- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2009-04-24 00:12:39+12:00
- Desc:
- committing version01 of cortassa_aon_winslow_orourke_2004
- Permanent Source URI:
- https://models.cellml.org/workspace/cortassa_aon_winslow_orourke_2004/rawfile/9a5f95b7609311f7fe76407f258e7b2549149f3e/cortassa_aon_winslow_orourke_2004.cellml
<?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_aon_marban_winslow_orourke_2004_version01" name="cortassa_aon_marban_winslow_orourke_2004_version01">
<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 is the original unchecked version of the model imported from the previous
CellML model repository, 24-Jan-2006.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
In order to be able to rapidly adapt to environmental changes, biological systems require dynamic control systems which function near the edge of instability. Dynamic control can be in the form of oscillations, such as cytosolic calcium concentration oscillations(eg Sneyd et al., Modelling the Control of Calcium Oscillations by Membrane Fluxes, 2004), electrical pacemaker cells (eg Lovell et al., A Gradient Model Of Cardiac Pacemaker Myocytes, 2004), and secretion of insulin from pancreatic islets (eg Keener, A Model of Diffusion Induced Oscillatory Insulin Secretion in Pancreatic Beta Cells, 2001)
</para>
<para>
Oscillations in energy metabolism also occur for example in mitochondria, there are oscillations in the transmembrane ionic currents. Experimental data have shown that oscillation of the mitochondrial energy state occur as a consequence of the interactions between mitochondrial reactive oxygen species (ROS) production and the ROS scavenging systems of the cell. In the current study, Cortassa et al. use this experimental data as the basis for their mathematical model, which incorporates mitochondrial ROS synthesis, ROS scavenging, and ion channels within the mitochondrial membrane (see Figure 1 below). This mathematical model of a mitochondrial oscillator is embedded within a previously published model of cardiac mitochondrial energetics (see Cortassa et al. Modelling Mitochondrial Energy Metabolism, 2003, and also see Figure 2 below for more details)
</para>
<para>
Model simulations have generated data which match experimental results. Furthermore, the model simulations also demonstrate that the period of the mitochondrial oscillator can be modulated over a wide range of timescales, from milliseconds to hours, by altering a single parameter, the rate of ROS scavenging by the enzyme superoxide dismutase.
</para>
<para>
The complete 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, <ulink url="http://www.biophysj.org/">
<emphasis>Biophysical Journal</emphasis>
</ulink>, 87, 2060-2073. (Full text (HTML) and PDF versions of the article are available to subscribers on the Biophysical Journal website.) <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15345581&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>
<!--
Below, we define some additional units for association with variables and
mitochondrial_membrane within the model.
-->
<units name="millivolt">
<unit units="volt" prefix="milli"/>
</units>
<units name="millimolar">
<unit units="mole" prefix="milli"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="millimolar_per_volt">
<unit units="millimolar"/>
<unit units="volt" exponent="-1"/>
</units>
<units name="micromolar">
<unit units="mole" prefix="micro"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="micromolar_per_second">
<unit units="micromolar" exponent="-1"/>
<unit units="second" exponent="-1"/>
</units>
<units name="flux">
<unit units="millimolar"/>
<unit units="second" exponent="-1"/>
</units>
<units name="first_order_rate_constant">
<unit units="second" exponent="-1"/>
</units>
<units name="second_order_rate_constant">
<unit units="millimolar" exponent="-1"/>
<unit units="second" exponent="-1"/>
</units>
<units name="millimolar_second">
<unit units="millimolar"/>
<unit units="second"/>
</units>
<units name="second_order_rate_constant_per_volt">
<unit units="second_order_rate_constant"/>
<unit units="volt" exponent="-1"/>
</units>
<units name="per_volt">
<unit units="volt" exponent="-1"/>
</units>
<units name="flux_per_volt">
<unit units="flux"/>
<unit units="volt" exponent="-1"/>
</units>
<units base_units="yes" name="pH"/>
<units name="joule_per_mole_kelvin">
<unit units="joule"/>
<unit units="mole" exponent="-1"/>
<unit units="kelvin" exponent="-1"/>
</units>
<units name="coulomb_per_mole">
<unit units="coulomb"/>
<unit units="mole" exponent="-1"/>
</units>
<units name="volt_coulomb_per_mole_kelvin">
<unit units="volt"/>
<unit units="coulomb_per_mole"/>
<unit units="kelvin" exponent="-1"/>
</units>
<component name="environment">
<variable units="second" public_interface="out" name="time"/>
</component>
<!--
The following components describe all the reactants and products involved in
reactions.
