<?xml version="1.0"?>

<!--  FILE :  fatty_acid_synthesis_model.xml

CREATED :  14th June 2002

LAST MODIFIED : 22nd July 2002

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
               fatty acid synthesis.

CHANGES:  
   22/07/2002 - CML - Added more metadata.
-->

<model name="fatty_acid_synthesis_model" pathway_editor:rendering_config_file="fatty_acid_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>2002-06-14</dcterms:W3CDTF>
      </dcterms:created>
      
      <!--
        The Last Modified Date metadata. This is the date on which
        the model was last changed.
      -->
      
      <!-- 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 "fatty_acid_synthesis_mode1", which is declared on 
      the <model> element.
    -->
    <rdf:Description rdf:about="#fatty_acid_synthesis_mode1">
      <!-- A human readable name for the model. -->
      <dc:title>A Generic Model Of Fatty Acid 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 fatty acid 
          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>

 <!--  
   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 fatty acid synthesis.
  -->

  <component name="Acetyl_CoA" cmeta:id="Acetyl_CoA">
    <variable name="Acetyl_CoA" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_Acetyl_CoA_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>Acetyl_CoA</ci>
        </apply>
        <ci>delta_Acetyl_CoA_rxn0</ci>
      </apply>
    </math>
  </component>

  <component name="Malonyl_CoA" cmeta:id="Malonyl_CoA">
    <variable name="Malonyl_CoA" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_Malonyl_CoA_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>Malonyl_CoA</ci>
        </apply>
        <ci>delta_Malonyl_CoA_rxn1</ci>
      </apply>
    </math>
  </component>

  <component name="Malonyl_ACP" cmeta:id="Malonyl_ACP">
    <variable name="Malonyl_ACP" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_Malonyl_ACP_rxn1" public_interface="in" units="flux" />
    <variable name="delta_Malonyl_ACP_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>Malonyl_ACP</ci>
        </apply>
        <apply><plus />
          <ci>delta_Malonyl_ACP_rxn1</ci>
          <ci>delta_Malonyl_ACP_rxn3</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="Acetyl_ACP" cmeta:id="Acetyl_ACP">
    <variable name="Acetyl_ACP" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_Acetyl_ACP_rxn0" public_interface="in" units="flux" />
    <variable name="delta_Acetyl_ACP_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>Acetyl_ACP</ci>
        </apply>
        <apply><plus />
          <ci>delta_Acetyl_ACP_rxn0</ci>
          <ci>delta_Acetyl_ACP_rxn2</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="Acetoacetyl_ACP" cmeta:id="Acetoacetyl_ACP">
    <variable name="Acetoacetyl_ACP" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_Acetoacetyl_ACP_rxn3" public_interface="in" units="flux" />
    <variable name="delta_Acetoacetyl_ACP_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>Acetoacetyl_ACP</ci>
        </apply>
        <apply><plus />
          <ci>delta_Acetoacetyl_ACP_rxn3</ci>
          <ci>delta_Acetoacetyl_ACP_rxn4</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="D_beta_Hydroxybutyryl_ACP" cmeta:id="D_beta_Hydroxybutyryl_ACP">
    <variable name="D_beta_Hydroxybutyryl_ACP" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_D_beta_Hydroxybutyryl_ACP_rxn4" public_interface="in" units="flux" />
    <variable name="delta_D_beta_Hydroxybutyryl_ACP_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>D_beta_Hydroxybutyryl_ACP</ci>
        </apply>
        <apply><plus />
          <ci>delta_D_beta_Hydroxybutyryl_ACP_rxn4</ci>
          <ci>delta_D_beta_Hydroxybutyryl_ACP_rxn6</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="alpha_beta_trans_Butenoyl_ACP" cmeta:id="alpha_beta_trans_Butenoyl_ACP">
    <variable name="alpha_beta_trans_Butenoyl_ACP" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_alpha_beta_trans_Butenoyl_ACP_rxn6" public_interface="in" units="flux" />
    <variable name="delta_alpha_beta_trans_Butenoyl_ACP_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>alpha_beta_trans_Butenoyl_ACP</ci>
        </apply>
        <apply><plus />
          <ci>delta_alpha_beta_trans_Butenoyl_ACP_rxn6</ci>
          <ci>delta_alpha_beta_trans_Butenoyl_ACP_rxn5</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="Butyryl_ACP" cmeta:id="Butyryl_ACP">
    <variable name="Butyryl_ACP" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_Butyryl_ACP_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>Butyryl_ACP</ci>
        </apply>
        <ci>delta_Butyryl_ACP_rxn5</ci>
      </apply>
    </math>
  </component>

