- Author:
- rcai987 <devnull@localhost>
- Date:
- 2015-01-20 11:30:25+13:00
- Desc:
- Added annotations to cortassa_aon_marban_winslow_orourke_2003 model
- Permanent Source URI:
- https://models.cellml.org/workspace/cortassa_aon_marban_winslow_orourke_2003/rawfile/d9e5670aec75ecf8535b2cb3c747f105ab802af4/cortassa_aon_marban_winslow_orourke_2003.cellml
<?xml version='1.0'?>
<!-- FILE : cortassa_model_2003.xml
CREATED : 13th May 2003
LAST MODIFIED : 13th May 2003
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 2003 integrated model of cardiac mitochondrial energy metabolism and calcium dynamics.
CHANGES:
-->
<model name="cortassa_aon_marban_winslow_orourke_2003_version01" xmlns="http://www.cellml.org/cellml/1.0#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="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:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Modelling Mitochondrial Energy Metabolism</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, 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>
The high metabolic rate of cardiac tissue necessitates close agreement between the rates of energy production and consumption. About 2 percent of cellular ATP is consumed per heartbeat, and under normal conditions, almost all of this energy is provided by mitochondrial oxidative phosphorylation. Although the chemiosmotic theory of energy transduction was developed by Michell in 1961, remarkably little has since been elucidated about the mechanisms underlying the control of mitochondrial metabolism.
</para>
<para>
The thermokinetic model describes the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and mitochondrial Ca<superscript>2+</superscript> dynamics (see <xref linkend="fig_reaction_diagram"/> below). The kinetic portion of the model includes effectors of the TCA cycle enzymes regulating production of NADH and FADH<subscript>2</subscript>. In turn, these are used by the electron transport chain to establish a proton motive force driving the F<subscript>1</subscript>F<subscript>0</subscript>-ATPase. In addition, mitochondrial matrix Ca<superscript>2+</superscript>, determined by Ca<superscript>2+</superscript> uniporter and Ca<superscript>2+</superscript>/Na<superscript>+</superscript> exchanger activities, controls the activity of the TCA cycle enzymes isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase. Model simulations are used to predict the response of mitochondria to changes in substrate delivery, metabolic inhibition, the rate of ATP/ADP exchange, and Ca<superscript>2+</superscript> concentration. Model simulations are able to reproduce experimental data, which was taken as supporting evidence for the validity of the model. The steady-state and time-dependent behaviour of the model supports the hypothesis that mitochondrial matrix Ca<superscript>2+</superscript> plays an important role in matching energy supply with demand in cardiac myocytes.
</para>
<para>
Previously published models of mitochondrial energetics include the models of pancreatic beta-cell mitochondrial metabolism by Magnus and Keizer (see <ulink url="${HTML_EXMPL_MITOCHONDRIAL_CA_HANDLING}">Mitochondrial Ca<superscript>2+</superscript> Handling Model, 1997</ulink>). An oxidative phosphorylation model has been developed by Korzeniewski (see <ulink url="${HTML_EXMPL_OXIDATIVE_PHOSPHORYLATION}">The Oxidative Phosphorylation Pathway, 2001</ulink>). However, these models, in common with other previously developed models of mitochondrial energetics, fail to include all the necessary variables. Together with the desire to improve understanding of mitochondrial metabolism, this has led Cortassa <emphasis>et al.</emphasis> to develop an integrated kinetic and thermodynamic model of cardiac mitochondrial energy metabolism. Their model has been described here in CellML (the raw CellML description of the Cortassa <emphasis>et al.</emphasis> model can be downloaded in various formats as described in <xref linkend="sec_download_this_model"/>).
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
An Integrated Model of Cardiac Mitochondrial Energy Metabolism and Calcium Dynamics, Sonia Cortassa, Miguel A. Aon, Eduardo Marban, Raimond L. Winslow, and Brian O'Rourke, 2003, <emphasis>Biophysical Journal</emphasis>, 84, 2734-2755.<ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12668482&dopt=Abstract">PubMed ID: 12668482</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>reaction diagram</title>
</objectinfo>
<imagedata fileref="cortassa_2003.png"/>
</imageobject>
</mediaobject>
<caption>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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<unit prefix="milli" units="mole"/>
<unit exponent="-1" units="litre"/>
</units>
<units name="millimolar_per_volt">
<unit units="millimolar"/>
<unit exponent="-1" units="volt"/>
</units>
<units name="micromolar">
<unit prefix="micro" units="mole"/>
<unit exponent="-1" units="litre"/>
</units>
<units name="micromolar_per_second">
<unit units="micromolar"/>
<unit exponent="-1" units="second"/>
</units>
<units name="micromolar_per_millimolar">
<unit units="micromolar"/>
<unit exponent="-1" units="millimolar"/>
</units>
<units name="flux">
<unit units="millimolar"/>
<unit exponent="-1" units="second"/>
</units>
<units name="first_order_rate_constant">
<unit exponent="-1" units="second"/>
</units>
<units name="second_order_rate_constant">
<unit exponent="-1" units="millimolar"/>
<unit exponent="-1" units="second"/>
</units>
<units name="millimolar_per_second_volt">
<unit units="millimolar"/>
<unit exponent="-1" units="second"/>
<unit exponent="-1" units="volt"/>
</units>
<units name="volt_coulomb_per_mole_kelvin">
<unit units="volt"/>