-->
<component cmeta:id="ADP_m" name="ADP_m">
<rdf:RDF>
<rdf:Description rdf:about="#ADP_m">
<dc:title>ADP_m</dc:title>
<dcterms:alternative>
mitochondrial adenosine diphosphate
</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="ADP_m"/>
<variable units="flux" public_interface="in" name="V_ANT"/>
<variable units="flux" public_interface="in" name="V_ATPase"/>
<variable units="flux" public_interface="in" name="V_SL"/>
<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>ADP_m</ci>
</apply>
<apply>
<minus/>
<ci>V_ANT</ci>
<apply>
<plus/>
<ci>V_ATPase</ci>
<ci>V_SL</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="NADH" name="NADH">
<rdf:RDF>
<rdf:Description rdf:about="#NADH">
<dc:title>NADH</dc:title>
<dcterms:alternative>
nicotinamide adenine dinucleotide
</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="NADH"/>
<variable units="flux" public_interface="in" name="V_O2"/>
<variable units="flux" public_interface="in" name="V_IDH"/>
<variable units="flux" public_interface="in" name="V_KGDH"/>
<variable units="flux" public_interface="in" name="V_MDH"/>
<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>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">
<rdf:RDF>
<rdf:Description rdf:about="#ISOC">
<dc:title>ISOC</dc:title>
<dcterms:alternative>isocitrate</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="ISOC"/>
<variable units="flux" public_interface="in" name="V_ACO"/>
<variable units="flux" public_interface="in" name="V_IDH"/>
<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>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">
<rdf:RDF>
<rdf:Description rdf:about="#alpha_KG">
<dc:title>alpha_KG</dc:title>
<dcterms:alternative>alpha-ketoglutarate</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="alpha_KG"/>
<variable units="flux" public_interface="in" name="V_IDH"/>
<variable units="flux" public_interface="in" name="V_KGDH"/>
<variable units="flux" public_interface="in" name="V_AAT"/>
<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>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">
<rdf:RDF>
<rdf:Description rdf:about="#SCoA">
<dc:title>SCoA</dc:title>
<dcterms:alternative>succinyl CoA</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="SCoA"/>
<variable units="flux" public_interface="in" name="V_KGDH"/>
<variable units="flux" public_interface="in" name="V_SL"/>
<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>SCoA</ci>
</apply>
<apply>
<minus/>
<ci>V_KGDH</ci>
<ci>V_SL</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Suc" name="Suc">
<rdf:RDF>
<rdf:Description rdf:about="#Suc">
<dc:title>Suc</dc:title>
<dcterms:alternative>succinate</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="Suc"/>
<variable units="flux" public_interface="in" name="V_SL"/>
<variable units="flux" public_interface="in" name="V_SDH"/>
<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>Suc</ci>
</apply>
<apply>
<minus/>
<ci>V_SL</ci>
<ci>V_SDH</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="FUM" name="FUM">
<rdf:RDF>
<rdf:Description rdf:about="#FUM">
<dc:title>FUM</dc:title>
<dcterms:alternative>fumarate</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="FUM"/>
<variable units="flux" public_interface="in" name="V_SDH"/>
<variable units="flux" public_interface="in" name="V_FH"/>
<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>FUM</ci>
</apply>
<apply>
<minus/>
<ci>V_SDH</ci>
<ci>V_FH</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="MAL" name="MAL">
<rdf:RDF>
<rdf:Description rdf:about="#MAL">
<dc:title>MAL</dc:title>
<dcterms:alternative>malate</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="MAL"/>
<variable units="flux" public_interface="in" name="V_FH"/>
<variable units="flux" public_interface="in" name="V_MDH"/>
<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>MAL</ci>
</apply>
<apply>
<minus/>
<ci>V_FH</ci>
<ci>V_MDH</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="OAA" name="OAA">
<rdf:RDF>
<rdf:Description rdf:about="#OAA">
<dc:title>OAA</dc:title>
<dcterms:alternative>oxaloacetate</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="OAA"/>
<variable units="flux" public_interface="in" name="V_MDH"/>
<variable units="flux" public_interface="in" name="V_CS"/>
<variable units="flux" public_interface="in" name="V_AAT"/>
<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>OAA</ci>
</apply>
<apply>
<minus/>
<ci>V_MDH</ci>
<apply>
<plus/>
<ci>V_CS</ci>
<ci>V_AAT</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="ASP" name="ASP">
<rdf:RDF>
<rdf:Description rdf:about="#ASP">
<dc:title>ASP</dc:title>
<dcterms:alternative>aspartate</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="ASP"/>
<variable units="flux" public_interface="in" name="V_AAT"/>
<variable units="flux" public_interface="in" name="V_C_ASP"/>
<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>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">
<rdf:RDF>
<rdf:Description rdf:about="#Ca_m">
<dc:title>Ca_m</dc:title>
<dcterms:alternative>mitochondrial calcium</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="Ca_m"/>
<variable units="dimensionless" name="f" initial_value="0.0003"/>
<variable units="flux" public_interface="in" name="V_uni"/>
<variable units="flux" public_interface="in" name="V_NaCa"/>
<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>Ca_m</ci>
</apply>
<apply>
<times/>
<ci>f</ci>
<apply>
<minus/>
<ci>V_uni</ci>
<ci>V_NaCa</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Ca_i" name="Ca_i">
<rdf:RDF>
<rdf:Description rdf:about="#Ca_i">
<dc:title>Ca_i</dc:title>
<dcterms:alternative>cytosolic calcium</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="Ca_i" initial_value="2E-2"/>
</component>
<component cmeta:id="Na_i" name="Na_i">
<rdf:RDF>
<rdf:Description rdf:about="#Na_i">
<dc:title>Na_i</dc:title>
<dcterms:alternative>cytosolic sodium</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="Na_i" initial_value="10.0"/>
</component>
<component cmeta:id="ATP_i" name="ATP_i">
<rdf:RDF>
<rdf:Description rdf:about="#ATP_i">
<dc:title>ATP_i</dc:title>
<dcterms:alternative>
cytosolic adenosine triphosphate
</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="ATP_i" initial_value="6.5"/>
