<?xml version="1.0"?>

<!--  FILE :  wolf_model_2000.xml

CREATED :  4th April 2001

LAST MODIFIED : 9th April 2003

AUTHOR :  Catherine Lloyd
          Bioengineering Institute
          The University of Auckland
          
MODEL STATUS :  This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/01/2002 CellML Metadata 1.0 Specification.

DESCRIPTION :  This file contains a CellML description of Wolf et al's 2000 model of the intracellular and intercellular dynamics in yeast glycolytic oscillations.

CHANGES:  
  19/07/2002 - CML - Added more metadata.
  09/04/2003 - AAC - Added publication date information.  
-->

<model name="wolf_model_2000" cmeta:id="wolf_model_2000" xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:pathway_editor="http://www.physiome.com/pathway_editor/1.0#">
  <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">
    <!--
      The following RDF block contains metadata that applies to this document
      as a whole, as indicated by the empty about attribute on the 
      <rdf:Description> element.
    -->
    <rdf:Description rdf:about="">
      <!--
        The Model Builder Metadata.  The Dublin Core "creator" element is used  
        to indicate the person who translated the model into CellML.
      -->
      <dc:creator rdf:parseType="Resource">
        <vCard:N rdf:parseType="Resource">
          <vCard:Family>Lloyd</vCard:Family>
          <vCard:Given>Catherine</vCard:Given>
          <vCard:Other>May</vCard:Other>
        </vCard:N>
        <vCard:EMAIL rdf:parseType="Resource">
          <rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
          <rdf:type rdf:resource="http://imc.org/vCard/3.0#internet" />
        </vCard:EMAIL>
        <vCard:ORG rdf:parseType="Resource">
          <vCard:Orgname>The University of Auckland</vCard:Orgname>
          <vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
        </vCard:ORG>
      </dc:creator>
      
      <!--
        The Creation Date metadata. This is the date on which the model
        was translated into CellML.
      -->
      <dcterms:created rdf:parseType="Resource">
        <dcterms:W3CDTF>2002-04-04</dcterms:W3CDTF>
      </dcterms:created>
      
      <!--
        The Modification History metadata. This lists the changes that have been
        made to the document, who made the changes, and when they were made.
      -->
      <cmeta:modification rdf:parseType="Resource">
        <rdf:value>
          Added publication date information.
        </rdf:value>
        <cmeta:modifier rdf:parseType="Resource">
          <vCard:N rdf:parseType="Resource">
            <vCard:Family>Cuellar</vCard:Family>
            <vCard:Given>Autumn</vCard:Given>
            <vCard:Other>A</vCard:Other>
          </vCard:N>
        </cmeta:modifier>
        <dcterms:modified rdf:parseType="Resource"> 
          <dcterms:W3CDTF>2003-04-09</dcterms:W3CDTF>
        </dcterms:modified>
      </cmeta:modification>
      <cmeta:modification rdf:parseType="Resource">
        <rdf:value>
          Added more metadata.
        </rdf:value>
        <cmeta:modifier rdf:parseType="Resource">
          <vCard:N rdf:parseType="Resource">
            <vCard:Family>Lloyd</vCard:Family>
            <vCard:Given>Catherine</vCard:Given>
            <vCard:Other>May</vCard:Other>
          </vCard:N>
        </cmeta:modifier>
        <dcterms:modified rdf:parseType="Resource"> 
          <dcterms:W3CDTF>2002-07-19</dcterms:W3CDTF>
        </dcterms:modified>
      </cmeta:modification>
      
      <!-- The Publisher metadata. -->
      <dc:publisher>
        The University of Auckland, Bioengineering Institute
      </dc:publisher>
    </rdf:Description>
    
    <!--
      The following metadata refers to the model itself, as indicated by the
      reference to the ID "wolf_model_2000", which is declared on
      the <model> element.
    -->
    <rdf:Description rdf:about="#wolf_model_2000">
      <!-- A human readable name for the model. -->
      <dc:title>A dynamic model of glycolytic oscillations in yeast</dc:title>
      
      <!-- A comment regarding the model. -->
      <cmeta:comment rdf:parseType="Resource">
        <rdf:value>
          This is the CellML description of Wolf et al's mathematical model of 
          intracellular and intercellular dynamics in yeast glycolytic 
          oscillations.
        </rdf:value>
        <!-- The creator of the comment. -->
        <dc:creator rdf:parseType="Resource">
          <vCard:FN>Catherine Lloyd</vCard:FN>
        </dc:creator>
      </cmeta:comment>
    
