<?xml version="1.0" encoding="utf-8"?>
<!--
This CellML file was generated on 4/05/2010 at 9:54:38 at a.m. using:
COR (0.9.31.1371)
Copyright 2002-2010 Dr Alan Garny
http://cor.physiol.ox.ac.uk/ - cor@physiol.ox.ac.uk
CellML 1.0 was used to generate this model
http://www.cellml.org/
-->
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<title>Metabolic Engineering of Lactococcus lactis</title>
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<firstname>Catherine</firstname>
<surname>Lloyd</surname>
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<shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
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<title>Model Status</title>
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This model runs in OpenCell and COR and the units are consistent throughout. The output is similar to the original model simulation, but differs for unknown reasons. The CellML model translation is based on the the original model code which is available online at the JWS website.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: Everyone who has ever tried to radically change metabolic fluxes knows that it is often harder to determine which enzymes have to be modified than it is to actually implement these changes. In the more traditional genetic engineering approaches 'bottle-necks' are pinpointed using qualitative, intuitive approaches, but the alleviation of suspected 'rate-limiting' steps has not often been successful. Here the authors demonstrate that a model of pyruvate distribution in Lactococcus lactis based on enzyme kinetics in combination with metabolic control analysis clearly indicates the key control points in the flux to acetoin and diacetyl, important flavour compounds. The model presented here (available at http://jjj.biochem.sun.ac.za/wcfs.html) showed that the enzymes with the greatest effect on this flux resided outside the acetolactate synthase branch itself. Experiments confirmed the predictions of the model, i.e. knocking out lactate dehydrogenase and overexpressing NADH oxidase increased the flux through the acetolactate synthase branch from 0 to 75% of measured product formation rates.
</para>
<para>
Metabolic engineering of lactic acid bacteria, the combined approach: kinetic modelling, metabolic control and experimental analysis, Marcel H.N. Hoefnagel, Marjo J.C. Starrenburg, Dirk E. Martens, Jeroen Hugenholtz, Michiel Kleerebezem, Iris I. Van Swam, Roger Bongers, Hans V. Westerhoff, and Jacky L. Snoep, 2002, <emphasis>Microbiology</emphasis>, 148, 1003-1013. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11932446&dopt=Abstract">PubMed ID: 11932446</ulink>
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<title>reaction diagram</title>
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<caption>A schematic diagram of the reactions included in the model to describe the distribution of carbon from pyruvate in <emphasis>L. lactis</emphasis>.</caption>
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</sect1>
</article>
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Metabolic engineering of lactic acid bacteria, the combined
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<variable name="V_ALDC" units="flux" public_interface="in"/>
<variable name="V_NEALC" units="flux" public_interface="in"/>
<variable name="V_ACETDH" units="flux" public_interface="in"/>
<variable name="V_ACETEFF" units="flux" public_interface="in"/>
<variable name="time" units="minute" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ACET</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>V_ALDC</ci>
<ci>V_NEALC</ci>
</apply>
<apply>
<plus/>
<ci>V_ACETDH</ci>
<ci>V_ACETEFF</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="ATP">
<variable name="ATP" units="millimolar" initial_value="0.1" public_interface="out"/>
<variable name="V_GLYC" units="flux" public_interface="in"/>
<variable name="V_ACK" units="flux" public_interface="in"/>
<variable name="V_ATPase" units="flux" public_interface="in"/>
<variable name="time" units="minute" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ATP</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>V_GLYC</ci>
<ci>V_ACK</ci>
</apply>
<ci>V_ATPase</ci>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="ADP">
<variable name="ADP" units="millimolar" public_interface="out"/>
<variable name="A_tot" units="millimolar" initial_value="5"/>
<variable name="ATP" units="millimolar" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>ADP</ci>
<apply>
<minus/>
<ci>A_tot</ci>
<ci>ATP</ci>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="NADH">
