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metaid_0000029
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value: 800000.0
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metaid_0000035
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metaid_0000018
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metaid_0000008
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metaid_0000060
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metaid_0000061
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metaid_0000010
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type: Parameter

metaid_0000025
constant: true
value: 14.0
type: Parameter

metaid_0000039
constant: true
value: 200000.0
type: Parameter

metaid_0000056
constant: false
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has only substance units: false
initial concentration: 2.1
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metaid_0000065
kinetic law: MODEL6655501972#
product: MODEL6655501972#
reactant: MODEL6655501972#
fast: false
reversible: false
type: Reaction

metaid_0000020
constant: true
value: 16200.0
type: Parameter

metaid_0000075
kinetic law: MODEL6655501972#
product: MODEL6655501972#
reactant: MODEL6655501972#
fast: false
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type: Reaction

metaid_0000066
kinetic law: MODEL6655501972#
product: MODEL6655501972#
reactant: MODEL6655501972#
fast: false
reversible: false
type: Reaction

metaid_0000005
constant: true
value: 0.0013
type: Parameter

metaid_0000011
constant: true
value: 50.0
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metaid_0000041
constant: true
value: 2.0
type: Parameter

metaid_0000070
kinetic law: MODEL6655501972#
product: MODEL6655501972#
reactant: MODEL6655501972#
fast: false
reversible: false
type: Reaction

metaid_0000015
constant: true
value: 43.0
type: Parameter

metaid_0000051
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initial concentration: 6.0
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metaid_0000046
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metaid_0000062
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metaid_0000034
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metaid_0000009
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value: 6000.0
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metaid_0000028
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value: 0.5
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metaid_0000038
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value: 3200.0
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metaid_0000019
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value: 5.9
type: Parameter

metaid_0000057
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type: Species

metaid_0000024
constant: true
value: 6.3
type: Parameter

metaid_0000076
kinetic law: MODEL6655501972#
product: MODEL6655501972#
reactant: MODEL6655501972#
fast: false
reversible: false
type: Reaction

ORG:
  orgname: University of Washington
n:
  given: Michal
  family: Galdzicki

metaid_0000077
kinetic law: MODEL6655501972#
product: MODEL6655501972#
reactant: MODEL6655501972#
fast: false
reversible: false
type: Reaction

metaid_0000083
constant: true
value: 3.3333333E-4
type: Parameter

metaid_0000004
constant: true
value: 12.0
type: Parameter

MODEL6655501972
reaction: metaid_0000069
parameter: metaid_0000014
parameter: metaid_0000004
parameter: metaid_0000030
parameter: metaid_0000035
parameter: metaid_0000020
parameter: metaid_0000025
species: metaid_0000050
name: Nijhout2004_FolateCycle
curated: false
species: metaid_0000051
substance units: 106194
species: metaid_0000058
parameter: metaid_0000017
parameter: metaid_0000011
species: metaid_0000059
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species: metaid_0000049
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area units: area
reaction: metaid_0000071
species: metaid_0000061
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reaction: metaid_0000073
reaction: metaid_0000068
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parameter: metaid_0000040
species: metaid_0000062
species: metaid_0000055
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reaction: metaid_0000076
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species: metaid_0000052
species: metaid_0000053
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parameter: metaid_0000021
parameter: metaid_0000026
parameter: metaid_0000042
notes: This is an SBML version of the folate cycle model model from: A mathematical model of the folate cycle: new insights into folate homeostasis. Nijhout HF, Reed MC, Budu P, Ulrich CM J. Biol. Chem.,2004, 279 (53),55008-16 Reference publication: 15496403 Abstract: A mathematical model is developed for the folate cycle based on standard biochemical kinetics. We use the model to provide new insights into several different mechanisms of folate homeostasis. The model reproduces the known pool sizes of folate substrates and the fluxes through each of the loops of the folate cycle and has the qualitative behavior observed in a variety of experimental studies. Vitamin B(12) deficiency, modeled as a reduction in the V(max) of the methionine synthase reaction, results in a secondary folate deficiency via the accumulation of folate as 5-methyltetrahydrofolate (the "methyl trap"). One form of homeostasis is revealed by the fact that a 100-fold up-regulation of thymidylate synthase and dihydrofolate reductase (known to occur at the G(1)/S transition) dramatically increases pyrimidine production without affecting the other reactions of the folate cycle. The model also predicts that an almost total inhibition of dihydrofolate reductase is required to significantly inhibit the thymidylate synthase reaction, consistent with experimental and clinical studies on the effects of methotrexate. Sensitivity to variation in enzymatic parameters tends to be local in the cycle and inversely proportional to the number of reactions that interconvert two folate substrates. Another form of homeostasis is a consequence of the nonenzymatic binding of folate substrates to folate enzymes. Without folate binding, the velocities of the reactions decrease approximately linearly as total folate is decreased. In the presence of folate binding and allosteric inhibition, the velocities show a remarkable constancy as total folate is decreased. A curated version of this model is available: BIOMD0000000213 . Thi…
reaction: metaid_0000070
time units: 013121
parameter: metaid_0000039
parameter: metaid_0000029
parameter: metaid_0000008
reaction: metaid_0000067
parameter: metaid_0000023
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volume units: metaid_0000217
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species: metaid_0000063
species: metaid_0000056
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parameter: metaid_0000015
parameter: metaid_0000005
reaction: metaid_0000075
parameter: metaid_0000031
parameter: metaid_0000036
species: metaid_0000064
species: metaid_0000057
parameter: metaid_0000012
reaction: metaid_0000077
parameter: metaid_0000033
species: metaid_0000054
species: metaid_0000047
parameter: metaid_0000041
type: SBMLModel
compartment: metaid_0000045
species: metaid_0000048
parameter: metaid_0000038
parameter: metaid_0000028
reaction: metaid_0000066