</component>
<component cmeta:id="ATP_m" name="ATP_m">
<rdf:RDF>
<rdf:Description rdf:about="#ATP_m">
<dc:title>ATP_m</dc:title>
<dcterms:alternative>
mitochondrial adenosine triphosphate
</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="ATP_m"/>
<variable units="millimolar" name="Cm" initial_value="15.0"/>
<variable units="millimolar" public_interface="in" name="ADP_m"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>ATP_m</ci>
<apply>
<minus/>
<ci>Cm</ci>
<ci>ADP_m</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="ADP_i" name="ADP_i">
<rdf:RDF>
<rdf:Description rdf:about="#ADP_i">
<dc:title>ADP_i</dc:title>
<dcterms:alternative>
cytosolic adenosine diphosphate
</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="ADP_i" initial_value="0.05"/>
</component>
<component cmeta:id="GLU" name="GLU">
<rdf:RDF>
<rdf:Description rdf:about="#GLU">
<dc:title>GLU</dc:title>
<dcterms:alternative>glucose</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="GLU"/>
</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="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="O2_m" name="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"/>
<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 cmeta:id="O2_i" name="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"/>
<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 cmeta:id="H2O2" name="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"/>
<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 cmeta:id="GSH" name="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"/>
<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 cmeta:id="GSSG" name="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"/>
<variable units="joule_per_mole_kelvin" public_interface="out" name="R"/>
<variable units="kelvin" public_interface="out" name="T"/>
<variable units="coulomb_per_mole" public_interface="out" name="F"/>
<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>
<!--
The following components describe the reactions of the main model.
-->
<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="CoA"/>
<variable units="millimolar" name="Km_CoA" 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_CoA </ci>
<ci> CoA </ci>
</apply>
<apply>
<divide/>
<ci> Km_OAA </ci>
<ci> OAA </ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<ci> Km_CoA </ci>
<ci> CoA </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="millimolar" 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="millimolar" name="Ka_Ca" initial_value="0.00141"/>
<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"/>
<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="millimolar" 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="millimolar" name="Kd_Ca" initial_value="1.27E-3"/>
<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="dimensionless" 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="millimolar" name="fh_a" initial_value="30.0"/>
<variable units="millimolar" name="fh_i" initial_value="0.15"/>
<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>
<plus/>
<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>
<ci> k_offset </ci>
</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="first_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="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="joule_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="millivolt" 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="millimolar" name="Ares"/>
<variable units="millimolar" 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="second_order_rate_constant_per_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="dimensionless" name="delta_mu_H"/>
<variable units="pH" 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="millimolar" 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="dimensionless" 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/>
<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>
<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/>
<ci> g </ci>
<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/>
<ci> g </ci>
<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="millimolar" public_interface="in" name="Ca_i"/>
<variable units="millimolar" public_interface="in" name="Ca_m"/>
<variable units="millimolar" public_interface="in" name="Na_i"/>
<variable units="joule_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="first_order_rate_constant" 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="second_order_rate_constant" name="Vmax_uni" initial_value="0.625"/>
<variable units="millimolar" name="K_act" initial_value="3.8E-4"/>
<variable units="millimolar" name="K_trans" initial_value="0.019"/>
<variable units="dimensionless" name="n" initial_value="3.0"/>
<variable units="second_order_rate_constant" name="Vmax_NaCa" initial_value="0.005"/>
<variable units="millimolar" name="KNa" initial_value="9.4"/>
<variable units="millimolar" name="KCa" initial_value="3.75E-4"/>
<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>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> Ca_i </ci>
<ci> K_trans </ci>
</apply>
</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>
<component cmeta:id="V_SOD" name="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 cmeta:id="V_CAT" name="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="dimensionless" 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 cmeta:id="V_GPX" name="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 cmeta:id="V_GR" name="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" 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 cmeta:id="V_IMAC" name="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="flux_per_volt" name="Gmax" initial_value="7.82"/>
<variable units="flux_per_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="millimolar" name="GT" initial_value="1.0"/>
<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 cmeta:id="VTr_ROS" name="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="joule_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>
<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"/>
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