<?xml version="1.0"?>
<!-- FILE : fatty_acid_activation_and_oxidation_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 activation and oxidation.
CHANGES:
22/07/2002 - CML - Added more metadata.
-->
<model name="fatty_acid_activation_and_oxidation_model" pathway_editor:rendering_config_file="fatty_acid_activation_and_oxidation_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_activation_and_oxidation_mode1", which is
declared on the <model> element.
-->
<rdf:Description rdf:about="#fatty_acid_activation_and_oxidation_mode1">
<!-- A human readable name for the model. -->
<dc:title>A Generic Model Of Fatty Acid Activation And
Oxidation</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
activation and oxidation. 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="second_order_rate_constant">
<unit units="micromolar" exponent="-1" />
<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 activation and oxidation.
-->
<component name="fatty_acid" cmeta:id="fatty_acid">
<variable name="fatty_acid" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_fatty_acid_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>fatty_acid</ci>
</apply>
<ci>delta_fatty_acid_rxn0</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_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>ATP</ci>
</apply>
<ci>delta_ATP_rxn0</ci>
</apply>
</math>
</component>
<component name="Pyrophosphate" cmeta:id="Pyrophosphate">
<variable name="Pyrophosphate" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_Pyrophosphate_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>Pyrophosphate</ci>
</apply>
<ci>delta_Pyrophosphate_rxn0</ci>
</apply>
</math>
</component>
<component name="Fatty_acyl_CoA" cmeta:id="Fatty_acyl_CoA">
<variable name="Fatty_acyl_CoA" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_Fatty_acyl_CoA_rxn1" public_interface="in" units="flux" />
<variable name="delta_Fatty_acyl_CoA_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>Fatty_acyl_CoA</ci>
</apply>
<apply><plus />
<ci>delta_Fatty_acyl_CoA_rxn1</ci>
<ci>delta_Fatty_acyl_CoA_rxn2</ci>
</apply>
</apply>
</math>
</component>
<component name="AMP" cmeta:id="AMP">
<variable name="AMP" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_AMP_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>AMP</ci>
</apply>
<ci>delta_AMP_rxn1</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_rxn1" public_interface="in" units="flux" />
<variable name="delta_CoA_SH_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>CoA_SH</ci>
</apply>
<apply><plus />
<ci>delta_CoA_SH_rxn1</ci>
<ci>delta_CoA_SH_rxn5</ci>
</apply>
</apply>
</math>
</component>
<component name="Acyladenylate_mixed_anhydride" cmeta:id="Acyladenylate_mixed_anhydride">
<variable name="Acyladenylate_mixed_anhydride" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_Acyladenylate_mixed_anhydride_rxn0" public_interface="in" units="flux" />
<variable name="delta_Acyladenylate_mixed_anhydride_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>Acyladenylate_mixed_anhydride</ci>
</apply>
<apply><plus />
<ci>delta_Acyladenylate_mixed_anhydride_rxn0</ci>
<ci>delta_Acyladenylate_mixed_anhydride_rxn1</ci>
</apply>
</apply>
</math>
</component>
<component name="trans_Enol_CoA" cmeta:id="trans_Enol_CoA">
<variable name="trans_Enol_CoA" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_trans_Enol_CoA_rxn2" public_interface="in" units="flux" />
<variable name="delta_trans_Enol_CoA_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>trans_Enol_CoA</ci>
</apply>
<apply><plus />
<ci>delta_trans_Enol_CoA_rxn2</ci>
<ci>delta_trans_Enol_CoA_rxn3</ci>
</apply>
</apply>
</math>
</component>
<component name="L_3_Hydroxyacyl_CoA" cmeta:id="L_3_Hydroxyacyl_CoA">
<variable name="L_3_Hydroxyacyl_CoA" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_L_3_Hydroxyacyl_CoA_rxn3" public_interface="in" units="flux" />
<variable name="delta_L_3_Hydroxyacyl_CoA_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>L_3_Hydroxyacyl_CoA</ci>
</apply>
<apply><plus />
<ci>delta_L_3_Hydroxyacyl_CoA_rxn3</ci>
<ci>delta_L_3_Hydroxyacyl_CoA_rxn4</ci>
</apply>
</apply>
</math>
</component>
<component name="beta_Ketoacyl_CoA" cmeta:id="beta_Ketoacyl_CoA">
<variable name="beta_Ketoacyl_CoA" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_beta_Ketoacyl_CoA_rxn4" public_interface="in" units="flux" />
<variable name="delta_beta_Ketoacyl_CoA_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>beta_Ketoacyl_CoA</ci>
</apply>
<apply><plus />
<ci>delta_beta_Ketoacyl_CoA_rxn4</ci>
<ci>delta_beta_Ketoacyl_CoA_rxn5</ci>
</apply>
</apply>
</math>
</component>
<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_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>Acetyl_CoA</ci>
</apply>
<ci>delta_Acetyl_CoA_rxn5</ci>
</apply>
</math>
</component>
<component name="Fatty_acyl_CoA_minus_2C" cmeta:id="Fatty_acyl_CoA_minus_2C">
<variable name="Fatty_acyl_CoA_minus_2C" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_Fatty_acyl_CoA_minus_2C_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>Fatty_acyl_CoA_minus_2C</ci>
</apply>
<ci>delta_Fatty_acyl_CoA_minus_2C_rxn5</ci>
</apply>
</math>
</component>
<component name="FAD" cmeta:id="FAD">
<variable name="FAD" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_FAD_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>FAD</ci>
</apply>
<ci>delta_FAD_rxn2</ci>
</apply>
</math>
</component>
<component name="FADH2" cmeta:id="FADH2">
<variable name="FADH2" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_FADH2_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>FADH2</ci>
</apply>
<ci>delta_FADH2_rxn2</ci>
</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_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>H2O</ci>
</apply>
<ci>delta_H2O_rxn3</ci>
</apply>
</math>
</component>
<component name="NAD" cmeta:id="NAD">
<variable name="NAD" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_NAD_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>NAD</ci>
</apply>
<ci>delta_NAD_rxn4</ci>
</apply>
</math>
</component>
<component name="NADH" cmeta:id="NADH">
<variable name="NADH" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_NADH_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>NADH</ci>
</apply>
<ci>delta_NADH_rxn4</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_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>H</ci>
</apply>
<ci>delta_H_rxn4</ci>
</apply>
</math>
</component>
<!--
The following components describe all the enzymes involved in fatty acid
activation and oxidation.
