Rendering of the source text

<?xml version='1.0' encoding='utf-8'?>
<!--  FILE :  cortassa_model_2004.xml

CREATED :  28th September 2004

LAST MODIFIED : 28th September 2004

AUTHOR :  Catherine Lloyd
          Bioengineering Institute
          The University of Auckland
          
MODEL STATUS :  This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/1/02 CellML Metadata 1.0 Specification.

DESCRIPTION :  This file contains a CellML description of Cortassa et al.'s 2004 mathematical model of a mitochondrial oscillator which is dependent on Reactive Oxygen Species.

CHANGES:  
  
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="cortassa_2004" name="cortassa_2004">

  
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
  <articleinfo>
  <title>Modelling Mitochondrial Energy Metabolism</title>
  <author>
    <firstname>Catherine</firstname>
          <surname>Lloyd</surname>
    <affiliation>
      <shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
    </affiliation>
  </author>
</articleinfo>
  <section id="sec_status">
    <title>Model Status</title>
    <para>
            This CellML model has been checked in both OpenCell and COR and the units are consistent.  Unfortunately the model will not integrate at the moment.  We are working with the model author to complete the curation of this model.
          </para>
  </section>
  <sect1 id="sec_structure">
<title>Model Structure</title>

<para>
ABSTRACT: We describe a unique mitochondrial oscillator that depends on oxidative phosphorylation, reactive oxygen species (ROS), and mitochondrial inner membrane ion channels. Cell-wide synchronized oscillations in mitochondrial membrane potential (Delta Psi(m)), NADH, and ROS production have been recently described in isolated cardiomyocytes, and we have hypothesized that the balance between superoxide anion efflux through inner membrane anion channels and the intracellular ROS scavenging capacity play a key role in the oscillatory mechanism. Here, we formally test the hypothesis using a computational model of mitochondrial energetics and Ca(2+) handling including mitochondrial ROS production, cytoplasmic ROS scavenging, and ROS activation of inner membrane anion flux. The mathematical model reproduces the period and phase of the observed oscillations in Delta Psi(m), NADH, and ROS. Moreover, we experimentally verify model predictions that the period of the oscillator can be modulated by altering the concentration of ROS scavengers or the rate of oxidative phosphorylation, and that the redox state of the glutathione pool oscillates. In addition to its role in cellular dysfunction during metabolic stress, the period of the oscillator can be shown to span a wide range, from milliseconds to hours, suggesting that it may also be a mechanism for physiological timekeeping and/or redox signaling.
</para>

<para>
The original paper reference is cited below:
</para>

<para>
A Mitochondrial Oscillator Dependent on Reactive Oxygen Species, Sonia Cortassa, Miguel A. Aon, Raimond L. Winslow, and Brian O'Rourke, 2004, <emphasis>Biophysical Journal</emphasis>, 87, 2060-2073.<ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=15345581&amp;dopt=Abstract">PubMed ID: 15345581</ulink>
</para>

<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>reaction diagram</title>
    </objectinfo>
    <imagedata fileref="cortassa_2004a.png"/>
  </imageobject>
</mediaobject>
<caption>Figure 1. A schematic diagram of mitochondrial energetics coupled to ROS production, transport, and scavenging. These processes are described by the equations in Cortassa et al.'s 2004 mathematical model</caption>
</informalfigure>

<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>reaction diagram</title>
    </objectinfo>
    <imagedata fileref="cortassa_2004b.png"/>
  </imageobject>
</mediaobject>
<caption>Figure 2. A schematic diagram of the reactions used in the model of the glycogenolysis pathway in skeletal muscle.</caption>
</informalfigure>


</sect1>
</article>
</documentation>
  
  
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    <variable units="second" public_interface="in" name="time"/> 
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      <apply>
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          <bvar>
            <ci>time</ci>
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          <ci>alpha_KG</ci> 
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      <rdf:Description rdf:about="#SCoA">
        <dc:title>SCoA</dc:title>
        <dcterms:alternative>succinyl CoA</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
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        <dc:title>FUM</dc:title>
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          <ci>V_SDH</ci>
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    </math> 
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  <component cmeta:id="MAL" name="MAL">
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      <rdf:Description rdf:about="#MAL">
        <dc:title>MAL</dc:title>
        <dcterms:alternative>malate</dcterms:alternative>  
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    <rdf:RDF>
      <rdf:Description rdf:about="#OAA">
        <dc:title>OAA</dc:title>
        <dcterms:alternative>oxaloacetate</dcterms:alternative>  
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            <ci>V_CS</ci>
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    <variable units="dimensionless" name="f" initial_value="0.0003"/> 
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                <ci>time</ci>
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                <ci>time</ci>
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    <variable units="millimolar" name="Cm" initial_value="15.0"/>
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        <dc:title>ADP_i</dc:title>
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          cytosolic adenosine diphosphate
        </dcterms:alternative>  
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    </rdf:RDF> 
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	<variable units="millimolar" name="pulse_value" initial_value="0.15"/>
	
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                <ci>time</ci>
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  </component>
 
  <component cmeta:id="GLU" name="GLU">
    <rdf:RDF>
      <rdf:Description rdf:about="#GLU">
        <dc:title>GLU</dc:title>
        <dcterms:alternative>glutamate</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="millimolar" public_interface="out" name="GLU" initial_value="20"/>
  </component>
  
  <component cmeta:id="Mg" name="Mg">
    <rdf:RDF>
      <rdf:Description rdf:about="#Mg">
        <dc:title>Mg</dc:title>
        <dcterms:alternative>magnesium</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="millimolar" public_interface="out" name="Mg" initial_value="0.4"/>
  </component>
  
  <component cmeta:id="H" name="H">
    <rdf:RDF>
      <rdf:Description rdf:about="#H">
        <dc:title>H</dc:title>
        <dcterms:alternative>proton</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="millimolar" public_interface="out" name="H" initial_value="2.5E-5"/>
  </component>
  
  <component cmeta:id="Pi" name="Pi">
    <rdf:RDF>
      <rdf:Description rdf:about="#Pi">
        <dc:title>Pi</dc:title>
        <dcterms:alternative>inorganic phosphate</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="millimolar" public_interface="out" name="Pi" initial_value="20.0"/>
  </component>
  
  <component cmeta:id="CoA" name="CoA">
    <rdf:RDF>
      <rdf:Description rdf:about="#CoA">
        <dc:title>CoA</dc:title>
        <dcterms:alternative>Coenzyme A</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="millimolar" public_interface="out" name="CoA" initial_value="0.02"/>
  </component>
  
  <component cmeta:id="AcCoA" name="AcCoA">
    <rdf:RDF>
      <rdf:Description rdf:about="#AcCoA">
        <dc:title>AcCoA</dc:title>
        <dcterms:alternative>acetyl Coenzyme A</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="millimolar" public_interface="out" name="AcCoA" initial_value="0.0002"/>
  </component>
  
  <component cmeta:id="FAD" name="FAD">
    <rdf:RDF>
      <rdf:Description rdf:about="#FAD">
        <dc:title>FAD</dc:title>
        <dcterms:alternative>
          flavin adenine dinucleotide (oxidised)
        </dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="millimolar" public_interface="out" name="FAD" initial_value="0.01"/>
  </component>
  
  <component cmeta:id="FADH2" name="FADH2">
    <rdf:RDF>
      <rdf:Description rdf:about="#FADH2">
        <dc:title>FADH2</dc:title>
        <dcterms:alternative>
          flavin adenine dinucleotide (reduced)
        </dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="millimolar" public_interface="out" name="FADH2" initial_value="1.24"/>
  </component>
  
  <component cmeta:id="NAD" name="NAD">
    <rdf:RDF>
      <rdf:Description rdf:about="#NAD">
        <dc:title>NAD</dc:title>
        <dcterms:alternative>
          charged nicotinamide adenine dinucleotide
        </dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="millimolar" public_interface="out" name="NAD"/>
    <variable units="millimolar" public_interface="in" name="NADH"/>
    <variable units="millimolar" name="C_PN" initial_value="10.0"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="NAD_calculation">
        <eq/>
        <ci> NAD </ci>
        <apply>
          <minus/>
          <ci> C_PN </ci>
          <ci> NADH </ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component cmeta:id="NADPH" name="NADPH">
    <rdf:RDF>
      <rdf:Description rdf:about="#NADPH">
        <dc:title>NADPH</dc:title>
        <dcterms:alternative>
          reduced nicotinamide adenine dinucleotide phosphate
        </dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="millimolar" public_interface="out" name="NADPH" initial_value="1.0"/>
  </component>
  
  <component name="O2_m" cmeta:id="O2_m">
    <rdf:RDF>
      <rdf:Description rdf:about="#O2_m">
        <dc:title>O2_m</dc:title>
        <dcterms:alternative>mitochondrial superoxide radical</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="millimolar" public_interface="out" name="O2_m" initial_value="0.01"/>
    
    <variable units="dimensionless" name="shunt" initial_value="0.05"/> 
    
    <variable units="flux" public_interface="in" name="V_O2"/>
    <variable units="flux" public_interface="in" name="VTr_ROS"/>
    <variable units="second" public_interface="in" name="time"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML"> 
      <apply>
        <eq/> 
        <apply>
          <diff/> 
          <bvar>
            <ci> time </ci>
          </bvar> 
          <ci> O2_m </ci> 
        </apply>
        <apply>
          <minus/>
          <apply>
            <times/>
            <ci> shunt </ci>
            <ci> V_O2 </ci>
          </apply>
          <ci> VTr_ROS </ci>
        </apply> 
      </apply> 
    </math> 
  </component>
  
  <component name="O2_i" cmeta:id="O2_i">
    <rdf:RDF>
      <rdf:Description rdf:about="#O2_i">
        <dc:title>O2_i</dc:title>
        <dcterms:alternative>cytoplasmic superoxide radical</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="millimolar" public_interface="out" name="O2_i" initial_value="0.01"/>
    
    <variable units="flux" public_interface="in" name="V_SOD"/>
    <variable units="flux" public_interface="in" name="VTr_ROS"/>
    <variable units="second" public_interface="in" name="time"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML"> 
      <apply>
        <eq/> 
        <apply>
          <diff/> 
          <bvar>
            <ci> time </ci>
          </bvar> 
          <ci> O2_i </ci> 
        </apply>
        <apply>
          <minus/>
          <ci> VTr_ROS </ci>
          <ci> V_SOD </ci>
        </apply> 
      </apply> 
    </math> 
  </component>
  