<variable name="NADH" units="millimolar" initial_value="3.67" public_interface="out"/>
<variable name="V_GLYC" units="flux" public_interface="in"/>
<variable name="V_PDH" units="flux" public_interface="in"/>
<variable name="V_LDH" units="flux" public_interface="in"/>
<variable name="V_ACALDH" units="flux" public_interface="in"/>
<variable name="V_ADH" units="flux" public_interface="in"/>
<variable name="V_ACETDH" units="flux" public_interface="in"/>
<variable name="V_NOX" units="flux" public_interface="in"/>
<variable name="time" units="minute" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>NADH</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>V_GLYC</ci>
<ci>V_PDH</ci>
</apply>
<apply>
<plus/>
<ci>V_LDH</ci>
<ci>V_ACALDH</ci>
<ci>V_ADH</ci>
<ci>V_ACETDH</ci>
<ci>V_NOX</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="NAD">
<variable name="NAD" units="millimolar" public_interface="out"/>
<variable name="NAD_tot" units="millimolar" initial_value="10"/>
<variable name="NADH" units="millimolar" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>NAD</ci>
<apply>
<minus/>
<ci>NAD_tot</ci>
<ci>NADH</ci>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="ACCOA">
<variable name="ACCOA" units="millimolar" initial_value="0.11" public_interface="out"/>
<variable name="V_PDH" units="flux" public_interface="in"/>
<variable name="V_ACALDH" units="flux" public_interface="in"/>
<variable name="V_PTA" units="flux" public_interface="in"/>
<variable name="time" units="minute" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ACCOA</ci>
</apply>
<apply>
<minus/>
<ci>V_PDH</ci>
<apply>
<plus/>
<ci>V_ACALDH</ci>
<ci>V_PTA</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="COA">
<variable name="COA" units="millimolar" public_interface="out"/>
<variable name="C_tot" units="millimolar" initial_value="1"/>
<variable name="ACCOA" units="millimolar" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>COA</ci>
<apply>
<minus/>
<ci>C_tot</ci>
<ci>ACCOA</ci>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="AC">
<variable name="AC" units="millimolar" initial_value="0.01" public_interface="out"/>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="BUT">
<variable name="BUT" units="millimolar" initial_value="0.01" public_interface="out"/>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="ETOH">
<variable name="ETOH" units="millimolar" initial_value="0.1" public_interface="out"/>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="GLC">
<variable name="GLC" units="millimolar" initial_value="15" public_interface="out"/>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="LAC">
<variable name="LAC" units="millimolar" initial_value="0.1" public_interface="out"/>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="O">
<variable name="O" units="millimolar" initial_value="0.2" public_interface="out"/>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="P">
<variable name="P" units="millimolar" initial_value="10" public_interface="out"/>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="V_GLYC">
<variable name="V_GLYC" units="flux" public_interface="out"/>
<variable name="V_GLYC_temp" units="flux" public_interface="out"/>
<variable name="GLC" units="millimolar" public_interface="in"/>
<variable name="NAD" units="millimolar" public_interface="in"/>
<variable name="ADP" units="millimolar" public_interface="in"/>
<variable name="ATP" units="millimolar" public_interface="in"/>
<variable name="PYR" units="millimolar" public_interface="in"/>
<variable name="NADH" units="millimolar" public_interface="in"/>
<variable name="Km_GLC" units="millimolar" initial_value="0.1"/>
<variable name="Km_NAD" units="millimolar" initial_value="0.1412"/>
<variable name="Km_ADP" units="millimolar" initial_value="0.04699"/>
<variable name="Km_PYR" units="millimolar" initial_value="2.5"/>
<variable name="Km_NADH" units="millimolar" initial_value="0.08999"/>
<variable name="Km_ATP" units="millimolar" initial_value="0.01867"/>
<variable name="V_GLYC_max" units="flux" initial_value="2397"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_GLYC</ci>
<piecewise>
<piece>
<ci>V_GLYC_temp</ci>
<apply>
<geq/>
<ci>V_GLYC_temp</ci>
<cn cellml:units="flux">0</cn>
</apply>
</piece>
<otherwise>
<ci>V_GLYC_temp</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>V_GLYC_temp</ci>
<apply>
<divide/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>V_GLYC_max</ci>
<ci>GLC</ci>
</apply>
<ci>Km_GLC</ci>
</apply>
<ci>NAD</ci>
</apply>
<ci>Km_NAD</ci>
</apply>
<ci>ADP</ci>
</apply>
<ci>Km_ADP</ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>GLC</ci>
<ci>Km_GLC</ci>
</apply>
<apply>
<divide/>
<ci>PYR</ci>
