<?xml version="1.0" encoding="UTF-8"?>
<sbml xmlns="http://www.sbml.org/sbml/level2" level="2" version="1">
<model id="MorrisonAllegra">
<notes>
 <body xmlns="http://www.w3.org/1999/xhtml">
   <p> This is a folate model that includes MTX polyglutamation.  </p>
   <p> Morrison and Allegra, JBC:264,10552-10566 (1989)  </p>
   <p> Folate cycle kinetics in breast cancer cells.  </p>
   <p> o                                               </p>
   <p> Two flow BCs were converted into two downstream  </p>
   <p> concentration BCs, thus removing the GAR and dUMP state variables.  </p>
   <p> This dropped the number of ODEs from 21 to 19.  </p>
   <p> o                                                 </p>
   <p> The subscript b following some species names implies bound to DHFR.  </p>
   <p> FH2 free and bound to DHFR are in rapid equilibrium.  </p>
   <p> DHFRsyn(thesis) parameters were picked to get SS concentration   </p>
   <p> right with kdeg=.03 and also to get 1uM MTX to ramp DHFR up by a factor of 3.3.  </p>
   <p> MTX1 efflux is strong enough that GGH21 overwhelms MTX2 export.  </p>
   <p> Keq is a global parameter; this wouldn't be needed if rules had local parameters!  </p>
   <p> DHFR protein degradation reactions are independent of folate binding.  </p>
   <p> In DHFRdeg, since mass cannot come out of the BC it was taken form free DHFR  </p>
   <p> In FH2bdeg we create back the FH2 missing from DHFR protein degradation.  </p>
   <p> The units in this model are concentrations in micromolar and time in hours.  </p>
   <p> Volume sizes of 1 were picked to equate concentrations to mass or moles  </p>
 </body>
</notes>
<listOfCompartments>
   <compartment id="cell"  size="1" />
   <compartment id="ext"  size="1" />
</listOfCompartments>
<listOfSpecies>
   <species id="FH2f"  initialConcentration="0.0012"  compartment="cell" boundaryCondition="false"/>
   <species id="FH2b"  initialConcentration="0.0024"  compartment="cell" boundaryCondition="true"/>
   <species id="DHFRf"  initialConcentration="0.64"  compartment="cell" boundaryCondition="false"/>
   <species id="DHFRtot"  initialConcentration="0.64"  compartment="cell" boundaryCondition="true"/>
   <species id="FH4"  initialConcentration="0.46"  compartment="cell" boundaryCondition="false"/>
   <species id="CH2FH4"  initialConcentration="0.26"  compartment="cell" boundaryCondition="false"/>
   <species id="CH3FH4"  initialConcentration="1.63"  compartment="cell" boundaryCondition="false"/>
   <species id="CHOFH4"  initialConcentration="1"  compartment="cell" boundaryCondition="false"/>
   <species id="FFH2"  initialConcentration="0.000332"  compartment="cell" boundaryCondition="false"/>
   <species id="HCHO"  initialConcentration="0.0074"  compartment="cell" boundaryCondition="false"/>
   <species id="FGAR"  initialConcentration="16.49"  compartment="cell" boundaryCondition="false"/>
   <species id="AICAR"  initialConcentration="3.695"  compartment="cell" boundaryCondition="false"/>
   <species id="MTX1"  initialConcentration="0"  compartment="cell" boundaryCondition="false"/>
   <species id="MTX2"  initialConcentration="0"  compartment="cell" boundaryCondition="false"/>
   <species id="MTX3"  initialConcentration="0"  compartment="cell" boundaryCondition="false"/>
   <species id="MTX4"  initialConcentration="0"  compartment="cell" boundaryCondition="false"/>
   <species id="MTX5"  initialConcentration="0"  compartment="cell" boundaryCondition="false"/>
   <species id="MTX1b"  initialConcentration="0"  compartment="cell" boundaryCondition="false"/>
   <species id="MTX2b"  initialConcentration="0"  compartment="cell" boundaryCondition="false"/>
   <species id="MTX3b"  initialConcentration="0"  compartment="cell" boundaryCondition="false"/>
   <species id="MTX4b"  initialConcentration="0"  compartment="cell" boundaryCondition="false"/>
   <species id="MTX5b"  initialConcentration="0"  compartment="cell" boundaryCondition="false"/>
   <species id="EMTX"  initialConcentration="0"  compartment="ext" boundaryCondition="true"/>
   <species id="dUMP"  initialConcentration="20.76"  compartment="cell" boundaryCondition="true"/>
   <species id="GAR"  initialConcentration="689.6"  compartment="cell" boundaryCondition="true"/>
   <species id="serine"  initialConcentration="123.3"  compartment="cell" boundaryCondition="true"/>
   <species id="formate"  initialConcentration="500"  compartment="cell" boundaryCondition="true"/>
   <species id="ATP"  initialConcentration="2980"  compartment="cell" boundaryCondition="true"/>
   <species id="glutamine"  initialConcentration="7170"  compartment="cell" boundaryCondition="true"/>
   <species id="glycine"  initialConcentration="1600"  compartment="cell" boundaryCondition="true"/>
   <species id="NADP"  initialConcentration="6.73"  compartment="cell" boundaryCondition="true"/>
   <species id="NADPH"  initialConcentration="294"  compartment="cell" boundaryCondition="true"/>
   <species id="homocysteine"  initialConcentration="10"  compartment="cell" boundaryCondition="true"/>
</listOfSpecies>
<listOfParameters>
   <parameter id="Keq"  value="0.32" />
</listOfParameters>
<listOfRules>
  <assignmentRule variable="FH2b">
