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BIOMD0000000268 - Reed2008_Glutathione_Metabolism

 

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Reference Publication
Publication ID: 18442411
Reed MC, Thomas RL, Pavisic J, James SJ, Ulrich CM, Nijhout HF.
A mathematical model of glutathione metabolism.
Theor Biol Med Model 2008; 5: 8
Department of Mathematics, Duke University, Durham, NC 27708, USA. reed@math.duke.edu  [more]
Model
Original Model: BIOMD0000000268.origin
Submitter: Lukas Endler
Submission ID: MODEL1007200001
Submission Date: 20 Jul 2010 14:33:55 UTC
Last Modification Date: 10 Oct 2014 11:34:39 UTC
Creation Date: 07 Sep 2010 16:28:04 UTC
Encoders:  Lukas Endler
set #1
bqbiol:hasProperty Human Disease Ontology autistic disorder
Human Disease Ontology Down syndrome
Human Disease Ontology cardiovascular system disease
Human Disease Ontology cancer
Human Disease Ontology Parkinson's disease
Human Disease Ontology Alzheimer's disease
set #2
bqmodel:isDerivedFrom BioModels Database Nijhout2006_Hepatic_Folate_Metab
set #3
bqbiol:occursIn Taxonomy Homo sapiens
Brenda Tissue Ontology hepatocyte
set #4
bqbiol:isVersionOf Gene Ontology glutathione metabolic process
Notes

This is the model described in the article:
A mathematical model of glutathione metabolism.
Michael C Reed, Rachel L Thomas, Jovana Pavisic, S. Jill James, Cornelia M Ulrich and H. Frederik Nijhout, Theor Biol Med Model 2008,5:8; PubmedID:18442411 ; DOI:10.1186/1742-4682-5-8;
Abstract:
BACKGROUND: Glutathione (GSH) plays an important role in anti-oxidant defense and detoxification reactions. It is primarily synthesized in the liver by the transsulfuration pathway and exported to provide precursors for in situ GSH synthesis by other tissues. Deficits in glutathione have been implicated in aging and a host of diseases including Alzheimer's disease, Parkinson's disease, cardiovascular disease, cancer, Down syndrome and autism.
APPROACH: We explore the properties of glutathione metabolism in the liver by experimenting with a mathematical model of one-carbon metabolism, the transsulfuration pathway, and glutathione synthesis, transport, and breakdown. The model is based on known properties of the enzymes and the regulation of those enzymes by oxidative stress. We explore the half-life of glutathione, the regulation of glutathione synthesis, and its sensitivity to fluctuations in amino acid input. We use the model to simulate the metabolic profiles previously observed in Down syndrome and autism and compare the model results to clinical data.
CONCLUSION: We show that the glutathione pools in hepatic cells and in the blood are quite insensitive to fluctuations in amino acid input and offer an explanation based on model predictions. In contrast, we show that hepatic glutathione pools are highly sensitive to the level of oxidative stress. The model shows that overexpression of genes on chromosome 21 and an increase in oxidative stress can explain the metabolic profile of Down syndrome. The model also correctly simulates the metabolic profile of autism when oxidative stress is substantially increased and the adenosine concentration is raised. Finally, we discuss how individual variation arises and its consequences for one-carbon and glutathione metabolism.

parameter orig. article this model
Vm_CBS 700000 420000
Vm_GNMT 245 260
K_sam_GNMT 32 63
Vr_MTD(mito) 600000 595000
V_CBS kinetic law rearranged
V_bmetc 913 913.4
Vm_GR 8925 892.5

This version of the model contains a feeding rhythm as used in figure 5 of the original article. Four parameters, breakfast, lunch dinner and fasting, describe the relative level of amino acids, described by the parameter aa_input or Aminoacid_input, in the blood. To remove the daily feeding rhythm, either set the parameters for meals and fasting to 1 (or for figure 3 to 0.333), or remove the assignment rule for the Aminoacid_input. For the steady state evaluations for figure 6, the mealtime parameters were set to one, which, while making Copasi complain about explicit time dependency, still gives valid results.

This version of the model differs slightly from the version described in the supplement, in which contains some typos. It was corrected using the version of JWS-online, created using the original matlab files, thankfully provided by the articles authors. Many thanks to Jacky Snoep for his help and support.