<ci>Km_PYR</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>NAD</ci>
<ci>Km_NAD</ci>
</apply>
<apply>
<divide/>
<ci>NADH</ci>
<ci>Km_NADH</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>ADP</ci>
<ci>Km_ADP</ci>
</apply>
<apply>
<divide/>
<ci>ATP</ci>
<ci>Km_ATP</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="V_LDH">
<variable name="V_LDH" units="flux" public_interface="out"/>
<variable name="V_LDH_temp" units="flux" public_interface="out"/>
<variable name="LAC" units="millimolar" public_interface="in"/>
<variable name="NAD" units="millimolar" public_interface="in"/>
<variable name="PYR" units="millimolar" public_interface="in"/>
<variable name="NADH" units="millimolar" public_interface="in"/>
<variable name="Keq" units="dimensionless" initial_value="21120.69"/>
<variable name="Km_LAC" units="millimolar" initial_value="100"/>
<variable name="Km_NAD" units="millimolar" initial_value="2.4"/>
<variable name="Km_PYR" units="millimolar" initial_value="1.5"/>
<variable name="Km_NADH" units="millimolar" initial_value="0.08"/>
<variable name="V_LDH_max" units="flux" initial_value="5118"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_LDH</ci>
<piecewise>
<piece>
<ci>V_LDH_temp</ci>
<apply>
<geq/>
<ci>V_LDH_temp</ci>
<cn cellml:units="flux">0</cn>
</apply>
</piece>
<otherwise>
<ci>V_LDH_temp</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>V_LDH_temp</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>V_LDH_max</ci>
<apply>
<times/>
<ci>Km_PYR</ci>
<ci>Km_NADH</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>PYR</ci>
<ci>NADH</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>LAC</ci>
<ci>NAD</ci>
</apply>
<ci>Keq</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>PYR</ci>
<ci>Km_PYR</ci>
</apply>
<apply>
<divide/>
<ci>LAC</ci>
<ci>Km_LAC</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>NADH</ci>
<ci>Km_NADH</ci>
</apply>
<apply>
<divide/>
<ci>NAD</ci>
<ci>Km_NAD</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="V_PDH">
<variable name="V_PDH" units="flux" public_interface="out"/>
<variable name="V_PDH_temp" units="flux" public_interface="out"/>
<variable name="NAD" units="millimolar" public_interface="in"/>
<variable name="COA" units="millimolar" public_interface="in"/>
<variable name="ACCOA" units="millimolar" public_interface="in"/>
<variable name="PYR" units="millimolar" public_interface="in"/>
<variable name="NADH" units="millimolar" public_interface="in"/>
<variable name="Ki" units="dimensionless" initial_value="46.4159"/>
<variable name="Km_NAD" units="millimolar" initial_value="0.4"/>
<variable name="Km_COA" units="millimolar" initial_value="0.014"/>
<variable name="Km_PYR" units="millimolar" initial_value="1"/>
<variable name="Km_NADH" units="millimolar" initial_value="0.1"/>
<variable name="Km_ACCOA" units="millimolar" initial_value="0.008"/>
<variable name="V_PDH_max" units="flux" initial_value="259"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_PDH</ci>
<piecewise>
<piece>
<ci>V_PDH_temp</ci>
<apply>
<geq/>
<ci>V_PDH_temp</ci>
<cn cellml:units="flux">0</cn>
</apply>
</piece>
<otherwise>
<ci>V_PDH_temp</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>V_PDH_temp</ci>
<apply>
<divide/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>V_PDH_max</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>Ki</ci>
<ci>NADH</ci>
</apply>
<ci>NAD</ci>
</apply>
</apply>
</apply>
<ci>PYR</ci>
</apply>
<ci>Km_PYR</ci>
</apply>
<ci>NAD</ci>
</apply>
<ci>Km_NAD</ci>
</apply>
<ci>COA</ci>
</apply>
<ci>Km_COA</ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>PYR</ci>
<ci>Km_PYR</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>NAD</ci>
<ci>Km_NAD</ci>
</apply>
<apply>
<divide/>
<ci>NADH</ci>
<ci>Km_NADH</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>COA</ci>
<ci>Km_COA</ci>
</apply>
<apply>
<divide/>
<ci>ACCOA</ci>
<ci>Km_ACCOA</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="V_PTA">
<variable name="V_PTA" units="flux" public_interface="out"/>
<variable name="V_PTA_temp" units="flux" public_interface="out"/>
<variable name="P" units="millimolar" public_interface="in"/>
<variable name="COA" units="millimolar" public_interface="in"/>
<variable name="ACCOA" units="millimolar" public_interface="in"/>
<variable name="ACP" units="millimolar" public_interface="in"/>
<variable name="Keq" units="dimensionless" initial_value="0.0065"/>
<variable name="Km_P" units="millimolar" initial_value="2.6"/>
<variable name="Ki_P" units="millimolar" initial_value="2.6"/>
<variable name="Ki_COA" units="millimolar" initial_value="0.029"/>
<variable name="Km_ACP" units="millimolar" initial_value="0.7"/>
