<?xml version="1.0"?>

<!--  FILE :  purine_nucleotide_synthesis_model.xml

CREATED :  5th June 2002

LAST MODIFIED : 5th April 2003

AUTHOR :  Catherine Lloyd
          The 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 a generic model of
               purine nucleotide synthesis.

CHANGES:  
  22/07/2002 - CML - Added more metadata.
  05/04/2003 - AAC - Changed the model name so the model loads in the database 
                     easier.
-->

<model name="purine_nucleotide_synthesis_model" pathway_editor:rendering_config_file="purine_nucleotide_synthesis_CellMLrender.xml" 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>2002-06-05</dcterms:W3CDTF>
      </dcterms:created>
      
      <!--
        The Last Modified Date metadata. This is the date on which
        the model was last changed.
      -->
      <cmeta:modification rdf:parseType="Resource">
        <rdf:value>
          Including the species N-Formylglycinamidine ribonucleotide which is 
          the intermediate species from Rxn 4 to Rxn 5.
        </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>2003-09-11</dcterms:W3CDTF>
        </dcterms:modified>
      </cmeta:modification>
      <cmeta:modification rdf:parseType="Resource">
        <rdf:value>
          Changed the model name so the model loads in the database easier.
        </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>2003-04-05</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 "purine_nucleotide_synthesis_model", which is 
      declared on the <model> element.
    -->
    <rdf:Description rdf:about="#purine_nucleotide_synthesis_model">
      <!-- A human readable name for the model. -->
      <dc:title>A Generic Model Of Purine Nucleotide Synthesis</dc:title>
      
      <!-- A comment regarding the model. -->
      <cmeta:comment rdf:parseType="Resource">
        <rdf:value>
          Below is a CellML description of a general model of purine 
          nucleotide synthesis.  It is not based on a specific published 
          mathematical model, but instead it is based on a textbook defined 
          pathway.  The general sequential structure and all the reactant, 
          product and enzyme components are included.  Michaelis-Menten enzyme 
          kinetics are assumed.
          
          The purpose of this description is to illustrate how CellML can be
          used to model a general metabolic pathway.
        </rdf:value>
        <!-- The creator of the comment. -->
        <dc:creator>
          <vCard:FN>Catherine Lloyd</vCard:FN>
        </dc:creator>
      </cmeta:comment>
      
      <cmeta:species>Homo sapiens</cmeta:species>
      
      <!--  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>
      
      <bqs:Book rdf:parseType="Resource">
        <dc:creator rdf:parseType="Resource">
          <bqs:Person rdf:parseType="Resource">
            <vCard:N rdf:parseType="Resource">
              <vCard:Family>Bronk</vCard:Family>
              <vCard:Given>J</vCard:Given>
              <vCard:Other>Ramsey</vCard:Other>
            </vCard:N>
          </bqs:Person>
        </dc:creator>
        <dc:title>Human Metabolism</dc:title>
        <dcterms:issued rdf:parseType="Resource">
          <dcterms:W3CDTF>1999</dcterms:W3CDTF>
        </dcterms:issued>
        <dc:publisher rdf:parseType="Resource">
          <bqs:Organisation>Addison Wesley Longman Limited</bqs:Organisation>
          <bqs:Property rdf:parseType="Resource">
            <bqs:property_type>location</bqs:property_type>
            <rdf:value>England</rdf:value>
          </bqs:Property>
        </dc:publisher>
      </bqs:Book>
    </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="micromolar">
   <unit prefix="micro" units="mole" />
   <unit units="litre" exponent="-1" />
  </units>

  <units name="flux">
    <unit units="micromolar" />
    <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="micromolar" exponent="-1" />
    <unit units="second" exponent="-1" />
  </units>

  <units name="third_order_rate_constant">
    <unit units="micromolar" exponent="-2" />
    <unit units="second" exponent="-1" />
  </units>

  <units name="forth_order_rate_constant">
    <unit units="micromolar" exponent="-3" />
    <unit units="second" exponent="-1" />
  </units>

  <!--  
   The following component is defined for modelling convenience.  It contains 
   all the universal variables, in this case, only time.
  -->
  <component name="global_variables">
    <variable name="time" public_interface="out" units="second" />
  </component>

  <!--  
   The following components describe all the metabolites - both reactants and 
   products - involved in purine nucleotide synthesis.
  -->

  <component name="PRPP" cmeta:id="PRPP">
    <variable name="PRPP" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_PRPP_rxn0" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>PRPP</ci>
        </apply>
        <ci>delta_PRPP_rxn0</ci>
      </apply>
    </math>
  </component>