<unit units="coulomb"/>
<unit exponent="-1" units="mole"/>
<unit exponent="-1" units="kelvin"/>
</units>
<units name="coulomb_per_mole">
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</units>
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<variable name="time" public_interface="out" units="second"/>
</component>
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<variable cmeta:id="id_00001" initial_value="0.1" name="ADP_m" public_interface="out" units="millimolar"/>
<variable cmeta:id="id_00003" name="V_ANT" public_interface="in" units="flux"/>
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</bvar>
<ci>ADP_m</ci>
</apply>
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<minus/>
<ci>V_ANT</ci>
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<plus/>
<ci>V_ATPase</ci>
<ci>V_SL</ci>
</apply>
</apply>
</apply>
</math>
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<variable cmeta:id="id_00006" initial_value="0.01" name="NADH" public_interface="out" units="millimolar"/>
<variable name="V_O2" public_interface="in" units="flux"/>
<variable cmeta:id="id_00007" name="V_IDH" public_interface="in" units="flux"/>
<variable cmeta:id="id_00008" name="V_KGDH" public_interface="in" units="flux"/>
<variable cmeta:id="id_00009" name="V_MDH" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>NADH</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>V_O2</ci>
</apply>
<ci>V_IDH</ci>
<ci>V_KGDH</ci>
<ci>V_MDH</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="ISOC" name="ISOC">
<variable cmeta:id="id_00010" initial_value="0.01" name="ISOC" public_interface="out" units="millimolar"/>
<variable name="V_ACO" public_interface="in" units="flux"/>
<variable cmeta:id="id_00011" name="V_IDH" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ISOC</ci>
</apply>
<apply>
<minus/>
<ci>V_ACO</ci>
<ci>V_IDH</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="alpha_KG" name="alpha_KG">
<variable cmeta:id="id_00012" initial_value="0.01" name="alpha_KG" public_interface="out" units="millimolar"/>
<variable name="V_IDH" public_interface="in" units="flux"/>
<variable cmeta:id="id_00013" name="V_KGDH" public_interface="in" units="flux"/>
<variable cmeta:id="id_00014" name="V_AAT" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>alpha_KG</ci>
</apply>
<apply>
<plus/>
<ci>V_AAT</ci>
<ci>V_IDH</ci>
<apply>
<minus/>
<ci>V_KGDH</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="SCoA" name="SCoA">
<variable cmeta:id="id_00015" initial_value="0.01" name="SCoA" public_interface="out" units="millimolar"/>
<variable cmeta:id="id_00016" name="V_KGDH" public_interface="in" units="flux"/>
<variable cmeta:id="id_00017" name="V_SL" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>SCoA</ci>
</apply>
<apply>
<minus/>
<ci>V_KGDH</ci>
<ci>V_SL</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Suc" name="Suc">
<variable cmeta:id="id_00023" initial_value="0.01" name="Suc" public_interface="out" units="millimolar"/>
<variable cmeta:id="id_00018" name="V_SL" public_interface="in" units="flux"/>
<variable cmeta:id="id_00024" name="V_SDH" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Suc</ci>
</apply>
<apply>
<minus/>
<ci>V_SL</ci>
<ci>V_SDH</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="FUM" name="FUM">
<variable cmeta:id="id_00026" initial_value="0.01" name="FUM" public_interface="out" units="millimolar"/>
<variable cmeta:id="id_00025" name="V_SDH" public_interface="in" units="flux"/>
<variable cmeta:id="id_00027" name="V_FH" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
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<ci>time</ci>
</bvar>
<ci>FUM</ci>
</apply>
<apply>
<minus/>
<ci>V_SDH</ci>
<ci>V_FH</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="MAL" name="MAL">
<variable cmeta:id="id_00028" initial_value="0.01" name="MAL" public_interface="out" units="millimolar"/>
<variable cmeta:id="id_00029" name="V_FH" public_interface="in" units="flux"/>
<variable cmeta:id="id_00030" name="V_MDH" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
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<bvar>
<ci>time</ci>
</bvar>
<ci>MAL</ci>
</apply>
<apply>
<minus/>
<ci>V_FH</ci>
<ci>V_MDH</ci>
</apply>
</apply>
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</component>
<component cmeta:id="OAA" name="OAA">
<variable cmeta:id="id_00036" initial_value="0.01" name="OAA" public_interface="out" units="millimolar"/>
<variable cmeta:id="id_00031" name="V_MDH" public_interface="in" units="flux"/>
<variable cmeta:id="id_00044" name="V_CS" public_interface="in" units="flux"/>
<variable cmeta:id="id_00041" name="V_AAT" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
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<bvar>
<ci>time</ci>
</bvar>
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<minus/>
<ci>V_MDH</ci>
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<plus/>
<ci>V_CS</ci>
<ci>V_AAT</ci>
</apply>
</apply>
</apply>
</math>
</component>
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<variable cmeta:id="id_00050" initial_value="0.01" name="ASP" public_interface="out" units="millimolar"/>
<variable cmeta:id="id_00049" name="V_AAT" public_interface="in" units="flux"/>
<variable cmeta:id="id_00049" name="V_C_ASP" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
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<eq/>
<apply>
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<bvar>
<ci>time</ci>
</bvar>
<ci>ASP</ci>
</apply>
<apply>
<minus/>
<ci>V_AAT</ci>
<ci>V_C_ASP</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Ca_m" name="Ca_m">
<variable cmeta:id="id_00051" initial_value="0.01" name="Ca_m" public_interface="out" units="micromolar"/>
