Personal tools
You are here: Home → Model Repository → Glycolysis in Bloodstream Form Trypanosoma brucei Can Be Understood in Terms of the Kinetics of the Glycolytic Enzymes
 
Views

Glycolysis in Bloodstream Form Trypanosoma brucei Can Be Understood in Terms of the Kinetics of the Glycolytic Enzymes

The CellML code.

XML source view

<!--  FILE :  bakker_model_1997.xml

CREATED :  1st August 2002

LAST MODIFIED : 27th April 2005

AUTHOR :  Catherine Lloyd
          Department of Engineering Science
          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 the 1997 Bakker et al. mathematical model of glycolysis in the parasite Trypanosoma brucei.

CHANGES:  
  09/04/2003 - AAC - Added publication date information.
  01/09/2003 - CML - Changed model structure to remove the model element from 
                     the CellML.
  27/04/2005 - PJV - Modified names to conform with cellml1.1 naming
                     conventions and alligned comment brackets correctly.
  
-->
<model xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:pathway_editor="http://www.physiome.com/pathway_editor/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns="http://www.cellml.org/cellml/1.0#" pathway_editor:rendering_config_file="bakker_model_1997_cellmlrender.xml" cmeta:id="bakker_michels_opperdoes_westerhoff_1997_version01" name="bakker_michels_opperdoes_westerhoff_1997_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
  <articleinfo>
  <title>Modelling Glycolysis in Trypanosoma brucei, Bakker et al, 1997</title>
  <author>
    <firstname>Catherine</firstname>
          <surname>Lloyd</surname>
    <affiliation>
      <shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
    </affiliation>
  </author>
</articleinfo>
  <section id="sec_status">
    <title>Model Status</title>
    <para>
            This is the original unchecked version of the model imported from the previous
            CellML model repository, 24-Jan-2006.
          </para>
  </section>
  <sect1 id="sec_structure">
<title>Model Structure</title>

<para>
Salivarian trypanosomes are extracellular parasites of the blood and tissue fluids of mammals.  When it is within the bloodstream of its host <emphasis>Homo sapiens</emphasis>, <emphasis>Trypanosoma brucei</emphasis>, (the parasite that causes African sleeping disease in humans), displays very simple metabolism.  In the bloodstream form (within its host) the parasite lacks a Krebs cycle and oxidative phosphorylation, and its metabolism is restricted to the glycolytic pathway alone.  As in all trypansomes, most of the glycolytic enzymes of <emphasis>Trypanosoma brucei</emphasis> are contained within a specialised organelle called a glycosome (see <xref linkend="fig_reaction_diagram" /> below).  In addition to this structural difference beween trypanosomes and other eukaryotic cells, trypanosomes also display differences at the biochemical level of their metabolism.  Their glycolitic pathway is simplier, with few side chains and reduced allosteric enzymatic regulation.  These differences between the host and parasite metabolism make the glycolytic pathway a potential target for drugs against African sleeping disease.      
</para>

<para>
Most of the glycolytic enzymes of <emphasis>Trypanosoma brucei</emphasis> have been isolated and kinetically characterised.  From this experimental data, Bakker <emphasis>et al</emphasis>. developed a mathematical model of trypanosomal glycolysis.  Model simulations predict how the steady-state glycolytic flux and metabolite concentrations depend on the substrate and product concentrations and the enzyme-kinetic parameters.  The model explains certain aspects of cell physiology, but it does have its limitations.  Further experimental data on the transmembrane flux dynamics of metabolites would help to improve the accuracey of the model.
</para>

<para>
The complete original paper reference is cited below:
</para>

<para>
<ulink url="http://www.jbc.org/cgi/content/abstract/272/6/3207">Glycolysis in Bloodstream Form <emphasis>Trypanosoma brucei</emphasis> Can Be Understood in Terms of the Kinetics of the Glycolytic Enzymes</ulink>, Barbara M. Bakker, Paul A. M. Michels, Fred R. Opperdoes, and Hans V. Westerhoff, 1997, <ulink url="http://www.jbc.org/">
            <emphasis>The Journal of Biological Chemistry</emphasis>
          </ulink>, 272, 3207-3215. (<ulink url="http://www.jbc.org/cgi/content/full/272/6/3207">Full text</ulink> and <ulink url="http://www.jbc.org/cgi/reprint/272/6/3207.pdf">PDF versions</ulink> of the article are available to subscribers of the JBC website.)  <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=9013556&amp;dopt=Abstract">PubMed ID: 9013556</ulink> 
</para>

<para>
The raw CellML description of the model of trypanosome glycolysis can be downloaded in various formats as described in <xref linkend="sec_download_this_model" />.
</para>

<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>A reaction diagram of glycolysis</title>
    </objectinfo>
    <imagedata fileref="../images/bakker_model_1997/reaction_diagram.gif" />
  </imageobject>
</mediaobject>
<caption>The stoichiometric scheme of the model of glycolysis in the bloodstream form of the parasite <emphasis>Trypanosoma brucei</emphasis>.</caption>
</informalfigure>

</sect1>
</article>
</documentation>
  
  
  <!--
    We start the model definition with a definition of some named
    sets of units for use throughout the model.
  -->
  
   <units name="minute">
      <unit units="second" multiplier="60.0" />
   </units>
   