In the SBML version of the model the volumes of the mitochondrion, the cytoplasm and the cell were all set to one to obtain the same equations as described in the supplemental materials of the article. The total folate is equally split between the cytosol and the mitochondrion and divided by 3/4 for the cytosol and 1/4 for the mitochondrion, respectively. To obtain an SBML model in which the volumes of the compartments, cytosol and mito, are used, the model needs to be altered as follows:

  • for the initial distribution of folate the terms 3/4 and 1/4 have to be replaced by volumes of cytosol and mitochondria respectively
  • in the transport reactions between mitochondrion and cytosol the stoichiometry of the mitochondrial reactants has to be set from 3 to 1 and in the first part of the according rate laws the factor mito/3 should simply be replaced with mito.
  • the stoichiometries of src and dmg have to be changed to cell/mito for mitchondrial and cell/cytosol for cytosolic reactions involving these two species (for the relative volumes used in the article this would be 4 for mitochondrial reactions and 1.33333 for cytosolic ones).
While the concentrations stay the same after these alteration, the reaction fluxes change by a factor of cytosol and mito for cytosolic and mitchondrial reactions, respectively.

Originally created by libAntimony v1.3 (using libSBML 3.4.1)

Model
Publication ID: 18442411 Submission Date: 20 Jul 2010 14:33:55 UTC Last Modification Date: 10 Oct 2014 11:34:39 UTC Creation Date: 07 Sep 2010 16:28:04 UTC
Mathematical expressions
Reactions
b_gsh_decomp b_gsg_decomp b_cys_cystine_conv b_cys_loss
b_glu_loss b_gly_loss b_gsh_loss b_gsg_loss
b_cys_import b_gly_import b_glu_import V_c_gshHb
V_c_gshLb V_c_gsgHb V_c_gsgLb V_b_CYS_c
V_b_GLU_c V_b_GLY_c V_b_SER_c V_b_MET_c
VmFTD VmSHMT VmFTS VmNE
V_GDC V_SDH V_DMGD VmMTD
VmMTCH VmSERc VmHCOOHc VmGLYc
V_MS V_DHFR VcFTD V_PGT
VcFTS VcSHMT VcNE V_TS
V_MTHFR VcMTD VcMTCH V_ART
V_BHMT V_MATI V_MATIII V_GNMT
V_DNMT V_SAHH gluconeogenesis_ser V_CBS
V_CTGL V_GCS cys_usage c_glu_usage
V_GS V_GPX V_GR c_gsh_degr
c_gsg_degr      
Rules
Assignment Rule (variable: b_Met) Assignment Rule (variable: b_Ser) Assignment Rule (variable: tot_cfol) Assignment Rule (variable: tot_mfol)
Assignment Rule (variable: V_oCys_b) Assignment Rule (variable: V_oGly_b) Assignment Rule (variable: V_oGlu_b) Assignment Rule (variable: daytime)
Assignment Rule (variable: Aminoacid_input)      
Physical entities
Compartments Species
blood b_Met b_Ser b_Glycine
b_Glutamate b_Cysteine b_GSSG
b_GSH    
cytosol GAR NADPH Betaine
dUMP H2O2 c_THF
c_5-methyl-THF c_5-10-methylene-THF c_5-10-methenyl-THF
c_10-formyl-THF c_DHF AICAR
c_Glutamate c_Cysteine Glutamyl-Cysteine
c_Glycine c_GSSG c_GSH
Cystathione Homocysteine c_Serine
S-adenosylhomocysteine S-adenosylmethionine c_Methionine
c_formate    
mitochondrion CO2 m_THF m_5-10-methylene-THF
m_5-10-methenyl-THF m_10-formyl-THF m_Serine
m_Glycine m_Formate  
cell Folate Formaldehyde Sarcosine
Dimethylglycine    
Global parameters
tot_cfol tot_mfol V_oCys_b V_oGly_b
V_oGlu_b V_gshHb K_gshHb V_gshLb
h_gshLb K_gshLb V_gsgHb K_gsgHb
V_gsgLb K_gsgLb V_bcysc K_bcysc
V_bglutc K_bglutc k_out_glu V_bglyc
K_bglyc k_out_gly V_bserc K_bserc
k_out_ser V_bmetc K_bmetc k_out_met
Vm_mFTD K_10f_FTD Vf_mSHMT K_thf_SHMT
K_ser_SHMT Vr_mSHMT K_gly_SHMT K_2cf_SHMT
Vf_mFTS K_thf_mFTS K_coo_mFTS Vr_mFTS
K_10f_mFTS k1_mNE k2_mNE Vm_GDC
K_thf_GDC K_gly_GDC Vm_SDH K_thf_SDH
K_src_SDH Vm_DMGD K_thf_DMGD K_dmg_DMGD
Vf_mMTD K_2cf_MTD Vr_MTD K_1cf_MTD
Vf_mMTCH K_1cf_MTCH Vr_MTCH K_10f_MTCH
V_mser K_mser V_cser K_cser
k_in_coo k_out_coo V_mgly K_mgly
V_cgly K_cgly Vm_MS K_5mf_MS
K_hcy_MS ssH2O2 Ki_MS Vm_DHFR
K_dhf_DHFR K_NADPH_DHFR Vm_cFTD Vm_PGT
K_10f_PGT K_GAR_PGT Vm_cFTS K_thf_cFTS
K_coo_cFTS Vf_cSHMT Vr_cSHMT k1_cNE
k2_cNE Vm_TS K_DUMP_TS K_2cf_TS
Vm_MTHFR K_2cf_MTHFR K_NADPH_MTHFR Vf_cMTD
Vr_cMTD Vf_cMTCH Vm_ART K_10f_ART
K_aic_ART Vm_BHMT K_hcy_BHMT K_bet_BHMT
Ki_BHMT Vm_MAT1 Km_MAT1 Ki_MAT1
Vm_MAT3 Km_MAT3 Ka_MAT3 Ki_MAT3
Vm_GNMT K_sam_GNMT K_gly_GNMT Ki_GNMT
Vm_DNMT Km_DNMT Ki_DNMT Vf_SAHH
K_sah_SAHH Vr_SAHH K_hcy_SAHH Vm_CBS
K_hcy_CBS K_ser_CBS Ka_CBS Vm_CTGL
K_cyt_CTGL Vm_GCS Ke_GCS K_cys_GCS
K_glu_GCS Ki_GCS Kp_GCS Ka_GCS
Vm_GS Ke_GS K_gly_GS K_glc_GS
Kp_GS Vm_GPX K_gsh_GPX K_H2O2_GPX
Vm_GR K_gsg_GR K_NADPH_GR dinner
lunch breakfast fasting daytime
Aminoacid_input b_met_basal b_ser_basal V_oGly_b_basal
V_oGlu_b_basal V_oCys_b_basal k_out_cys  
Reactions (61)
 