<variable initial_value="0.0003" name="f" units="dimensionless"/>
<variable name="V_uni" public_interface="in" units="flux"/>
<variable cmeta:id="id_00052" name="V_NaCa" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
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<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_m</ci>
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<apply>
<times/>
<ci>f</ci>
<cn cellml:units="micromolar_per_millimolar">1</cn>
<apply>
<minus/>
<ci>V_uni</ci>
<ci>V_NaCa</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Ca_i" name="Ca_i">
<variable cmeta:id="id_00053" name="Ca_i" public_interface="out" units="micromolar"/>
<variable initial_value="0" name="stim_start" units="second"/>
<variable initial_value="10000" name="stim_end" units="second"/>
<variable name="stim_period" units="second"/>
<variable initial_value="0.4" name="stim_duration" units="second"/>
<variable initial_value="1" name="pulse_value" units="micromolar"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
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<ci>stim_start</ci>
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<ci>stim_start</ci>
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<ci>stim_duration</ci>
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<otherwise>
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</otherwise>
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<apply>
<eq/>
<ci>stim_period</ci>
<piecewise>
<piece>
<cn cellml:units="second">0.5</cn>
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<and/>
<apply>
<geq/>
<ci>time</ci>
<cn cellml:units="second">100</cn>
</apply>
<apply>
<lt/>
<ci>time</ci>
<cn cellml:units="second">300</cn>
</apply>
</apply>
</piece>
<otherwise>
<cn cellml:units="second">4</cn>
</otherwise>
</piecewise>
</apply>
</math>
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<variable cmeta:id="id_00054" initial_value="10.0" name="Na_i" public_interface="out" units="millimolar"/>
</component>
<component cmeta:id="ATP_i" name="ATP_i">
<variable cmeta:id="id_00055" initial_value="6.5" name="ATP_i" public_interface="out" units="millimolar"/>
</component>
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<variable cmeta:id="id_00056" name="ATP_m" public_interface="out" units="millimolar"/>
<variable initial_value="15.0" name="Cm" units="millimolar"/>
<variable cmeta:id="id_00057" name="ADP_m" public_interface="in" units="millimolar"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>ATP_m</ci>
<apply>
<minus/>
<ci>Cm</ci>
<ci>ADP_m</ci>
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</math>
</component>
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<variable cmeta:id="id_00002" name="ADP_i" public_interface="out" units="millimolar"/>
<variable initial_value="0.15" name="pulse_value" units="millimolar"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
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<ci>ADP_i</ci>
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<piece>
<ci>pulse_value</ci>
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<ci>time</ci>
<cn cellml:units="second">100</cn>
</apply>
<apply>
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<ci>time</ci>
<cn cellml:units="second">300</cn>
</apply>
</apply>
</piece>
<otherwise>
<cn cellml:units="millimolar">0.05</cn>
</otherwise>
</piecewise>
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</component>
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<variable cmeta:id="id_00058" initial_value="20" name="GLU" public_interface="out" units="millimolar"/>
</component>
<component cmeta:id="Mg" name="Mg">
<variable cmeta:id="id_00059" initial_value="0.4" name="Mg" public_interface="out" units="millimolar"/>
</component>
<component cmeta:id="H" name="H">
<variable initial_value="2.5E-5" name="H" public_interface="out" units="millimolar"/>
</component>
<component cmeta:id="Pi" name="Pi">
<variable initial_value="20.0" name="Pi" public_interface="out" units="millimolar"/>
</component>
<component cmeta:id="CoA" name="CoA">
<variable cmeta:id="id_000000036" initial_value="0.02" name="CoA" public_interface="out" units="millimolar"/>
</component>
<component cmeta:id="AcCoA" name="AcCoA">
<variable cmeta:id="id_00060" initial_value="0.0002" name="AcCoA" public_interface="out" units="millimolar"/>
</component>
<component cmeta:id="FAD" name="FAD">
<variable cmeta:id="id_00061" initial_value="0.01" name="FAD" public_interface="out" units="millimolar"/>
</component>
<component cmeta:id="FADH2" name="FADH2">
<variable cmeta:id="id_00062" initial_value="1.24" name="FADH2" public_interface="out" units="millimolar"/>
</component>
<component cmeta:id="NAD" name="NAD">
<variable cmeta:id="id_00063" name="NAD" public_interface="out" units="millimolar"/>
<variable cmeta:id="id_00064" name="NADH" public_interface="in" units="millimolar"/>
<variable initial_value="10.0" name="C_PN" units="millimolar"/>
<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="CIT" name="CIT">
<variable cmeta:id="id_00065" name="CIT" public_interface="out" units="millimolar"/>
<variable cmeta:id="id_00067" name="ISOC" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_00070" name="alpha_KG" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_00068" name="SCoA" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_00071" name="Suc" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_00072" name="FUM" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_00073" name="MAL" public_interface="in" units="millimolar"/>
<variable name="OAA" public_interface="in" units="millimolar"/>
<variable initial_value="1.0" name="C_Kint" units="millimolar"/>
