// This model generated automatically from SBML

// unit definitions
import nsrunit;
unit conversion off;

// SBML property definitions
property sbmlRole=string;
property sbmlName=string;
property sbmlCompartment=string;

// SBML reactions
// SHMT: FH4 serine <=> CH2FH4 
// SHMTr: CH2FH4 <=> FH4 
// HCHOtoCH2FH4: FH4 HCHO <=> CH2FH4 
// CH2FH4toHCHO: CH2FH4 <=> FH4 HCHO 
// MTHFR: CH2FH4 NADPH <=> CH3FH4 
// MTR: CH3FH4 homocysteine <=> FH4 
// HCOOHtoCHOFH4: FH4 formate ATP <=> CHOFH4 
// GARFT: CHOFH4 GAR <=> FGAR FH4 
// ATIC7: CHOFH4 AICAR <=> FH4 
// MTHFD: CH2FH4 NADP <=> CHOFH4 
// TYMS: CH2FH4 dUMP <=> FH2f 
// DHFReductase: FH2f <=> FH4 
// FFH2syn: FH2f <=> FFH2 
// ATIC12: FFH2 AICAR <=> FH2f 
// AICARsyn: FGAR <=> AICAR 
// FPGS12: MTX1 <=> MTX2 
// FPGS23: MTX2 <=> MTX3 
// FPGS34: MTX3 <=> MTX4 
// FPGS45: MTX4 <=> MTX5 
// GGH21: MTX2 <=> MTX1 
// GGH32: MTX3 <=> MTX2 
// GGH43: MTX4 <=> MTX3 
// GGH54: MTX5 <=> MTX4 
// RFC: EMTX <=> MTX1 
// MTX1export: MTX1 
// MTX2export: MTX2 
// MTX3export: MTX3 
// MTX4export: MTX4 
// MTX5export: MTX5 
// MTX1on: MTX1 DHFRf <=> MTX1b 
// MTX2on: MTX2 DHFRf <=> MTX2b 
// MTX3on: MTX3 DHFRf <=> MTX3b 
// MTX4on: MTX4 DHFRf <=> MTX4b 
// MTX5on: MTX5 DHFRf <=> MTX5b 
// MTX1off: MTX1b <=> MTX1 DHFRf 
// MTX2off: MTX2b <=> MTX2 DHFRf 
// MTX3off: MTX3b <=> MTX3 DHFRf 
// MTX4off: MTX4b <=> MTX4 DHFRf 
// MTX5off: MTX5b <=> MTX5 DHFRf 
// DHFRfsyn: <=> DHFRf 
// DHFRdeg: DHFRf 
// FH2bdeg: <=> FH2f 
// MTX1deg: MTX1b <=> MTX1 
// MTX2deg: MTX2b <=> MTX2 
// MTX3deg: MTX3b <=> MTX3 
// MTX4deg: MTX4b <=> MTX4 
// MTX5deg: MTX5b <=> MTX5 

math main {
  realDomain time second;
  time.min=0;
  extern time.max;
  extern time.delta;

  // variable definitions
  real ext = 1 L;
  real cell = 1 L;
  real Keq = .32;
  real FH2f(time) uM;
  real FH2b(time) uM;
  real DHFRf(time) uM;
  real DHFRtot(time) uM;
  real FH4(time) uM;
  real CH2FH4(time) uM;
  real CH3FH4(time) uM;
  real CHOFH4(time) uM;
  real FFH2(time) uM;
  real HCHO(time) uM;
  real FGAR(time) uM;
  real AICAR(time) uM;
  real MTX1(time) uM;
  real MTX2(time) uM;
  real MTX3(time) uM;
  real MTX4(time) uM;
  real MTX5(time) uM;
  real MTX1b(time) uM;
  real MTX2b(time) uM;
  real MTX3b(time) uM;
  real MTX4b(time) uM;
  real MTX5b(time) uM;
  real EMTX = 0 uM;
  real dUMP = 20.76 uM;
  real GAR = 689.6 uM;
  real serine = 123.3 uM;
  real formate = 500 uM;
  real ATP = 2980 uM;
  real glutamine = 7170 uM;
  real glycine = 1600 uM;
  real NADP = 6.73 uM;
  real NADPH = 294 uM;
  real homocysteine = 10 uM;