 b_gsh_decomp [b_GSH] ↔ [b_Cysteine] + [b_Glycine] + [b_Glutamate];  
 
 b_gsg_decomp [b_GSSG] ↔ 2.0 × [b_Cysteine] + 2.0 × [b_Glycine] + 2.0 × [b_Glutamate];  
 
 b_cys_cystine_conv [b_Cysteine] ↔ ;  
 
 b_cys_loss [b_Cysteine] ↔ ;  
 
 b_glu_loss [b_Glutamate] ↔ ;  
 
 b_gly_loss [b_Glycine] ↔ ;  
 
 b_gsh_loss [b_GSH] ↔ ;  
 
 b_gsg_loss [b_GSSG] ↔ ;  
 
 b_cys_import  ↔ [b_Cysteine];  
 
 b_gly_import  ↔ [b_Glycine];  
 
 b_glu_import  ↔ [b_Glutamate];  
 
 V_c_gshHb [c_GSH] ↔ [b_GSH];  
 
 V_c_gshLb [c_GSH] ↔ [b_GSH];  
 
 V_c_gsgHb [c_GSSG] ↔ [b_GSSG];  
 
 V_c_gsgLb [c_GSSG] ↔ [b_GSSG];  
 
 V_b_CYS_c [b_Cysteine] ↔ [c_Cysteine];  
 
 V_b_GLU_c [b_Glutamate] ↔ [c_Glutamate];  
 
 V_b_GLY_c [b_Glycine] ↔ [c_Glycine];  
 
 V_b_SER_c [b_Ser] ↔ [c_Serine];  
 
 V_b_MET_c [b_Met] ↔ [c_Methionine];  
 
 VmFTD [m_10-formyl-THF] ↔ [m_THF];  
 
 VmSHMT [m_THF] + [m_Serine] ↔ [m_Glycine] + [m_5-10-methylene-THF];  
 
 VmFTS [m_THF] + [m_Formate] ↔ [m_10-formyl-THF];  
 
 VmNE [m_THF] + [Formaldehyde] ↔ [m_5-10-methylene-THF];  
 
 V_GDC [m_THF] + [m_Glycine] ↔ [m_5-10-methylene-THF] + [CO2];  
 
 V_SDH [m_THF] + [Sarcosine] ↔ [m_5-10-methylene-THF] + [m_Glycine];  
 