<variable name="Ki_ACP" units="millimolar" initial_value="0.2"/>
<variable name="Ki_ACCOA" units="millimolar" initial_value="0.2"/>
<variable name="V_PTA_max" units="flux" initial_value="42"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_PTA</ci>
<piecewise>
<piece>
<ci>V_PTA_temp</ci>
<apply>
<geq/>
<ci>V_PTA_temp</ci>
<cn cellml:units="flux">0</cn>
</apply>
</piece>
<otherwise>
<ci>V_PTA_temp</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>V_PTA_temp</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>V_PTA_max</ci>
<apply>
<times/>
<ci>Ki_ACCOA</ci>
<ci>Km_P</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>ACCOA</ci>
<ci>P</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>ACP</ci>
<ci>COA</ci>
</apply>
<ci>Keq</ci>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>ACCOA</ci>
<ci>Ki_ACCOA</ci>
</apply>
<apply>
<divide/>
<ci>P</ci>
<ci>Ki_P</ci>
</apply>
<apply>
<divide/>
<ci>ACP</ci>
<ci>Ki_ACP</ci>
</apply>
<apply>
<divide/>
<ci>COA</ci>
<ci>Ki_COA</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>ACCOA</ci>
<ci>P</ci>
</apply>
<apply>
<times/>
<ci>Ki_ACCOA</ci>
<ci>Km_P</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>ACP</ci>
<ci>COA</ci>
</apply>
<apply>
<times/>
<ci>Km_ACP</ci>
<ci>Ki_COA</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="V_ACK">
<variable name="V_ACK" units="flux" public_interface="out"/>
<variable name="V_ACK_temp" units="flux" public_interface="out"/>
<variable name="AC" units="millimolar" public_interface="in"/>
<variable name="ATP" units="millimolar" public_interface="in"/>
<variable name="ADP" units="millimolar" public_interface="in"/>
<variable name="ACP" units="millimolar" public_interface="in"/>
<variable name="Keq" units="dimensionless" initial_value="174.217"/>
<variable name="Km_AC" units="millimolar" initial_value="7"/>
<variable name="Km_ATP" units="millimolar" initial_value="0.07"/>
<variable name="Km_ADP" units="millimolar" initial_value="0.5"/>
<variable name="Km_ACP" units="millimolar" initial_value="0.16"/>
<variable name="V_ACK_max" units="flux" initial_value="2700"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_ACK</ci>
<piecewise>
<piece>
<ci>V_ACK_temp</ci>
<apply>
<geq/>
<ci>V_ACK_temp</ci>
<cn cellml:units="flux">0</cn>
</apply>
</piece>
<otherwise>
<ci>V_ACK_temp</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>V_ACK_temp</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>V_ACK_max</ci>
<apply>
<times/>
<ci>Km_ADP</ci>
<ci>Km_ACP</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>ACP</ci>
<ci>ADP</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>AC</ci>
<ci>ATP</ci>
</apply>
<ci>Keq</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>ACP</ci>
<ci>Km_ACP</ci>
</apply>
<apply>
<divide/>
<ci>AC</ci>
<ci>Km_AC</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>ADP</ci>
<ci>Km_ADP</ci>
</apply>
<apply>
<divide/>
<ci>ATP</ci>
<ci>Km_ATP</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="V_ACALDH">
<variable name="V_ACALDH" units="flux" public_interface="out"/>
<variable name="V_ACALDH_temp" units="flux" public_interface="out"/>
<variable name="NAD" units="millimolar" public_interface="in"/>
<variable name="NADH" units="millimolar" public_interface="in"/>
<variable name="COA" units="millimolar" public_interface="in"/>
<variable name="ACCOA" units="millimolar" public_interface="in"/>
<variable name="ACAL" units="millimolar" public_interface="in"/>
<variable name="Keq" units="millimolar" initial_value="1"/>
<variable name="Km_NAD" units="millimolar" initial_value="0.08"/>
<variable name="Km_NADH" units="millimolar" initial_value="0.025"/>
<variable name="Km_COA" units="millimolar" initial_value="0.008"/>
<variable name="Km_ACCOA" units="millimolar" initial_value="0.007"/>
<variable name="Km_ACAL" units="millimolar" initial_value="10"/>
<variable name="V_ACALDH_max" units="flux" initial_value="97"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_ACALDH</ci>
<piecewise>
<piece>
<ci>V_ACALDH_temp</ci>
<apply>
<geq/>
<ci>V_ACALDH_temp</ci>
<cn cellml:units="flux">0</cn>
</apply>
</piece>
<otherwise>
<ci>V_ACALDH_temp</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>V_ACALDH_temp</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>V_ACALDH_max</ci>
<apply>
<times/>
<ci>Km_ACCOA</ci>
<ci>Km_NADH</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>ACCOA</ci>
<ci>NADH</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>NAD</ci>
<ci>COA</ci>
<ci>ACAL</ci>
</apply>
<ci>Keq</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>NAD</ci>
<ci>Km_NAD</ci>
</apply>
<apply>
<divide/>
<ci>NADH</ci>
<ci>Km_NADH</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>ACCOA</ci>