  real SHMT(time) umol/hr;
  real Vm = 18330;
  real Km1 = 1.7;
  real Km2 = 210;
  real SHMTr(time) umol/hr;
  real HCHOtoCH2FH4(time) umol/hr;
  real hp = 23.2;
  real CH2FH4toHCHO(time) umol/hr;
  real hl = .3;
  real MTHFR(time) umol/hr;
  real Ki1 = .4;
  real Ki21 = 59;
  real Ki22 = 21.3;
  real Ki23 = 7.68;
  real Ki24 = 2.77;
  real Ki25 = 1;
  real MTR(time) umol/hr;
  real HCOOHtoCHOFH4(time) umol/hr;
  real Km3 = 1600;
  real GARFT(time) umol/hr;
  real Ki1f = 1;
  real ATIC7(time) umol/hr;
  real MTHFD(time) umol/hr;
  real TYMS(time) umol/hr;
  real DHFReductase(time) umol/hr;
  real kter = 2109.4;
  real FFH2syn(time) umol/hr;
  real ATIC12(time) umol/hr;
  real AICARsyn(time) umol/hr;
  real FPGS12(time) umol/hr;
  real FPGS23(time) umol/hr;
  real FPGS34(time) umol/hr;
  real FPGS45(time) umol/hr;
  real GGH21(time) umol/hr;
  real GGH32(time) umol/hr;
  real GGH43(time) umol/hr;
  real GGH54(time) umol/hr;
  real RFC(time) umol/hr;
  real Km = 8.2;
  real MTX1export(time) umol/hr;
  real MTX2export(time) umol/hr;
  real MTX3export(time) umol/hr;
  real MTX4export(time) umol/hr;
  real MTX5export(time) umol/hr;
  real MTX1on(time) umol/hr;
  real MTX2on(time) umol/hr;
  real MTX3on(time) umol/hr;
  real MTX4on(time) umol/hr;
  real MTX5on(time) umol/hr;
  real MTX1off(time) umol/hr;
  real MTX2off(time) umol/hr;
  real MTX3off(time) umol/hr;
  real MTX4off(time) umol/hr;
  real MTX5off(time) umol/hr;
  real DHFRfsyn(time) umol/hr;
  real k0 = .0192;
  real k1 = .04416;
  real DHFRdeg(time) umol/hr;
  real FH2bdeg(time) umol/hr;
  real MTX1deg(time) umol/hr;
  real MTX2deg(time) umol/hr;
  real MTX3deg(time) umol/hr;
  real MTX4deg(time) umol/hr;
  real MTX5deg(time) umol/hr;

  // equations
  when (time=time.min) FH2f = .0012;
  FH2f:time = (TYMS + -1*DHFReductase + -1*FFH2syn + ATIC12 + FH2bdeg)/cell;
  FH2b = FH2f*DHFRf/Keq;
  when (time=time.min) DHFRf = .64;
  DHFRf:time = (-1*MTX1on + -1*MTX2on + -1*MTX3on + -1*MTX4on + -1*MTX5on + MTX1off + MTX2off + MTX3off + MTX4off + MTX5off + DHFRfsyn + -1*DHFRdeg)/cell;
  DHFRtot = FH2b+DHFRf+MTX1b+MTX2b+MTX3b+MTX4b+MTX5b;
  when (time=time.min) FH4 = .46;
  FH4:time = (-1*SHMT + SHMTr + -1*HCHOtoCH2FH4 + CH2FH4toHCHO + MTR + -1*HCOOHtoCHOFH4 + GARFT + ATIC7 + DHFReductase)/cell;
  when (time=time.min) CH2FH4 = .26;
  CH2FH4:time = (SHMT + -1*SHMTr + HCHOtoCH2FH4 + -1*CH2FH4toHCHO + -1*MTHFR + -1*MTHFD + -1*TYMS)/cell;
  when (time=time.min) CH3FH4 = 1.63;
  CH3FH4:time = (MTHFR + -1*MTR)/cell;
  when (time=time.min) CHOFH4 = 1;