 V_DMGD [m_THF] + [Dimethylglycine] ↔ [m_5-10-methylene-THF] + [Sarcosine];  
 
 VmMTD [m_5-10-methylene-THF] ↔ [m_5-10-methenyl-THF];  
 
 VmMTCH [m_5-10-methenyl-THF] ↔ [m_10-formyl-THF];  
 
 VmSERc 3.0 × [m_Serine] ↔ [c_Serine];  
 
 VmHCOOHc 3.0 × [m_Formate] ↔ [c_formate];  
 
 VmGLYc 3.0 × [m_Glycine] ↔ [c_Glycine];  
 
 V_MS [c_5-methyl-THF] + [Homocysteine] ↔ [c_THF] + [c_Methionine];   {H2O2}
 
 V_DHFR [c_DHF] + [NADPH] ↔ [c_THF];  
 
 VcFTD [c_10-formyl-THF] ↔ [c_THF];  
 
 V_PGT [c_10-formyl-THF] + [GAR] ↔ [AICAR] + [c_THF];  
 
 VcFTS [c_THF] + [c_formate] ↔ [c_10-formyl-THF];  
 
 VcSHMT [c_Serine] + [c_THF] ↔ [c_Glycine] + [c_5-10-methylene-THF];  
 
 VcNE [c_THF] + [Formaldehyde] ↔ [c_5-10-methylene-THF];  
 
 V_TS [dUMP] + [c_5-10-methylene-THF] ↔ [c_DHF];  
 
 V_MTHFR [c_5-10-methylene-THF] + [NADPH] ↔ [c_5-methyl-THF];   {S-adenosylhomocysteine} , {S-adenosylmethionine}
 
 VcMTD [c_5-10-methylene-THF] ↔ [c_5-10-methenyl-THF] + [NADPH];  
 
 VcMTCH [c_5-10-methenyl-THF] ↔ [c_10-formyl-THF];  
 
 V_ART [c_10-formyl-THF] + [AICAR] ↔ [c_THF];  
 
 V_BHMT [Homocysteine] + [Betaine] ↔ [c_Methionine] + [Dimethylglycine];   {H2O2} , {S-adenosylhomocysteine} , {S-adenosylmethionine}
 
 V_MATI [c_Methionine] ↔ [S-adenosylmethionine];   {c_GSSG}
 
 V_MATIII [c_Methionine] ↔ [S-adenosylmethionine];   {c_GSSG}
 
 V_GNMT [S-adenosylmethionine] + [c_Glycine] ↔ [S-adenosylhomocysteine] + [Sarcosine];   {c_5-methyl-THF}
 
 V_DNMT [S-adenosylmethionine] ↔ [S-adenosylhomocysteine];  
 
 V_SAHH [S-adenosylhomocysteine] ↔ [Homocysteine];  
 
 gluconeogenesis_ser [c_Serine] ↔ ;  
 
 V_CBS [Homocysteine] + [c_Serine] ↔ [Cystathione];   {H2O2} , {S-adenosylhomocysteine} , {S-adenosylmethionine}
 
 V_CTGL [Cystathione] ↔ [c_Cysteine];  
 
 V_GCS [c_Cysteine] + [c_Glutamate] ↔ [Glutamyl-Cysteine];   {H2O2} , {c_GSH}
 
 cys_usage [c_Cysteine] ↔ ;  
 
 c_glu_usage [c_Glutamate] ↔ ;  
 
 V_GS [Glutamyl-Cysteine] + [c_Glycine] ↔ [c_GSH];  
 
 V_GPX 2.0 × [c_GSH] + [H2O2] ↔ [c_GSSG];  
 
 V_GR [c_GSSG] + [NADPH] ↔ 2.0 × [c_GSH];  
 
 c_gsh_degr [c_GSH] ↔ ;  
 
 c_gsg_degr [c_GSSG] ↔ ;  
 
Rules (9)
 
 Assignment Rule (name: b_met) b_Met = aa_input*b_met_basal
 
 Assignment Rule (name: b_ser) b_Ser = aa_input*b_ser_basal
 
 Assignment Rule (name: tot_cfol) tot_cfol = c_5mf+c_2cf+c_1cf+c_10f+c_dhf+c_thf
 
 Assignment Rule (name: tot_mfol) tot_mfol = m_thf+m_2cf+m_1cf+m_10f
 
 Assignment Rule (name: V_oCys_b) V_oCys_b = aa_input*V_oCys_b_basal
 
 Assignment Rule (name: V_oGly_b) V_oGly_b = aa_input*V_oGly_b_basal
 
 Assignment Rule (name: V_oGlu_b) V_oGlu_b = aa_input*V_oGlu_b_basal
 
 Assignment Rule (name: daytime) daytime = time-24*floor(time/24)
 