<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 cmeta:id="id_00077" name="mitochondrial_membrane">
<variable initial_value="0.01" name="delta_psi_m" public_interface="out" units="volt"/>
<variable initial_value="8.315" name="R" public_interface="out" units="volt_coulomb_per_mole_kelvin"/>
<variable initial_value="310.16" name="T" public_interface="out" units="kelvin"/>
<variable initial_value="96480" name="F" public_interface="out" units="coulomb_per_mole"/>
<variable initial_value="1.812" name="C_mito" units="millimolar_per_volt"/>
<variable name="V_He" public_interface="in" units="flux"/>
<variable name="V_He_F" public_interface="in" units="flux"/>
<variable name="V_Hu" public_interface="in" units="flux"/>
<variable name="V_ANT" public_interface="in" units="flux"/>
<variable name="V_Hleak" public_interface="in" units="flux"/>
<variable cmeta:id="id_00075" name="V_NaCa" public_interface="in" units="flux"/>
<variable cmeta:id="id_00076" name="V_uni" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<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 cmeta:id="id_00045" name="V_CS">
<variable cmeta:id="id_00046" name="V_CS" public_interface="out" units="flux"/>
<variable name="OAA" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_00074" name="AcCoA" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_00078" initial_value="1.26E-2" name="Km_AcCoA" units="millimolar"/>
<variable initial_value="6.4E-4" name="Km_OAA" units="millimolar"/>
<variable cmeta:id="id_00047" initial_value="3.2" name="Kcat_CS" units="first_order_rate_constant"/>
<variable cmeta:id="id_00048" initial_value="0.4" name="ET_CS" units="millimolar"/>
<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 name="V_ACO" public_interface="out" units="flux"/>
<variable cmeta:id="id_00066" name="CIT" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000001" name="ISOC" public_interface="in" units="millimolar"/>
<variable initial_value="12.5" name="Kf_ACO" units="first_order_rate_constant"/>
<variable initial_value="2.22" name="KE_ACO" units="dimensionless"/>
<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 cmeta:id="id_000000002" name="V_IDH">
<variable cmeta:id="id_000000003" name="V_IDH" public_interface="out" units="flux"/>
<variable cmeta:id="id_000000006" name="NAD" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000010" name="NADH" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000016" name="ADP_m" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000021" name="Ca_m" public_interface="in" units="micromolar"/>
<variable name="H" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000024" name="ISOC" public_interface="in" units="millimolar"/>
<variable initial_value="8.1E-5" name="Kh_1" units="millimolar"/>
<variable initial_value="5.98E-5" name="Kh_2" units="millimolar"/>
<variable cmeta:id="id_000000025" initial_value="1.52" name="Km_ISOC" units="millimolar"/>
<variable cmeta:id="id_000000017" initial_value="6.2E-2" name="Ka_ADP" units="millimolar"/>
<variable initial_value="1.41" name="Ka_Ca" units="micromolar"/>
<variable cmeta:id="id_000000011" initial_value="0.923" name="Km_NAD" units="millimolar"/>
<variable cmeta:id="id_000000014" initial_value="0.19" name="Ki_NADH" units="millimolar"/>
<variable cmeta:id="id_000000004" initial_value="1.94" name="Kcat_IDH" units="first_order_rate_constant"/>
<variable cmeta:id="id_000000005" initial_value="0.109" name="ET_IDH" units="millimolar"/>
<variable initial_value="1" name="ni" units="dimensionless"/>
<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 cmeta:id="id_000000026" name="V_KGDH">
<variable cmeta:id="id_000000027" name="V_KGDH" public_interface="out" units="flux"/>
<variable name="Mg" public_interface="in" units="millimolar"/>
<variable name="Ca_m" public_interface="in" units="micromolar"/>
<variable cmeta:id="id_000000007" name="NAD" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000030" name="alpha_KG" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000031" initial_value="1.94" name="Km_alpha_KG" units="millimolar"/>
<variable cmeta:id="id_000000028" initial_value="0.15" name="Kcat_KGDH" units="first_order_rate_constant"/>
<variable cmeta:id="id_000000029" initial_value="0.5" name="ET_KGDH" units="millimolar"/>
<variable initial_value="0.0308" name="Kd_Mg" units="millimolar"/>
<variable cmeta:id="id_000000034" initial_value="1.27" name="Kd_Ca" units="micromolar"/>
<variable cmeta:id="id_000000032" initial_value="1.2" name="n_alpha_KG" units="dimensionless"/>
<variable cmeta:id="id_000000012" initial_value="38.7" name="Km_NAD" units="millimolar"/>
<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 cmeta:id="id_00019" name="V_SL">
<variable cmeta:id="id_00020" name="V_SL" public_interface="out" units="flux"/>
<variable cmeta:id="id_00069" name="SCoA" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000018" name="ADP_m" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000037" name="Suc" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000038" name="ATP_m" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000035" name="CoA" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_00022" initial_value="0.127" name="kf_SL" units="second_order_rate_constant"/>
<variable cmeta:id="id_00021" initial_value="3.115" name="Ke_SL" units="millimolar"/>
<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 cmeta:id="id_000000041" name="V_SDH">
<variable cmeta:id="id_000000042" name="V_SDH" public_interface="out" units="flux"/>
<variable cmeta:id="id_000000045" name="Suc" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000046" name="FUM" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_00037" name="OAA" public_interface="in" units="millimolar"/>