<ci>Km_ACCOA</ci>
</apply>
<apply>
<divide/>
<ci>COA</ci>
<ci>Km_COA</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>ACAL</ci>
<ci>Km_ACAL</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="V_ADH">
<variable name="V_ADH" units="flux" public_interface="out"/>
<variable name="V_ADH_temp" units="flux" public_interface="out"/>
<variable name="NAD" units="millimolar" public_interface="in"/>
<variable name="NADH" units="millimolar" public_interface="in"/>
<variable name="ETOH" units="millimolar" public_interface="in"/>
<variable name="ACAL" units="millimolar" public_interface="in"/>
<variable name="Keq" units="dimensionless" initial_value="12354.9"/>
<variable name="Km_NAD" units="millimolar" initial_value="0.08"/>
<variable name="Km_NADH" units="millimolar" initial_value="0.05"/>
<variable name="Km_ETOH" units="millimolar" initial_value="1"/>
<variable name="Km_ACAL" units="millimolar" initial_value="0.03"/>
<variable name="V_ADH_max" units="flux" initial_value="162"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_ADH</ci>
<piecewise>
<piece>
<ci>V_ADH_temp</ci>
<apply>
<geq/>
<ci>V_ADH_temp</ci>
<cn cellml:units="flux">0</cn>
</apply>
</piece>
<otherwise>
<ci>V_ADH_temp</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>V_ADH_temp</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>V_ADH_max</ci>
<apply>
<times/>
<ci>Km_ACAL</ci>
<ci>Km_NADH</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>ACAL</ci>
<ci>NADH</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>ETOH</ci>
<ci>NAD</ci>
</apply>
<ci>Keq</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>NAD</ci>
<ci>Km_NAD</ci>
</apply>
<apply>
<divide/>
<ci>NADH</ci>
<ci>Km_NADH</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>ACAL</ci>
<ci>Km_ACAL</ci>
</apply>
<apply>
<divide/>
<ci>ETOH</ci>
<ci>Km_ETOH</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="V_ALS">
<variable name="V_ALS" units="flux" public_interface="out"/>
<variable name="V_ALS_temp" units="flux" public_interface="out"/>
<variable name="ACLAC" units="millimolar" public_interface="in"/>
<variable name="PYR" units="millimolar" public_interface="in"/>
<variable name="N" units="dimensionless" initial_value="2.4"/>
<variable name="Keq" units="dimensionless" initial_value="9e12"/>
<variable name="Km_ACLAC" units="millimolar" initial_value="100"/>
<variable name="Km_PYR" units="millimolar" initial_value="50"/>
<variable name="V_ALS_max" units="flux" initial_value="600"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_ALS</ci>
<piecewise>
<piece>
<ci>V_ALS_temp</ci>
<apply>
<geq/>
<ci>V_ALS_temp</ci>
<cn cellml:units="flux">0</cn>
</apply>
</piece>
<otherwise>
<ci>V_ALS_temp</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>V_ALS_temp</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>V_ALS_max</ci>
<ci>PYR</ci>
</apply>
<ci>Km_PYR</ci>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>ACLAC</ci>
<apply>
<times/>
<ci>PYR</ci>
<ci>Keq</ci>
</apply>
</apply>
</apply>
<apply>
<power/>
<apply>
<plus/>
<apply>
<divide/>
<ci>PYR</ci>
<ci>Km_PYR</ci>
</apply>
<apply>
<divide/>
<ci>ACLAC</ci>
<ci>Km_ACLAC</ci>
</apply>
</apply>
<apply>
<minus/>
<ci>N</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<plus/>
<apply>
<divide/>
<ci>PYR</ci>
<ci>Km_PYR</ci>
</apply>
<apply>
<divide/>
<ci>ACLAC</ci>
<ci>Km_ACLAC</ci>
</apply>
</apply>
<ci>N</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="V_ALDC">
<variable name="V_ALDC" units="flux" public_interface="out"/>
<variable name="V_ALDC_temp" units="flux" public_interface="out"/>
<variable name="ACLAC" units="millimolar" public_interface="in"/>
<variable name="ACET" units="millimolar" public_interface="in"/>
<variable name="Km_ACLAC" units="millimolar" initial_value="10"/>
<variable name="Km_ACET" units="millimolar" initial_value="100"/>
<variable name="V_ALDC_max" units="flux" initial_value="106"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_ALDC</ci>
<piecewise>
<piece>
<ci>V_ALDC_temp</ci>
<apply>
<geq/>
<ci>V_ALDC_temp</ci>
<cn cellml:units="flux">0</cn>
</apply>
</piece>
<otherwise>
<ci>V_ALDC_temp</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>V_ALDC_temp</ci>
<apply>
<divide/>
<apply>
<divide/>
<apply>
<times/>
<ci>V_ALDC_max</ci>
<ci>ACLAC</ci>
</apply>
<ci>Km_ACLAC</ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>ACLAC</ci>
<ci>Km_ACLAC</ci>
</apply>
<apply>
<divide/>
<ci>ACET</ci>
<ci>Km_ACET</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="V_ACETEFF">
<variable name="V_ACETEFF" units="flux" public_interface="out"/>
<variable name="V_ACETEFF_temp" units="flux" public_interface="out"/>