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <divide/>
    <apply>
      <times/>
     <ci>FH2f</ci>
     <ci>DHFRf</ci>
    </apply>
     <ci>Keq</ci>
    </apply>
    </math>
  </assignmentRule>
  <assignmentRule variable="DHFRtot">
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
     <ci>FH2b</ci>
     <ci>DHFRf</ci>
    </apply>
     <ci>MTX1b</ci>
    </apply>
     <ci>MTX2b</ci>
    </apply>
     <ci>MTX3b</ci>
    </apply>
     <ci>MTX4b</ci>
    </apply>
     <ci>MTX5b</ci>
    </apply>
    </math>
  </assignmentRule>
</listOfRules>
<listOfReactions>
  <reaction id="SHMT"  reversible="false">
    <listOfReactants>
      <speciesReference species = "FH4" />
      <speciesReference species = "serine" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "CH2FH4" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
    <apply>
      <times/>
     <ci>Vm</ci>
    <apply>
      <divide/>
    <apply>
      <divide/>
     <ci>serine</ci>
     <ci>Km2</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>serine</ci>
     <ci>Km2</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    <apply>
      <divide/>
    <apply>
      <divide/>
     <ci>FH4</ci>
     <ci>Km1</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>FH4</ci>
     <ci>Km1</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "18330"/>
      <parameter id = "Km1" value = "1.7"/>
      <parameter id = "Km2" value = "210"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="SHMTr"  reversible="false">
    <listOfReactants>
      <speciesReference species = "CH2FH4" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "FH4" />
    </listOfProducts>
    <listOfModifiers>
      <modifierSpeciesReference species = "glycine" />
    </listOfModifiers>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
    <apply>
      <times/>
     <ci>Vm</ci>
    <apply>
      <divide/>
    <apply>
      <divide/>
     <ci>glycine</ci>
     <ci>Km2</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>glycine</ci>
     <ci>Km2</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    <apply>
      <divide/>
    <apply>
      <divide/>
     <ci>CH2FH4</ci>
     <ci>Km1</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>CH2FH4</ci>
     <ci>Km1</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "1.22e+007"/>
      <parameter id = "Km1" value = "3200"/>
      <parameter id = "Km2" value = "10000"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="HCHOtoCH2FH4"  reversible="false">
    <listOfReactants>
      <speciesReference species = "FH4" />
      <speciesReference species = "HCHO" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "CH2FH4" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
    <apply>
      <times/>
     <ci>hp</ci>
     <ci>FH4</ci>
    </apply>
     <ci>HCHO</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "hp" value = "23.2"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="CH2FH4toHCHO"  reversible="false">
    <listOfReactants>
      <speciesReference species = "CH2FH4" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "FH4" />
      <speciesReference species = "HCHO" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>hl</ci>
     <ci>CH2FH4</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "hl" value = "0.3"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTHFR"  reversible="false">
    <listOfReactants>
      <speciesReference species = "CH2FH4" />
      <speciesReference species = "NADPH" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "CH3FH4" />
    </listOfProducts>
    <listOfModifiers>
      <modifierSpeciesReference species = "FH2f" />
      <modifierSpeciesReference species = "MTX1" />
      <modifierSpeciesReference species = "MTX2" />
      <modifierSpeciesReference species = "MTX3" />
      <modifierSpeciesReference species = "MTX4" />
      <modifierSpeciesReference species = "MTX5" />
    </listOfModifiers>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
    <apply>
      <times/>
     <ci>Vm</ci>
    <apply>
      <divide/>
    <apply>
      <divide/>
     <ci>NADPH</ci>
     <ci>Km2</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>NADPH</ci>
     <ci>Km2</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>CH2FH4</ci>
    <apply>
      <plus/>
     <ci>CH2FH4</ci>
    <apply>
      <times/>
     <ci>Km1</ci>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>MTX1</ci>
     <ci>Ki21</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX2</ci>
     <ci>Ki22</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX3</ci>
     <ci>Ki23</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX4</ci>
     <ci>Ki24</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX5</ci>
     <ci>Ki25</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>FH2f</ci>
     <ci>Ki1</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    </apply>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "224.8"/>
      <parameter id = "Km1" value = "50"/>
      <parameter id = "Km2" value = "50"/>
      <parameter id = "Ki1" value = "0.4"/>
      <parameter id = "Ki21" value = "59"/>
      <parameter id = "Ki22" value = "21.3"/>