<variable initial_value="0.15" name="Kisdh_OAA" units="millimolar"/>
<variable cmeta:id="id_000000043" initial_value="1.0" name="Kcat_SDH" units="first_order_rate_constant"/>
<variable cmeta:id="id_000000044" initial_value="0.5" name="ET_SDH" units="millimolar"/>
<variable cmeta:id="id_000000049" initial_value="3.0E-2" name="Km_Suc" units="millimolar"/>
<variable cmeta:id="id_000000048" initial_value="1.3" name="Ki_FUM" units="millimolar"/>
<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 cmeta:id="id_00033" name="V_MDH">
<variable cmeta:id="id_00032" name="V_MDH" public_interface="out" units="flux"/>
<variable cmeta:id="id_000000050" name="MAL" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_00039" name="OAA" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000008" name="NAD" public_interface="in" units="millimolar"/>
<variable name="H" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000051" initial_value="1.493" name="Km_MAL" units="millimolar"/>
<variable cmeta:id="id_00034" initial_value="2.775E1" name="Kcat_MDH" units="first_order_rate_constant"/>
<variable cmeta:id="id_00035" initial_value="0.154" name="ET_MDH" units="millimolar"/>
<variable cmeta:id="id_00040" initial_value="3.1E-3" name="Ki_OAA" units="millimolar"/>
<variable name="fh_a" units="dimensionless"/>
<variable name="fh_i" units="dimensionless"/>
<variable cmeta:id="id_000000013" initial_value="0.2244" name="Km_NAD" units="millimolar"/>
<variable initial_value="1.13E-5" name="kh1" units="millimolar"/>
<variable initial_value="26.7" name="kh2" units="millimolar"/>
<variable initial_value="6.68E-9" name="kh3" units="millimolar"/>
<variable initial_value="5.62E-6" name="kh4" units="millimolar"/>
<variable initial_value="3.99E-2" name="k_offset" units="dimensionless"/>
<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 cmeta:id="id_000000053" name="V_FH">
<variable cmeta:id="id_000000054" name="V_FH" public_interface="out" units="flux"/>
<variable cmeta:id="id_000000052" name="MAL" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000047" name="FUM" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000055" initial_value="1.0" name="Ke_FH" units="dimensionless"/>
<variable cmeta:id="id_000000056" initial_value="0.83" name="kf_FH" units="first_order_rate_constant"/>
<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 cmeta:id="id_000000057" name="V_AAT">
<variable cmeta:id="id_000000058" name="V_AAT" public_interface="out" units="flux"/>
<variable cmeta:id="id_00038" name="OAA" public_interface="in" units="millimolar"/>
<variable name="GLU" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000059" name="ASP" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000033" name="alpha_KG" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_00043" initial_value="6.6" name="Ke_AAT" units="dimensionless"/>
<variable cmeta:id="id_00042" initial_value="0.644" name="kf_AAT" units="second_order_rate_constant"/>
<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 cmeta:id="id_000000060" name="V_C_ASP">
<variable cmeta:id="id_000000061" name="V_C_ASP" public_interface="out" units="flux"/>
<variable cmeta:id="id_000000062" name="ASP" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000063" initial_value="0.01" name="k_C_ASP" units="first_order_rate_constant"/>
<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 cmeta:id="id_000000064" name="oxidative_phosphorylation">
<variable name="V_O2" public_interface="out" units="flux"/>
<variable name="V_He" public_interface="out" units="flux"/>
<variable name="V_He_F" public_interface="out" units="flux"/>
<variable name="V_ATPase" public_interface="out" units="flux"/>
<variable name="V_Hu" public_interface="out" units="flux"/>
<variable name="V_Hleak" public_interface="out" units="flux"/>
<variable name="R" public_interface="in" units="volt_coulomb_per_mole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_mole"/>
<variable cmeta:id="id_000000009" name="NAD" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000015" name="NADH" public_interface="in" units="millimolar"/>
<variable name="FAD" public_interface="in" units="millimolar"/>
<variable name="FADH2" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000019" name="ADP_m" public_interface="in" units="millimolar"/>
<variable name="ATP_m" public_interface="in" units="millimolar"/>
<variable name="Pi" public_interface="in" units="millimolar"/>
<variable name="delta_psi_m" public_interface="in" units="volt"/>
<variable initial_value="0.0006" name="rho_res" units="millimolar"/>
<variable initial_value="0.0045" name="rho_res_F" units="millimolar"/>
<variable initial_value="6.394E-10" name="ra" units="first_order_rate_constant"/>
<variable initial_value="2.656E-19" name="rc1" units="first_order_rate_constant"/>
<variable name="Ares" units="volt"/>
<variable name="Ares_F" units="volt"/>
<variable initial_value="2.077E-18" name="r1" units="dimensionless"/>
<variable initial_value="1.728E-9" name="r2" units="dimensionless"/>
<variable initial_value="1.059E-26" name="r3" units="dimensionless"/>
<variable initial_value="1.762E-13" name="rb" units="first_order_rate_constant"/>
<variable initial_value="8.632E-27" name="rc2" units="first_order_rate_constant"/>
<variable initial_value="1.35E18" name="Kres" units="dimensionless"/>
<variable initial_value="5.765E13" name="Kres_F" units="dimensionless"/>
<variable initial_value="0.01" name="gH" units="millimolar_per_second_volt"/>
<variable initial_value="0.05" name="delta_psi_B" units="volt"/>
<variable initial_value="0.85" name="g" units="dimensionless"/>
<variable name="delta_mu_H" units="volt"/>
<variable initial_value="-0.6" name="delta_pH" units="dimensionless"/>
<variable initial_value="0.06" name="rho_F1" units="millimolar"/>