  <component name="H2O2" cmeta:id="H2O2">
    <rdf:RDF>
      <rdf:Description rdf:about="#H2O2">
        <dc:title>H2O2</dc:title>
        <dcterms:alternative>hydrogen peroxide</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="millimolar" public_interface="out" name="H2O2" initial_value="0.01"/>
    
    <variable units="flux" public_interface="in" name="V_SOD"/>
    <variable units="flux" public_interface="in" name="V_CAT"/>
    <variable units="flux" public_interface="in" name="V_GPX"/>
    <variable units="second" public_interface="in" name="time"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML"> 
      <apply>
        <eq/> 
        <apply>
          <diff/> 
          <bvar>
            <ci> time </ci>
          </bvar> 
          <ci> H2O2 </ci> 
        </apply>
        <apply>
          <minus/>
          <ci> V_SOD </ci>
          <apply>
            <plus/>
            <ci> V_CAT </ci>
            <ci> V_GPX </ci>
          </apply>
        </apply> 
      </apply> 
    </math> 
  </component>
  
  <component name="GSH" cmeta:id="GSH">
    <rdf:RDF>
      <rdf:Description rdf:about="#GSH">
        <dc:title>GSH</dc:title>
        <dcterms:alternative>glutathione</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="millimolar" public_interface="out" name="GSH" initial_value="0.01"/>
    
    <variable units="flux" public_interface="in" name="V_GR"/>
    <variable units="flux" public_interface="in" name="V_GPX"/>
    <variable units="second" public_interface="in" name="time"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML"> 
      <apply>
        <eq/> 
        <apply>
          <diff/> 
          <bvar>
            <ci> time </ci>
          </bvar> 
          <ci> GSH </ci> 
        </apply>
        <apply>
          <minus/>
          <ci> V_GR </ci>
          <ci> V_GPX </ci>
        </apply> 
      </apply> 
    </math> 
  </component>
  
  <component name="GSSG" cmeta:id="GSSG">
    <rdf:RDF>
      <rdf:Description rdf:about="#GSSG">
        <dc:title>GSSG</dc:title>
        <dcterms:alternative>glutathione disulphide</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="millimolar" public_interface="out" name="GSSG"/>
    
    <variable units="millimolar" name="GT" initial_value="1.0"/>
    
    <variable units="millimolar" public_interface="in" name="GSH"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <ci> GSSG </ci>
        <apply>
          <times/>
          <cn cellml:units="dimensionless"> 2.0 </cn>
          <apply>
            <minus/>
            <ci> GT </ci>   
            <ci> GSH </ci>
          </apply>
        </apply> 
      </apply>  
    </math>
  </component> 
  
  <component cmeta:id="CIT" name="CIT">
    <rdf:RDF>
      <rdf:Description rdf:about="#CIT">
        <dc:title>CIT</dc:title>
        <dcterms:alternative>citric acid</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="millimolar" public_interface="out" name="CIT"/>
    <variable units="millimolar" public_interface="in" name="ISOC"/>
    <variable units="millimolar" public_interface="in" name="alpha_KG"/>
    <variable units="millimolar" public_interface="in" name="SCoA"/>
    <variable units="millimolar" public_interface="in" name="Suc"/>
    <variable units="millimolar" public_interface="in" name="FUM"/>
    <variable units="millimolar" public_interface="in" name="MAL"/>
    <variable units="millimolar" public_interface="in" name="OAA"/>
    <variable units="millimolar" name="C_Kint" initial_value="1.0"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="CIT_calculation">
        <eq/>
        <ci> CIT </ci>
        <apply>
          <minus/>
          <ci> C_Kint </ci>
          <apply>
            <plus/>
            <ci> ISOC </ci>
            <ci> alpha_KG </ci>
            <ci> SCoA </ci>
            <ci> Suc </ci>
            <ci> FUM </ci>
            <ci> MAL </ci>
            <ci> OAA </ci>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="mitochondrial_membrane">
    <variable units="volt" public_interface="out" name="delta_psi_m" initial_value="0.01"/>
    <variable units="volt_coulomb_per_mole_kelvin" public_interface="out" name="R" initial_value="8.315"/>
    <variable units="kelvin" public_interface="out" name="T" initial_value="310.16"/>
    <variable units="coulomb_per_mole" public_interface="out" name="F" initial_value="96480"/>
	
    <variable units="millimolar_per_volt" name="C_mito" initial_value="1.812"/>
    
    <variable units="flux" public_interface="in" name="V_He"/>
    <variable units="flux" public_interface="in" name="V_He_F"/>
    <variable units="flux" public_interface="in" name="V_Hu"/>
    <variable units="flux" public_interface="in" name="V_ANT"/>
    <variable units="flux" public_interface="in" name="V_Hleak"/>
    <variable units="flux" public_interface="in" name="V_NaCa"/>
    <variable units="flux" public_interface="in" name="V_uni"/>
    <variable units="second" public_interface="in" name="time"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="delta_psi_m_diff_eq">
        <eq/>
        <apply>
          <diff/>
          <bvar>
            <ci> time </ci>
          </bvar>
          <ci> delta_psi_m </ci>
        </apply>
        <apply>
          <divide/>
          <apply>
            <plus/>
            <ci> V_He </ci>
            <ci> V_He_F </ci>
            <apply>
              <minus/>
              <apply>
                <plus/>
                <ci> V_Hu </ci>
                <ci> V_ANT </ci>
                <ci> V_Hleak </ci>
                <ci> V_NaCa </ci>
                <apply>
                  <times/>
                  <cn cellml:units="dimensionless"> 2.0 </cn>
                  <ci> V_uni </ci>
                </apply>
              </apply>
            </apply>    
          </apply>
          <ci> C_mito </ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="V_CS">
    <variable units="flux" public_interface="out" name="V_CS"/>
    
    <variable units="millimolar" public_interface="in" name="OAA"/>
    <variable units="millimolar" public_interface="in" name="AcCoA"/>
    
    <variable units="millimolar" name="Km_AcCoA" initial_value="1.26E-2"/>
    <variable units="millimolar" name="Km_OAA" initial_value="6.4E-4"/>
    <variable units="first_order_rate_constant" name="Kcat_CS" initial_value="3.2"/>
    <variable units="millimolar" name="ET_CS" initial_value="0.4"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="V_CS_calculation">
        <eq/>
        <ci> V_CS </ci>
        <apply>
          <divide/>
          <apply>
            <times/>
            <ci> Kcat_CS </ci>
            <ci> ET_CS </ci>
          </apply>
          <apply>
            <plus/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <divide/>
              <ci> Km_AcCoA </ci>
              <ci> AcCoA </ci>
            </apply>
            <apply>
              <divide/>
              <ci> Km_OAA </ci>
              <ci> OAA </ci>
            </apply>
            <apply>
              <times/>
              <apply>
                <divide/>
                <ci> Km_AcCoA </ci>
                <ci> AcCoA </ci>
              </apply>
              <apply>
                <divide/>
                <ci> Km_OAA </ci>
                <ci> OAA </ci>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="V_ACO">
    <variable units="flux" public_interface="out" name="V_ACO"/>
    
    <variable units="millimolar" public_interface="in" name="CIT"/>
    <variable units="millimolar" public_interface="in" name="ISOC"/>
    
    <variable units="first_order_rate_constant" name="Kf_ACO" initial_value="12.5"/>
    <variable units="dimensionless" name="KE_ACO" initial_value="2.22"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="V_ACO_calculation">
        <eq/>
        <ci> V_ACO </ci>
        <apply>
          <times/>
          <ci> Kf_ACO </ci>
          <apply>
            <minus/>
            <ci> CIT </ci>
            <apply>
              <divide/>
              <ci> ISOC </ci>
              <ci> KE_ACO </ci>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="V_IDH">
    <variable units="flux" public_interface="out" name="V_IDH"/>
    
    <variable units="millimolar" public_interface="in" name="NAD"/>
    <variable units="millimolar" public_interface="in" name="NADH"/>
    <variable units="millimolar" public_interface="in" name="ADP_m"/>
    <variable units="micromolar" public_interface="in" name="Ca_m"/>
    <variable units="millimolar" public_interface="in" name="H"/>
    <variable units="millimolar" public_interface="in" name="ISOC"/>
    
    <variable units="millimolar" name="Kh_1" initial_value="8.1E-5"/>
    <variable units="millimolar" name="Kh_2" initial_value="5.98E-5"/>
    <variable units="millimolar" name="Km_ISOC" initial_value="1.52"/>
    <variable units="millimolar" name="Ka_ADP" initial_value="6.2E-2"/>
    <variable units="micromolar" name="Ka_Ca" initial_value="1.41"/>
    <variable units="millimolar" name="Km_NAD" initial_value="0.923"/>
    <variable units="millimolar" name="Ki_NADH" initial_value="0.19"/>
    <variable units="first_order_rate_constant" name="Kcat_IDH" initial_value="1.94"/>
    <variable units="millimolar" name="ET_IDH" initial_value="0.109"/>
    <variable units="dimensionless" name="ni" initial_value="1"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="V_IDH_calculation">
        <eq/>
        <ci> V_IDH </ci>
        <apply>
          <divide/>
          <apply>
            <times/>
            <ci> Kcat_IDH </ci>
            <ci> ET_IDH </ci>
          </apply>
          <apply>
            <plus/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <divide/>
              <ci> H </ci>
              <ci> Kh_1 </ci>
            </apply>
            <apply>
              <divide/>
              <ci> Kh_2 </ci>
              <ci> H </ci>
            </apply>
            <apply>
              <divide/>
              <apply>
                <power/>
                <apply>
                  <divide/>
                  <ci> Km_ISOC </ci>
                  <ci> ISOC </ci>
                </apply>
                <ci> ni </ci>
              </apply>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <divide/>
                    <ci> ADP_m </ci>
                    <ci> Ka_ADP </ci>
                  </apply>
                </apply>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <divide/>
                    <ci> Ca_m </ci>
                    <ci> Ka_Ca </ci>
                  </apply>
                </apply>
              </apply>
            </apply>
            <apply>
              <times/>
              <apply>
                <divide/>
                <ci> Km_NAD </ci>
                <ci> NAD </ci>
              </apply>
              <apply>
                <plus/>
                <cn cellml:units="dimensionless"> 1.0 </cn>
                <apply>
                  <divide/>
                  <ci> NADH </ci>
                  <ci> Ki_NADH </ci>
                </apply>
              </apply>
            </apply>
            <apply>
              <divide/>
              <apply>
                <times/>
                <apply>
                  <power/>
                  <apply>
                    <divide/>
                    <ci> Km_ISOC </ci>
                    <ci> ISOC </ci>
                  </apply>
                  <ci> ni </ci>
                </apply>
                <apply>
                  <divide/>
                  <ci> Km_NAD </ci>
                  <ci> NAD </ci>
                </apply>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <divide/>
                    <ci> NADH </ci>
                    <ci> Ki_NADH </ci>
                  </apply>
                </apply>
              </apply>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <divide/>
                    <ci> ADP_m </ci>
                    <ci> Ka_ADP </ci>
                  </apply>
                </apply>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <divide/>
                    <ci> Ca_m </ci>
                    <ci> Ka_Ca </ci>
                  </apply>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="V_KGDH">
    <variable units="flux" public_interface="out" name="V_KGDH"/>
    
