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MODEL1007200000
parameter: 761227
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species: 760929
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units def: 826144
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name: Nijhout2006_Hepatic_Folate_Metab
parameter: 761283
species: 760943
units def: 825927
notes: This is the model described in the article: In silico experimentation with a model of hepatic mitochondrial folate metabolism. H. Frederik Nijhout, Michael C Reed, Shi-Ling Lam, Barry Shane, Jesse F Gregory and Cornelia M Ulrich, Theor Biol Med Model 2006,3:40; PubmedID: 17150100 ; DOI: 10.1186/1742-4682-3-40 ; Abstract: BACKGROUND: In eukaryotes, folate metabolism is compartmentalized and occurs in both the cytosol and the mitochondria. The function of this compartmentalization and the great changes that occur in the mitochondrial compartment during embryonic development and in rapidly growing cancer cells are gradually becoming understood, though many aspects remain puzzling and controversial. APPROACH: We explore the properties of cytosolic and mitochondrial folate metabolism by experimenting with a mathematical model of hepatic one-carbon metabolism. The model is based on known biochemical properties of mitochondrial and cytosolic enzymes. We use the model to study questions about the relative roles of the cytosolic and mitochondrial folate cycles posed in the experimental literature. We investigate: the control of the direction of the mitochondrial and cytosolic serine hydroxymethyltransferase (SHMT) reactions, the role of the mitochondrial bifunctional enzyme, the role of the glycine cleavage system, the effects of variations in serine and glycine inputs, and the effects of methionine and protein loading. CONCLUSION: The model reproduces many experimental findings and gives new insights into the underlying properties of mitochondrial folate metabolism. Particularly interesting is the remarkable stability of formate production in the mitochondria in the face of large changes in serine and glycine input. The model shows that in the presence of the bifunctional enzyme (as in embryonic tissues and cancer cells), the mitochondria primarily support cytosolic purine and pyrimidine synthesis via the export of formate, while in adult tissues the mitochondria produce se…
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type: SBMLUnitsDef

761171
constant: true
value: 100.0
type: Parameter

827575
stoichiometry: 1.0
species: 760970
type: SpeciesReference

827092
stoichiometry: 1.0
species: 760950
type: SpeciesReference

827404
stoichiometry: 1.0
species: 760950
type: SpeciesReference

826632
stoichiometry: 1.0
species: 760983
type: SpeciesReference

761252
constant: true
value: 100.0
type: Parameter

761132
constant: true
value: 6300.0
type: Parameter

761291
constant: true
value: 1000.0
type: Parameter

761014
kinetic law: 826910
product: 826897
product: 826885
reactant: 826873
reactant: 826861
fast: false
reversible: true
type: Reaction

827224
stoichiometry: 1.0
species: 760931
type: SpeciesReference

761028
modifier: 827320
modifier: 827308
reactant: 827284
fast: false
product: 827296
kinetic law: 827332
reactant: 827272
reversible: true
type: Reaction

761116
constant: true
value: 50.0
type: Parameter

761088
constant: true
value: 2.71828
type: Parameter

826983
stoichiometry: 1.0
species: 760939
type: SpeciesReference

827296
stoichiometry: 1.0
species: 760943
type: SpeciesReference

826885
stoichiometry: 1.0
species: 760939
type: SpeciesReference

761270
constant: true
value: 130.0
type: Parameter

760966
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 760917
type: Species

761009
kinetic law: 826776
product: 826764
reactant: 826752
fast: false
reversible: true
type: Reaction

761192
constant: true
value: 500.0
type: Parameter

761165
constant: true
value: 10.0
type: Parameter

760990
kinetic law: 826328
product: 826316
reactant: 826304
fast: false
reversible: true
type: Reaction