<variable initial_value="1.656E-5" name="pa" units="first_order_rate_constant"/>
<variable initial_value="9.651E-14" name="pc1" units="first_order_rate_constant"/>
<variable name="AF1" units="volt"/>
<variable initial_value="1.346E-8" name="p1" units="dimensionless"/>
<variable initial_value="7.739E-7" name="p2" units="dimensionless"/>
<variable initial_value="6.65E-15" name="p3" units="dimensionless"/>
<variable initial_value="3.373E-7" name="pb" units="first_order_rate_constant"/>
<variable initial_value="4.585E-14" name="pc2" units="first_order_rate_constant"/>
<variable initial_value="1.71E6" name="KF1" units="millimolar"/>
<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 name="V_ANT" public_interface="out" units="flux"/>
<variable name="V_uni" public_interface="out" units="flux"/>
<variable cmeta:id="id_000000065" name="V_NaCa" public_interface="out" units="flux"/>
<variable cmeta:id="id_000000020" name="ADP_i" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000040" name="ATP_i" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000066" name="ADP_m" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000039" name="ATP_m" public_interface="in" units="millimolar"/>
<variable cmeta:id="id_000000022" name="Ca_i" public_interface="in" units="micromolar"/>
<variable cmeta:id="id_000000023" name="Ca_m" public_interface="in" units="micromolar"/>
<variable name="Na_i" public_interface="in" units="millimolar"/>
<variable name="R" public_interface="in" units="volt_coulomb_per_mole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_mole"/>
<variable name="delta_psi_m" public_interface="in" units="volt"/>
<variable initial_value="0.5" name="h" units="dimensionless"/>
<variable initial_value="0.091" name="delta_psi_0" units="volt"/>
<variable initial_value="0.05" name="Vmax_ANT" units="flux"/>
<variable initial_value="110.0" name="L" units="dimensionless"/>
<variable initial_value="2.8" name="na" units="dimensionless"/>
<variable initial_value="0.000625" name="Vmax_uni" units="flux"/>
<variable initial_value="0.38" name="K_act" units="micromolar"/>
<variable initial_value="19.0" name="K_trans" units="micromolar"/>
<variable initial_value="3.0" name="n" units="dimensionless"/>
<variable cmeta:id="id_000000067" initial_value="0.005" name="Vmax_NaCa" units="flux"/>
<variable initial_value="9.4" name="KNa" units="millimolar"/>
<variable initial_value="3.75E-1" name="KCa" units="micromolar"/>
<variable initial_value="0.5" name="b" units="dimensionless"/>
<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_1="ADP_m" component_2="oxidative_phosphorylation"/>
<map_variables variable_1="ADP_m" variable_2="ADP_m"/>
<map_variables variable_1="V_ATPase" variable_2="V_ATPase"/>
</connection>
<connection>
<map_components component_1="ADP_m" component_2="calcium_dynamics"/>
<map_variables variable_1="ADP_m" variable_2="ADP_m"/>
<map_variables variable_1="V_ANT" variable_2="V_ANT"/>
</connection>
<connection>
<map_components component_1="ADP_m" component_2="V_SL"/>
<map_variables variable_1="ADP_m" variable_2="ADP_m"/>
<map_variables variable_1="V_SL" variable_2="V_SL"/>
</connection>
<connection>
<map_components component_1="NADH" component_2="oxidative_phosphorylation"/>
<map_variables variable_1="NADH" variable_2="NADH"/>
<map_variables variable_1="V_O2" variable_2="V_O2"/>
</connection>
<connection>
<map_components component_1="NADH" component_2="V_IDH"/>
<map_variables variable_1="NADH" variable_2="NADH"/>
<map_variables variable_1="V_IDH" variable_2="V_IDH"/>
</connection>
<connection>
<map_components component_1="NADH" component_2="V_KGDH"/>
<map_variables variable_1="V_KGDH" variable_2="V_KGDH"/>
</connection>
<connection>
<map_components component_1="NADH" component_2="V_MDH"/>
<map_variables variable_1="V_MDH" variable_2="V_MDH"/>
</connection>
<connection>
<map_components component_1="ISOC" component_2="V_ACO"/>
<map_variables variable_1="ISOC" variable_2="ISOC"/>
<map_variables variable_1="V_ACO" variable_2="V_ACO"/>
</connection>
<connection>
<map_components component_1="ISOC" component_2="V_IDH"/>
<map_variables variable_1="ISOC" variable_2="ISOC"/>
<map_variables variable_1="V_IDH" variable_2="V_IDH"/>
</connection>
<connection>
<map_components component_1="alpha_KG" component_2="V_IDH"/>
<map_variables variable_1="V_IDH" variable_2="V_IDH"/>
</connection>
<connection>
<map_components component_1="alpha_KG" component_2="V_KGDH"/>
<map_variables variable_1="alpha_KG" variable_2="alpha_KG"/>
<map_variables variable_1="V_KGDH" variable_2="V_KGDH"/>
</connection>
<connection>
<map_components component_1="alpha_KG" component_2="V_AAT"/>
<map_variables variable_1="alpha_KG" variable_2="alpha_KG"/>
<map_variables variable_1="V_AAT" variable_2="V_AAT"/>
</connection>
<connection>
<map_components component_1="SCoA" component_2="V_KGDH"/>
<map_variables variable_1="V_KGDH" variable_2="V_KGDH"/>
</connection>
<connection>
<map_components component_1="SCoA" component_2="V_SL"/>
<map_variables variable_1="SCoA" variable_2="SCoA"/>
<map_variables variable_1="V_SL" variable_2="V_SL"/>
</connection>
<connection>
<map_components component_1="Suc" component_2="V_SL"/>
<map_variables variable_1="Suc" variable_2="Suc"/>
<map_variables variable_1="V_SL" variable_2="V_SL"/>
</connection>
<connection>
<map_components component_1="Suc" component_2="V_SDH"/>
<map_variables variable_1="Suc" variable_2="Suc"/>
<map_variables variable_1="V_SDH" variable_2="V_SDH"/>
</connection>
<connection>
<map_components component_1="FUM" component_2="V_SDH"/>
<map_variables variable_1="FUM" variable_2="FUM"/>
<map_variables variable_1="V_SDH" variable_2="V_SDH"/>
</connection>
<connection>
<map_components component_1="FUM" component_2="V_FH"/>