 Assignment Rule (name: aa_input) Aminoacid_input = piecewise(breakfast, (7 <= daytime) && (daytime <= 10), lunch, (12 <= daytime) && (daytime <= 15), dinner, (18 <= daytime) && (daytime <= 21), fasting)
 
Functions (2)
 
 MM lambda(Vmax, Km, S, Vmax*S/(Km+S))
 
 MM_twosubst lambda(Vmax, Km1, Km2, S1, S2, Vmax*S1*S2/((Km1+S1)*(Km2+S2)))
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
  b_Met
Compartment: blood
 
  b_Ser
Compartment: blood
 
 b_Glycine
Compartment: blood
Initial concentration: 221.101111778807
 
 b_Glutamate
Compartment: blood
Initial concentration: 60.4330872702655
 
 b_Cysteine
Compartment: blood
Initial concentration: 185.50378543937
 
 b_GSSG
Compartment: blood
Initial concentration: 0.484328542816829
 
 b_GSH
Compartment: blood
Initial concentration: 12.6996048211362
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 GAR
Compartment: cytosol
Initial concentration: 10.0
 
 NADPH
Compartment: cytosol
Initial concentration: 50.0
 
 Betaine
Compartment: cytosol
Initial concentration: 50.0
 
 dUMP
Compartment: cytosol
Initial concentration: 20.0
 
 H2O2
Compartment: cytosol
Initial concentration: 0.01
 
 c_THF
Compartment: cytosol
 
 c_5-methyl-THF
Compartment: cytosol
Initial concentration: 4.4965335653401
 
 c_5-10-methylene-THF
Compartment: cytosol
Initial concentration: 0.506278119133034
 
 c_5-10-methenyl-THF
Compartment: cytosol
Initial concentration: 0.278602708139276
 
 c_10-formyl-THF
Compartment: cytosol
Initial concentration: 3.40907070478307
 
 c_DHF
Compartment: cytosol
Initial concentration: 0.0385952337473159
 
 AICAR
Compartment: cytosol
Initial concentration: 0.942750394171554
 
 c_Glutamate
Compartment: cytosol
Initial concentration: 3219.39793573653
 
 c_Cysteine
Compartment: cytosol
Initial concentration: 194.96740946034
 
 Glutamyl-Cysteine
Compartment: cytosol
Initial concentration: 9.80842470037426
 
 c_Glycine
Compartment: cytosol
Initial concentration: 924.429820216685
 
 c_GSSG
Compartment: cytosol
Initial concentration: 61.3019611792609
 
 c_GSH
Compartment: cytosol
Initial concentration: 6590.56824161192
 
 Cystathione
Compartment: cytosol
Initial concentration: 36.8825861752429
 
 Homocysteine
Compartment: cytosol
Initial concentration: 1.12248362561721
 
 c_Serine
Compartment: cytosol
Initial concentration: 562.834377270222
 
 S-adenosylhomocysteine
Compartment: cytosol
Initial concentration: 19.1432773636787
 
 S-adenosylmethionine
Compartment: cytosol
Initial concentration: 81.1684566962769
 
 c_Methionine
Compartment: cytosol
Initial concentration: 49.18682158
 
 c_formate
Compartment: cytosol
Initial concentration: 13.0888186429922
 
 mitochondrion Spatial dimensions: 3.0  Compartment size: 1.0
 
 CO2
Compartment: mitochondrion
Initial concentration: 0.0
 
 m_THF
Compartment: mitochondrion
 
 m_5-10-methylene-THF
Compartment: mitochondrion
Initial concentration: 1.66610924423152
 
 m_5-10-methenyl-THF
Compartment: mitochondrion
Initial concentration: 1.54929073348709
 
 m_10-formyl-THF
Compartment: mitochondrion
Initial concentration: 15.9087989350187
 
 m_Serine
Compartment: mitochondrion
Initial concentration: 2114.87119909779
 
 m_Glycine
Compartment: mitochondrion
Initial concentration: 2040.43402532595
 
 m_Formate
Compartment: mitochondrion
Initial concentration: 55.820116666595
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 Folate
Compartment: cell
Initial concentration: 20.1
 