  CHOFH4:time = (HCOOHtoCHOFH4 + -1*GARFT + -1*ATIC7 + MTHFD)/cell;
  when (time=time.min) FFH2 = 3.32E-4;
  FFH2:time = (FFH2syn + -1*ATIC12)/cell;
  when (time=time.min) HCHO = .0074;
  HCHO:time = (-1*HCHOtoCH2FH4 + CH2FH4toHCHO)/cell;
  when (time=time.min) FGAR = 16.49;
  FGAR:time = (GARFT + -1*AICARsyn)/cell;
  when (time=time.min) AICAR = 3.695;
  AICAR:time = (-1*ATIC7 + -1*ATIC12 + AICARsyn)/cell;
  when (time=time.min) MTX1 = 0;
  MTX1:time = (-1*FPGS12 + GGH21 + RFC + -1*MTX1export + -1*MTX1on + MTX1off + MTX1deg)/cell;
  when (time=time.min) MTX2 = 0;
  MTX2:time = (FPGS12 + -1*FPGS23 + -1*GGH21 + GGH32 + -1*MTX2export + -1*MTX2on + MTX2off + MTX2deg)/cell;
  when (time=time.min) MTX3 = 0;
  MTX3:time = (FPGS23 + -1*FPGS34 + -1*GGH32 + GGH43 + -1*MTX3export + -1*MTX3on + MTX3off + MTX3deg)/cell;
  when (time=time.min) MTX4 = 0;
  MTX4:time = (FPGS34 + -1*FPGS45 + -1*GGH43 + GGH54 + -1*MTX4export + -1*MTX4on + MTX4off + MTX4deg)/cell;
  when (time=time.min) MTX5 = 0;
  MTX5:time = (FPGS45 + -1*GGH54 + -1*MTX5export + -1*MTX5on + MTX5off + MTX5deg)/cell;
  when (time=time.min) MTX1b = 0;
  MTX1b:time = (MTX1on + -1*MTX1off + -1*MTX1deg)/cell;
  when (time=time.min) MTX2b = 0;
  MTX2b:time = (MTX2on + -1*MTX2off + -1*MTX2deg)/cell;
  when (time=time.min) MTX3b = 0;
  MTX3b:time = (MTX3on + -1*MTX3off + -1*MTX3deg)/cell;
  when (time=time.min) MTX4b = 0;
  MTX4b:time = (MTX4on + -1*MTX4off + -1*MTX4deg)/cell;
  when (time=time.min) MTX5b = 0;
  MTX5b:time = (MTX5on + -1*MTX5off + -1*MTX5deg)/cell;
  SHMT = cell*(Vm*(serine/Km2/(1+serine/Km2))*(FH4/Km1)/(1+FH4/Km1));
  SHMTr = cell*(Vm*(glycine/Km2/(1+glycine/Km2))*(CH2FH4/Km1)/(1+CH2FH4/Km1));
  HCHOtoCH2FH4 = cell*hp*FH4*HCHO;
  CH2FH4toHCHO = cell*hl*CH2FH4;
  MTHFR = cell*(Vm*CH2FH4*NADPH/(NADPH*CH2FH4+CH2FH4*Km2+(NADPH+Km2)*Km1*(1+MTX1/Ki21+MTX2/Ki22+MTX3/Ki23+MTX4/Ki24+MTX5/Ki25+FH2f/Ki1)));
  MTR = cell*(Vm*(homocysteine/Km2/(1+homocysteine/Km2))*(CH3FH4/Km1)/(1+CH3FH4/Km1));
  HCOOHtoCHOFH4 = cell*(Vm/((1+Km1/FH4)*(1+Km2/ATP)*(1+Km3/formate)));
  GARFT = cell*(Vm*CHOFH4*GAR/(GAR*CHOFH4+CHOFH4*Km2+(GAR+Km2)*Km1*(1+MTX1/Ki21+MTX2/Ki22+MTX3/Ki23+MTX4/Ki24+MTX5/Ki25+FH2f/Ki1+FFH2/Ki1f)));
  ATIC7 = cell*(Vm*CHOFH4*AICAR/(AICAR*CHOFH4+CHOFH4*Km2+(AICAR+Km2)*Km1*(1+MTX1/Ki21+MTX2/Ki22+MTX3/Ki23+MTX4/Ki24+MTX5/Ki25+FH2f/Ki1+FFH2/Ki1f)));
  MTHFD = cell*Vm*(CH2FH4/Km1/(1+CH2FH4/Km1))*(NADP/Km2/(1+NADP/Km2));
  TYMS = cell*(Vm*CH2FH4*dUMP/(dUMP*CH2FH4*(1+MTX1/Ki21+MTX2/Ki22+MTX3/Ki23+MTX4/Ki24+MTX5/Ki25+FH2f/Ki1)+Km1*dUMP*(FFH2/Ki1f*(MTX1/Ki21)+(1+FFH2/Ki1f)*(1+MTX2/Ki22+MTX3/Ki23+MTX4/Ki24+MTX5/Ki25+FH2f/Ki1))+Km1*Km2*(1+MTX2/Ki22+MTX3/Ki23+MTX4/Ki24+MTX5/Ki25+FH2f/Ki1)));
