
   LPSslopezero
Value: 2.0   (Units: perh)
Constant
 
   LPSslope1
Value: -0.6667   (Units: perh)
Constant
 
   LPSslope3
Constant
 
   LPSintzero
Constant
 
   LPSint1
Value: 1.3335   (Units: dimensionless)
Constant
 
   LPSint3
Constant
 
   DGactivity
Value: 1.0   (Units: dimensionless)
 
   DGint
Value: 1.0   (Units: dimensionless)
 
   DGslope
Value: 1.0   (Units: perh)
 
   DGslopezero
Value: 0.3014   (Units: perh)
Constant
 
   DGslope1
Value: -0.1572   (Units: perh)
Constant
 
   DGslope2
Value: 0.0439   (Units: perh)
Constant
 
   DGslope3
Value: -0.0913   (Units: perh)
Constant
 
   DGslope4
Value: 0.0976   (Units: perh)
Constant
 
   DGslope5
Value: 0.0711   (Units: perh)
Constant
 
   DGslope6
Value: 0.0846   (Units: perh)
Constant
 
   DGintzero
Value: 1.0   (Units: dimensionless)
Constant
 
   DGint1
Value: 1.2292   (Units: dimensionless)
Constant
 
   DGint2
Value: 1.0282   (Units: dimensionless)
Constant
 
   DGint3
Value: 1.2987   (Units: dimensionless)
Constant
 
   DGint4
Value: 0.543   (Units: dimensionless)
Constant
 
   DGint5
Value: 0.7549   (Units: dimensionless)
Constant
 
   DGint6
Value: 0.5927   (Units: dimensionless)
Constant
 
   GPChoratio
Value: 1.0   (Units: dimensionless)
 
   GPChoint
Value: 315.3137   (Units: pmol)
 
   GPChoslope
Value: -158.43   (Units: pmolperh)
 
   GPChoslopezero
Value: -158.43   (Units: pmolperh)
Constant
 
   GPChoslope1
Value: 112.28   (Units: pmolperh)
Constant
 
   GPChoslope2
Value: 24.31   (Units: pmolperh)
Constant
 
   GPChoslope3
Value: -39.93   (Units: pmolperh)
Constant
 
   GPChoslope4
Value: 5.48   (Units: pmolperh)
Constant
 
   GPChoslope5
Value: 27.08   (Units: pmolperh)
Constant
 
   GPChoslope6
Value: -4.874   (Units: pmolperh)
Constant
 
   GPChointzero
Value: 315.3137   (Units: pmol)
Constant
 
   GPChoint1
Value: 179.96   (Units: pmol)
Constant
 
   GPChoint2
Value: 267.93   (Units: pmol)
Constant
 
   GPChoint3
Value: 396.41   (Units: pmol)
Constant
 
   GPChoint4
Value: 214.77   (Units: pmol)
Constant
 
   GPChoint5
Value: 41.93   (Units: pmol)
Constant
 
   GPChoint6
Value: 425.43   (Units: pmol)
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000436

Curator's comment: (updated: 12 Sep 2012 14:55:06 BST)

The model reproduces figure 2 (predicted response of treatment with KDO2-lipid A) of the reference publication. The simulation data were obtained by using Copasi v4.8 (Build 35) and plotted using Gnuplot.

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