MODEL0568648427
type: SBMLModel
reaction: 526975
reaction: 527035
reaction: 527000
reaction: 526972
reaction: 527032
reaction: 526978
compartment: 526852
species: 526916
reaction: 527029
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Lukas
    family: Endler
reaction: 526959
species: 526888
species: 526898
species: 526886
reaction: 526981
species: 526892
is described by: http://identifiers.org/pubmed/19025648
reaction: 527044
reaction: 527038
reaction: 527004
substance units: 469466
species: 526908
species: 526918
reaction: 527023
species: 526912
reaction: 527041
reaction: 526988
species: 526868
species: 526878
species: 526884
species: 526894
curated: false
species: 526882
compartment: 526850
reaction: 526991
length unit: 222721
reaction: 526947
reaction: 527010
species: 526904
species: 526914
reaction: 527007
species: 526920
species: 526876
reaction: 526969
species: 526864
species: 526874
species: 526880
species: 526890
reaction: 527019
compartment: 526854
reaction: 526997
reaction: 526962
reaction: 527016
reaction: 526994
species: 526906
reaction: 526966
species: 526900
species: 526910
species: 526856
species: 526866
reaction: 526984
species: 526872
species: 526860
species: 526870
time units: 469490
reaction: 527013
name: Kervizic2008_Cholesterol_SREBP
notes: Model of cholesterol regulation (with Boolean Formulae) (2008) This model is described in Dynamical modeling of the cholesterol regulatory pathway with Boolean networks ; Gwenael Kervizic and Laurent Corcos, BMC Systems Biology 2008, 2:99 doi: 10.1186/1752-0509-2-99 Abstract: Background: Qualitative dynamics of small gene regulatory networks have been studied in quite some details both with synchronous and asynchronous analysis. However, both methods have their drawbacks: synchronous analysis leads to spurious attractors and asynchronous analysis lacks computational efficiency, which is a problem to simulate large networks. We addressed this question through the analysis of a major biosynthesis pathway. Indeed the cholesterol synthesis pathway plays a pivotal role in dislypidemia and, ultimately, in cancer through intermediates such as mevalonate, farnesyl pyrophosphate and geranyl geranyl pyrophosphate, but no dynamic model of this pathway has been proposed until now. Results: We set up a computational framework to dynamically analyze large biological networks. This framework associates a classical and computationally efficient synchronous Boolean analysis with a newly introduced method based on Markov chains, which identifies spurious cycles among the results of the synchronous simulation. Based on this method, we present here the results of the analysis of the cholesterol biosynthesis pathway and its physiological regulation by the Sterol Response Element Binding Proteins (SREBPs), as well as the modeling of the action of statins, inhibitor drugs, on this pathway. The in silico experiments show the blockade of the cholesterol endogenous synthesis by statins and its regulation by SREPBs, in full agreement with the known biochemical features of the pathway. Conclusion: We believe that the method described here to identify spurious cycles opens new routes to compute large and biologically relevant models, thanks to the computational efficiency of synchronous simulat…
volume units: volume
reaction: 527026
reaction: 526953
species: 526902
species: 526858
reaction: 526950
species: 526862
reaction: 526922
reaction: 526956
species: 526896
area units: area

526975
type: Reaction
product: 478552
reactant: 478539
fast: false
reversible: false

478552
type: SpeciesReference
stoichiometry: 1.0
species: 526876

526876
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526852
name: FPP_Synthase_RNA

526852
type: Compartment
constant: true
size: NaN
spatial dimensions: 3.0
name: Nucleus

478539
type: SpeciesReference
stoichiometry: 1.0
species: 526874

526874
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526852
name: FPP_Synthase_gene

527035
type: Reaction
product: 479085
reactant: 479072
fast: false
reversible: false

479085
type: SpeciesReference
stoichiometry: 1.0
species: 526914

526914
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: Desmosterol

526850
type: Compartment
constant: true
size: NaN
spatial dimensions: 3.0
name: Cytoplasm

479072
type: SpeciesReference
stoichiometry: 1.0
species: 526912

526912
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: Lanosterol

527000
type: Reaction
product: 478744
reactant: 478732
fast: false
reversible: false

478744
type: SpeciesReference
stoichiometry: 1.0
species: 526892

526892
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: Acetyl_CoA

478732
type: SpeciesReference
stoichiometry: 1.0
species: 526892

526972
type: Reaction
product: 478527
reactant: 478514
fast: false
reversible: false

478527
type: SpeciesReference
stoichiometry: 1.0
species: 526874

478514
type: SpeciesReference
stoichiometry: 1.0
species: 526860

526860
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526854
name: mSREBP

526854
type: Compartment
constant: true
size: NaN
spatial dimensions: 3.0
name: Golgi

527032
type: Reaction
product: 479060
reactant: 479048
fast: false
reversible: false