  DHFReductase = cell*kter*FH2b;
  FFH2syn = cell*Vm*FH2f;
  ATIC12 = cell*(Vm*FFH2*AICAR/(AICAR*FFH2+FFH2*Km2+(AICAR+Km2)*Km1*(1+MTX1/Ki21+MTX2/Ki22+MTX3/Ki23+MTX4/Ki24+MTX5/Ki25+FH2f/Ki1+FFH2/Ki1f)));
  AICARsyn = cell*Vm*(glutamine/Km1/(1+glutamine/Km1))*(FGAR/Km2/(1+FGAR/Km2));
  FPGS12 = cell*Vm*MTX1;
  FPGS23 = cell*Vm*MTX2;
  FPGS34 = cell*Vm*MTX3;
  FPGS45 = cell*Vm*MTX4;
  GGH21 = cell*Vm*MTX2;
  GGH32 = cell*Vm*MTX3;
  GGH43 = cell*Vm*MTX4;
  GGH54 = cell*Vm*MTX5;
  RFC = ext*(Vm*EMTX/(Km+EMTX));
  MTX1export = cell*Vm*MTX1;
  MTX2export = cell*Vm*MTX2;
  MTX3export = cell*Vm*MTX3;
  MTX4export = cell*Vm*MTX4;
  MTX5export = cell*Vm*MTX5;
  MTX1on = cell*Vm*DHFRf*MTX1;
  MTX2on = cell*Vm*DHFRf*MTX2;
  MTX3on = cell*Vm*DHFRf*MTX3;
  MTX4on = cell*Vm*DHFRf*MTX4;
  MTX5on = cell*Vm*DHFRf*MTX5;
  MTX1off = cell*Vm*MTX1b;
  MTX2off = cell*Vm*MTX2b;
  MTX3off = cell*Vm*MTX3b;
  MTX4off = cell*Vm*MTX4b;
  MTX5off = cell*Vm*MTX5b;
  DHFRfsyn = cell*(k0+k1*EMTX);
  DHFRdeg = Vm*cell*(DHFRf+FH2b);
  FH2bdeg = cell*Vm*FH2b;
  MTX1deg = cell*Vm*MTX1b;
  MTX2deg = cell*Vm*MTX2b;
  MTX3deg = cell*Vm*MTX3b;
  MTX4deg = cell*Vm*MTX4b;
  MTX5deg = cell*Vm*MTX5b;

  // variable properties
  ext.sbmlRole="compartment";
  cell.sbmlRole="compartment";
  Keq.sbmlRole="parameter";
  FH2f.sbmlRole="species";
  FH2f.sbmlCompartment="cell";
  FH2b.sbmlRole="species";
  FH2b.sbmlCompartment="cell";
  DHFRf.sbmlRole="species";
  DHFRf.sbmlCompartment="cell";
  DHFRtot.sbmlRole="species";
  DHFRtot.sbmlCompartment="cell";
  FH4.sbmlRole="species";
  FH4.sbmlCompartment="cell";
  CH2FH4.sbmlRole="species";
  CH2FH4.sbmlCompartment="cell";
  CH3FH4.sbmlRole="species";
  CH3FH4.sbmlCompartment="cell";
  CHOFH4.sbmlRole="species";
  CHOFH4.sbmlCompartment="cell";
  FFH2.sbmlRole="species";
  FFH2.sbmlCompartment="cell";
  HCHO.sbmlRole="species";
  HCHO.sbmlCompartment="cell";
  FGAR.sbmlRole="species";
  FGAR.sbmlCompartment="cell";
  AICAR.sbmlRole="species";
  AICAR.sbmlCompartment="cell";
  MTX1.sbmlRole="species";
  MTX1.sbmlCompartment="cell";
  MTX2.sbmlRole="species";
  MTX2.sbmlCompartment="cell";
  MTX3.sbmlRole="species";
  MTX3.sbmlCompartment="cell";
  MTX4.sbmlRole="species";
  MTX4.sbmlCompartment="cell";
  MTX5.sbmlRole="species";
  MTX5.sbmlCompartment="cell";
  MTX1b.sbmlRole="species";
  MTX1b.sbmlCompartment="cell";
  MTX2b.sbmlRole="species";
  MTX2b.sbmlCompartment="cell";
  MTX3b.sbmlRole="species";