    <variable units="millimolar" public_interface="in" name="Mg"/>
    <variable units="micromolar" public_interface="in" name="Ca_m"/>
    <variable units="millimolar" public_interface="in" name="NAD"/>
    <variable units="millimolar" public_interface="in" name="alpha_KG"/>
    
    <variable units="millimolar" name="Km_alpha_KG" initial_value="1.94"/>
    <variable units="first_order_rate_constant" name="Kcat_KGDH" initial_value="0.15"/>
    <variable units="millimolar" name="ET_KGDH" initial_value="0.5"/>
    <variable units="millimolar" name="Kd_Mg" initial_value="0.0308"/>
    <variable units="micromolar" name="Kd_Ca" initial_value="1.27"/>
    <variable units="dimensionless" name="n_alpha_KG" initial_value="1.2"/>
    <variable units="millimolar" name="Km_NAD" initial_value="38.7"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="V_KGDH_calculation">
        <eq/>
        <ci> V_KGDH </ci>
        <apply>
          <divide/>
          <apply>
            <times/>
            <ci> Kcat_KGDH </ci>
            <ci> ET_KGDH </ci>
          </apply>
          <apply>
            <plus/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <divide/>
              <apply>
                <power/>
                <apply>
                  <divide/>
                  <ci> Km_alpha_KG </ci>
                  <ci> alpha_KG </ci>
                </apply>
                <ci> n_alpha_KG </ci>
              </apply>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <divide/>
                    <ci> Mg </ci>
                    <ci> Kd_Mg </ci>
                  </apply>
                </apply>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <divide/>
                    <ci> Ca_m </ci>
                    <ci> Kd_Ca </ci>
                  </apply>
                </apply>
              </apply>
            </apply>
            <apply>
              <divide/>
              <apply>
                <divide/>
                <ci> Km_NAD </ci>
                <ci> NAD </ci>
              </apply>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <divide/>
                    <ci> Mg </ci>
                    <ci> Kd_Mg </ci>
                  </apply>
                </apply>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <divide/>
                    <ci> Ca_m </ci>
                    <ci> Kd_Ca </ci>
                  </apply>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="V_SL">
    <variable units="flux" public_interface="out" name="V_SL"/>
    
    <variable units="millimolar" public_interface="in" name="SCoA"/>
    <variable units="millimolar" public_interface="in" name="ADP_m"/>
    <variable units="millimolar" public_interface="in" name="Suc"/>
    <variable units="millimolar" public_interface="in" name="ATP_m"/>
    <variable units="millimolar" public_interface="in" name="CoA"/>
    
    <variable units="second_order_rate_constant" name="kf_SL" initial_value="0.127"/>
    <variable units="millimolar" name="Ke_SL" initial_value="3.115"/>
  
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="V_SL_calculation">
        <eq/>
        <ci> V_SL </ci>
        <apply>
          <times/>
          <ci> kf_SL </ci>
          <apply>
            <minus/>
            <apply>
              <times/>
              <ci> SCoA </ci>
              <ci> ADP_m </ci>
            </apply>
            <apply>
              <divide/>
              <apply>
                <times/>
                <ci> Suc </ci>
                <ci> ATP_m </ci>
                <ci> CoA </ci>
              </apply>
              <ci> Ke_SL </ci>
            </apply>     
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="V_SDH">
    <variable units="flux" public_interface="out" name="V_SDH"/>
    
    <variable units="millimolar" public_interface="in" name="Suc"/>
    <variable units="millimolar" public_interface="in" name="FUM"/>
    <variable units="millimolar" public_interface="in" name="OAA"/>
    
    <variable units="millimolar" name="Kisdh_OAA" initial_value="0.15"/>
    <variable units="first_order_rate_constant" name="Kcat_SDH" initial_value="1.0"/>
    <variable units="millimolar" name="ET_SDH" initial_value="0.5"/>
    <variable units="millimolar" name="Km_Suc" initial_value="3.0E-2"/>
    <variable units="millimolar" name="Ki_FUM" initial_value="1.3"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="V_SDH_calculation">
        <eq/>
        <ci> V_SDH </ci>
        <apply>
          <divide/>
          <apply>
            <times/>
            <ci> Kcat_SDH </ci>
            <ci> ET_SDH </ci>
          </apply>
          <apply>
            <plus/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <times/>
              <apply>
                <divide/>
                <ci> Km_Suc </ci>
                <ci> Suc </ci>
              </apply>
              <apply>
                <plus/>
                <cn cellml:units="dimensionless"> 1.0 </cn>
                <apply>
                  <divide/>
                  <ci> OAA </ci>
                  <ci> Kisdh_OAA </ci>
                </apply>
              </apply>
              <apply>
                <plus/>
                <cn cellml:units="dimensionless"> 1.0 </cn>
                <apply>
                  <divide/>
                  <ci> FUM </ci>
                  <ci> Ki_FUM </ci>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component> 
  
  <component name="V_MDH">
    <variable units="flux" public_interface="out" name="V_MDH"/>
    
    <variable units="millimolar" public_interface="in" name="MAL"/>
    <variable units="millimolar" public_interface="in" name="OAA"/>
    <variable units="millimolar" public_interface="in" name="NAD"/>
    <variable units="millimolar" public_interface="in" name="H"/>
    
    <variable units="millimolar" name="Km_MAL" initial_value="1.493"/>
    <variable units="first_order_rate_constant" name="Kcat_MDH" initial_value="2.775E1"/>
    <variable units="millimolar" name="ET_MDH" initial_value="0.154"/>
    <variable units="millimolar" name="Ki_OAA" initial_value="3.1E-3"/>
    <variable units="dimensionless" name="fh_a"/>
    <variable units="dimensionless" name="fh_i"/>
    <variable units="millimolar" name="Km_NAD" initial_value="0.2244"/>
    <variable units="millimolar" name="kh1" initial_value="1.13E-5"/>
    <variable units="millimolar" name="kh2" initial_value="26.7"/>
    <variable units="millimolar" name="kh3" initial_value="6.68E-9"/>
    <variable units="millimolar" name="kh4" initial_value="5.62E-6"/>
    <variable units="dimensionless" name="k_offset" initial_value="3.99E-2"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="V_MDH_calculation">
        <eq/>
        <ci> V_MDH </ci>
        <apply>
          <divide/>
          <apply>
            <times/>
            <ci> Kcat_MDH </ci>
            <ci> ET_MDH </ci>
            <ci> fh_a </ci>
            <ci> fh_i </ci>
          </apply>
          <apply>
            <plus/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <times/>
              <apply>
                <divide/>
                <ci> Km_MAL </ci>
                <ci> MAL </ci>
              </apply>
              <apply>
                <plus/>
                <cn cellml:units="dimensionless"> 1.0 </cn>
                <apply>
                  <divide/>
                  <ci> OAA </ci>
                  <ci> Ki_OAA </ci>
                </apply>
              </apply>
            </apply>
            <apply>
              <divide/>
              <ci> Km_NAD </ci>
              <ci> NAD </ci>
            </apply>
            <apply>
              <times/>
              <apply>
                <divide/>
                <ci> Km_MAL </ci>
                <ci> MAL </ci>
              </apply>
              <apply>
                <plus/>
                <cn cellml:units="dimensionless"> 1.0 </cn>
                <apply>
                  <divide/>
                  <ci> OAA </ci>
                  <ci> Ki_OAA </ci>
                </apply>
              </apply>
              <apply>
                <divide/>
                <ci> Km_NAD </ci>
                <ci> NAD </ci>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
      
      <apply id="fh_a_calculation">
        <eq/>
        <ci> fh_a </ci>
        <apply>
          <plus/>
          <apply>
            <divide/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <plus/>
              <cn cellml:units="dimensionless"> 1.0 </cn>
              <apply>
                <divide/>
                <ci> H </ci>
                <ci> kh1 </ci>
              </apply>
              <apply>
                <divide/>
                <apply>
                  <power/>
                  <ci> H </ci>
                  <cn cellml:units="dimensionless"> 2.0 </cn>
                </apply>
                <apply>
                  <times/>
                  <ci> kh1 </ci>
                  <ci> kh2 </ci> 
                </apply>
              </apply>
            </apply>
          </apply>
          <ci> k_offset </ci>
        </apply>
      </apply> 
      
      <apply id="fh_i_calculation">
        <eq/>
        <ci> fh_i </ci>
        <apply>
          <power/>
          <apply>
            <divide/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <plus/>
              <cn cellml:units="dimensionless"> 1.0 </cn>
              <apply>
                <divide/>
                <ci> kh3 </ci>
                <ci> H </ci>
              </apply>
              <apply>
                <divide/>
                <apply>
                  <times/>
                  <ci> kh3 </ci>
                  <ci> kh4 </ci> 
                </apply>
                <apply>
                  <power/>
                  <ci> H </ci>
                  <cn cellml:units="dimensionless"> 2.0 </cn>
                </apply>
              </apply>
            </apply>
          </apply>
          <cn cellml:units="dimensionless"> 2.0 </cn>
        </apply>
      </apply> 
    </math>
  </component>
  
  <component name="V_FH">
    <variable units="flux" public_interface="out" name="V_FH"/>
    
    <variable units="millimolar" public_interface="in" name="MAL"/>
    <variable units="millimolar" public_interface="in" name="FUM"/>
    
    <variable units="dimensionless" name="Ke_FH" initial_value="1.0"/>
    <variable units="first_order_rate_constant" name="kf_FH" initial_value="0.83"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="V_FH_calculation">
        <eq/>
        <ci> V_FH </ci>
        <apply>
          <times/>
          <ci> kf_FH </ci>
          <apply>
            <minus/>
            <ci> FUM </ci>
            <apply>
              <divide/>
              <ci> MAL </ci>
              <ci> Ke_FH </ci>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component> 
  