      <parameter id = "Ki23" value = "7.68"/>
      <parameter id = "Ki24" value = "2.77"/>
      <parameter id = "Ki25" value = "1"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTR"  reversible="false">
    <listOfReactants>
      <speciesReference species = "CH3FH4" />
      <speciesReference species = "homocysteine" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "FH4" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
    <apply>
      <times/>
     <ci>Vm</ci>
    <apply>
      <divide/>
    <apply>
      <divide/>
     <ci>homocysteine</ci>
     <ci>Km2</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>homocysteine</ci>
     <ci>Km2</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    <apply>
      <divide/>
    <apply>
      <divide/>
     <ci>CH3FH4</ci>
     <ci>Km1</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>CH3FH4</ci>
     <ci>Km1</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "22600"/>
      <parameter id = "Km1" value = "125"/>
      <parameter id = "Km2" value = "2900"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="HCOOHtoCHOFH4"  reversible="false">
    <listOfReactants>
      <speciesReference species = "FH4" />
      <speciesReference species = "formate" />
      <speciesReference species = "ATP" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "CHOFH4" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
    <apply>
      <times/>
    <apply>
      <times/>
     <ci>Vm</ci>
    <apply>
      <divide/>
    <apply>
      <divide/>
     <ci>FH4</ci>
     <ci>Km1</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>FH4</ci>
     <ci>Km1</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    <apply>
      <divide/>
    <apply>
      <divide/>
     <ci>ATP</ci>
     <ci>Km2</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>ATP</ci>
     <ci>Km2</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    <apply>
      <divide/>
    <apply>
      <divide/>
     <ci>formate</ci>
     <ci>Km3</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>formate</ci>
     <ci>Km3</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "3600"/>
      <parameter id = "Km1" value = "230"/>
      <parameter id = "Km2" value = "56"/>
      <parameter id = "Km3" value = "1600"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="GARFT"  reversible="false">
    <listOfReactants>
      <speciesReference species = "CHOFH4" />
      <speciesReference species = "GAR" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "FGAR" />
      <speciesReference species = "FH4" />
    </listOfProducts>
    <listOfModifiers>
      <modifierSpeciesReference species = "FH2f" />
      <modifierSpeciesReference species = "FFH2" />
      <modifierSpeciesReference species = "MTX1" />
      <modifierSpeciesReference species = "MTX2" />
      <modifierSpeciesReference species = "MTX3" />
      <modifierSpeciesReference species = "MTX4" />
      <modifierSpeciesReference species = "MTX5" />
    </listOfModifiers>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
    <apply>
      <times/>
     <ci>Vm</ci>
    <apply>
      <divide/>
    <apply>
      <divide/>
     <ci>GAR</ci>
     <ci>Km2</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>GAR</ci>
     <ci>Km2</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>CHOFH4</ci>
    <apply>
      <plus/>
     <ci>CHOFH4</ci>
    <apply>
      <times/>
     <ci>Km1</ci>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>MTX1</ci>
     <ci>Ki21</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX2</ci>
     <ci>Ki22</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX3</ci>
     <ci>Ki23</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX4</ci>
     <ci>Ki24</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX5</ci>
     <ci>Ki25</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>FH2f</ci>
     <ci>Ki1</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>FFH2</ci>
     <ci>Ki1f</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    </apply>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "4126"/>
      <parameter id = "Km1" value = "4.9"/>
      <parameter id = "Km2" value = "52"/>
      <parameter id = "Ki1" value = "5"/>
      <parameter id = "Ki1f" value = "1"/>
      <parameter id = "Ki21" value = "84"/>
      <parameter id = "Ki22" value = "60"/>
      <parameter id = "Ki23" value = "43"/>
      <parameter id = "Ki24" value = "31"/>
      <parameter id = "Ki25" value = "22"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="ATIC7"  reversible="false">
    <listOfReactants>
      <speciesReference species = "CHOFH4" />
      <speciesReference species = "AICAR" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "FH4" />
    </listOfProducts>
    <listOfModifiers>
      <modifierSpeciesReference species = "FH2f" />
      <modifierSpeciesReference species = "FFH2" />
      <modifierSpeciesReference species = "MTX1" />
      <modifierSpeciesReference species = "MTX2" />
      <modifierSpeciesReference species = "MTX3" />
      <modifierSpeciesReference species = "MTX4" />
      <modifierSpeciesReference species = "MTX5" />
    </listOfModifiers>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