826120
exponent: -1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

761228
constant: true
value: 5000.0
type: Parameter

827781
stoichiometry: 1.0
species: 760966
type: SpeciesReference

826680
stoichiometry: 1.0
species: 760954
type: SpeciesReference

761105
constant: true
value: 150.0
type: Parameter

761172
constant: true
value: 10000.0
type: Parameter

761145
constant: true
value: 15000.0
type: Parameter

826498
stoichiometry: 1.0
species: 760942
type: SpeciesReference

826800
stoichiometry: 1.0
species: 760974
type: SpeciesReference

760935
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 760920
name: CO2
type: Species

826728
stoichiometry: 1.0
species: 760958
type: SpeciesReference

826035
unit: 826047
name: 1/h
type: SBMLUnitsDef

761029
kinetic law: 827380
product: 827368
product: 827356
reactant: 827344
fast: false
reversible: true
type: Reaction

761015
kinetic law: 826959
product: 826947
reactant: 826934
reactant: 826922
fast: false
reversible: true
type: Reaction

761006
kinetic law: 826740
product: 826728
reactant: 826716
fast: false
reversible: true
type: Reaction

760939
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: NaN
in compartment: 760917
type: Species

760963
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 760917
name: Homocysteine
type: Species

761087
constant: true
value: 0.0
type: Parameter

826474
stoichiometry: 1.0
species: 760954
type: SpeciesReference

826401
stoichiometry: 1.0
species: 760942
type: SpeciesReference

827236
stoichiometry: 1.0
species: 760946
type: SpeciesReference

761240
constant: true
value: 16.0
type: Parameter

826620
stoichiometry: 1.0
species: 760942
type: SpeciesReference

761144
constant: true
value: 3400.0
type: Parameter

761048
kinetic law: 827793
reactant: 827781
fast: false
reversible: true
type: Reaction

761016
kinetic law: 826995
product: 826983
reactant: 826971
fast: false
reversible: true
type: Reaction

761104
constant: true
value: 910.0
type: Parameter

761183
constant: true
value: 100.0
type: Parameter

827757
stoichiometry: 1.0
species: 760963
type: SpeciesReference

761153
constant: true
value: 50.0
type: Parameter

760938
constant: false
boundary condition: true
has only substance units: false
initial concentration: 500.0
initial amount: NaN
in compartment: 760921
name: Formaldehyde
type: Species

761216
constant: true
value: 3.0
type: Parameter

826230
stoichiometry: 1.0
species: 760927
type: SpeciesReference

826971
stoichiometry: 1.0
species: 760950
type: SpeciesReference

761203
constant: true
value: 0.5
type: Parameter

826316
stoichiometry: 1.0
species: 760942
type: SpeciesReference

826897
stoichiometry: 1.0
species: 760971
type: SpeciesReference

827489
stoichiometry: 1.0
species: 760930
type: SpeciesReference

760978
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 760920
name: mit_Glycine
type: Species

827284
stoichiometry: 1.0
species: 760929
type: SpeciesReference

826023
exponent: -1.0
scale: 0
multipler: 3600.0
kind: SECOND
type: SBMLUnit

761241
constant: true
value: 80000.0
type: Parameter

827031
stoichiometry: 1.0
species: 760959
type: SpeciesReference

760923
constant: false
boundary condition: true
has only substance units: false
initial concentration: 300.0
initial amount: NaN
in compartment: 760916
type: Species

761049
modifier: 827829
type: Reaction
modifier: 827853
modifier: 827865
kinetic law: 827878
reactant: 827817
reactant: 827805
modifier: 827841
fast: false
reversible: true

826692
stoichiometry: 1.0
species: 760955
type: SpeciesReference

761117
constant: true
value: 600.0
type: Parameter

827501
stoichiometry: 1.0
species: 760971
type: SpeciesReference

827428
stoichiometry: 1.0
species: 760950
type: SpeciesReference

761133
constant: true
value: 22.0
type: Parameter

761184
constant: true
value: 10000.0
type: Parameter

760950
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 760917
name: c_10-formyl-THF
type: Species

827817
stoichiometry: 1.0
species: 760966
type: SpeciesReference