 Formaldehyde
Compartment: cell
Initial concentration: 500.0
 
 Sarcosine
Compartment: cell
Initial concentration: 9.16245914628594
 
 Dimethylglycine
Compartment: cell
Initial concentration: 0.707382712261505
 
Global Parameters (159)
 
   tot_cfol
Value: NaN   (Units: uM)
 
   tot_mfol
Value: NaN   (Units: uM)
 
   V_oCys_b
Value: NaN   (Units: uM/h)
 
   V_oGly_b
Value: NaN   (Units: uM/h)
 
   V_oGlu_b
Value: NaN   (Units: uM/h)
 
   V_gshHb
Value: 150.0   (Units: uM/h)
Constant
 
   K_gshHb
Value: 150.0   (Units: uM)
Constant
 
   V_gshLb
Value: 1100.0   (Units: uM/h)
Constant
 
   h_gshLb
Value: 3.0   (Units: dimensionless)
Constant
 
   K_gshLb
Value: 3000.0   (Units: uM)
Constant
 
   V_gsgHb
Value: 40.0   (Units: uM/h)
Constant
 
   K_gsgHb
Value: 1250.0   (Units: uM)
Constant
 
   V_gsgLb
Value: 4025.0   (Units: uM/h)
Constant
 
   K_gsgLb
Value: 7100.0   (Units: uM)
Constant
 
   V_bcysc
Value: 14950.0   (Units: uM/h)
Constant
 
   K_bcysc
Value: 2100.0   (Units: uM)
Constant
 
   V_bglutc
Value: 28000.0   (Units: uM/h)
Constant
 
   K_bglutc
Value: 300.0   (Units: uM)
Constant
 
   k_out_glu
Value: 1.0   (Units: 1/h)
Constant
 
   V_bglyc
Value: 4600.0   (Units: uM/h)
Constant
 
   K_bglyc
Value: 150.0   (Units: uM)
Constant
 
   k_out_gly
Value: 1.0   (Units: 1/h)
Constant
 
   V_bserc
Value: 2700.0   (Units: uM/h)
Constant
 
   K_bserc
Value: 150.0   (Units: uM)
Constant
 
   k_out_ser
Value: 1.0   (Units: 1/h)
Constant
 
   V_bmetc
Value: 913.4   (Units: uM/h)
Constant
 
   K_bmetc
Value: 150.0   (Units: uM)
Constant
 
   k_out_met
Value: 1.0   (Units: 1/h)
Constant
 
   Vm_mFTD
Value: 1050.0   (Units: uM/h)
Constant
 
   K_10f_FTD
Value: 20.0   (Units: uM)
Constant
 
   Vf_mSHMT
Value: 11440.0   (Units: uM/h)
Constant
 
   K_thf_SHMT
Value: 50.0   (Units: uM)
Constant
 
   K_ser_SHMT
Value: 600.0   (Units: uM)
Constant
 
   Vr_mSHMT
Value: 3.0E7   (Units: uM/h)
Constant
 
   K_gly_SHMT
Value: 10000.0   (Units: uM)
Constant
 
   K_2cf_SHMT
Value: 3200.0   (Units: uM)
Constant
 
   Vf_mFTS
Value: 2000.0   (Units: uM/h)
Constant
 
   K_thf_mFTS
Value: 3.0   (Units: uM)
Constant
 
   K_coo_mFTS
Value: 43.0   (Units: uM)
Constant
 
   Vr_mFTS
Value: 6300.0   (Units: uM/h)
Constant
 
   K_10f_mFTS
Value: 22.0   (Units: uM)
Constant
 
   k1_mNE
Value: 0.03   (Units: 1/(uM*h))
Constant
 
   k2_mNE
Value: 20.0   (Units: 1/h)
Constant
 
   Vm_GDC
Value: 15000.0   (Units: uM/h)
Constant
 
   K_thf_GDC
Value: 50.0   (Units: uM)
Constant
 
   K_gly_GDC
Value: 3400.0   (Units: uM)
Constant
 
   Vm_SDH
Value: 15000.0   (Units: uM/h)
Constant
 
   K_thf_SDH
Value: 50.0   (Units: uM)
Constant
 
   K_src_SDH
Value: 320.0   (Units: uM)
Constant
 
   Vm_DMGD
Value: 15000.0   (Units: uM/h)
Constant
 
   K_thf_DMGD
Value: 50.0   (Units: uM)
Constant
 
   K_dmg_DMGD
Value: 50.0   (Units: uM)
Constant
 
   Vf_mMTD
Value: 180000.0   (Units: uM/h)