    <apply>
      <times/>
     <ci>Vm</ci>
    <apply>
      <divide/>
    <apply>
      <divide/>
     <ci>AICAR</ci>
     <ci>Km2</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>AICAR</ci>
     <ci>Km2</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>CHOFH4</ci>
    <apply>
      <plus/>
     <ci>CHOFH4</ci>
    <apply>
      <times/>
     <ci>Km1</ci>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>MTX1</ci>
     <ci>Ki21</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX2</ci>
     <ci>Ki22</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX3</ci>
     <ci>Ki23</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX4</ci>
     <ci>Ki24</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX5</ci>
     <ci>Ki25</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>FH2f</ci>
     <ci>Ki1</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>FFH2</ci>
     <ci>Ki1f</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    </apply>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "31675"/>
      <parameter id = "Km1" value = "5.5"/>
      <parameter id = "Km2" value = "24"/>
      <parameter id = "Ki1" value = "2.89"/>
      <parameter id = "Ki1f" value = "5.3"/>
      <parameter id = "Ki21" value = "40"/>
      <parameter id = "Ki22" value = "31.5"/>
      <parameter id = "Ki23" value = "2.33"/>
      <parameter id = "Ki24" value = "3.61"/>
      <parameter id = "Ki25" value = "5.89"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTHFD"  reversible="false">
    <listOfReactants>
      <speciesReference species = "CH2FH4" />
      <speciesReference species = "NADP" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "CHOFH4" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
    <apply>
      <times/>
     <ci>Vm</ci>
    <apply>
      <divide/>
    <apply>
      <divide/>
     <ci>CH2FH4</ci>
     <ci>Km1</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>CH2FH4</ci>
     <ci>Km1</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    <apply>
      <divide/>
    <apply>
      <divide/>
     <ci>NADP</ci>
     <ci>Km2</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>NADP</ci>
     <ci>Km2</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "68500"/>
      <parameter id = "Km1" value = "3"/>
      <parameter id = "Km2" value = "21.8"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="TYMS"  reversible="false">
    <listOfReactants>
      <speciesReference species = "CH2FH4" />
      <speciesReference species = "dUMP" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "FH2f" />
    </listOfProducts>
    <listOfModifiers>
      <modifierSpeciesReference species = "FH2f" />
      <modifierSpeciesReference species = "FFH2" />
      <modifierSpeciesReference species = "MTX1" />
      <modifierSpeciesReference species = "MTX2" />
      <modifierSpeciesReference species = "MTX3" />
      <modifierSpeciesReference species = "MTX4" />
      <modifierSpeciesReference species = "MTX5" />
    </listOfModifiers>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <divide/>
    <apply>
      <times/>
    <apply>
      <times/>
     <ci>Vm</ci>
    <apply>
      <divide/>
     <ci>CH2FH4</ci>
     <ci>Km1</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>dUMP</ci>
     <ci>Km2</ci>
    </apply>
    </apply>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <times/>
    <apply>
      <times/>
    <apply>
      <divide/>
     <ci>CH2FH4</ci>
     <ci>Km1</ci>
    </apply>
    <apply>
      <divide/>
     <ci>dUMP</ci>
     <ci>Km2</ci>
    </apply>
    </apply>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>MTX1</ci>
     <ci>Ki21</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX2</ci>
     <ci>Ki22</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX3</ci>
     <ci>Ki23</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX4</ci>
     <ci>Ki24</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX5</ci>
     <ci>Ki25</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>FH2f</ci>
     <ci>Ki1</ci>
    </apply>
    </apply>
    </apply>
    <apply>
      <times/>
    <apply>
      <divide/>
     <ci>dUMP</ci>
     <ci>Km2</ci>
    </apply>
    <apply>
      <plus/>
    <apply>
      <times/>
    <apply>
      <divide/>
     <ci>FFH2</ci>
     <ci>Ki1f</ci>
    </apply>
    <apply>
      <divide/>
     <ci>MTX1</ci>
     <ci>Ki21</ci>
    </apply>
    </apply>
    <apply>
      <times/>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>FFH2</ci>
     <ci>Ki1f</ci>
    </apply>
    </apply>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>MTX2</ci>
     <ci>Ki22</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX3</ci>
     <ci>Ki23</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX4</ci>
     <ci>Ki24</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX5</ci>
     <ci>Ki25</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>FH2f</ci>
     <ci>Ki1</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    </apply>
    </apply>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>MTX2</ci>
     <ci>Ki22</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX3</ci>
