<?xml version="1.0" encoding="UTF-8"?>
<!-- Created by COPASI version 4.0 (Build 18) on 2006-10-24 10:39 with libsbml version 2.3.4. -->
<sbml xmlns="http://www.sbml.org/sbml/level2" level="2" version="1">
  <model id="Model_0" name="Kholodenko2000 Model">
    <notes>
      <html><head><meta name="qrichtext" content="1" /></head><body style="font-size:8pt;font-family:MS Shell Dlg">
<p>This model was original downloaded from the SBML Model Repository, which has now been incorporated into BioModels.</p>
<p></p>
<p>http://sbml.org/model-repository-moved.html</p>
<p>http://www.ebi.ac.uk/biomodels/ </p>
<p></p>
<p>Richard Orton</p>
</body></html>

    </notes>
    <listOfFunctionDefinitions>
      <functionDefinition id="function_1">
        <math xmlns="http://www.w3.org/1998/Math/MathML">
          <lambda>
            <bvar>
              <ci> E </ci>
            </bvar>
            <bvar>
              <ci> s </ci>
            </bvar>
            <bvar>
              <ci> kcat </ci>
            </bvar>
            <bvar>
              <ci> Km </ci>
            </bvar>
            <apply>
              <divide/>
              <apply>
                <times/>
                <ci> E </ci>
                <ci> s </ci>
                <ci> kcat </ci>
              </apply>
              <apply>
                <plus/>
                <ci> Km </ci>
                <ci> s </ci>
              </apply>
            </apply>
          </lambda>
        </math>
      </functionDefinition>
      <functionDefinition id="function_0">
        <math xmlns="http://www.w3.org/1998/Math/MathML">
          <lambda>
            <bvar>
              <ci> V </ci>
            </bvar>
            <bvar>
              <ci> substrate </ci>
            </bvar>
            <bvar>
              <ci> Km </ci>
            </bvar>
            <apply>
              <divide/>
              <apply>
                <times/>
                <ci> V </ci>
                <ci> substrate </ci>
              </apply>
              <apply>
                <plus/>
                <ci> Km </ci>
                <ci> substrate </ci>
              </apply>
            </apply>
          </lambda>
        </math>
      </functionDefinition>
      <functionDefinition id="Kholodenk2000_Feedback">
        <math xmlns="http://www.w3.org/1998/Math/MathML">
          <lambda>
            <bvar>
              <ci> Vmax </ci>
            </bvar>
            <bvar>
              <ci> S </ci>
            </bvar>
            <bvar>
              <ci> E </ci>
            </bvar>
            <bvar>
              <ci> Ki </ci>
            </bvar>
            <bvar>
              <ci> n </ci>
            </bvar>
            <bvar>
              <ci> Km </ci>
            </bvar>
            <apply>
              <divide/>
              <apply>
                <times/>
                <ci> Vmax </ci>
                <ci> S </ci>
              </apply>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <cn> 1 </cn>
                  <apply>
                    <power/>
                    <apply>
                      <divide/>
                      <ci> E </ci>
                      <ci> Ki </ci>
                    </apply>
                    <ci> n </ci>
                  </apply>
                </apply>
                <apply>
                  <plus/>
                  <ci> Km </ci>
                  <ci> S </ci>
                </apply>
              </apply>
            </apply>
          </lambda>
        </math>
      </functionDefinition>
    </listOfFunctionDefinitions>
    <listOfUnitDefinitions>
      <unitDefinition id="volume">
        <listOfUnits>
          <unit kind="litre" scale="-3" multiplier="1" offset="0"/>
        </listOfUnits>
      </unitDefinition>
      <unitDefinition id="substance">
        <listOfUnits>
          <unit kind="mole" scale="-3" multiplier="1" offset="0"/>
        </listOfUnits>
      </unitDefinition>
    </listOfUnitDefinitions>
    <listOfCompartments>
      <compartment id="compartment_0" name="uVol" size="1"/>
    </listOfCompartments>
    <listOfSpecies>
      <species id="species_0" name="MKKK" compartment="compartment_0" initialConcentration="90"/>
      <species id="species_1" name="MKKK_P" compartment="compartment_0" initialConcentration="10"/>
      <species id="species_2" name="MKK" compartment="compartment_0" initialConcentration="280"/>
      <species id="species_3" name="MKK_P" compartment="compartment_0" initialConcentration="10"/>
      <species id="species_4" name="MKK_PP" compartment="compartment_0" initialConcentration="10"/>
      <species id="species_5" name="MAPK" compartment="compartment_0" initialConcentration="280"/>
      <species id="species_6" name="MAPK_P" compartment="compartment_0" initialConcentration="10"/>
      <species id="species_7" name="MAPK_PP" compartment="compartment_0" initialConcentration="10"/>
    </listOfSpecies>
    <listOfReactions>
      <reaction id="reaction_0" name="J0" reversible="false">
        <listOfReactants>
          <speciesReference species="species_0"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="species_1"/>
        </listOfProducts>
        <listOfModifiers>
          <modifierSpeciesReference species="species_7"/>
        </listOfModifiers>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <times/>
              <ci> compartment_0 </ci>
              <apply>
                <ci> Kholodenk2000_Feedback </ci>
                <ci> Vmax </ci>
                <ci> species_0 </ci>
                <ci> species_7 </ci>
                <ci> Ki </ci>
                <ci> n </ci>
                <ci> Km </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="Vmax" value="2.5"/>
            <parameter id="Ki" value="9"/>
            <parameter id="n" value="1"/>
            <parameter id="Km" value="10"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
      <reaction id="reaction_1" name="J1" reversible="false">
        <listOfReactants>
          <speciesReference species="species_1"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="species_0"/>
        </listOfProducts>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <times/>