479060
type: SpeciesReference
stoichiometry: 1.0
species: 526912

479048
type: SpeciesReference
stoichiometry: 1.0
species: 526910

526910
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: Squalene

526978
type: Reaction
product: 478576
reactant: 478564
fast: false
reversible: false

478576
type: SpeciesReference
stoichiometry: 1.0
species: 526878

526878
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: FPP_Synthase

478564
type: SpeciesReference
stoichiometry: 1.0
species: 526876

526916
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: Septdehydrocholesterol

527029
type: Reaction
product: 479036
reactant: 479023
fast: false
reversible: false

479036
type: SpeciesReference
stoichiometry: 1.0
species: 526910

479023
type: SpeciesReference
stoichiometry: 1.0
species: 526908

526908
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: Farnesyl_pyrophosphate

526959
type: Reaction
product: 478418
reactant: 478406
fast: false
reversible: false

478418
type: SpeciesReference
stoichiometry: 1.0
species: 526866

526866
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: HMG_CoA_Synthase

478406
type: SpeciesReference
stoichiometry: 1.0
species: 526864

526864
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526852
name: HMG_CoA_Synthase_RNA

526888
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526852
name: Cyp51_RNA

526898
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: Mevalonic_Acid

526886
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526852
name: Cyp51_gene

526981
type: Reaction
product: 478600
reactant: 478588
fast: false
reversible: false

478600
type: SpeciesReference
stoichiometry: 1.0
species: 526880

526880
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526852
name: Acetyl_CoA_C_acetyltransferase_gene

478588
type: SpeciesReference
stoichiometry: 1.0
species: 526860

527044
type: Reaction
product: 479170
reactant: 479158
fast: false
reversible: false

479170
type: SpeciesReference
stoichiometry: 1.0
species: 526920

526920
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: Statins

479158
type: SpeciesReference
stoichiometry: 1.0
species: 526920

527038
type: Reaction
product: 479110
reactant: 479097
fast: false
reversible: false

479110
type: SpeciesReference
stoichiometry: 1.0
species: 526916

479097
type: SpeciesReference
stoichiometry: 1.0
species: 526912

527004
type: Reaction
product: 478780
reactant: 478768
reactant: 478756
fast: false
reversible: false

478780
type: SpeciesReference
stoichiometry: 1.0
species: 526894

526894
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: Acetoacetyl_CoA

478768
type: SpeciesReference
stoichiometry: 1.0
species: 526884

526884
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: Acetyl_CoA_C_acetyltransferase

478756
type: SpeciesReference
stoichiometry: 1.0
species: 526892

526918
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: Cholesterol

527023
type: Reaction
product: 478973
reactant: 478961
reactant: 478949
fast: false
reversible: false

478973
type: SpeciesReference
stoichiometry: 1.0
species: 526906

526906
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: Geranyl_pyrophosphate

478961
type: SpeciesReference
stoichiometry: 1.0
species: 526904

526904
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: Dimethyl_allyl_pyrophosphate

478949
type: SpeciesReference
stoichiometry: 1.0
species: 526902

526902
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: Isopentenyl_pyrophosphate

527041
type: Reaction
product: 479146
reactant: 479134
reactant: 479122
fast: false
reversible: false

479146
type: SpeciesReference
stoichiometry: 1.0
species: 526918

479134
type: SpeciesReference
stoichiometry: 1.0
species: 526916

479122
type: SpeciesReference
stoichiometry: 1.0
species: 526914

526988
type: Reaction
product: 478648
reactant: 478636
fast: false
reversible: false

478648
type: SpeciesReference
stoichiometry: 1.0
species: 526884

478636
type: SpeciesReference
stoichiometry: 1.0
species: 526882

526882
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526852
name: Acetyl_CoA_C_acetyltransferase_RNA

526868
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526852
name: HMG_CoA_Reductase_gene

526991
type: Reaction
product: 478672
reactant: 478660
fast: false
reversible: false

478672
type: SpeciesReference
stoichiometry: 1.0
species: 526886

478660
type: SpeciesReference
stoichiometry: 1.0
species: 526860

526947
type: Reaction
product: 478322
reactant: 478310
fast: false
reversible: false

478322
type: SpeciesReference
stoichiometry: 1.0
species: 526858

526858
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526854
name: pSREBP

478310
type: SpeciesReference
stoichiometry: 1.0
species: 526856

526856
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526854
name: SREBP_SCAP

527010
type: Reaction
product: 478865
reactant: 478853
reactant: 478841
fast: false
reversible: false

478865
type: SpeciesReference
stoichiometry: 1.0
species: 526898

478853
type: SpeciesReference
stoichiometry: 1.0
species: 526872

526872
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: HMG_CoA_Reductase

478841
type: SpeciesReference
stoichiometry: 1.0
species: 526896

526896
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: HMG_CoA

527007
type: Reaction
product: 478829
reactant: 478817
reactant: 478805
reactant: 478792
fast: false
reversible: false