  <component name="Glutamine" cmeta:id="Glutamine">
    <variable name="Glutamine" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_Glutamine_rxn1" public_interface="in" units="flux" />
    <variable name="delta_Glutamine_rxn0" public_interface="in" units="flux" />
    <variable name="delta_Glutamine_rxn4" public_interface="in" units="flux" />
    <variable name="delta_Glutamine_rxn13" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>Glutamine</ci>
        </apply>
        <apply><plus />
          <ci>delta_Glutamine_rxn1</ci>
          <ci>delta_Glutamine_rxn0</ci>
          <ci>delta_Glutamine_rxn4</ci>
          <ci>delta_Glutamine_rxn13</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="Glutamate" cmeta:id="Glutamate">
    <variable name="Glutamate" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_Glutamate_rxn0" public_interface="in" units="flux" />
    <variable name="delta_Glutamate_rxn4" public_interface="in" units="flux" />
    <variable name="delta_Glutamate_rxn13" public_interface="in" units="flux" />
    <variable name="delta_Glutamate_rxn1" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>Glutamate</ci>
        </apply>
        <apply><plus />
          <ci>delta_Glutamate_rxn0</ci>
          <ci>delta_Glutamate_rxn4</ci>
          <ci>delta_Glutamate_rxn13</ci>
          <ci>delta_Glutamate_rxn1</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="Phosphoribosylamine" cmeta:id="Phosphoribosylamine">
    <variable name="Phosphoribosylamine" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_Phosphoribosylamine_rxn0" public_interface="in" units="flux" />
    <variable name="delta_Phosphoribosylamine_rxn2" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>Phosphoribosylamine</ci>
        </apply>
        <apply><plus />
          <ci>delta_Phosphoribosylamine_rxn0</ci>
          <ci>delta_Phosphoribosylamine_rxn2</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="Glycinamide_ribonucleotide" cmeta:id="Glycinamide_ribonucleotide">
    <variable name="Glycinamide_ribonucleotide" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_Glycinamide_ribonucleotide_rxn2" public_interface="in" units="flux" />
    <variable name="delta_Glycinamide_ribonucleotide_rxn3" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>Glycinamide_ribonucleotide</ci>
        </apply>
        <apply><plus />
          <ci>delta_Glycinamide_ribonucleotide_rxn2</ci>
          <ci>delta_Glycinamide_ribonucleotide_rxn3</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="Glycine" cmeta:id="Glycine">
    <variable name="Glycine" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_Glycine_rxn2" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>Glycine</ci>
        </apply>
        <ci>delta_Glycine_rxn2</ci>
      </apply>
    </math>
  </component>

  <component name="ATP" cmeta:id="ATP">
    <variable name="ATP" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_ATP_rxn1" public_interface="in" units="flux" />
    <variable name="delta_ATP_rxn2" public_interface="in" units="flux" />
    <variable name="delta_ATP_rxn4" public_interface="in" units="flux" />
    <variable name="delta_ATP_rxn5" public_interface="in" units="flux" />
    <variable name="delta_ATP_rxn7" public_interface="in" units="flux" />
    <variable name="delta_ATP_rxn13" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>ATP</ci>
        </apply>
        <apply><plus />
          <ci>delta_ATP_rxn1</ci>
          <ci>delta_ATP_rxn2</ci>
          <ci>delta_ATP_rxn4</ci>
          <ci>delta_ATP_rxn5</ci>
          <ci>delta_ATP_rxn7</ci>
          <ci>delta_ATP_rxn13</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="ADP" cmeta:id="ADP">
    <variable name="ADP" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_ADP_rxn1" public_interface="in" units="flux" />
    <variable name="delta_ADP_rxn2" public_interface="in" units="flux" />
    <variable name="delta_ADP_rxn4" public_interface="in" units="flux" />
    <variable name="delta_ADP_rxn5" public_interface="in" units="flux" />
    <variable name="delta_ADP_rxn7" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>ADP</ci>
        </apply>
        <apply><plus />
          <ci>delta_ADP_rxn1</ci>
          <ci>delta_ADP_rxn2</ci>
          <ci>delta_ADP_rxn4</ci>
          <ci>delta_ADP_rxn5</ci>
          <ci>delta_ADP_rxn7</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="Pi" cmeta:id="Pi">
    <variable name="Pi" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_Pi_rxn1" public_interface="in" units="flux" />
    <variable name="delta_Pi_rxn2" public_interface="in" units="flux" />
    <variable name="delta_Pi_rxn4" public_interface="in" units="flux" />
    <variable name="delta_Pi_rxn5" public_interface="in" units="flux" />
    <variable name="delta_Pi_rxn7" public_interface="in" units="flux" />
    <variable name="delta_Pi_rxn10" public_interface="in" units="flux" />
    <variable name="delta_Pi_rxn13" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>Pi</ci>
        </apply>
        <apply><plus />
          <ci>delta_Pi_rxn1</ci>
          <ci>delta_Pi_rxn2</ci>
          <ci>delta_Pi_rxn4</ci>
          <ci>delta_Pi_rxn5</ci>
          <ci>delta_Pi_rxn7</ci>
          <ci>delta_Pi_rxn10</ci>
          <ci>delta_Pi_rxn13</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="NH4" cmeta:id="NH4">
    <variable name="NH4" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_NH4_rxn1" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>NH4</ci>
        </apply>
        <ci>delta_NH4_rxn1</ci>
      </apply>
    </math>
  </component>