              <ci> compartment_0 </ci>
              <apply>
                <ci> function_0 </ci>
                <ci> V </ci>
                <ci> species_1 </ci>
                <ci> Km </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="V" value="0.25"/>
            <parameter id="Km" value="8"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
      <reaction id="reaction_2" name="J2" reversible="false">
        <listOfReactants>
          <speciesReference species="species_2"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="species_3"/>
        </listOfProducts>
        <listOfModifiers>
          <modifierSpeciesReference species="species_1"/>
        </listOfModifiers>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <times/>
              <ci> compartment_0 </ci>
              <apply>
                <ci> function_1 </ci>
                <ci> species_1 </ci>
                <ci> species_2 </ci>
                <ci> kcat </ci>
                <ci> Km </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="kcat" value="0.025"/>
            <parameter id="Km" value="15"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
      <reaction id="reaction_3" name="J3" reversible="false">
        <listOfReactants>
          <speciesReference species="species_3"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="species_4"/>
        </listOfProducts>
        <listOfModifiers>
          <modifierSpeciesReference species="species_1"/>
        </listOfModifiers>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <times/>
              <ci> compartment_0 </ci>
              <apply>
                <ci> function_1 </ci>
                <ci> species_1 </ci>
                <ci> species_3 </ci>
                <ci> kcat </ci>
                <ci> Km </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="kcat" value="0.025"/>
            <parameter id="Km" value="15"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
      <reaction id="reaction_4" name="J4" reversible="false">
        <listOfReactants>
          <speciesReference species="species_4"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="species_3"/>
        </listOfProducts>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <times/>
              <ci> compartment_0 </ci>
              <apply>
                <ci> function_0 </ci>
                <ci> V </ci>
                <ci> species_4 </ci>
                <ci> Km </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="V" value="0.75"/>
            <parameter id="Km" value="15"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
      <reaction id="reaction_5" name="J5" reversible="false">
        <listOfReactants>
          <speciesReference species="species_3"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="species_2"/>
        </listOfProducts>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <times/>
              <ci> compartment_0 </ci>
              <apply>
                <ci> function_0 </ci>
                <ci> V </ci>
                <ci> species_3 </ci>
                <ci> Km </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="V" value="0.75"/>
            <parameter id="Km" value="15"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
      <reaction id="reaction_6" name="J6" reversible="false">
        <listOfReactants>
          <speciesReference species="species_5"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="species_6"/>
        </listOfProducts>
        <listOfModifiers>
          <modifierSpeciesReference species="species_4"/>
        </listOfModifiers>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <times/>
              <ci> compartment_0 </ci>
              <apply>
                <ci> function_1 </ci>
                <ci> species_4 </ci>
                <ci> species_5 </ci>
                <ci> kcat </ci>
                <ci> Km </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="kcat" value="0.025"/>
            <parameter id="Km" value="15"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
      <reaction id="reaction_7" name="J7" reversible="false">
        <listOfReactants>
          <speciesReference species="species_6"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="species_7"/>
        </listOfProducts>
        <listOfModifiers>
          <modifierSpeciesReference species="species_4"/>
        </listOfModifiers>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <times/>
              <ci> compartment_0 </ci>
              <apply>
                <ci> function_1 </ci>
                <ci> species_4 </ci>
                <ci> species_6 </ci>
                <ci> kcat </ci>
                <ci> Km </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="kcat" value="0.025"/>
            <parameter id="Km" value="15"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
      <reaction id="reaction_8" name="J8" reversible="false">
        <listOfReactants>
          <speciesReference species="species_7"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="species_6"/>
        </listOfProducts>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <times/>
              <ci> compartment_0 </ci>
              <apply>
                <ci> function_0 </ci>
                <ci> V </ci>
                <ci> species_7 </ci>
                <ci> Km </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="V" value="0.5"/>
            <parameter id="Km" value="15"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
      <reaction id="reaction_9" name="J9" reversible="false">
        <listOfReactants>
          <speciesReference species="species_6"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="species_5"/>
        </listOfProducts>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <times/>
              <ci> compartment_0 </ci>
              <apply>
                <ci> function_0 </ci>
                <ci> V </ci>
                <ci> species_6 </ci>
                <ci> Km </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="V" value="0.5"/>
            <parameter id="Km" value="15"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
    </listOfReactions>
  </model>
</sbml>