     <ci>Ki23</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX4</ci>
     <ci>Ki24</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX5</ci>
     <ci>Ki25</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>FH2f</ci>
     <ci>Ki1</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "58"/>
      <parameter id = "Km1" value = "2.5"/>
      <parameter id = "Km2" value = "1.8"/>
      <parameter id = "Ki1" value = "3"/>
      <parameter id = "Ki1f" value = "1.6"/>
      <parameter id = "Ki21" value = "13"/>
      <parameter id = "Ki22" value = "0.08"/>
      <parameter id = "Ki23" value = "0.07"/>
      <parameter id = "Ki24" value = "0.065"/>
      <parameter id = "Ki25" value = "0.047"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="DHFReductase"  reversible="false">
    <listOfReactants>
      <speciesReference species = "FH2f" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "FH4" />
    </listOfProducts>
    <listOfModifiers>
      <modifierSpeciesReference species = "FH2b" />
    </listOfModifiers>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>kter</ci>
     <ci>FH2b</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "kter" value = "2109.4"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="FFH2syn"  reversible="false">
    <listOfReactants>
      <speciesReference species = "FH2f" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "FFH2" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>FH2f</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "65"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="ATIC12"  reversible="false">
    <listOfReactants>
      <speciesReference species = "FFH2" />
      <speciesReference species = "AICAR" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "FH2f" />
    </listOfProducts>
    <listOfModifiers>
      <modifierSpeciesReference species = "CHOFH4" />
      <modifierSpeciesReference species = "FH2f" />
      <modifierSpeciesReference species = "MTX1" />
      <modifierSpeciesReference species = "MTX2" />
      <modifierSpeciesReference species = "MTX3" />
      <modifierSpeciesReference species = "MTX4" />
      <modifierSpeciesReference species = "MTX5" />
    </listOfModifiers>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
    <apply>
      <times/>
     <ci>Vm</ci>
    <apply>
      <divide/>
    <apply>
      <divide/>
     <ci>AICAR</ci>
     <ci>Km2</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>AICAR</ci>
     <ci>Km2</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>FFH2</ci>
    <apply>
      <plus/>
     <ci>FFH2</ci>
    <apply>
      <times/>
     <ci>Km1</ci>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>MTX1</ci>
     <ci>Ki21</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX2</ci>
     <ci>Ki22</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX3</ci>
     <ci>Ki23</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX4</ci>
     <ci>Ki24</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>MTX5</ci>
     <ci>Ki25</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>FH2f</ci>
     <ci>Ki1</ci>
    </apply>
    </apply>
    <apply>
      <divide/>
     <ci>CHOFH4</ci>
     <ci>Ki1f</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    </apply>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "9503"/>
      <parameter id = "Km1" value = "5.3"/>
      <parameter id = "Km2" value = "24"/>
      <parameter id = "Ki1" value = "2.89"/>
      <parameter id = "Ki1f" value = "5.5"/>
      <parameter id = "Ki21" value = "40"/>
      <parameter id = "Ki22" value = "31.5"/>
      <parameter id = "Ki23" value = "2.33"/>
      <parameter id = "Ki24" value = "3.61"/>
      <parameter id = "Ki25" value = "5.89"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="AICARsyn"  reversible="false">
    <listOfReactants>
      <speciesReference species = "FGAR" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "AICAR" />
    </listOfProducts>
    <listOfModifiers>
      <modifierSpeciesReference species = "glutamine" />
    </listOfModifiers>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
    <apply>
      <times/>
     <ci>Vm</ci>
    <apply>
      <divide/>
    <apply>
      <divide/>
     <ci>glutamine</ci>
     <ci>Km1</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>glutamine</ci>
     <ci>Km1</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    <apply>
      <divide/>
    <apply>
      <divide/>
     <ci>FGAR</ci>
     <ci>Km2</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>FGAR</ci>
     <ci>Km2</ci>
    </apply>
    </apply>
    </apply>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "4656"/>
      <parameter id = "Km1" value = "100"/>