  MTX3b.sbmlCompartment="cell";
  MTX4b.sbmlRole="species";
  MTX4b.sbmlCompartment="cell";
  MTX5b.sbmlRole="species";
  MTX5b.sbmlCompartment="cell";
  EMTX.sbmlRole="species";
  EMTX.sbmlCompartment="ext";
  dUMP.sbmlRole="species";
  dUMP.sbmlCompartment="cell";
  GAR.sbmlRole="species";
  GAR.sbmlCompartment="cell";
  serine.sbmlRole="species";
  serine.sbmlCompartment="cell";
  formate.sbmlRole="species";
  formate.sbmlCompartment="cell";
  ATP.sbmlRole="species";
  ATP.sbmlCompartment="cell";
  glutamine.sbmlRole="species";
  glutamine.sbmlCompartment="cell";
  glycine.sbmlRole="species";
  glycine.sbmlCompartment="cell";
  NADP.sbmlRole="species";
  NADP.sbmlCompartment="cell";
  NADPH.sbmlRole="species";
  NADPH.sbmlCompartment="cell";
  homocysteine.sbmlRole="species";
  homocysteine.sbmlCompartment="cell";
  SHMT.sbmlRole="rate";
  Vm.sbmlRole="parameter";
  Km1.sbmlRole="parameter";
  Km2.sbmlRole="parameter";
  SHMTr.sbmlRole="rate";
  HCHOtoCH2FH4.sbmlRole="rate";
  hp.sbmlRole="parameter";
  CH2FH4toHCHO.sbmlRole="rate";
  hl.sbmlRole="parameter";
  MTHFR.sbmlRole="rate";
  Ki1.sbmlRole="parameter";
  Ki21.sbmlRole="parameter";
  Ki22.sbmlRole="parameter";
  Ki23.sbmlRole="parameter";
  Ki24.sbmlRole="parameter";
  Ki25.sbmlRole="parameter";
  MTR.sbmlRole="rate";
  HCOOHtoCHOFH4.sbmlRole="rate";
  Km3.sbmlRole="parameter";
  GARFT.sbmlRole="rate";
  Ki1f.sbmlRole="parameter";
  ATIC7.sbmlRole="rate";
  MTHFD.sbmlRole="rate";
  TYMS.sbmlRole="rate";
  DHFReductase.sbmlRole="rate";
  kter.sbmlRole="parameter";
  FFH2syn.sbmlRole="rate";
  ATIC12.sbmlRole="rate";
  AICARsyn.sbmlRole="rate";
  FPGS12.sbmlRole="rate";
  FPGS23.sbmlRole="rate";
  FPGS34.sbmlRole="rate";
  FPGS45.sbmlRole="rate";
  GGH21.sbmlRole="rate";
  GGH32.sbmlRole="rate";
  GGH43.sbmlRole="rate";
  GGH54.sbmlRole="rate";
  RFC.sbmlRole="rate";
  Km.sbmlRole="parameter";
  MTX1export.sbmlRole="rate";
  MTX2export.sbmlRole="rate";
  MTX3export.sbmlRole="rate";
  MTX4export.sbmlRole="rate";
  MTX5export.sbmlRole="rate";
  MTX1on.sbmlRole="rate";
  MTX2on.sbmlRole="rate";
  MTX3on.sbmlRole="rate";
  MTX4on.sbmlRole="rate";
  MTX5on.sbmlRole="rate";
  MTX1off.sbmlRole="rate";
  MTX2off.sbmlRole="rate";
  MTX3off.sbmlRole="rate";
  MTX4off.sbmlRole="rate";
  MTX5off.sbmlRole="rate";
  DHFRfsyn.sbmlRole="rate";
  k0.sbmlRole="parameter";
  k1.sbmlRole="parameter";
  DHFRdeg.sbmlRole="rate";
  FH2bdeg.sbmlRole="rate";
  MTX1deg.sbmlRole="rate";
  MTX2deg.sbmlRole="rate";
  MTX3deg.sbmlRole="rate";
  MTX4deg.sbmlRole="rate";
  MTX5deg.sbmlRole="rate";
}