  <component name="H" cmeta:id="H">
    <variable name="H" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_H_rxn1" public_interface="in" units="flux" />
    <variable name="delta_H_rxn12" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>H</ci>
        </apply>
        <apply><plus />
          <ci>delta_H_rxn1</ci>
          <ci>delta_H_rxn12</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="H2O" cmeta:id="H2O">
    <variable name="H2O" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_H2O_rxn6" public_interface="in" units="flux" />
    <variable name="delta_H2O_rxn9" public_interface="in" units="flux" />
    <variable name="delta_H2O_rxn4" public_interface="in" units="flux" />
    <variable name="delta_H2O_rxn12" public_interface="in" units="flux" />
    <variable name="delta_H2O_rxn13" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>H2O</ci>
        </apply>
        <apply><plus />
          <ci>delta_H2O_rxn6</ci>
          <ci>delta_H2O_rxn9</ci>
          <ci>delta_H2O_rxn4</ci>
          <ci>delta_H2O_rxn12</ci>
          <ci>delta_H2O_rxn13</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="HCO3" cmeta:id="HCO3">
    <variable name="HCO3" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_HCO3_rxn6" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>HCO3</ci>
        </apply>
        <ci>delta_HCO3_rxn6</ci>
      </apply>
    </math>
  </component>

  <component name="THF" cmeta:id="THF">
    <variable name="THF" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_THF_rxn3" public_interface="in" units="flux" />
    <variable name="delta_THF_rxn8" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>THF</ci>
        </apply>
        <apply><plus />
          <ci>delta_THF_rxn3</ci>
          <ci>delta_THF_rxn8</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="N_Formyl_THF" cmeta:id="N_Formyl_THF">
    <variable name="N_Formyl_THF" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_N_Formyl_THF_rxn3" public_interface="in" units="flux" />
    <variable name="delta_N_Formyl_THF_rxn8" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>N_Formyl_THF</ci>
        </apply>
        <apply><plus />
          <ci>delta_N_Formyl_THF_rxn3</ci>
          <ci>delta_N_Formyl_THF_rxn8</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="N_Formylglycinamide_ribonucleotide" cmeta:id="N_Formylglycinamide_ribonucleotide">
    <variable name="N_Formylglycinamide_ribonucleotide" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_N_Formylglycinamide_ribonucleotide_rxn3" public_interface="in" units="flux" />
    <variable name="delta_N_Formylglycinamide_ribonucleotide_rxn4" public_interface="in" units="flux" /> 
    <variable name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>N_Formylglycinamide_ribonucleotide</ci>
        </apply>
        <apply><plus />
          <ci>delta_N_Formylglycinamide_ribonucleotide_rxn3</ci>
          <ci>delta_N_Formylglycinamide_ribonucleotide_rxn4</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="N_Formylglycinamidine_ribonucleotide" cmeta:id="N_Formylglycinamidine_ribonucleotide">
    <variable name="N_Formylglycinamidine_ribonucleotide" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_N_Formylglycinamidine_ribonucleotide_rxn4" public_interface="in" units="flux" /> 
    <variable name="delta_N_Formylglycinamidine_ribonucleotide_rxn5" public_interface="in" units="flux" />
    <variable name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply><eq />
        <apply><diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>N_Formylglycinamidine_ribonucleotide</ci>
        </apply>
        <apply><plus />
          <ci>delta_N_Formylglycinamidine_ribonucleotide_rxn4</ci>
          <ci>delta_N_Formylglycinamidine_ribonucleotide_rxn5</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component