      <!-- The model is relevant to yeast cells. -->
      <cmeta:bio_entity>yeast</cmeta:bio_entity>
      
      <!--  Keyword(s) -->
      <bqs:reference rdf:parseType="Resource">
        <dc:subject rdf:parseType="Resource">
          <bqs:subject_type>keyword</bqs:subject_type>
          <rdf:value>metabolism</rdf:value>
        </dc:subject>
      </bqs:reference>

      <!-- 
        The CellML Metadata Specification recommends that bibliographic metadata
        is used to provide information about the original model reference.  The 
        "identifier" attribute on the "BibliographicReference" class provides an
        elegant way to identify a cited reference using a database identifier   
        such as Pubmed.  All associated data such as author, journal title,     
        date, etc can be looked up on the database.  The following Pubmed ID             refers to the publication.
      -->
      <bqs:reference rdf:parseType="Resource">
        <bqs:Pubmed_id>10692304</bqs:Pubmed_id>
        <bqs:JournalArticle rdf:parseType="Resource">
          <dc:creator>
            <rdf:Seq>
              <rdf:li rdf:parseType="Resource">
                <bqs:Person rdf:parseType="Resource">
                  <vCard:N rdf:parseType="Resource">
                    <vCard:Family>Wolf</vCard:Family>
                    <vCard:Given>Jana</vCard:Given>
                  </vCard:N>
                </bqs:Person>
              </rdf:li>
              <rdf:li rdf:parseType="Resource">
                <bqs:Person rdf:parseType="Resource">
                  <vCard:N rdf:parseType="Resource">
                    <vCard:Family>Passarge</vCard:Family>
                    <vCard:Given>Jutta</vCard:Given>
                  </vCard:N>
                </bqs:Person>
              </rdf:li>
              <rdf:li rdf:parseType="Resource">
                <bqs:Person rdf:parseType="Resource">
                  <vCard:N rdf:parseType="Resource">
                    <vCard:Family>Somsen</vCard:Family>
                    <vCard:Given>Oscar</vCard:Given>
                    <vCard:Other>J</vCard:Other>
                    <vCard:Other>G</vCard:Other>
                  </vCard:N>
                </bqs:Person>
              </rdf:li>
              <rdf:li rdf:parseType="Resource">
                <bqs:Person rdf:parseType="Resource">
                  <vCard:N rdf:parseType="Resource">
                    <vCard:Family>Snoep</vCard:Family>
                    <vCard:Given>Jacky</vCard:Given>
                    <vCard:Other>L</vCard:Other>
                  </vCard:N>
                </bqs:Person>
              </rdf:li>
              <rdf:li rdf:parseType="Resource">
                <bqs:Person rdf:parseType="Resource">
                  <vCard:N rdf:parseType="Resource">
                    <vCard:Family>Heinrich</vCard:Family>
                    <vCard:Given>Reinhart</vCard:Given>
                  </vCard:N>
                </bqs:Person>
              </rdf:li>
              <rdf:li rdf:parseType="Resource">
                <bqs:Person rdf:parseType="Resource">
                  <vCard:N rdf:parseType="Resource">
                    <vCard:Family>Westerhoff</vCard:Family>
                    <vCard:Given>Hans</vCard:Given>
                    <vCard:Other>V</vCard:Other>
                  </vCard:N>
                </bqs:Person>
              </rdf:li>
            </rdf:Seq>
          </dc:creator>
          <dc:title>
            Transduction of Intracellular and Intercellular Dynamics in Yeast                Glycolytic Oscillations
          </dc:title>
          <dcterms:issued rdf:parseType="Resource">
            <dcterms:W3CDTF>2000-03</dcterms:W3CDTF>
          </dcterms:issued>
          <bqs:Journal rdf:parseType="Resource">
            <dc:title>Biophysical Journal</dc:title>
          </bqs:Journal>
          <bqs:volume>78</bqs:volume>
          <bqs:first_page>1145</bqs:first_page>
          <bqs:last_page>1153</bqs:last_page>
        </bqs:JournalArticle>
      </bqs:reference>
    </rdf:Description>
  </rdf:RDF>
  
  <!--
    We start the model definition with a definition of some named
    sets of units for use throughout the model.
  -->
  
  <units name="minute">
    <unit multiplier="60.0" units="second" />
  </units>
  
  <units name="millimolar">
    <unit prefix="milli" units="mole" />
    <unit units="litre" exponent="-1" />
  </units>

  <units name="flux">
    <unit units="millimolar" />
    <unit units="minute" exponent="-1" />
  </units>

  <units name="first_order_rate_constant">
    <unit units="minute" exponent="-1" />
  </units>
  