Constant
 
   K_2cf_MTD
Value: 2.0   (Units: uM)
Constant
 
   Vr_MTD
Value: 594000.0   (Units: uM/h)
Constant
 
   K_1cf_MTD
Value: 10.0   (Units: uM)
Constant
 
   Vf_mMTCH
Value: 790000.0   (Units: uM/h)
Constant
 
   K_1cf_MTCH
Value: 250.0   (Units: uM)
Constant
 
   Vr_MTCH
Value: 20000.0   (Units: uM/h)
Constant
 
   K_10f_MTCH
Value: 100.0   (Units: uM)
Constant
 
   V_mser
Value: 10000.0   (Units: uM/h)
Constant
 
   K_mser
Value: 5700.0   (Units: uM)
Constant
 
   V_cser
Value: 10000.0   (Units: uM/h)
Constant
 
   K_cser
Value: 5700.0   (Units: uM)
Constant
 
   k_in_coo
Value: 100.0   (Units: 1/h)
Constant
 
   k_out_coo
Value: 100.0   (Units: 1/h)
Constant
 
   V_mgly
Value: 10000.0   (Units: uM/h)
Constant
 
   K_mgly
Value: 5700.0   (Units: uM)
Constant
 
   V_cgly
Value: 10000.0   (Units: uM/h)
Constant
 
   K_cgly
Value: 5700.0   (Units: uM)
Constant
 
   Vm_MS
Value: 500.0   (Units: uM/h)
Constant
 
   K_5mf_MS
Value: 25.0   (Units: uM)
Constant
 
   K_hcy_MS
Value: 1.0   (Units: uM)
Constant
 
   ssH2O2
Value: 0.01   (Units: uM)
Constant
 
   Ki_MS
Value: 0.01   (Units: uM)
Constant
 
   Vm_DHFR
Value: 2000.0   (Units: uM/h)
Constant
 
   K_dhf_DHFR
Value: 0.5   (Units: uM)
Constant
 
   K_NADPH_DHFR
Value: 4.0   (Units: uM)
Constant
 
   Vm_cFTD
Value: 500.0   (Units: uM/h)
Constant
 
   Vm_PGT
Value: 24300.0   (Units: uM/h)
Constant
 
   K_10f_PGT
Value: 4.9   (Units: uM)
Constant
 
   K_GAR_PGT
Value: 520.0   (Units: uM)
Constant
 
   Vm_cFTS
Value: 3900.0   (Units: uM/h)
Constant
 
   K_thf_cFTS
Value: 3.0   (Units: uM)
Constant
 
   K_coo_cFTS
Value: 43.0   (Units: uM)
Constant
 
   Vf_cSHMT
Value: 5200.0   (Units: uM/h)
Constant
 
   Vr_cSHMT
Value: 1.5E7   (Units: uM/h)
Constant
 
   k1_cNE
Value: 0.03   (Units: 1/(uM*h))
Constant
 
   k2_cNE
Value: 22.0   (Units: 1/h)
Constant
 
   Vm_TS
Value: 5000.0   (Units: uM/h)
Constant
 
   K_DUMP_TS
Value: 6.3   (Units: uM)
Constant
 
   K_2cf_TS
Value: 14.0   (Units: uM)
Constant
 
   Vm_MTHFR
Value: 5300.0   (Units: uM/h)
Constant
 
   K_2cf_MTHFR
Value: 50.0   (Units: uM)
Constant
 
   K_NADPH_MTHFR
Value: 16.0   (Units: uM)
Constant
 
   Vf_cMTD
Value: 80000.0   (Units: uM/h)
Constant
 
   Vr_cMTD
Value: 600000.0   (Units: uM/h)
Constant
 
   Vf_cMTCH
Value: 500000.0   (Units: uM/h)
Constant
 
   Vm_ART
Value: 55000.0   (Units: uM/h)
Constant
 
   K_10f_ART
Value: 5.9   (Units: uM)
Constant
 
   K_aic_ART
Value: 100.0   (Units: uM)
Constant
 
   Vm_BHMT
Value: 2160.0   (Units: uM/h)
Constant
 
   K_hcy_BHMT
Value: 12.0   (Units: uM)
Constant
 
   K_bet_BHMT
Value: 100.0   (Units: uM)
Constant
 
   Ki_BHMT
Value: 0.01   (Units: uM)
Constant
 
   Vm_MAT1
Value: 260.0   (Units: uM/h)
Constant
 
   Km_MAT1
Value: 41.0   (Units: uM)
Constant
 
   Ki_MAT1
Value: 2140.0   (Units: uM)
Constant
 
   Vm_MAT3
Value: 220.0   (Units: uM/h)
Constant
 
   Km_MAT3
Value: 300.0   (Units: uM)