  <component name="V_AAT">
    <variable units="flux" public_interface="out" name="V_AAT"/>
    
    <variable units="millimolar" public_interface="in" name="OAA"/>
    <variable units="millimolar" public_interface="in" name="GLU"/>
    <variable units="millimolar" public_interface="in" name="ASP"/>
    <variable units="millimolar" public_interface="in" name="alpha_KG"/>
    
    <variable units="dimensionless" name="Ke_AAT" initial_value="6.6"/>
    <variable units="second_order_rate_constant" name="kf_AAT" initial_value="0.644"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="V_AAT_calculation">
        <eq/>
        <ci> V_AAT </ci>
        <apply>
          <times/>
          <ci> kf_AAT </ci>
          <apply>
            <minus/>
            <apply>
              <times/>
              <ci> OAA </ci>
              <ci> GLU </ci>
            </apply>
            <apply>
              <divide/>
              <apply>
                <times/>
                <ci> alpha_KG </ci>
                <ci> ASP </ci>
              </apply>
              <ci> Ke_AAT </ci>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="V_C_ASP">
    <variable units="flux" public_interface="out" name="V_C_ASP"/>
    
    <variable units="millimolar" public_interface="in" name="ASP"/>
    
    <variable units="first_order_rate_constant" name="k_C_ASP" initial_value="0.01"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="V_C_ASP_calculation">
        <eq/>
        <ci> V_C_ASP </ci>
        <apply>
          <times/>
          <ci> k_C_ASP </ci>
          <ci> ASP </ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="V_SOD" cmeta:id="V_SOD">
    <rdf:RDF>
      <rdf:Description rdf:about="#V_SOD">
        <dc:title>V_SOD</dc:title>
        <dcterms:alternative>superoxide dismutase</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="flux" public_interface="out" name="V_SOD"/>
    
    <variable units="second_order_rate_constant" name="k1_SOD" initial_value="2.4E6"/>
    <variable units="second_order_rate_constant" name="k3_SOD" initial_value="4.8E4"/>
    <variable units="first_order_rate_constant" name="k5_SOD" initial_value="5.0E-1"/>
    <variable units="millimolar" name="ET_SOD" initial_value="0.4E-3"/>
    <variable units="millimolar" name="Ki_H2O2" initial_value="0.5"/>
    
    <variable units="millimolar" public_interface="in" name="O2_i"/>
    <variable units="millimolar" public_interface="in" name="H2O2"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <ci> V_SOD </ci>
        <apply>
          <divide/>
          <apply>
            <times/>
            <cn cellml:units="dimensionless"> 2.0 </cn>
            <ci> k1_SOD </ci>
            <ci> k5_SOD </ci>
            <apply>
              <plus/>
              <ci> k1_SOD </ci>
              <apply>
                <times/>
                <ci> k3_SOD </ci>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <divide/>
                    <ci> H2O2 </ci>
                    <ci> Ki_H2O2 </ci>
                  </apply>
                </apply>
              </apply>
            </apply>
            <ci> ET_SOD </ci>
            <ci> O2_i </ci>
          </apply>
          <apply>
            <plus/>
            <apply>
              <times/>
              <ci> k5_SOD </ci>
              <apply>
                <plus/>
                <apply>
                  <times/>
                  <cn cellml:units="dimensionless"> 2.0 </cn>
                  <ci> k1_SOD </ci>
                </apply>
                <apply>
                  <times/>
                  <ci> k3_SOD </ci>
                  <apply>
                    <plus/>
                    <cn cellml:units="dimensionless"> 1.0 </cn>
                    <apply>
                      <divide/>
                      <ci> H2O2 </ci>
                      <ci> Ki_H2O2 </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
            </apply>
            <apply>
              <times/>
              <ci> O2_i </ci>
              <ci> k1_SOD </ci>
              <ci> k3_SOD </ci>
              <apply>
                <plus/>
                <cn cellml:units="dimensionless"> 1.0 </cn>
                <apply>
                  <divide/>
                  <ci> H2O2 </ci>
                  <ci> Ki_H2O2 </ci>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>  
      </apply> 
    </math> 
  </component>
  
  <component name="V_CAT" cmeta:id="V_CAT">
    <rdf:RDF>
      <rdf:Description rdf:about="#V_CAT">
        <dc:title>V_CAT</dc:title>
        <dcterms:alternative>Catalase</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="flux" public_interface="out" name="V_CAT"/>
    
    <variable units="second_order_rate_constant" name="k1_CAT" initial_value="1.7E4"/>
    <variable units="millimolar" name="ET_CAT" initial_value="0.001"/>
    <variable units="per_millimolar" name="fr" initial_value="50.0"/>
    
    <variable units="millimolar" public_interface="in" name="H2O2"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <ci> V_CAT </ci>
        <apply>
          <times/>
          <cn cellml:units="dimensionless"> 2.0 </cn>
          <ci> k1_CAT </ci>
          <ci> ET_CAT </ci>
          <ci> H2O2 </ci>
          <apply>
            <exp/>
            <apply>
              <times/>
              <apply>
                <minus/>
                <ci> fr </ci>
              </apply>
              <ci> H2O2 </ci>
            </apply>
          </apply>
        </apply>
      </apply> 
    </math> 
  </component>
  
  <component name="V_GPX" cmeta:id="V_GPX">
    <rdf:RDF>
      <rdf:Description rdf:about="#V_GPX">
        <dc:title>V_GPX</dc:title>
        <dcterms:alternative>Glutathione peroxidase</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="flux" public_interface="out" name="V_GPX"/>
    
    <variable units="millimolar_second" name="phi1_GPX" initial_value="0.15"/>
    <variable units="millimolar_second" name="phi2_GPX" initial_value="0.5"/>
    <variable units="millimolar" name="ET_GPX" initial_value="0.00141"/>
    
    <variable units="millimolar" public_interface="in" name="H2O2"/>
    <variable units="millimolar" public_interface="in" name="GSH"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <ci> V_GPX </ci>
        <apply>
          <divide/>
          <apply>
            <times/>
            <ci> ET_GPX </ci>
            <ci> H2O2 </ci>
            <ci> GSH </ci>
          </apply>
          <apply>
            <plus/>
            <apply>
              <times/>
              <ci> phi1_GPX </ci>
              <ci> GSH </ci>
            </apply>
            <apply>
              <times/>
              <ci> phi2_GPX </ci>
              <ci> H2O2 </ci>
            </apply>
          </apply>
        </apply>
      </apply> 
    </math> 
  </component>
  
  <component name="V_GR" cmeta:id="V_GR">
    <rdf:RDF>
      <rdf:Description rdf:about="#V_GR">
        <dc:title>V_GR</dc:title>
        <dcterms:alternative>Glutathione reductase</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="flux" public_interface="out" name="V_GR"/>
    
    <variable units="first_order_rate_constant" name="k1_GR" initial_value="0.0308"/>
    <variable units="millimolar" name="KM_GSSG" initial_value="1.94"/>
    <variable units="millimolar" name="KM_NADPH" initial_value="38.7"/>
    <variable units="millimolar" name="ET_GR" initial_value="1.27E-3"/>
    
	<variable units="millimolar" public_interface="in" name="NADPH"/>
    <variable units="millimolar" public_interface="in" name="GSSG"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <ci> V_GR </ci>
        <apply>
          <divide/>
          <apply>
            <times/>
            <ci> k1_GR </ci>
            <ci> ET_GR </ci>
          </apply>
          <apply>
            <plus/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <divide/>
              <ci> KM_GSSG </ci>
              <ci> GSSG </ci>
            </apply>
            <apply>
              <divide/>
              <ci> KM_NADPH </ci>
              <ci> NADPH </ci>
            </apply>
            <apply>
              <times/>
              <apply>
                <divide/>
                <ci> KM_GSSG </ci>
                <ci> GSSG </ci>
              </apply>
              <apply>
                <divide/>
                <ci> KM_NADPH </ci>
                <ci> NADPH </ci>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply> 
    </math> 
  </component>
  
  <component name="V_IMAC" cmeta:id="V_IMAC">
    <rdf:RDF>
      <rdf:Description rdf:about="#V_IMAC">
        <dc:title>V_IMAC</dc:title>
        <dcterms:alternative>mitochondrial inner membrane anion channel conductance</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="flux" public_interface="out" name="V_IMAC"/>
    
    <variable units="millimolar_per_second_volt" name="Gmax" initial_value="7.82"/>
    <variable units="millimolar_per_second_volt" name="GL" initial_value="0.0782"/>
    <variable units="dimensionless" name="a" initial_value="1.0E-3"/>
    <variable units="dimensionless" name="b" initial_value="1.0E4"/>
    <variable units="per_volt" name="kappa" initial_value="70.0"/>
    <variable units="volt" name="delta_psi_bm" initial_value="0.004"/>
    <variable units="millimolar" name="Kcc" initial_value="0.01"/>
    
    <variable units="volt" public_interface="in" name="delta_psi_m"/>
    <variable units="millimolar" public_interface="in" name="O2_i"/>
    <variable units="millimolar" public_interface="in" name="GSSG"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <ci> V_IMAC </ci>
        <apply>
          <times/>
          <apply>
            <plus/>
            <ci> a </ci>
            <apply>
              <divide/>
              <ci> b </ci>
              <apply>
                <plus/>
                <cn cellml:units="dimensionless"> 1.0 </cn>
                <apply>
                  <divide/>
                  <ci> Kcc </ci>
                  <ci> O2_i </ci>
                </apply>
              </apply>
            </apply>
          </apply>
          <apply>
            <plus/>
            <ci> GL </ci>
            <apply>
              <divide/>
              <ci> Gmax </ci>
              <apply>
                <plus/>
                <cn cellml:units="dimensionless"> 1.0 </cn>
                <apply>
                  <exp/>
                  <apply>
                    <times/>
                    <ci> kappa </ci>
                    <apply>
                      <minus/>
                      <ci> delta_psi_bm </ci>
                      <ci> delta_psi_m </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
            </apply>
          </apply>
          <ci> delta_psi_m </ci>
        </apply>
      </apply> 
    </math> 
  </component>
  
  <component name="VTr_ROS" cmeta:id="VTr_ROS">
    <rdf:RDF>
      <rdf:Description rdf:about="#VTr_ROS">
        <dc:title>VTr_ROS</dc:title>
        <dcterms:alternative>transport of reactive oxygen species across the inner mitochondrial membrane</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="flux" public_interface="out" name="VTr_ROS"/>
    