<map_variables variable_1="FUM" variable_2="FUM"/>
<map_variables variable_1="V_FH" variable_2="V_FH"/>
</connection>
<connection>
<map_components component_1="MAL" component_2="V_FH"/>
<map_variables variable_1="MAL" variable_2="MAL"/>
<map_variables variable_1="V_FH" variable_2="V_FH"/>
</connection>
<connection>
<map_components component_1="MAL" component_2="V_MDH"/>
<map_variables variable_1="MAL" variable_2="MAL"/>
<map_variables variable_1="V_MDH" variable_2="V_MDH"/>
</connection>
<connection>
<map_components component_1="OAA" component_2="V_MDH"/>
<map_variables variable_1="OAA" variable_2="OAA"/>
<map_variables variable_1="V_MDH" variable_2="V_MDH"/>
</connection>
<connection>
<map_components component_1="OAA" component_2="V_CS"/>
<map_variables variable_1="OAA" variable_2="OAA"/>
<map_variables variable_1="V_CS" variable_2="V_CS"/>
</connection>
<connection>
<map_components component_1="OAA" component_2="V_AAT"/>
<map_variables variable_1="OAA" variable_2="OAA"/>
<map_variables variable_1="V_AAT" variable_2="V_AAT"/>
</connection>
<connection>
<map_components component_1="ASP" component_2="V_AAT"/>
<map_variables variable_1="ASP" variable_2="ASP"/>
<map_variables variable_1="V_AAT" variable_2="V_AAT"/>
</connection>
<connection>
<map_components component_1="ASP" component_2="V_C_ASP"/>
<map_variables variable_1="ASP" variable_2="ASP"/>
<map_variables variable_1="V_C_ASP" variable_2="V_C_ASP"/>
</connection>
<connection>
<map_components component_1="Ca_m" component_2="calcium_dynamics"/>
<map_variables variable_1="Ca_m" variable_2="Ca_m"/>
<map_variables variable_1="V_uni" variable_2="V_uni"/>
<map_variables variable_1="V_NaCa" variable_2="V_NaCa"/>
</connection>
<connection>
<map_components component_1="AcCoA" component_2="V_CS"/>
<map_variables variable_1="AcCoA" variable_2="AcCoA"/>
</connection>
<connection>
<map_components component_1="CIT" component_2="V_ACO"/>
<map_variables variable_1="CIT" variable_2="CIT"/>
</connection>
<connection>
<map_components component_1="NAD" component_2="V_IDH"/>
<map_variables variable_1="NAD" variable_2="NAD"/>
</connection>
<connection>
<map_components component_1="H" component_2="V_IDH"/>
<map_variables variable_1="H" variable_2="H"/>
</connection>
<connection>
<map_components component_1="NAD" component_2="V_KGDH"/>
<map_variables variable_1="NAD" variable_2="NAD"/>
</connection>
<connection>
<map_components component_1="Mg" component_2="V_KGDH"/>
<map_variables variable_1="Mg" variable_2="Mg"/>
</connection>
<connection>
<map_components component_1="CoA" component_2="V_SL"/>
<map_variables variable_1="CoA" variable_2="CoA"/>
</connection>
<connection>
<map_components component_1="ATP_m" component_2="V_SL"/>
<map_variables variable_1="ATP_m" variable_2="ATP_m"/>
</connection>
<connection>
<map_components component_1="NAD" component_2="V_MDH"/>
<map_variables variable_1="NAD" variable_2="NAD"/>
</connection>
<connection>
<map_components component_1="H" component_2="V_MDH"/>
<map_variables variable_1="H" variable_2="H"/>
</connection>
<connection>
<map_components component_1="GLU" component_2="V_AAT"/>
<map_variables variable_1="GLU" variable_2="GLU"/>
</connection>
<connection>
<map_components component_1="NAD" component_2="oxidative_phosphorylation"/>
<map_variables variable_1="NAD" variable_2="NAD"/>
</connection>
<connection>
<map_components component_1="Pi" component_2="oxidative_phosphorylation"/>
<map_variables variable_1="Pi" variable_2="Pi"/>
</connection>
<connection>
<map_components component_1="FAD" component_2="oxidative_phosphorylation"/>
<map_variables variable_1="FAD" variable_2="FAD"/>
</connection>
<connection>
<map_components component_1="FADH2" component_2="oxidative_phosphorylation"/>
<map_variables variable_1="FADH2" variable_2="FADH2"/>
</connection>
<connection>
<map_components component_1="ATP_m" component_2="oxidative_phosphorylation"/>
<map_variables variable_1="ATP_m" variable_2="ATP_m"/>
</connection>
<connection>
<map_components component_1="ATP_i" component_2="calcium_dynamics"/>
<map_variables variable_1="ATP_i" variable_2="ATP_i"/>
</connection>
<connection>
<map_components component_1="ADP_i" component_2="calcium_dynamics"/>
<map_variables variable_1="ADP_i" variable_2="ADP_i"/>
</connection>
<connection>
<map_components component_1="ATP_m" component_2="calcium_dynamics"/>
<map_variables variable_1="ATP_m" variable_2="ATP_m"/>
</connection>
<connection>
<map_components component_1="Ca_i" component_2="calcium_dynamics"/>
<map_variables variable_1="Ca_i" variable_2="Ca_i"/>
</connection>
<connection>
<map_components component_1="Na_i" component_2="calcium_dynamics"/>
<map_variables variable_1="Na_i" variable_2="Na_i"/>
</connection>
<connection>
<map_components component_1="oxidative_phosphorylation" component_2="mitochondrial_membrane"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
<map_variables variable_1="delta_psi_m" variable_2="delta_psi_m"/>
<map_variables variable_1="V_He" variable_2="V_He"/>
<map_variables variable_1="V_He_F" variable_2="V_He_F"/>
<map_variables variable_1="V_Hu" variable_2="V_Hu"/>
<map_variables variable_1="V_Hleak" variable_2="V_Hleak"/>
</connection>
<connection>
<map_components component_1="calcium_dynamics" component_2="mitochondrial_membrane"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
<map_variables variable_1="delta_psi_m" variable_2="delta_psi_m"/>
<map_variables variable_1="V_NaCa" variable_2="V_NaCa"/>
<map_variables variable_1="V_uni" variable_2="V_uni"/>
<map_variables variable_1="V_ANT" variable_2="V_ANT"/>
</connection>
<connection>
<map_components component_1="ADP_m" component_2="V_IDH"/>
<map_variables variable_1="ADP_m" variable_2="ADP_m"/>