<variable name="ACET" units="millimolar" public_interface="in"/>
<variable name="Km_ACET" units="millimolar" initial_value="5"/>
<variable name="V_ACETEFF_max" units="flux" initial_value="200"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_ACETEFF</ci>
<piecewise>
<piece>
<ci>V_ACETEFF_temp</ci>
<apply>
<geq/>
<ci>V_ACETEFF_temp</ci>
<cn cellml:units="flux">0</cn>
</apply>
</piece>
<otherwise>
<ci>V_ACETEFF_temp</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>V_ACETEFF_temp</ci>
<apply>
<divide/>
<apply>
<divide/>
<apply>
<times/>
<ci>V_ACETEFF_max</ci>
<ci>ACET</ci>
</apply>
<ci>Km_ACET</ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>ACET</ci>
<ci>Km_ACET</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="V_ACETDH">
<variable name="V_ACETDH" units="flux" public_interface="out"/>
<variable name="V_ACETDH_temp" units="flux" public_interface="out"/>
<variable name="NAD" units="millimolar" public_interface="in"/>
<variable name="NADH" units="millimolar" public_interface="in"/>
<variable name="BUT" units="millimolar" public_interface="in"/>
<variable name="ACET" units="millimolar" public_interface="in"/>
<variable name="Keq" units="dimensionless" initial_value="1400"/>
<variable name="Km_NAD" units="millimolar" initial_value="0.16"/>
<variable name="Km_NADH" units="millimolar" initial_value="0.02"/>
<variable name="Km_BUT" units="millimolar" initial_value="2.6"/>
<variable name="Km_ACET" units="millimolar" initial_value="0.06"/>
<variable name="V_ACETDH_max" units="flux" initial_value="105"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_ACETDH</ci>
<piecewise>
<piece>
<ci>V_ACETDH_temp</ci>
<apply>
<geq/>
<ci>V_ACETDH_temp</ci>
<cn cellml:units="flux">0</cn>
</apply>
</piece>
<otherwise>
<ci>V_ACETDH_temp</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>V_ACETDH_temp</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>V_ACETDH_max</ci>
<apply>
<times/>
<ci>Km_ACET</ci>
<ci>Km_NADH</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>ACET</ci>
<ci>NADH</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>BUT</ci>
<ci>NAD</ci>
</apply>
<ci>Keq</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>ACET</ci>
<ci>Km_ACET</ci>
</apply>
<apply>
<divide/>
<ci>BUT</ci>
<ci>Km_BUT</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>NADH</ci>
<ci>Km_NADH</ci>
</apply>
<apply>
<divide/>
<ci>NAD</ci>
<ci>Km_NAD</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="V_ATPase">
<variable name="V_ATPase" units="flux" public_interface="out"/>
<variable name="V_ATPase_temp" units="flux" public_interface="out"/>
<variable name="ADP" units="millimolar" public_interface="in"/>
<variable name="ATP" units="millimolar" public_interface="in"/>
<variable name="N" units="dimensionless" initial_value="2.58"/>
<variable name="Km_ATP" units="dimensionless" initial_value="6.196"/>
<variable name="V_ATPase_max" units="flux" initial_value="900"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_ATPase</ci>
<piecewise>
<piece>
<ci>V_ATPase_temp</ci>
<apply>
<geq/>
<ci>V_ATPase_temp</ci>
<cn cellml:units="flux">0</cn>
</apply>
</piece>
<otherwise>
<ci>V_ATPase_temp</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>V_ATPase_temp</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>V_ATPase_max</ci>
<apply>
<power/>
<apply>
<divide/>
<ci>ATP</ci>
<ci>ADP</ci>
</apply>
<ci>N</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<power/>
<ci>Km_ATP</ci>
<ci>N</ci>
</apply>
<apply>
<power/>
<apply>
<divide/>
<ci>ATP</ci>
<ci>ADP</ci>
</apply>
<ci>N</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="V_NOX">
<variable name="V_NOX" units="flux" public_interface="out"/>
<variable name="V_NOX_temp" units="flux" public_interface="out"/>
<variable name="NAD" units="millimolar" public_interface="in"/>
<variable name="NADH" units="millimolar" public_interface="in"/>
<variable name="O" units="millimolar" public_interface="in"/>
<variable name="Km_NAD" units="millimolar" initial_value="1"/>
<variable name="Km_NADH" units="millimolar" initial_value="0.041"/>
<variable name="Km_O" units="millimolar" initial_value="0.2"/>
<variable name="V_NOX_max" units="flux" initial_value="118"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_NOX</ci>
<piecewise>
<piece>
<ci>V_NOX_temp</ci>
<apply>
<geq/>
<ci>V_NOX_temp</ci>
<cn cellml:units="flux">0</cn>
</apply>
</piece>
<otherwise>
<ci>V_NOX_temp</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>V_NOX_temp</ci>
<apply>
<divide/>
<apply>
<divide/>
<apply>
<times/>
<ci>V_NOX_max</ci>
<ci>NADH</ci>
<ci>O</ci>
</apply>
<apply>
<times/>
<ci>Km_NADH</ci>
<ci>Km_O</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>NADH</ci>