Constant
 
   Ka_MAT3
Value: 360.0   (Units: uM)
Constant
 
   Ki_MAT3
Value: 4030.0   (Units: uM)
Constant
 
   Vm_GNMT
Value: 260.0   (Units: uM/h)
Constant
 
   K_sam_GNMT
Value: 63.0   (Units: uM)
Constant
 
   K_gly_GNMT
Value: 130.0   (Units: uM)
Constant
 
   Ki_GNMT
Value: 18.0   (Units: uM)
Constant
 
   Vm_DNMT
Value: 180.0   (Units: uM/h)
Constant
 
   Km_DNMT
Value: 1.4   (Units: uM)
Constant
 
   Ki_DNMT
Value: 1.4   (Units: uM)
Constant
 
   Vf_SAHH
Value: 320.0   (Units: uM/h)
Constant
 
   K_sah_SAHH
Value: 6.5   (Units: uM)
Constant
 
   Vr_SAHH
Value: 4530.0   (Units: uM/h)
Constant
 
   K_hcy_SAHH
Value: 150.0   (Units: uM)
Constant
 
   Vm_CBS
Value: 420000.0   (Units: uM/h)
Constant
 
   K_hcy_CBS
Value: 1000.0   (Units: uM)
Constant
 
   K_ser_CBS
Value: 2000.0   (Units: uM)
Constant
 
   Ka_CBS
Value: 0.035   (Units: uM)
Constant
 
   Vm_CTGL
Value: 1500.0   (Units: uM/h)
Constant
 
   K_cyt_CTGL
Value: 500.0   (Units: uM)
Constant
 
   Vm_GCS
Value: 3600.0   (Units: uM/h)
Constant
 
   Ke_GCS
Value: 5597.0   (Units: 1/uM)
Constant
 
   K_cys_GCS
Value: 100.0   (Units: uM)
Constant
 
   K_glu_GCS
Value: 1900.0   (Units: uM)
Constant
 
   Ki_GCS
Value: 8200.0   (Units: uM)
Constant
 
   Kp_GCS
Value: 300.0   (Units: 1/uM)
Constant
 
   Ka_GCS
Value: 0.01   (Units: uM)
Constant
 
   Vm_GS
Value: 5400.0   (Units: uM/h)
Constant
 
   Ke_GS
Value: 5600.0   (Units: 1/uM)
Constant
 
   K_gly_GS
Value: 300.0   (Units: uM)
Constant
 
   K_glc_GS
Value: 22.0   (Units: uM)
Constant
 
   Kp_GS
Value: 30.0   (Units: 1/uM)
Constant
 
   Vm_GPX
Value: 4500.0   (Units: uM/h)
Constant
 
   K_gsh_GPX
Value: 1330.0   (Units: uM)
Constant
 
   K_H2O2_GPX
Value: 0.09   (Units: uM)
Constant
 
   Vm_GR
Value: 892.5   (Units: uM/h)
Constant
 
   K_gsg_GR
Value: 107.0   (Units: uM)
Constant
 
   K_NADPH_GR
Value: 10.4   (Units: uM)
Constant
 
   dinner
Value: 3.25   (Units: dimensionless)
Constant
 
   lunch
Value: 1.75   (Units: dimensionless)
Constant
 
   breakfast
Value: 1.75   (Units: dimensionless)
Constant
 
   fasting
Value: 0.25   (Units: dimensionless)
Constant
 
   daytime
Value: NaN   (Units: hours)
 
   Aminoacid_input
Value: NaN
 
   b_met_basal
Value: 30.0   (Units: uM)
Constant
 
   b_ser_basal
Value: 150.0   (Units: uM)
Constant
 
   V_oGly_b_basal
Value: 630.0   (Units: uM/h)
Constant
 
   V_oGlu_b_basal
Value: 273.0   (Units: uM/h)
Constant
 
   V_oCys_b_basal
Value: 70.0   (Units: uM/h)
Constant
 
   k_out_cys
Value: 1.0   (Units: 1/h)
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000268

Curator's comment: (updated: 07 Sep 2010 17:27:43 BST)

Reproduction of figure 5 of the original article. Only the second day was chosen to be displayed, as the initial concentrations for the time courses are not known.

The calculations were performed using Copasi 4.6.

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