    <variable units="dimensionless" name="j" initial_value="0.12"/>
    
    <variable units="volt_coulomb_per_mole_kelvin" public_interface="in" name="R"/>
    <variable units="kelvin" public_interface="in" name="T"/>
    <variable units="coulomb_per_mole" public_interface="in" name="F"/>
    <variable units="millimolar" public_interface="in" name="O2_i"/>
    <variable units="millimolar" public_interface="in" name="O2_m"/>
    <variable units="flux" public_interface="in" name="V_IMAC"/>
    <variable units="volt" public_interface="in" name="delta_psi_m"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <ci> VTr_ROS </ci>
        <apply>
          <times/>
          <ci> j </ci>
          <apply>
            <divide/>
            <ci> V_IMAC </ci>
            <ci> delta_psi_m </ci>
          </apply>
          <apply>
            <minus/>
            <ci> delta_psi_m </ci>
            <apply>
              <times/>
              <apply>
                <divide/>
                <apply>
                  <times/>
                  <ci> R </ci>
                  <ci> T </ci>
                </apply>
                <ci> F </ci>
              </apply>
              <apply>
                <log/>
                <apply>
                  <divide/>
                  <ci> O2_m </ci>
                  <ci> O2_i </ci>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply> 
    </math> 
  </component>  
  
  <component name="oxidative_phosphorylation">
    <variable units="flux" public_interface="out" name="V_O2"/>
    <variable units="flux" public_interface="out" name="V_He"/>
    <variable units="flux" public_interface="out" name="V_He_F"/>
    <variable units="flux" public_interface="out" name="V_ATPase"/>
    <variable units="flux" public_interface="out" name="V_Hu"/>
    <variable units="flux" public_interface="out" name="V_Hleak"/>
    
	<variable units="volt_coulomb_per_mole_kelvin" public_interface="in" name="R"/>
    <variable units="kelvin" public_interface="in" name="T"/>
    <variable units="coulomb_per_mole" public_interface="in" name="F"/>
    <variable units="millimolar" public_interface="in" name="NAD"/>
    <variable units="millimolar" public_interface="in" name="NADH"/>
    <variable units="millimolar" public_interface="in" name="FAD"/>
    <variable units="millimolar" public_interface="in" name="FADH2"/>
    <variable units="millimolar" public_interface="in" name="ADP_m"/>
    <variable units="millimolar" public_interface="in" name="ATP_m"/>
    <variable units="millimolar" public_interface="in" name="Pi"/>
    <variable units="volt" public_interface="in" name="delta_psi_m"/>
    
	<variable units="millimolar" name="rho_res" initial_value="0.0006"/>
    <variable units="millimolar" name="rho_res_F" initial_value="0.0045"/>
    <variable units="first_order_rate_constant" name="ra" initial_value="6.394E-10"/>
    <variable units="first_order_rate_constant" name="rc1" initial_value="2.656E-19"/>
    <variable units="volt" name="Ares"/>
    <variable units="volt" name="Ares_F"/>
    <variable units="dimensionless" name="r1" initial_value="2.077E-18"/>
    <variable units="dimensionless" name="r2" initial_value="1.728E-9"/>
    <variable units="dimensionless" name="r3" initial_value="1.059E-26"/>
    <variable units="first_order_rate_constant" name="rb" initial_value="1.762E-13"/>
    <variable units="first_order_rate_constant" name="rc2" initial_value="8.632E-27"/>
    <variable units="dimensionless" name="Kres" initial_value="1.35E18"/>
    <variable units="dimensionless" name="Kres_F" initial_value="5.765E13"/>
    <variable units="millimolar_per_second_volt" name="gH" initial_value="0.01"/>
    <variable units="volt" name="delta_psi_B" initial_value="0.05"/>
    <variable units="dimensionless" name="g" initial_value="0.85"/>
    <variable units="volt" name="delta_mu_H"/>
    <variable units="dimensionless" name="delta_pH" initial_value="-0.6"/>
    <variable units="millimolar" name="rho_F1" initial_value="0.06"/>
    <variable units="first_order_rate_constant" name="pa" initial_value="1.656E-5"/>
    <variable units="first_order_rate_constant" name="pc1" initial_value="9.651E-14"/>
    <variable units="volt" name="AF1"/>
    <variable units="dimensionless" name="p1" initial_value="1.346E-8"/>
    <variable units="dimensionless" name="p2" initial_value="7.739E-7"/>
    <variable units="dimensionless" name="p3" initial_value="6.65E-15"/>
    <variable units="first_order_rate_constant" name="pb" initial_value="3.373E-7"/>
    <variable units="first_order_rate_constant" name="pc2" initial_value="4.585E-14"/>
    <variable units="millimolar" name="KF1" initial_value="1.71E6"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="V_O2_calculation">
        <eq/>
        <ci> V_O2 </ci>
        <apply>
          <times/>
          <cn cellml:units="dimensionless"> 0.5 </cn>
          <ci> rho_res </ci>
          <apply>
            <divide/>
            <apply>
              <plus/>
              <apply>
                <minus/>
                <apply>
                  <times/>
                  <apply>
                    <plus/>
                    <ci> ra </ci>
                    <apply>
                      <times/>
                      <ci> rc1 </ci>
                      <apply>
                        <exp/>
                        <apply>
                          <divide/>
                          <apply>
                            <times/>
                            <cn cellml:units="dimensionless"> 6.0 </cn>
                            <ci> F </ci>
                            <ci> delta_psi_B </ci>
                          </apply>
                          <apply>
                            <times/>
                            <ci> R </ci>
                            <ci> T </ci>
                          </apply>
                        </apply>
                      </apply>
                    </apply>
                  </apply>
                  <apply>
                    <exp/>
                    <apply>
                      <divide/>
                      <apply>
                        <times/>
                        <ci> Ares </ci>
                        <ci> F </ci>
                      </apply>
                      <apply>
                        <times/>
                        <ci> R </ci>
                        <ci> T </ci>
                      </apply>
                    </apply>
                  </apply>
                </apply>
                <apply>
                  <times/>
                  <ci> ra </ci>
                  <apply>
                    <exp/>
                    <apply>
                      <divide/>
                      <apply>
                        <times/>
                        <ci> g </ci>
                        <cn cellml:units="dimensionless"> 6.0 </cn>
                        <ci> F </ci>
                        <ci> delta_mu_H </ci>
                      </apply>
                      <apply>
                        <times/>
                        <ci> R </ci>
                        <ci> T </ci>
                      </apply>
                    </apply>
                  </apply>
                </apply>
              </apply>
              <apply>
                <times/>
                <ci> rc2 </ci>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <ci> Ares </ci>
                      <ci> F </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <ci> g </ci>
                      <cn cellml:units="dimensionless"> 6.0 </cn>
                      <ci> F </ci>
                      <ci> delta_mu_H </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
            </apply>
            <apply>
              <plus/>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <times/>
                    <ci> r1 </ci>
                    <apply>
                      <exp/>
                      <apply>
                        <divide/>
                        <apply>
                          <times/>
                          <ci> F </ci>
                          <ci> Ares </ci>
                        </apply>
                        <apply>
                          <times/>
                          <ci> R </ci>
                          <ci> T </ci>
                        </apply>
                      </apply>
                    </apply>
                  </apply>
                </apply>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <cn cellml:units="dimensionless"> 6.0 </cn>
                      <ci> F </ci>
                      <ci> delta_psi_B </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <ci> r2 </ci>
                  <apply>
                    <times/>
                    <ci> r3 </ci>
                    <apply>
                      <exp/>
                      <apply>
                        <divide/>
                        <apply>
                          <times/>
                          <ci> F </ci>
                          <ci> Ares </ci>
                        </apply>
                        <apply>
                          <times/>
                          <ci> R </ci>
                          <ci> T </ci>
                        </apply>
                      </apply>
                    </apply>
                  </apply>
                </apply>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <ci> g </ci>
                      <cn cellml:units="dimensionless"> 6.0 </cn>
                      <ci> F </ci>
                      <ci> delta_mu_H </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
      
      <apply id="V_He_calculation">
        <eq/>
        <ci> V_He </ci>
        <apply>
          <times/>
          <cn cellml:units="dimensionless"> 6.0 </cn>
          <ci> rho_res </ci>
          <apply>
            <divide/>
            <apply>
              <minus/>
              <apply>
                <times/>
                <ci> ra </ci>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <ci> F </ci>
                      <ci> Ares </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <ci> ra </ci>
                  <ci> rb </ci>
                </apply>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <ci> g </ci>
                      <cn cellml:units="dimensionless"> 6.0 </cn>
                      <ci> F </ci>
                      <ci> delta_mu_H </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
            </apply>
            <apply>
              <plus/>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <times/>
                    <ci> r1 </ci>
                    <apply>
                      <exp/>
                      <apply>
                        <divide/>
                        <apply>
                          <times/>
                          <ci> F </ci>
                          <ci> Ares </ci>
                        </apply>
                        <apply>
                          <times/>
                          <ci> R </ci>
                          <ci> T </ci>
                        </apply>
                      </apply>
                    </apply>
                  </apply>
                </apply>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <cn cellml:units="dimensionless"> 6.0 </cn>
                      <ci> F </ci>
                      <ci> delta_psi_B </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <ci> r2 </ci>
                  <apply>
                    <times/>
                    <ci> r3 </ci>
                    <apply>
                      <exp/>
                      <apply>
                        <divide/>
                        <apply>
                          <times/>
                          <ci> F </ci>
                          <ci> Ares </ci>
                        </apply>
                        <apply>
                          <times/>
                          <ci> R </ci>
                          <ci> T </ci>
                        </apply>
                      </apply>
                    </apply>
                  </apply>
                </apply>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <ci> g </ci>
                      <cn cellml:units="dimensionless"> 6.0 </cn>
                      <ci> F </ci>
                      <ci> delta_mu_H </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
      
      <apply id="Ares_calculation">
        <eq/>
        <ci> Ares </ci>
        <apply>
          <times/>
          <apply>
            <divide/>
            <apply>
              <times/>
              <ci> R </ci>
              <ci> T </ci>
            </apply>
            <ci> F </ci>
          </apply>
          <apply>
            <ln/>
            <apply>
              <times/>
              <ci> Kres </ci>
              <apply>
                <power/>
                <apply>
                  <divide/>
                  <ci> NADH </ci>
                  <ci> NAD </ci>
                </apply>
                <cn cellml:units="dimensionless"> 0.5 </cn>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply> 
      