<ci>Km_NADH</ci>
</apply>
<apply>
<divide/>
<ci>NAD</ci>
<ci>Km_NAD</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>O</ci>
<ci>Km_O</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="V_NEALC">
<variable name="V_NEALC" units="flux" public_interface="out"/>
<variable name="ACLAC" units="millimolar" public_interface="in"/>
<variable name="k" units="first_order_rate_constant" initial_value="0.0003"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_NEALC</ci>
<apply>
<times/>
<ci>k</ci>
<ci>ACLAC</ci>
</apply>
</apply>
</math>
</component>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="PYR" component_2="V_GLYC"/>
<map_variables variable_1="PYR" variable_2="PYR"/>
<map_variables variable_1="V_GLYC" variable_2="V_GLYC"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="PYR" component_2="V_LDH"/>
<map_variables variable_1="PYR" variable_2="PYR"/>
<map_variables variable_1="V_LDH" variable_2="V_LDH"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="PYR" component_2="V_PDH"/>
<map_variables variable_1="PYR" variable_2="PYR"/>
<map_variables variable_1="V_PDH" variable_2="V_PDH"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="PYR" component_2="V_ALS"/>
<map_variables variable_1="PYR" variable_2="PYR"/>
<map_variables variable_1="V_ALS" variable_2="V_ALS"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACP" component_2="V_PTA"/>
<map_variables variable_1="ACP" variable_2="ACP"/>
<map_variables variable_1="V_PTA" variable_2="V_PTA"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACP" component_2="V_ACK"/>
<map_variables variable_1="ACP" variable_2="ACP"/>
<map_variables variable_1="V_ACK" variable_2="V_ACK"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACAL" component_2="V_ACALDH"/>
<map_variables variable_1="ACAL" variable_2="ACAL"/>
<map_variables variable_1="V_ACALDH" variable_2="V_ACALDH"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACAL" component_2="V_ADH"/>
<map_variables variable_1="ACAL" variable_2="ACAL"/>
<map_variables variable_1="V_ADH" variable_2="V_ADH"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACLAC" component_2="V_ALS"/>
<map_variables variable_1="ACLAC" variable_2="ACLAC"/>
<map_variables variable_1="V_ALS" variable_2="V_ALS"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACLAC" component_2="V_ALDC"/>
<map_variables variable_1="ACLAC" variable_2="ACLAC"/>
<map_variables variable_1="V_ALDC" variable_2="V_ALDC"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACLAC" component_2="V_NEALC"/>
<map_variables variable_1="ACLAC" variable_2="ACLAC"/>
<map_variables variable_1="V_NEALC" variable_2="V_NEALC"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACET" component_2="V_ALDC"/>
<map_variables variable_1="ACET" variable_2="ACET"/>
<map_variables variable_1="V_ALDC" variable_2="V_ALDC"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACET" component_2="V_NEALC"/>
<map_variables variable_1="V_NEALC" variable_2="V_NEALC"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACET" component_2="V_ACETDH"/>
<map_variables variable_1="ACET" variable_2="ACET"/>
<map_variables variable_1="V_ACETDH" variable_2="V_ACETDH"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACET" component_2="V_ACETEFF"/>
<map_variables variable_1="ACET" variable_2="ACET"/>
<map_variables variable_1="V_ACETEFF" variable_2="V_ACETEFF"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ATP" component_2="V_GLYC"/>
<map_variables variable_1="ATP" variable_2="ATP"/>
<map_variables variable_1="V_GLYC" variable_2="V_GLYC"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ATP" component_2="V_ACK"/>
<map_variables variable_1="ATP" variable_2="ATP"/>
<map_variables variable_1="V_ACK" variable_2="V_ACK"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ATP" component_2="V_ATPase"/>
<map_variables variable_1="ATP" variable_2="ATP"/>
<map_variables variable_1="V_ATPase" variable_2="V_ATPase"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="NADH" component_2="V_GLYC"/>
<map_variables variable_1="NADH" variable_2="NADH"/>
<map_variables variable_1="V_GLYC" variable_2="V_GLYC"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="NADH" component_2="V_PDH"/>
<map_variables variable_1="NADH" variable_2="NADH"/>
<map_variables variable_1="V_PDH" variable_2="V_PDH"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="NADH" component_2="V_LDH"/>
<map_variables variable_1="NADH" variable_2="NADH"/>
<map_variables variable_1="V_LDH" variable_2="V_LDH"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="NADH" component_2="V_ACALDH"/>
<map_variables variable_1="NADH" variable_2="NADH"/>