478829
type: SpeciesReference
stoichiometry: 1.0
species: 526896

478817
type: SpeciesReference
stoichiometry: 1.0
species: 526892

478805
type: SpeciesReference
stoichiometry: 1.0
species: 526866

478792
type: SpeciesReference
stoichiometry: 1.0
species: 526894

526969
type: Reaction
product: 478502
reactant: 478490
reactant: 478478
fast: false
reversible: false

478502
type: SpeciesReference
stoichiometry: 1.0
species: 526872

478490
type: SpeciesReference
stoichiometry: 1.0
species: 526920

478478
type: SpeciesReference
stoichiometry: 1.0
species: 526870

526870
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526852
name: HMG_CoA_Reductase_RNA

526890
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: Cyp51

527019
type: Reaction
product: 478937
reactant: 478925
fast: false
reversible: false

478937
type: SpeciesReference
stoichiometry: 1.0
species: 526904

478925
type: SpeciesReference
stoichiometry: 1.0
species: 526902

526997
type: Reaction
product: 478720
reactant: 478708
fast: false
reversible: false

478720
type: SpeciesReference
stoichiometry: 1.0
species: 526890

478708
type: SpeciesReference
stoichiometry: 1.0
species: 526888

526962
type: Reaction
product: 478442
reactant: 478430
fast: false
reversible: false

478442
type: SpeciesReference
stoichiometry: 1.0
species: 526868

478430
type: SpeciesReference
stoichiometry: 1.0
species: 526860

527016
type: Reaction
product: 478913
reactant: 478901
fast: false
reversible: false

478913
type: SpeciesReference
stoichiometry: 1.0
species: 526902

478901
type: SpeciesReference
stoichiometry: 1.0
species: 526900

526900
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526850
name: Mevalonyl_pyrophosphate

526994
type: Reaction
product: 478696
reactant: 478684
fast: false
reversible: false

478696
type: SpeciesReference
stoichiometry: 1.0
species: 526888

478684
type: SpeciesReference
stoichiometry: 1.0
species: 526886

526966
type: Reaction
product: 478466
reactant: 478454
fast: false
reversible: false

478466
type: SpeciesReference
stoichiometry: 1.0
species: 526870

478454
type: SpeciesReference
stoichiometry: 1.0
species: 526868

526984
type: Reaction
product: 478624
reactant: 478612
fast: false
reversible: false

478624
type: SpeciesReference
stoichiometry: 1.0
species: 526882

478612
type: SpeciesReference
stoichiometry: 1.0
species: 526880

527013
type: Reaction
product: 478889
reactant: 478877
fast: false
reversible: false

478889
type: SpeciesReference
stoichiometry: 1.0
species: 526900

478877
type: SpeciesReference
stoichiometry: 1.0
species: 526898

527026
type: Reaction
product: 479011
reactant: 478998
reactant: 478986
fast: false
reversible: false

479011
type: SpeciesReference
stoichiometry: 1.0
species: 526908

478998
type: SpeciesReference
stoichiometry: 1.0
species: 526878

478986
type: SpeciesReference
stoichiometry: 1.0
species: 526906

526953
type: Reaction
product: 478370
reactant: 478358
fast: false
reversible: false

478370
type: SpeciesReference
stoichiometry: 1.0
species: 526862

526862
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 526852
name: HMG_CoA_Synthase_gene

478358
type: SpeciesReference
stoichiometry: 1.0
species: 526860

526950
type: Reaction
product: 478346
reactant: 478334
fast: false
reversible: false

478346
type: SpeciesReference
stoichiometry: 1.0
species: 526860

478334
type: SpeciesReference
stoichiometry: 1.0
species: 526858

526922
type: Reaction
product: 478298
reactant: 478286
fast: false
reversible: false

478298
type: SpeciesReference
stoichiometry: 1.0
species: 526856

478286
type: SpeciesReference
stoichiometry: 1.0
species: 526918

526956
type: Reaction
product: 478394
reactant: 478382
fast: false
reversible: false

478394
type: SpeciesReference
stoichiometry: 1.0
species: 526864

478382
type: SpeciesReference
stoichiometry: 1.0
species: 526862

ORG:
  orgname: EMBL-EBI
n:
  given: Lukas
  family: Endler

ORG:
  orgname: University of Brest
n:
  given: Gwenael
  family: Kervizic

ORG:
  orgname: University of Brest
n:
  given: Gwenael
  family: Kervizic

W3 CDTF: Tue Dec 02 10:58:47 GMT 2008

W3 CDTF: Thu Feb 26 18:06:25 GMT 2009

ORG:
  orgname: EMBL-EBI
n:
  given: Lukas
  family: Endler

ORG:
  orgname: University of Brest
n:
  given: Gwenael
  family: Kervizic

W3 CDTF: Thu Feb 26 18:06:25 GMT 2009

W3 CDTF: Thu Feb 26 18:06:25 GMT 2009