  <component name="CoA_SH" cmeta:id="CoA_SH">
    <variable name="CoA_SH" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_CoA_SH_rxn0" public_interface="in" units="flux" />
    <variable name="delta_CoA_SH_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>CoA_SH</ci>
        </apply>
        <apply><plus />
          <ci>delta_CoA_SH_rxn0</ci>
          <ci>delta_CoA_SH_rxn1</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="CE_SH" cmeta:id="CE_SH">
    <variable name="CE_SH" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_CE_SH_rxn3" public_interface="in" units="flux" />
    <variable name="delta_CE_SH_rxn0" public_interface="in" units="flux" />
    <variable name="delta_CE_SH_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>CE_SH</ci>
        </apply>
        <apply><plus />
          <ci>delta_CE_SH_rxn3</ci>
          <ci>delta_CE_SH_rxn0</ci>
          <ci>delta_CE_SH_rxn2</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="ACP_SH" cmeta:id="ACP_SH">
    <variable name="ACP_SH" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_ACP_SH_rxn2" public_interface="in" units="flux" />
    <variable name="delta_ACP_SH_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>ACP_SH</ci>
        </apply>
        <apply><plus />
          <ci>delta_ACP_SH_rxn2</ci>
          <ci>delta_ACP_SH_rxn1</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="CO2" cmeta:id="CO2">
    <variable name="CO2" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_CO2_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>CO2</ci>
        </apply>
        <ci>delta_CO2_rxn3</ci>
      </apply>
    </math>
  </component>

  <component name="Acetyl_S_CE" cmeta:id="Acetyl_S_CE">
    <variable name="Acetyl_S_CE" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_Acetyl_S_CE_rxn2" public_interface="in" units="flux" />
    <variable name="delta_Acetyl_S_CE_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>Acetyl_S_CE</ci>
        </apply>
        <apply><plus />
          <ci>delta_Acetyl_S_CE_rxn2</ci>
          <ci>delta_Acetyl_S_CE_rxn3</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="NADPH" cmeta:id="NADPH">
    <variable name="NADPH" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_NADPH_rxn4" public_interface="in" units="flux" />
    <variable name="delta_NADPH_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>NADPH</ci>
        </apply>
        <apply><plus />
          <ci>delta_NADPH_rxn4</ci>
          <ci>delta_NADPH_rxn5</ci>
        </apply>
      </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_rxn4" public_interface="in" units="flux" />
    <variable name="delta_H_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>H</ci>
        </apply>
        <apply><plus />
          <ci>delta_H_rxn4</ci>
          <ci>delta_H_rxn5</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="NADP" cmeta:id="NADP">
    <variable name="NADP" public_interface="out" initial_value="1.0" units="micromolar" />
    <variable name="delta_NADP_rxn4" public_interface="in" units="flux" />
    <variable name="delta_NADP_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>NADP</ci>
        </apply>
        <apply><plus />
          <ci>delta_NADP_rxn4</ci>
          <ci>delta_NADP_rxn5</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="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>
        <ci>delta_H2O_rxn6</ci>
      </apply>
    </math>
  </component>