      <apply id="V_He_F_calculation">
        <eq/>
        <ci> V_He_F </ci>
        <apply>
          <times/>
          <cn cellml:units="dimensionless"> 6.0 </cn>
          <ci> rho_res_F </ci>
          <apply>
            <divide/>
            <apply>
              <minus/>
              <apply>
                <times/>
                <ci> ra </ci>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <ci> F </ci>
                      <ci> Ares_F </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <ci> ra </ci>
                  <ci> rb </ci>
                </apply>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <ci> g </ci>
                      <cn cellml:units="dimensionless"> 6.0 </cn>
                      <ci> F </ci>
                      <ci> delta_mu_H </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
            </apply>
            <apply>
              <plus/>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <times/>
                    <ci> r1 </ci>
                    <apply>
                      <exp/>
                      <apply>
                        <divide/>
                        <apply>
                          <times/>
                          <ci> F </ci>
                          <ci> Ares_F </ci>
                        </apply>
                        <apply>
                          <times/>
                          <ci> R </ci>
                          <ci> T </ci>
                        </apply>
                      </apply>
                    </apply>
                  </apply>
                </apply>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <cn cellml:units="dimensionless"> 6.0 </cn>
                      <ci> F </ci>
                      <ci> delta_psi_B </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <ci> r2 </ci>
                  <apply>
                    <times/>
                    <ci> r3 </ci>
                    <apply>
                      <exp/>
                      <apply>
                        <divide/>
                        <apply>
                          <times/>
                          <ci> F </ci>
                          <ci> Ares_F </ci>
                        </apply>
                        <apply>
                          <times/>
                          <ci> R </ci>
                          <ci> T </ci>
                        </apply>
                      </apply>
                    </apply>
                  </apply>
                </apply>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <ci> g </ci>
                      <cn cellml:units="dimensionless"> 6.0 </cn>
                      <ci> F </ci>
                      <ci> delta_mu_H </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
      
      <apply id="Ares_F_calculation">
        <eq/>
        <ci> Ares_F </ci>
        <apply>
          <times/>
          <apply>
            <divide/>
            <apply>
              <times/>
              <ci> R </ci>
              <ci> T </ci>
            </apply>
            <ci> F </ci>
          </apply>
          <apply>
            <ln/>
            <apply>
              <times/>
              <ci> Kres_F </ci>
              <apply>
                <power/>
                <apply>
                  <divide/>
                  <ci> FADH2 </ci>
                  <ci> FAD </ci>
                </apply>
                <cn cellml:units="dimensionless"> 0.5 </cn>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
      
      <apply id="V_Hleak_calculation">
        <eq/>
        <ci> V_Hleak </ci>
        <apply>
          <times/>
          <ci> gH </ci>
          <ci> delta_mu_H </ci>
        </apply>
      </apply>
      
      <apply id="delta_mu_H_calculation">
        <eq/>
        <ci> delta_mu_H </ci>
        <apply>
          <plus/>
          <apply>
            <times/>
            <apply>
              <divide/>
              <apply>
                <times/>
                <ci> R </ci>
                <ci> T </ci>
              </apply>
              <ci> F </ci>
            </apply>
            <ci> delta_pH </ci>
          </apply>
          <ci> delta_psi_m </ci>
        </apply>
      </apply>
    
      <apply id="V_ATPase_calculation">
        <eq/>
        <ci> V_ATPase </ci>
        <apply>
          <times/>
          <apply>
            <minus/>
            <ci> rho_F1 </ci>
          </apply>
          <apply>
            <divide/>
            <apply>
              <minus/>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <apply>
                    <times/>
                    <cn cellml:units="dimensionless"> 100.0 </cn>
                    <ci> pa </ci>
                  </apply>
                  <apply>
                    <times/>
                    <ci> pc1 </ci>
                    <apply>
                      <exp/>
                      <apply>
                        <divide/>
                        <apply>
                          <times/>
                          <cn cellml:units="dimensionless"> 3.0 </cn>
                          <ci> F </ci>
                          <ci> delta_psi_B </ci>
                        </apply>
                        <apply>
                          <times/>
                          <ci> R </ci>
                          <ci> T </ci>
                        </apply>
                      </apply>
                    </apply>
                  </apply>
                </apply>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <ci> AF1 </ci>
                      <ci> F </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
              <apply>
                <plus/>
                <apply>
                  <times/>
                  <ci> pa </ci>
                  <apply>
                    <exp/>
                    <apply>
                      <divide/>
                      <apply>
                        <times/>
                        <cn cellml:units="dimensionless"> 3.0 </cn>
                        <ci> F </ci>
                        <ci> delta_mu_H </ci>
                      </apply>
                      <apply>
                        <times/>
                        <ci> R </ci>
                        <ci> T </ci>
                      </apply>
                    </apply>
                  </apply>
                </apply>
                <apply>
                  <times/>
                  <ci> pc2 </ci>
                  <apply>
                    <exp/>
                    <apply>
                      <divide/>
                      <apply>
                        <times/>
                        <ci> AF1 </ci>
                        <ci> F </ci>
                      </apply>
                      <apply>
                        <times/>
                        <ci> R </ci>
                        <ci> T </ci>
                      </apply>
                    </apply>
                  </apply>
                  <apply>
                    <exp/>
                    <apply>
                      <divide/>
                      <apply>
                        <times/>
                        <cn cellml:units="dimensionless"> 3.0 </cn>
                        <ci> F </ci>
                        <ci> delta_mu_H </ci>
                      </apply>
                      <apply>
                        <times/>
                        <ci> R </ci>
                        <ci> T </ci>
                      </apply>
                    </apply>
                  </apply>
                </apply>
              </apply>
            </apply>
            <apply>
              <plus/>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <times/>
                    <ci> p1 </ci>
                    <apply>
                      <exp/>
                      <apply>
                        <divide/>
                        <apply>
                          <times/>
                          <ci> F </ci>
                          <ci> AF1 </ci>
                        </apply>
                        <apply>
                          <times/>
                          <ci> R </ci>
                          <ci> T </ci>
                        </apply>
                      </apply>
                    </apply>
                  </apply>
                </apply>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <cn cellml:units="dimensionless"> 3.0 </cn>
                      <ci> F </ci>
                      <ci> delta_psi_B </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <ci> p2 </ci>
                  <apply>
                    <times/>
                    <ci> p3 </ci>
                    <apply>
                      <exp/>
                      <apply>
                        <divide/>
                        <apply>
                          <times/>
                          <ci> F </ci>
                          <ci> AF1 </ci>
                        </apply>
                        <apply>
                          <times/>
                          <ci> R </ci>
                          <ci> T </ci>
                        </apply>
                      </apply>
                    </apply>
                  </apply>
                </apply>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <cn cellml:units="dimensionless"> 3.0 </cn>
                      <ci> F </ci>
                      <ci> delta_mu_H </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
      
      <apply id="V_Hu_calculation">
        <eq/>
        <ci> V_Hu </ci>
        <apply>
          <times/>
          <cn cellml:units="dimensionless"> -3.0 </cn>
          <ci> rho_F1 </ci>
          <apply>
            <divide/>
            <apply>
              <minus/>
              <apply>
                <times/>
                <cn cellml:units="dimensionless"> 100.0 </cn>
                <ci> pa </ci>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <exp/>
                    <apply>
                      <divide/>
                      <apply>
                        <times/>
                        <ci> F </ci>
                        <ci> AF1 </ci>
                      </apply>
                      <apply>
                        <times/>
                        <ci> R </ci>
                        <ci> T </ci>
                      </apply>
                    </apply>
                  </apply>
                </apply>
              </apply>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <ci> pa </ci>
                  <ci> pb </ci>
                </apply>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <cn cellml:units="dimensionless"> 3.0 </cn>
                      <ci> F </ci>
                      <ci> delta_mu_H </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
            </apply>
            <apply>
              <plus/>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <times/>
                    <ci> p1 </ci>
                    <apply>
                      <exp/>
                      <apply>
                        <divide/>
                        <apply>
                          <times/>
                          <ci> F </ci>
                          <ci> AF1 </ci>
                        </apply>
                        <apply>
                          <times/>
                          <ci> R </ci>
                          <ci> T </ci>
                        </apply>
                      </apply>
                    </apply>
                  </apply>
                </apply>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <cn cellml:units="dimensionless"> 3.0 </cn>
                      <ci> F </ci>
                      <ci> delta_psi_B </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <ci> p2 </ci>
                  <apply>
                    <times/>
                    <ci> p3 </ci>
                    <apply>
                      <exp/>
                      <apply>
                        <divide/>
                        <apply>
                          <times/>
                          <ci> F </ci>
                          <ci> AF1 </ci>
                        </apply>
                        <apply>
                          <times/>
                          <ci> R </ci>
                          <ci> T </ci>
                        </apply>
                      </apply>
                    </apply>
                  </apply>
                </apply>
                <apply>
                  <exp/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <cn cellml:units="dimensionless"> 3.0 </cn>
                      <ci> F </ci>
                      <ci> delta_mu_H </ci>
                    </apply>
                    <apply>
                      <times/>
                      <ci> R </ci>
                      <ci> T </ci>
                    </apply>
                  </apply>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
      
      <apply id="AF1_calculation">
        <eq/>
        <ci> AF1 </ci>
        <apply>
          <times/>
          <apply>
            <divide/>
            <apply>
              <times/>
              <ci> R </ci>
              <ci> T </ci>
            </apply>
            <ci> F </ci>
          </apply>
          <apply>
            <ln/>
            <apply>
              <times/>
              <ci> KF1 </ci>
              <apply>
                <divide/>
                <ci> ATP_m </ci>
                <apply>
                  <times/>
                  <ci> ADP_m </ci>
                  <ci> Pi </ci>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="calcium_dynamics">
    <variable units="flux" public_interface="out" name="V_ANT"/>
    <variable units="flux" public_interface="out" name="V_uni"/>
    <variable units="flux" public_interface="out" name="V_NaCa"/>
    
    <variable units="millimolar" public_interface="in" name="ADP_i"/>
    <variable units="millimolar" public_interface="in" name="ATP_i"/>
    <variable units="millimolar" public_interface="in" name="ADP_m"/>
    <variable units="millimolar" public_interface="in" name="ATP_m"/>
    <variable units="micromolar" public_interface="in" name="Ca_i"/>
    <variable units="micromolar" public_interface="in" name="Ca_m"/>
    <variable units="millimolar" public_interface="in" name="Na_i"/>
    <variable units="volt_coulomb_per_mole_kelvin" public_interface="in" name="R"/>
    <variable units="kelvin" public_interface="in" name="T"/>
    <variable units="coulomb_per_mole" public_interface="in" name="F"/>
    <variable units="volt" public_interface="in" name="delta_psi_m"/>
    