      <parameter id = "Km2" value = "100"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="FPGS12"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX1" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX2" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX1</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.129"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="FPGS23"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX2" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX3" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX2</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.369"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="FPGS34"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX3" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX4" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX3</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.118"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="FPGS45"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX4" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX5" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX4</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.185"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="GGH21"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX2" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX1" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX2</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.195"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="GGH32"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX3" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX2" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX3</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.025"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="GGH43"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX4" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX3" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX4</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.031"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="GGH54"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX5" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX4" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX5</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.191"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="RFC"  reversible="false">
    <listOfReactants>
      <speciesReference species = "EMTX" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX1" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <divide/>
    <apply>
      <divide/>
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>EMTX</ci>
    </apply>
     <ci>Km</ci>
    </apply>
    <apply>
      <plus/>
     <cn>1</cn>
    <apply>
      <divide/>
     <ci>EMTX</ci>
     <ci>Km</ci>
    </apply>
    </apply>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "82.2"/>
      <parameter id = "Km" value = "8.2"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX1export"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX1" />
    </listOfReactants>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX1</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "4.65"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX2export"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX2" />
    </listOfReactants>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX2</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX3export"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX3" />
    </listOfReactants>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX3</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.063"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX4export"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX4" />
    </listOfReactants>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX4</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.063"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX5export"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX5" />
    </listOfReactants>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX5</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.063"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX1on"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX1" />
      <speciesReference species = "DHFRf" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX1b" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>DHFRf</ci>
    </apply>
     <ci>MTX1</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "23100"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX2on"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX2" />
      <speciesReference species = "DHFRf" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX2b" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>DHFRf</ci>
    </apply>
     <ci>MTX2</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "44300"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX3on"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX3" />
      <speciesReference species = "DHFRf" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX3b" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>DHFRf</ci>
    </apply>
     <ci>MTX3</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "85100"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX4on"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX4" />
      <speciesReference species = "DHFRf" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX4b" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>DHFRf</ci>
    </apply>