<map_variables variable_1="V_ACALDH" variable_2="V_ACALDH"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="NADH" component_2="V_ADH"/>
<map_variables variable_1="NADH" variable_2="NADH"/>
<map_variables variable_1="V_ADH" variable_2="V_ADH"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="NADH" component_2="V_ACETDH"/>
<map_variables variable_1="NADH" variable_2="NADH"/>
<map_variables variable_1="V_ACETDH" variable_2="V_ACETDH"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="NADH" component_2="V_NOX"/>
<map_variables variable_1="NADH" variable_2="NADH"/>
<map_variables variable_1="V_NOX" variable_2="V_NOX"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="PYR" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACP" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACAL" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACLAC" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACET" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ATP" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="NADH" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACCOA" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACCOA" component_2="V_PDH"/>
<map_variables variable_1="ACCOA" variable_2="ACCOA"/>
<map_variables variable_1="V_PDH" variable_2="V_PDH"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACCOA" component_2="V_ACALDH"/>
<map_variables variable_1="ACCOA" variable_2="ACCOA"/>
<map_variables variable_1="V_ACALDH" variable_2="V_ACALDH"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ACCOA" component_2="V_PTA"/>
<map_variables variable_1="ACCOA" variable_2="ACCOA"/>
<map_variables variable_1="V_PTA" variable_2="V_PTA"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="GLC" component_2="V_GLYC"/>
<map_variables variable_1="GLC" variable_2="GLC"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="NAD" component_2="V_GLYC"/>
<map_variables variable_1="NAD" variable_2="NAD"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ADP" component_2="V_GLYC"/>
<map_variables variable_1="ADP" variable_2="ADP"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="LAC" component_2="V_LDH"/>
<map_variables variable_1="LAC" variable_2="LAC"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="NAD" component_2="V_LDH"/>
<map_variables variable_1="NAD" variable_2="NAD"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="NAD" component_2="V_PDH"/>
<map_variables variable_1="NAD" variable_2="NAD"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="COA" component_2="V_PDH"/>
<map_variables variable_1="COA" variable_2="COA"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="P" component_2="V_PTA"/>
<map_variables variable_1="P" variable_2="P"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="COA" component_2="V_PTA"/>
<map_variables variable_1="COA" variable_2="COA"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="AC" component_2="V_ACK"/>
<map_variables variable_1="AC" variable_2="AC"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ADP" component_2="ATP"/>
<map_variables variable_1="ATP" variable_2="ATP"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ADP" component_2="V_ACK"/>
<map_variables variable_1="ADP" variable_2="ADP"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="NAD" component_2="V_ACALDH"/>
<map_variables variable_1="NAD" variable_2="NAD"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="COA" component_2="V_ACALDH"/>
<map_variables variable_1="COA" variable_2="COA"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="NAD" component_2="V_ADH"/>
<map_variables variable_1="NAD" variable_2="NAD"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ETOH" component_2="V_ADH"/>
<map_variables variable_1="ETOH" variable_2="ETOH"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="NAD" component_2="NADH"/>
<map_variables variable_1="NADH" variable_2="NADH"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="COA" component_2="ACCOA"/>
<map_variables variable_1="ACCOA" variable_2="ACCOA"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="NAD" component_2="V_ACETDH"/>
<map_variables variable_1="NAD" variable_2="NAD"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="BUT" component_2="V_ACETDH"/>
<map_variables variable_1="BUT" variable_2="BUT"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="ADP" component_2="V_ATPase"/>
<map_variables variable_1="ADP" variable_2="ADP"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="NAD" component_2="V_NOX"/>
<map_variables variable_1="NAD" variable_2="NAD"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="O" component_2="V_NOX"/>
<map_variables variable_1="O" variable_2="O"/>
</connection>
</model>