    <variable units="dimensionless" name="h" initial_value="0.5"/>
    <variable units="volt" name="delta_psi_0" initial_value="0.091"/>
    <variable units="flux" name="Vmax_ANT" initial_value="0.05"/>
    <variable units="dimensionless" name="L" initial_value="110.0"/> 
    <variable units="dimensionless" name="na" initial_value="2.8"/>
    <variable units="flux" name="Vmax_uni" initial_value="0.000625"/>
    <variable units="micromolar" name="K_act" initial_value="0.38"/>
    <variable units="micromolar" name="K_trans" initial_value="19.0"/>
    <variable units="dimensionless" name="n" initial_value="3.0"/>
    <variable units="flux" name="Vmax_NaCa" initial_value="0.005"/>
    <variable units="millimolar" name="KNa" initial_value="9.4"/>
    <variable units="micromolar" name="KCa" initial_value="3.75E-1"/>
    <variable units="dimensionless" name="b" initial_value="0.5"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="V_ANT_calculation">
        <eq/>
        <ci> V_ANT </ci>
        <apply>
          <times/>
          <ci> Vmax_ANT </ci>
          <apply>
            <divide/>
            <apply>
              <minus/>
              <cn cellml:units="dimensionless"> 1.0 </cn>
              <apply>
                <divide/>
                <apply>
                  <times/>
                  <cn cellml:units="dimensionless"> 0.05 </cn>
                  <ci> ATP_i </ci>
                  <cn cellml:units="dimensionless"> 0.45 </cn>
                  <cn cellml:units="dimensionless"> 0.8 </cn>
                  <ci> ADP_m </ci>
                </apply>
                <apply>
                  <times/>
                  <cn cellml:units="dimensionless"> 0.45 </cn>
                  <ci> ADP_i </ci>
                  <cn cellml:units="dimensionless"> 0.05 </cn>
                  <ci> ATP_m </ci>
                </apply>
              </apply>
            </apply>
            <apply>
              <times/>
              <apply>
                <plus/>
                <cn cellml:units="dimensionless"> 1.0 </cn>
                <apply>
                  <times/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <cn cellml:units="dimensionless"> 0.05 </cn>
                      <ci> ATP_i </ci>
                    </apply>
                    <apply>
                      <times/>
                      <cn cellml:units="dimensionless"> 0.45 </cn>
                      <ci> ADP_i </ci>
                    </apply>
                  </apply>
                  <apply>
                    <exp/>
                    <apply>
                      <divide/>
                      <apply>
                        <times/>
                        <apply>
                          <minus/>
                          <ci> h </ci>
                        </apply>
                        <ci> F </ci>
                        <ci> delta_psi_0 </ci>
                      </apply>
                      <apply>
                        <times/>
                        <ci> R </ci>
                        <ci> T </ci>
                      </apply>
                    </apply>
                  </apply>
                </apply>
              </apply>
              <apply>
                <plus/>
                <cn cellml:units="dimensionless"> 1.0 </cn>
                <apply>
                  <divide/>
                  <apply>
                    <times/>
                    <cn cellml:units="dimensionless"> 0.45 </cn>
                    <cn cellml:units="dimensionless"> 0.8 </cn>
                    <ci> ADP_m </ci>
                  </apply>
                  <apply>
                    <times/>
                    <cn cellml:units="dimensionless"> 0.05 </cn>
                    <ci> ATP_m </ci>
                  </apply>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
    
      <apply id="V_uni_calculation">
        <eq/>
        <ci> V_uni </ci>
        <apply>
          <times/>
          <ci> Vmax_uni </ci>
          <apply>
            <divide/>
            <apply>
              <times/>
              <apply>
                <divide/>
                <ci> Ca_i </ci>
                <ci> K_trans </ci>
              </apply>
			  <apply>
                <power/>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <divide/>
                    <ci> Ca_i </ci>
                    <ci> K_trans </ci>
                  </apply>
				</apply>
				<cn cellml:units="dimensionless"> 3.0 </cn>
              </apply>
              <apply>
                <divide/>
                <apply>
                  <times/>
                  <cn cellml:units="dimensionless"> 2.0 </cn>
                  <ci> F </ci>
                  <apply>
                    <minus/>
                    <ci> delta_psi_m </ci>
                    <ci> delta_psi_0 </ci>
                  </apply>
                </apply>
                <apply>
                  <times/>
                  <ci> R </ci>
                  <ci> T </ci>
                </apply>
              </apply>
            </apply>
            <apply>
              <plus/>
              <apply>
                <power/>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <divide/>
                    <ci> Ca_i </ci>
                    <ci> K_trans </ci>
                  </apply>
                </apply>
                <cn cellml:units="dimensionless"> 4.0 </cn>
              </apply>
              <apply>
                <times/>
                <apply>
                  <divide/>
                  <ci> L </ci>
                  <apply>
                    <power/>
                    <apply>
                      <plus/>
                      <cn cellml:units="dimensionless"> 1.0 </cn>
                      <apply>
                        <divide/>
                        <ci> Ca_i </ci>
                        <ci> K_act </ci>
                      </apply>
                    </apply>
                    <ci> na </ci>
                  </apply>
                </apply>
                <apply>
                  <minus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <exp/>
                    <apply>
                      <divide/>
                      <apply>
                        <times/>
                        <cn cellml:units="dimensionless"> -2.0 </cn>
                        <ci> F </ci>
                        <apply>
                          <minus/>
                          <ci> delta_psi_m </ci>
                          <ci> delta_psi_0 </ci>
                        </apply>
                      </apply>
                      <apply>
                        <times/>
                        <ci> R </ci>
                        <ci> T </ci>
                      </apply>
                    </apply>
                  </apply>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
    
      <apply id="V_NaCa_calculation">
        <eq/>
        <ci> V_NaCa </ci>
        <apply>
          <times/>
          <ci> Vmax_NaCa </ci>
          <apply>
            <divide/>
            <apply>
              <times/>
              <apply>
                <exp/>
                <apply>
                  <divide/>
                  <apply>
                    <times/>
                    <ci> b </ci>
                    <ci> F </ci>
                    <apply>
                      <minus/>
                      <ci> delta_psi_m </ci>
                      <ci> delta_psi_0 </ci>
                    </apply>
                  </apply>
                  <apply>
                    <times/>
                    <ci> R </ci>
                    <ci> T </ci>
                  </apply>
                </apply>
              </apply>
              <apply>
                <exp/>
                <apply>
                  <ln/>
                  <apply>
                    <divide/>
                    <ci> Ca_i </ci>
                    <ci> Ca_m </ci>
                  </apply>
                </apply>
              </apply>
            </apply>
            <apply>
              <times/>
              <apply>
                <power/>
                <apply>
                  <plus/>
                  <cn cellml:units="dimensionless"> 1.0 </cn>
                  <apply>
                    <divide/>
                    <ci> KNa </ci>
                    <ci> Na_i </ci>
                  </apply>
                </apply>
                <ci> n </ci>
              </apply>
              <apply>
                <plus/>
                <cn cellml:units="dimensionless"> 1.0 </cn>
                <apply>
                  <divide/>
                  <ci> KCa </ci>
                  <ci> Ca_m </ci>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <connection>
    <map_components component_2="oxidative_phosphorylation" component_1="ADP_m"/>
    <map_variables variable_2="ADP_m" variable_1="ADP_m"/>
    <map_variables variable_2="V_ATPase" variable_1="V_ATPase"/>
  </connection>
  
  <connection>
    <map_components component_2="calcium_dynamics" component_1="ADP_m"/>
    <map_variables variable_2="ADP_m" variable_1="ADP_m"/>
    <map_variables variable_2="V_ANT" variable_1="V_ANT"/>
  </connection>
  
  <connection>
    <map_components component_2="V_SL" component_1="ADP_m"/>
    <map_variables variable_2="ADP_m" variable_1="ADP_m"/>
    <map_variables variable_2="V_SL" variable_1="V_SL"/>
  </connection>
  
  <connection>
    <map_components component_2="oxidative_phosphorylation" component_1="NADH"/>
    <map_variables variable_2="NADH" variable_1="NADH"/>
    <map_variables variable_2="V_O2" variable_1="V_O2"/>
  </connection>
  
  <connection>
    <map_components component_2="V_IDH" component_1="NADH"/>
    <map_variables variable_2="NADH" variable_1="NADH"/>
    <map_variables variable_2="V_IDH" variable_1="V_IDH"/>
  </connection>
  
  <connection>
    <map_components component_2="V_KGDH" component_1="NADH"/>
    <map_variables variable_2="V_KGDH" variable_1="V_KGDH"/>
  </connection>
  
  <connection>
    <map_components component_2="V_MDH" component_1="NADH"/>
    <map_variables variable_2="V_MDH" variable_1="V_MDH"/>
  </connection>
  
  <connection>
    <map_components component_2="V_ACO" component_1="ISOC"/>
    <map_variables variable_2="ISOC" variable_1="ISOC"/>
    <map_variables variable_2="V_ACO" variable_1="V_ACO"/>
  </connection>
  
  <connection>
    <map_components component_2="V_IDH" component_1="ISOC"/>
    <map_variables variable_2="ISOC" variable_1="ISOC"/>
    <map_variables variable_2="V_IDH" variable_1="V_IDH"/>
  </connection>
  
  <connection>
    <map_components component_2="V_IDH" component_1="alpha_KG"/>
    <map_variables variable_2="V_IDH" variable_1="V_IDH"/>
  </connection>
  
  <connection>
    <map_components component_2="V_KGDH" component_1="alpha_KG"/>
    <map_variables variable_2="alpha_KG" variable_1="alpha_KG"/>
    <map_variables variable_2="V_KGDH" variable_1="V_KGDH"/>
  </connection>
  
  <connection>
    <map_components component_2="V_AAT" component_1="alpha_KG"/>
    <map_variables variable_2="alpha_KG" variable_1="alpha_KG"/>
    <map_variables variable_2="V_AAT" variable_1="V_AAT"/>
  </connection>
  
  <connection>
    <map_components component_2="V_KGDH" component_1="SCoA"/>
    <map_variables variable_2="V_KGDH" variable_1="V_KGDH"/>
  </connection>
  
  <connection>
    <map_components component_2="V_SL" component_1="SCoA"/>
    <map_variables variable_2="SCoA" variable_1="SCoA"/>
    <map_variables variable_2="V_SL" variable_1="V_SL"/>
  </connection>
  