</connection>
<connection>
<map_components component_1="Ca_m" component_2="V_IDH"/>
<map_variables variable_1="Ca_m" variable_2="Ca_m"/>
</connection>
<connection>
<map_components component_1="Ca_m" component_2="V_KGDH"/>
<map_variables variable_1="Ca_m" variable_2="Ca_m"/>
</connection>
<connection>
<map_components component_1="OAA" component_2="V_SDH"/>
<map_variables variable_1="OAA" variable_2="OAA"/>
</connection>
<connection>
<map_components component_1="ADP_m" component_2="ATP_m"/>
<map_variables variable_1="ADP_m" variable_2="ADP_m"/>
</connection>
<connection>
<map_components component_1="NAD" component_2="NADH"/>
<map_variables variable_1="NADH" variable_2="NADH"/>
</connection>
<connection>
<map_components component_1="CIT" component_2="ISOC"/>
<map_variables variable_1="ISOC" variable_2="ISOC"/>
</connection>
<connection>
<map_components component_1="CIT" component_2="alpha_KG"/>
<map_variables variable_1="alpha_KG" variable_2="alpha_KG"/>
</connection>
<connection>
<map_components component_1="CIT" component_2="SCoA"/>
<map_variables variable_1="SCoA" variable_2="SCoA"/>
</connection>
<connection>
<map_components component_1="CIT" component_2="Suc"/>
<map_variables variable_1="Suc" variable_2="Suc"/>
</connection>
<connection>
<map_components component_1="CIT" component_2="FUM"/>
<map_variables variable_1="FUM" variable_2="FUM"/>
</connection>
<connection>
<map_components component_1="CIT" component_2="MAL"/>
<map_variables variable_1="MAL" variable_2="MAL"/>
</connection>
<connection>
<map_components component_1="CIT" component_2="OAA"/>
<map_variables variable_1="OAA" variable_2="OAA"/>
</connection>
<connection>
<map_components component_1="ADP_m" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="ADP_i" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="NADH" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="mitochondrial_membrane" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="ISOC" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="alpha_KG" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="SCoA" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Suc" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="FUM" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="MAL" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="OAA" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="ASP" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Ca_m" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Ca_i" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<rdf:RDF>
<rdf:Description rdf:about="#H">
<dc:title xml:lang="en">H</dc:title>
<dcterms:alternative xml:lang="en">proton</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#Pi">
<dc:title xml:lang="en">Pi</dc:title>
<dcterms:alternative xml:lang="en">inorganic phosphate</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#ADP_m">
<isVersionOf xmlns="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="http://identifiers.org/chebi/CHEBI:16761"/>
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<isVersionOf xmlns="http://biomodels.net/biology-qualifiers/">
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<isVersionOf xmlns="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="http://identifiers.org/go/GO:0051503"/>
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<isVersionOf xmlns="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="http://identifiers.org/go/GO:0000295"/>
</isVersionOf>
</rdf:Description>
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<isVersionOf xmlns="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="http://identifiers.org/go/GO:0000275"/>
</isVersionOf>
<isVersionOf xmlns="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="http://identifiers.org/go/GO:0000276"/>
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</rdf:Description>
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<isVersionOf xmlns="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="http://identifiers.org/go/GO:0004056"/>
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<rdf:Description rdf:about="#NADH">
<isVersionOf xmlns="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="http://identifiers.org/chebi/CHEBI:16908"/>
</isVersionOf>
</rdf:Description>
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<isVersionOf xmlns="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="http://identifiers.org/chebi/CHEBI:16908"/>
</isVersionOf>
</rdf:Description>
<rdf:Description rdf:about="#id_00007">
<hasVersion xmlns="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="http://identifiers.org/go/GO:0004448"/>
</hasVersion>
<hasVersion xmlns="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="http://identifiers.org/go/GO:0004449"/>
</hasVersion>
<hasVersion xmlns="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="http://identifiers.org/go/GO:0004450"/>
</hasVersion>
<hasVersion xmlns="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="http://identifiers.org/go/GO:0045242"/>
</hasVersion>
</rdf:Description>
<rdf:Description rdf:about="#id_00008">
<hasVersion xmlns="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="http://identifiers.org/go/GO:0005947"/>
</hasVersion>
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<rdf:Description rdf:about="#id_00009">
<hasVersion xmlns="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="http://identifiers.org/go/GO:0016615"/>
</hasVersion>
<hasVersion xmlns="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="http://identifiers.org/go/GO:0046554"/>
</hasVersion>
</rdf:Description>
<rdf:Description rdf:about="#ISOC">
<hasVersion xmlns="http://biomodels.net/biology-qualifiers/">
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