  <units name="second_order_rate_constant">
    <unit units="millimolar" exponent="-1" />
    <unit units="minute" exponent="-1" />
  </units>
  
  <component name="environment">
    <variable name="time" public_interface="out" units="minute" />
  </component>

  <component name="S1" cmeta:id="S1">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
      <rdf:Description rdf:about="S1">
        <dc:title>S1</dc:title>
        <dcterms:alternative>glucose</dcterms:alternative>
      </rdf:Description>
    </rdf:RDF>
    <variable name="S1" public_interface="out" units="millimolar" />
    <variable name="Jo" public_interface="in" units="flux" />
    <variable name="delta_S1_rxn1" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="minute" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>S1</ci>
        </apply>
        <apply><plus />
          <ci>Jo</ci>
          <ci>delta_S1_rxn1</ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="S2" cmeta:id="S2">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
      <rdf:Description rdf:about="S2">
        <dc:title>S2</dc:title>
        <dcterms:alternative>fructose-1,6-bisphosphate</dcterms:alternative>
      </rdf:Description>
    </rdf:RDF>
    <variable name="S2" public_interface="out" units="millimolar" />
    <variable name="delta_S2_rxn1" public_interface="in" units="flux" />
    <variable name="delta_S2_rxn2" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="minute" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>S2</ci>
        </apply>
        <apply><plus />
          <ci>delta_S2_rxn1</ci>
          <ci>delta_S2_rxn2</ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="S3" cmeta:id="S3">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
      <rdf:Description rdf:about="S3">
        <dc:title>S3</dc:title>
        <dcterms:alternative>triose phosphate pool</dcterms:alternative>
      </rdf:Description>
    </rdf:RDF>
    <variable name="S3" public_interface="out" units="millimolar" />
    <variable name="delta_S3_rxn2" public_interface="in" units="flux" />
    <variable name="delta_S3_rxn3" public_interface="in" units="flux" />
    <variable name="delta_S3_rxn8" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="minute" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>S3</ci>
        </apply>
        <apply><plus />
          <ci>delta_S3_rxn2</ci>
          <ci>delta_S3_rxn3</ci>
          <ci>delta_S3_rxn8</ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="S4" cmeta:id="S4">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
      <rdf:Description rdf:about="S4">
        <dc:title>S4</dc:title>
        <dcterms:alternative>3-phosphoglycerate</dcterms:alternative>
      </rdf:Description>
    </rdf:RDF>
    <variable name="S4" public_interface="out" units="millimolar" />
    <variable name="delta_S4_rxn3" public_interface="in" units="flux" />
    <variable name="delta_S4_rxn4" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="minute" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>S4</ci>
        </apply>
        <apply><plus />
          <ci>delta_S4_rxn3</ci>
          <ci>delta_S4_rxn4</ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="S5" cmeta:id="S5">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
      <rdf:Description rdf:about="S5">
        <dc:title>S5</dc:title>
        <dcterms:alternative>pyruvate</dcterms:alternative>
      </rdf:Description>
    </rdf:RDF>
    <variable name="S5" public_interface="out" units="millimolar" />
    <variable name="delta_S5_rxn4" public_interface="in" units="flux" />
    <variable name="delta_S5_rxn5" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="minute" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>S5</ci>
        </apply>
        <apply><plus />
          <ci>delta_S5_rxn4</ci>
          <ci>delta_S5_rxn5</ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="S6" cmeta:id="S6">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
      <rdf:Description rdf:about="S6">
        <dc:title>S6</dc:title>
        <dcterms:alternative>intracellular acetaldehyde</dcterms:alternative>
      </rdf:Description>
    </rdf:RDF>
    <variable name="S6" public_interface="out" units="millimolar" />
    <variable name="delta_S6_rxn5" public_interface="in" units="flux" />
    <variable name="delta_S6_rxn6" public_interface="in" units="flux" />
    <variable name="J" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="minute" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>S6</ci>
        </apply>
        <apply><plus />
          <ci>delta_S6_rxn5</ci>
          <ci>delta_S6_rxn6</ci>
          <ci>J</ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="S6_ex" cmeta:id="S6_ex">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
      <rdf:Description rdf:about="S6_ex">
        <dc:title>S6_ex</dc:title>
        <dcterms:alternative>extracellular acetaldehyde</dcterms:alternative>
      </rdf:Description>
    </rdf:RDF>
    <variable name="S6_ex" public_interface="out" units="millimolar" />
    <variable name="psi" initial_value="0.1" units="dimensionless" />