  <!--  
   The following components describe all the enzymes involved in fatty acid 
   synthesis.
  -->

  <component name="Acyltransferase" cmeta:id="Acyltransferase">
    <variable name="Acyltransferase" public_interface="out" initial_value="1.0" units="micromolar" />
  </component>

  <component name="Malonyltransferase" cmeta:id="Malonyltransferase">
    <variable name="Malonyltransferase" public_interface="out" initial_value="1.0" units="micromolar" />
  </component>

  <component name="beta_hydroxyacyl_ACP_dehydrase" cmeta:id="beta_hydroxyacyl_ACP_dehydrase">
    <variable name="beta_hydroxyacyl_ACP_dehydrase" public_interface="out" initial_value="1.0" units="micromolar" />
  </component>

  <component name="beta_Ketoacyl_ACP_reductase" cmeta:id="beta_Ketoacyl_ACP_reductase">
    <variable name="beta_Ketoacyl_ACP_reductase" public_interface="out" initial_value="1.0" units="micromolar" />
  </component>

  <component name="beta_Hydroxyacyl_ACP_dehydrase" cmeta:id="beta_Hydroxyacyl_ACP_dehydrase">
    <variable name="beta_Hydroxyacyl_ACP_dehydrase" public_interface="out" initial_value="1.0" units="micromolar" />
  </component>

  <component name="Enol_ACP_reductase" cmeta:id="Enol_ACP_reductase">
    <variable name="Enol_ACP_reductase" public_interface="out" initial_value="1.0" units="micromolar" />
  </component>

  <!--
   The following components represent the reaction steps of fatty acid 
   synthesis.
  -->

  <component name="reaction0">
    <variable name="Acetyl_CoA" public_interface="in" units="micromolar" />
    <variable name="CE_SH" public_interface="in" units="micromolar" />
    <variable name="Acetyl_ACP" public_interface="in" units="micromolar" />
    <variable name="CoA_SH" public_interface="in" units="micromolar" />
    <variable name="Acyltransferase" public_interface="in" units="micromolar" />
    <variable name="delta_Acetyl_CoA_rxn0" public_interface="out" units="flux" />
    <variable name="delta_CE_SH_rxn0" public_interface="out" units="flux" />
    <variable name="delta_Acetyl_ACP_rxn0" public_interface="out" units="flux" />
    <variable name="delta_CoA_SH_rxn0" public_interface="out" units="flux" />
    <variable name="km0" initial_value="1.0" units="micromolar" />
    <variable name="vmax0" initial_value="1.0" units="second_order_rate_constant" />
    <variable name="rate" units="flux" />
    <reaction reversible="no">
      <variable_ref variable="Acetyl_CoA">
        <role role="reactant" delta_variable="delta_Acetyl_CoA_rxn0" stoichiometry="1" />
      </variable_ref>
      <variable_ref variable="CE_SH">
        <role role="reactant" delta_variable="delta_CE_SH_rxn0" stoichiometry="1" />
      </variable_ref>
      <variable_ref variable="Acetyl_ACP">
        <role role="product" delta_variable="delta_Acetyl_ACP_rxn0" stoichiometry="1" />
      </variable_ref>
      <variable_ref variable="CoA_SH">
        <role role="product" delta_variable="delta_CoA_SH_rxn0" stoichiometry="1" />
      </variable_ref>
      <variable_ref variable="Acyltransferase">
        <role role="catalyst" />
      </variable_ref>
      <variable_ref variable="rate">
        <role role="rate">
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply><eq />
              <ci>rate</ci>
              <apply><divide />
                <apply><times />
                  <ci>Acetyl_CoA</ci>
                  <ci>CE_SH</ci>
                  <ci>vmax0</ci>
                </apply>
                <apply><plus />
                  <ci>km0</ci>
                  <ci>Acetyl_CoA</ci>
                  <ci>CE_SH</ci>
                </apply>
              </apply>
     &n