-->
<component name="Acyl_CoA_dehydrogenase" cmeta:id="Acyl_CoA_dehydrogenase">
<variable name="Acyl_CoA_dehydrogenase" public_interface="out" initial_value="1.0" units="micromolar" />
</component>
<component name="Acyl_CoA_synthetase" cmeta:id="Acyl_CoA_synthetase">
<variable name="Acyl_CoA_synthetase" public_interface="out" initial_value="1.0" units="micromolar" />
</component>
<component name="Enol_CoA_hydratase" cmeta:id="Enol_CoA_hydratase">
<variable name="Enol_CoA_hydratase" public_interface="out" initial_value="1.0" units="micromolar" />
</component>
<component name="L_3_Hydroxyacyl_CoA_dehydrogenase" cmeta:id="L_3_Hydroxyacyl_CoA_dehydrogenase">
<variable name="L_3_Hydroxyacyl_CoA_dehydrogenase" public_interface="out" initial_value="1.0" units="micromolar" />
</component>
<component name="Thiolase" cmeta:id="Thiolase">
<variable name="Thiolase" public_interface="out" initial_value="1.0" units="micromolar" />
</component>
<!--
The following components represent the reaction steps of fatty acid
activation and oxidation.
-->
<component name="reaction0">
<variable name="fatty_acid" public_interface="in" units="micromolar" />
<variable name="ATP" public_interface="in" units="micromolar" />
<variable name="Pyrophosphate" public_interface="in" units="micromolar" />
<variable name="Acyladenylate_mixed_anhydride" public_interface="in" units="micromolar" />
<variable name="Acyl_CoA_synthetase" public_interface="in" units="micromolar" />
<variable name="delta_fatty_acid_rxn0" public_interface="out" units="flux" />
<variable name="delta_ATP_rxn0" public_interface="out" units="flux" />
<variable name="delta_Pyrophosphate_rxn0" public_interface="out" units="flux" />
<variable name="delta_Acyladenylate_mixed_anhydride_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="fatty_acid">
<role role="reactant" delta_variable="delta_fatty_acid_rxn0" stoichiometry="1" />
</variable_ref>
<variable_ref variable="ATP">
<role role="reactant" delta_variable="delta_ATP_rxn0" stoichiometry="1" />
</variable_ref>
<variable_ref variable="Pyrophosphate">
<role role="product" delta_variable="delta_Pyrophosphate_rxn0" stoichiometry="1" />
</variable_ref>
<variable_ref variable="Acyladenylate_mixed_anhydride">
<role role="product" delta_variable="delta_Acyladenylate_mixed_anhydride_rxn0" stoichiometry="1" />
</variable_ref>
<variable_ref variable="Acyl_CoA_synthetase">
<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>fatty_acid</ci>
<ci>ATP</ci>
<ci>vmax0</ci>
</apply>
<apply><plus />
<ci>km0</ci>
<ci>fatty_acid</ci>
<ci>ATP</ci>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction1">
<variable name="Acyladenylate_mixed_anhydride" public_interface="in" units="micromolar" />
<variable name="CoA_SH" public_interface="in" units="micromolar" />
<variable name="Fatty_acyl_CoA" public_interface="in" units="micromolar" />
<variable name="AMP" public_interface="in" units="micromolar" />
<variable name="Acyl_CoA_synthetase" public_interface="in" units="micromolar" />
<variable name="delta_Acyladenylate_mixed_anhydride_rxn1" public_interface="out" units="flux" />
<variable name="delta_CoA_SH_rxn1" public_interface="out" units="flux" />
<variable name="delta_Fatty_acyl_CoA_rxn1" public_interface="out" units="flux" />
<variable name="delta_AMP_rxn1" public_interface="out" units="flux" />
<variable name="km1