    <variable name="delta_S6_ex_rxn9" public_interface="in" units="flux" />
    <variable name="J" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="minute" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>S6_ex</ci>
        </apply>
        <apply><plus />
          <apply><times />
            <ci> psi </ci>
            <ci> J </ci>
          </apply>
          <ci>delta_S6_ex_rxn9</ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="A3" cmeta:id="A3">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
      <rdf:Description rdf:about="A3">
        <dc:title>A3</dc:title>
        <dcterms:alternative>ATP</dcterms:alternative>
      </rdf:Description>
    </rdf:RDF>
    <variable name="A3" public_interface="out" units="millimolar" />
    <variable name="delta_A3_rxn1" public_interface="in" units="flux" />
    <variable name="delta_A3_rxn3" public_interface="in" units="flux" />
    <variable name="delta_A3_rxn4" public_interface="in" units="flux" />
    <variable name="delta_A3_rxn7" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="minute" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>A3</ci>
        </apply>
        <apply><plus />
          <ci>delta_A3_rxn1</ci>
          <ci>delta_A3_rxn3</ci>
          <ci>delta_A3_rxn4</ci>
          <ci>delta_A3_rxn7</ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="A" cmeta:id="A">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
      <rdf:Description rdf:about="A">
        <dc:title>A</dc:title>
        <dcterms:alternative>total adenosine phosphates</dcterms:alternative>
      </rdf:Description>
    </rdf:RDF>
    <variable name="A" initial_value="4.0" units="millimolar" />
    <variable name="A2" public_interface="out" units="millimolar" />
    <variable name="A3" public_interface="in" units="millimolar" />
    <variable name="time" public_interface="in" units="minute" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <ci>A</ci>
        <apply><plus />
          <ci> A2 </ci>
          <ci> A3 </ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="N2" cmeta:id="N2">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
      <rdf:Description rdf:about="N2">
        <dc:title>N2</dc:title>
        <dcterms:alternative>NADH</dcterms:alternative>
      </rdf:Description>
    </rdf:RDF>
    <variable name="N2" public_interface="out" units="millimolar" />
    <variable name="delta_N2_rxn3" public_interface="in" units="flux" />
    <variable name="delta_N2_rxn6" public_interface="in" units="flux" />
    <variable name="delta_N2_rxn8" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="minute" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>N2</ci>
        </apply>
        <apply><plus />
          <ci>delta_N2_rxn3</ci>
          <ci>delta_N2_rxn6</ci>
          <ci>delta_N2_rxn8</ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="N">
    <variable name="N" initial_value="1.0" units="millimolar" />
    <variable name="N1" public_interface="out" units="millimolar" />
    <variable name="N2" public_interface="in" units="millimolar" />
    <variable name="time" public_interface="in" units="minute" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <ci>N</ci>
        <apply><plus />
          <ci> N1 </ci>
          <ci> N2 </ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="reaction_1">
    <variable name="S1" public_interface="in" units="millimolar" />
    <variable name="A3" public_interface="in" units="millimolar" />
    <variable name="S2" public_interface="in" units="millimolar" />
    <variable name="A2" public_interface="in" units="millimolar" />
    <variable name="K_i" initial_value="1.0" units="millimolar" />
    <variable name="k_1" initial_value="550.0" units="second_order_rate_constant" />
    <variable name="delta_S1_rxn1" public_interface="out" units="flux" />
    <variable name="delta_A3_rxn1" public_interface="out" units="flux" />
    <variable name="delta_S2_rxn1" public_interface="out" units="flux" />
    <variable name="r" units="flux" />
    <reaction reversible="no">
      <variable_ref variable="S1">
        <role role="reactant" direction="forward" delta_variable="delta_S1_rxn1" stoichiometry="1" />
      </variable_ref>
      <variable_ref variable="A3">
        <role role="reactant" direction="forward" delta_variable="delta_A3_rxn1" stoichiometry="2" />
      </variable_ref>
      <variable_ref variable="S2">
        <role role="product" direction="forward" delta_variable="delta_S2_rxn1" stoichiometry="1" />
      </variable_ref> 
      <variable_ref variable="A2">
        <role role="product" direction="forward" />
      </variable_ref>
      <variable_ref variable="r">
        <role role="rate">
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply><eq />
              <ci> r </ci>
              <apply><times />
                <ci> k_1 </ci>
                <ci> S1 </ci>
                <ci> A3 </ci>
                <apply><power />
                  <apply><plus />
                    <cn cellml:units="dimensionless"> 1.0 </cn>
                    <apply><power />
                      <apply><divide />
                        <ci> A3 </ci>
          &nb