  <connection>
    <map_components component_2="V_SL" component_1="Suc"/>
    <map_variables variable_2="Suc" variable_1="Suc"/>
    <map_variables variable_2="V_SL" variable_1="V_SL"/>
  </connection>
  
  <connection>
    <map_components component_2="V_SDH" component_1="Suc"/>
    <map_variables variable_2="Suc" variable_1="Suc"/>
    <map_variables variable_2="V_SDH" variable_1="V_SDH"/>
  </connection>
  
  <connection>
    <map_components component_2="V_SDH" component_1="FUM"/>
    <map_variables variable_2="FUM" variable_1="FUM"/>
    <map_variables variable_2="V_SDH" variable_1="V_SDH"/>
  </connection>
  
  <connection>
    <map_components component_2="V_FH" component_1="FUM"/>
    <map_variables variable_2="FUM" variable_1="FUM"/>
    <map_variables variable_2="V_FH" variable_1="V_FH"/>
  </connection>
  
  <connection>
    <map_components component_2="V_FH" component_1="MAL"/>
    <map_variables variable_2="MAL" variable_1="MAL"/>
    <map_variables variable_2="V_FH" variable_1="V_FH"/>
  </connection>
  
  <connection>
    <map_components component_2="V_MDH" component_1="MAL"/>
    <map_variables variable_2="MAL" variable_1="MAL"/>
    <map_variables variable_2="V_MDH" variable_1="V_MDH"/>
  </connection>
  
  <connection>
    <map_components component_2="V_MDH" component_1="OAA"/>
    <map_variables variable_2="OAA" variable_1="OAA"/>
    <map_variables variable_2="V_MDH" variable_1="V_MDH"/>
  </connection>
  
  <connection>
    <map_components component_2="V_CS" component_1="OAA"/>
    <map_variables variable_2="OAA" variable_1="OAA"/>
    <map_variables variable_2="V_CS" variable_1="V_CS"/>
  </connection>
  
  <connection>
    <map_components component_2="V_AAT" component_1="OAA"/>
    <map_variables variable_2="OAA" variable_1="OAA"/>
    <map_variables variable_2="V_AAT" variable_1="V_AAT"/>
  </connection>
  
  <connection>
    <map_components component_2="V_AAT" component_1="ASP"/>
    <map_variables variable_2="ASP" variable_1="ASP"/>
    <map_variables variable_2="V_AAT" variable_1="V_AAT"/>
  </connection>
  
  <connection>
    <map_components component_2="V_C_ASP" component_1="ASP"/>
    <map_variables variable_2="ASP" variable_1="ASP"/>
    <map_variables variable_2="V_C_ASP" variable_1="V_C_ASP"/>
  </connection>
  
  <connection>
    <map_components component_2="calcium_dynamics" component_1="Ca_m"/>
    <map_variables variable_2="Ca_m" variable_1="Ca_m"/>
    <map_variables variable_2="V_uni" variable_1="V_uni"/>
    <map_variables variable_2="V_NaCa" variable_1="V_NaCa"/>
  </connection>
  
  <connection>
    <map_components component_2="V_CS" component_1="AcCoA"/>
    <map_variables variable_2="AcCoA" variable_1="AcCoA"/>
  </connection>
  
  <connection>
    <map_components component_2="V_ACO" component_1="CIT"/>
    <map_variables variable_2="CIT" variable_1="CIT"/>
  </connection>
  
  <connection>
    <map_components component_2="V_IDH" component_1="NAD"/>
    <map_variables variable_2="NAD" variable_1="NAD"/>
  </connection>
  
  <connection>
    <map_components component_2="V_IDH" component_1="H"/>
    <map_variables variable_2="H" variable_1="H"/>
  </connection>
  
  <connection>
    <map_components component_2="V_KGDH" component_1="NAD"/>
    <map_variables variable_2="NAD" variable_1="NAD"/>
  </connection>
  
  <connection>
    <map_components component_2="V_KGDH" component_1="Mg"/>
    <map_variables variable_2="Mg" variable_1="Mg"/>
  </connection>
  
  <connection>
    <map_components component_2="V_SL" component_1="CoA"/>
    <map_variables variable_2="CoA" variable_1="CoA"/>
  </connection>
  
  <connection>
    <map_components component_2="V_SL" component_1="ATP_m"/>
    <map_variables variable_2="ATP_m" variable_1="ATP_m"/>
  </connection>
  
  <connection>
    <map_components component_2="V_MDH" component_1="NAD"/>
    <map_variables variable_2="NAD" variable_1="NAD"/>
  </connection>
  
  <connection>
    <map_components component_2="V_MDH" component_1="H"/>
    <map_variables variable_2="H" variable_1="H"/>
  </connection>
  
  <connection>
    <map_components component_2="V_AAT" component_1="GLU"/>
    <map_variables variable_2="GLU" variable_1="GLU"/>
  </connection>
  
  <connection>
    <map_components component_2="oxidative_phosphorylation" component_1="NAD"/>
    <map_variables variable_2="NAD" variable_1="NAD"/>
  </connection>
  
  <connection>
    <map_components component_2="oxidative_phosphorylation" component_1="Pi"/>
    <map_variables variable_2="Pi" variable_1="Pi"/>
  </connection>
  
  <connection>
    <map_components component_2="oxidative_phosphorylation" component_1="FAD"/>
    <map_variables variable_2="FAD" variable_1="FAD"/>
  </connection>
  
  <connection>
    <map_components component_2="oxidative_phosphorylation" component_1="FADH2"/>
    <map_variables variable_2="FADH2" variable_1="FADH2"/>
  </connection>
  
  <connection>
    <map_components component_2="oxidative_phosphorylation" component_1="ATP_m"/>
    <map_variables variable_2="ATP_m" variable_1="ATP_m"/>
  </connection>
  
  <connection>
    <map_components component_2="calcium_dynamics" component_1="ATP_i"/>
    <map_variables variable_2="ATP_i" variable_1="ATP_i"/>
  </connection>
  
  <connection>
    <map_components component_2="calcium_dynamics" component_1="ADP_i"/>
    <map_variables variable_2="ADP_i" variable_1="ADP_i"/>
  </connection>
  
  <connection>
    <map_components component_2="calcium_dynamics" component_1="ATP_m"/>
    <map_variables variable_2="ATP_m" variable_1="ATP_m"/>
  </connection>
  
  <connection>
    <map_components component_2="calcium_dynamics" component_1="Ca_i"/>
    <map_variables variable_2="Ca_i" variable_1="Ca_i"/>
  </connection>
  
  <connection>
    <map_components component_2="calcium_dynamics" component_1="Na_i"/>
    <map_variables variable_2="Na_i" variable_1="Na_i"/>
  </connection>
  
  <connection>
    <map_components component_2="mitochondrial_membrane" component_1="oxidative_phosphorylation"/>
    <map_variables variable_2="R" variable_1="R"/>
    <map_variables variable_2="T" variable_1="T"/>
    <map_variables variable_2="F" variable_1="F"/>
    <map_variables variable_2="delta_psi_m" variable_1="delta_psi_m"/>
    <map_variables variable_2="V_He" variable_1="V_He"/>
    <map_variables variable_2="V_He_F" variable_1="V_He_F"/>
    <map_variables variable_2="V_Hu" variable_1="V_Hu"/>
    <map_variables variable_2="V_Hleak" variable_1="V_Hleak"/>
  </connection>
  
  <connection>
    <map_components component_2="mitochondrial_membrane" component_1="calcium_dynamics"/>
    <map_variables variable_2="R" variable_1="R"/>
    <map_variables variable_2="T" variable_1="T"/>
    <map_variables variable_2="F" variable_1="F"/>
    <map_variables variable_2="delta_psi_m" variable_1="delta_psi_m"/>
    <map_variables variable_2="V_NaCa" variable_1="V_NaCa"/>
    <map_variables variable_2="V_uni" variable_1="V_uni"/>
    <map_variables variable_2="V_ANT" variable_1="V_ANT"/>
  </connection>
  
  <connection>
    <map_components component_2="V_IDH" component_1="ADP_m"/>
    <map_variables variable_2="ADP_m" variable_1="ADP_m"/>
  </connection>
  
  <connection>
    <map_components component_2="V_IDH" component_1="Ca_m"/>
    <map_variables variable_2="Ca_m" variable_1="Ca_m"/>
  </connection>
  
  <connection>
    <map_components component_2="V_KGDH" component_1="Ca_m"/>
    <map_variables variable_2="Ca_m" variable_1="Ca_m"/>
  </connection>
  
  <connection>
    <map_components component_2="V_SDH" component_1="OAA"/>
    <map_variables variable_2="OAA" variable_1="OAA"/>
  </connection>
  
  <connection>
    <map_components component_2="ATP_m" component_1="ADP_m"/>
    <map_variables variable_2="ADP_m" variable_1="ADP_m"/>
  </connection>
  
  <connection>
    <map_components component_2="NADH" component_1="NAD"/>
    <map_variables variable_2="NADH" variable_1="NADH"/>
  </connection>
  
  <connection>
    <map_components component_2="ISOC" component_1="CIT"/>
    <map_variables variable_2="ISOC" variable_1="ISOC"/>
  </connection>
  
  <connection>
    <map_components component_2="alpha_KG" component_1="CIT"/>
    <map_variables variable_2="alpha_KG" variable_1="alpha_KG"/>
  </connection>
  
  <connection>
    <map_components component_2="SCoA" component_1="CIT"/>
    <map_variables variable_2="SCoA" variable_1="SCoA"/>
  </connection>
  
  <connection>
    <map_components component_2="Suc" component_1="CIT"/>
    <map_variables variable_2="Suc" variable_1="Suc"/>
  </connection>
  
  <connection>
    <map_components component_2="FUM" component_1="CIT"/>
    <map_variables variable_2="FUM" variable_1="FUM"/>
  </connection>
  
  <connection>
    <map_components component_2="MAL" component_1="CIT"/>
    <map_variables variable_2="MAL" variable_1="MAL"/>
  </connection>
  
  <connection>
    <map_components component_2="OAA" component_1="CIT"/>
    <map_variables variable_2="OAA" variable_1="OAA"/>
  </connection>
  
  <connection>
    <map_components component_2="environment" component_1="ADP_m"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
    <map_components component_2="environment" component_1="Ca_i"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
    <map_components component_2="environment" component_1="ADP_i"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
    <map_components component_2="environment" component_1="NADH"/>
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