metaid_0000067
kinetic law: MODEL6655501972#
product: MODEL6655501972#
reactant: MODEL6655501972#
fast: false
reversible: false
type: Reaction

metaid_0000042
constant: true
value: 594000.0
type: Parameter

W3 CDTF: Wed Feb 08 14:19:12 GMT 2012

metaid_0000047
constant: false
boundary condition: false
has only substance units: false
initial concentration: 6.0
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metaid_0000014
constant: true
value: 2000.0
type: Parameter

metaid_0000052
constant: false
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initial concentration: 468.0
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type: Species

metaid_0000044
constant: true
value: 10.0
type: Parameter

metaid_0000027
constant: true
value: 4.0
type: Parameter

metaid_0000063
constant: false
boundary condition: true
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metaid_0000037
constant: true
value: 10000.0
type: Parameter

metaid_0000032
constant: true
value: 100.0
type: Parameter

metaid_0000073
kinetic law: MODEL6655501972#
product: MODEL6655501972#
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fast: false
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type: Reaction

metaid_0000006
constant: true
value: 500.0
type: Parameter

metaid_0000023
constant: true
value: 50.0
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metaid_0000013
constant: true
value: 20.0
type: Parameter

metaid_0000068
kinetic law: MODEL6655501972#
product: MODEL6655501972#
reactant: MODEL6655501972#
fast: false
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type: Reaction

metaid_0000053
constant: false
boundary condition: true
has only substance units: false
initial concentration: 1850.0
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in compartment: metaid_0000045
type: Species

metaid_0000003
constant: true
value: 0.15
type: Parameter

metaid_0000058
constant: false
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metaid_0000033
constant: true
value: 40000.0
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metaid_0000017
constant: true
value: 45000.0
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metaid_0000078
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metaid_0000072
kinetic law: MODEL6655501972#
product: MODEL6655501972#
reactant: MODEL6655501972#
fast: false
reversible: false
type: Reaction

metaid_0000043
constant: true
value: 10.0
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metaid_0000048
constant: false
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initial concentration: 0.02
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metaid_0000026
constant: true
value: 50.0
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metaid_0000036
constant: true
value: 25000.0
type: Parameter

metaid_0000045
constant: true
size: 1.0
spatial dimensions: 3.0
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metaid_0000064
constant: false
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initial concentration: 0.0
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in compartment: metaid_0000045
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metaid_0000031
constant: true
value: 20000.0
type: Parameter

MODEL6655501972#
species: metaid_0000054
stoichiometry: 1.0
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type: SpeciesReference
species: metaid_0000048
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species: metaid_0000062

metaid_0000074
kinetic law: MODEL6655501972#
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reactant: MODEL6655501972#
fast: false
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type: Reaction

metaid_0000022
constant: true
value: 4.9
type: Parameter

metaid_0000055
constant: false
boundary condition: true
has only substance units: false
initial concentration: 10.0
initial amount: NaN
in compartment: metaid_0000045
type: Species

metaid_0000007
constant: true
value: 0.1
type: Parameter

metaid_0000054
constant: false
boundary condition: true
has only substance units: false
initial concentration: 20.0
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in compartment: metaid_0000045
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metaid_0000012
constant: true
value: 14000.0
type: Parameter

metaid_0000059
constant: false
boundary condition: true
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initial concentration: 1.0
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in compartment: metaid_0000045
type: Species

metaid_0000069
kinetic law: MODEL6655501972#
product: MODEL6655501972#
reactant: MODEL6655501972#
fast: false
reversible: false
type: Reaction

metaid_0000021
constant: true
value: 520.0
type: Parameter

metaid_0000040
constant: true
value: 10.0
type: Parameter

metaid_0000016
constant: true
value: 3.0
type: Parameter

metaid_0000049
constant: false
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initial concentration: 1.0
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metaid_0000071
kinetic law: MODEL6655501972#
product: MODEL6655501972#
reactant: MODEL6655501972#
fast: false
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type: Reaction

metaid_0000050
constant: false
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initial concentration: 1.1
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type: Species

orgname: EMBL-EBI

orgname: EMBL-EBI

given: Vijayalakshmi
family: Chelliah

given: Lukas
family: Endler

W3 CDTF: Fri Nov 28 13:51:12 GMT 2008

W3 CDTF: Fri Aug 01 11:41:34 BST 2008