     <ci>MTX4</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "163000"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX5on"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX5" />
      <speciesReference species = "DHFRf" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX5b" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>DHFRf</ci>
    </apply>
     <ci>MTX5</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "314000"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX1off"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX1b" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX1" />
      <speciesReference species = "DHFRf" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX1b</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.42"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX2off"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX2b" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX2" />
      <speciesReference species = "DHFRf" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX2b</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.42"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX3off"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX3b" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX3" />
      <speciesReference species = "DHFRf" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX3b</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.42"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX4off"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX4b" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX4" />
      <speciesReference species = "DHFRf" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX4b</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.42"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX5off"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX5b" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX5" />
      <speciesReference species = "DHFRf" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX5b</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.42"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="DHFRfsyn"  reversible="false">
    <listOfProducts>
      <speciesReference species = "DHFRf" />
    </listOfProducts>
    <listOfModifiers>
      <modifierSpeciesReference species = "EMTX" />
    </listOfModifiers>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <plus/>
     <ci>k0</ci>
    <apply>
      <times/>
     <ci>k1</ci>
     <ci>EMTX</ci>
    </apply>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "k0" value = "0.0192"/>
      <parameter id = "k1" value = "0.04416"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="DHFRdeg"  reversible="false">
    <listOfReactants>
      <speciesReference species = "DHFRf" />
    </listOfReactants>
    <listOfModifiers>
      <modifierSpeciesReference species = "FH2b" />
    </listOfModifiers>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
    <apply>
      <plus/>
     <ci>DHFRf</ci>
     <ci>FH2b</ci>
    </apply>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.03"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="FH2bdeg"  reversible="false">
    <listOfProducts>
      <speciesReference species = "FH2f" />
    </listOfProducts>
    <listOfModifiers>
      <modifierSpeciesReference species = "FH2b" />
    </listOfModifiers>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>FH2b</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.03"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX1deg"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX1b" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX1" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX1b</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.03"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX2deg"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX2b" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX2" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX2b</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.03"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX3deg"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX3b" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX3" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX3b</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.03"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX4deg"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX4b" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX4" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX4b</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.03"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
  <reaction id="MTX5deg"  reversible="false">
    <listOfReactants>
      <speciesReference species = "MTX5b" />
    </listOfReactants>
    <listOfProducts>
      <speciesReference species = "MTX5" />
    </listOfProducts>
  <kineticLaw>
    <math xmlns="http://www.w3.org/1998/Math/MathML">
    <apply>
      <times/>
     <ci>Vm</ci>
     <ci>MTX5b</ci>
    </apply>
    </math>
    <listOfParameters>
      <parameter id = "Vm" value = "0.03"/>
    </listOfParameters>
    </kineticLaw>
  </reaction>
</listOfReactions>
</model>
</sbml>