   <units name="micromolar">
      <unit units="mole" prefix="micro" />
      <unit units="litre" exponent="-1" />
   </units>
   
   <units name="millimolar">
      <unit units="mole" prefix="milli" />
      <unit units="litre" exponent="-1" />
   </units>
   
   <units name="nanomolar">
      <unit units="mole" prefix="nano" />
      <unit units="litre" exponent="-1" />
   </units>
   
   <units name="flux">
      <unit units="nanomolar" />
      <unit units="minute" exponent="-1" />
   </units>
   
   <units name="microlitre">
      <unit units="litre" prefix="micro" />
   </units>
   
  <component name="global_variables">
    <variable units="second" public_interface="out" name="time" />
  </component>
  
  <component name="volumes">
    <variable units="microlitre" public_interface="out" name="Vc" initial_value="0.244" />
    <variable units="microlitre" public_interface="out" name="Vg" initial_value="5.46" />
  </component>
  
  <!--
    The following components describe all the reactants and products involved in
    reactions. 
  -->

  <component name="Glc_o" cmeta:id="Glc_o">
    <rdf:RDF>
      <rdf:Description rdf:about="Glc_o">
        <dc:title>Glc_o</dc:title>
        <dcterms:alternative>external glucose</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="millimolar" public_interface="out" name="Glc_o" initial_value="5.0" />
  </component>

  <component name="Glc_i" cmeta:id="Glc_i">
    <rdf:RDF>
      <rdf:Description rdf:about="Glc_i">
        <dc:title>Glc_i</dc:title>
        <dcterms:alternative>cytosolic glucose</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="micromolar" public_interface="out" name="Glc_i" />
    <variable units="flux" public_interface="in" name="V_HK" />
    <variable units="flux" public_interface="in" name="V_glucose_transport" />
    <variable units="second" public_interface="in" name="time" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>Glc_i</ci>
        </apply>
        <apply>
          <minus />
          <ci>V_glucose_transport</ci>
          <ci>V_HK</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="Glc_6_P_g" cmeta:id="Glc_6_P_g">
    <rdf:RDF>
      <rdf:Description rdf:about="Glc_6_P_g">
        <dc:title>Glc_6_P_g</dc:title>
        <dcterms:alternative>glycosomal glucose-6-phopshate</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="micromolar" public_interface="out" name="Glc_6_P_g" />
    <variable units="dimensionless" name="Keq_PGI" initial_value="0.29" />    
    <variable units="micromolar" public_interface="in" name="Fru_6_P_g" />
    <variable units="micromolar" public_interface="in" name="hexose_P_g" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <ci>Glc_6_P_g</ci>
        <apply>
          <divide />
          <ci>hexose_P_g</ci>
          <ci>Keq_PGI</ci>
        </apply>
      </apply>
      
      <apply>
        <eq />
        <ci>Keq_PGI</ci>
        <apply>
          <divide />
          <ci>Fru_6_P_g</ci>
          <ci>Glc_6_P_g</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="Fru_6_P_g" cmeta:id="Fru_6_P_g">
   <rdf:RDF>
      <rdf:Description rdf:about="Fru_6_P_g">
        <dc:title>Fru_6_P_g</dc:title>
        <dcterms:alternative>glycosomal fructose 6-phopshate</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="micromolar" public_interface="out" name="Fru_6_P_g" />
    <variable units="micromolar" public_interface="in" name="Glc_6_P_g" />
    <variable units="micromolar" public_interface="in" name="hexose_P_g" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <ci>Fru_6_P_g</ci>
        <apply>
          <divide />
          <ci>hexose_P_g</ci>
          <ci>Glc_6_P_g</ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="hexose_P_g" cmeta:id="hexose_P_g">
   <rdf:RDF>
      <rdf:Description rdf:about="hexose_P_g">
        <dc:title>hexose_P_g</dc:title>
        <dcterms:alternative>total concentration of glycosomal six carbon phosphates</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="micromolar" public_interface="out" name="hexose_P_g" />
    <variable units="flux" public_interface="in" name="V_HK" />
    <variable units="flux" public_interface="in" name="V_PFK" />
    <variable units="second" public_interface="in" name="time" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>hexose_P_g</ci>
        </apply>
        <apply>
          <minus />
          <ci>V_HK</ci>
          <ci>V_PFK</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="Fru_1_6_BP_g" cmeta:id="Fru_1_6_BP_g">
    <rdf:RDF>
      <rdf:Description rdf:about="Fru_1_6_BP_g">
        <dc:title>Fru_1_6_BP_g</dc:title>
        <dcterms:alternative>glycosomal fructose 1,6-bisphopshate</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="micromolar" public_interface="out" name="Fru_1_6_BP_g" />
    <variable units="flux" public_interface="in" name="V_PFK" />
    <variable units="flux" public_interface="in" name="V_ALD" />
    <variable units="second" public_interface="in" name="time" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>Fru_1_6_BP_g</ci>
        </apply>
        <apply>
          <minus />
          <ci>V_PFK</ci>
          <ci>V_ALD</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="GA_3_P_g" cmeta:id="GA_3_P_g">
    <rdf:RDF>
      <rdf:Description rdf:about="GA_3_P_g">
        <dc:title>GA_3_P_g</dc:title>
        <dcterms:alternative>glycosomal glyceraldehyde 3-phopshate</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="micromolar" public_interface="out" name="GA_3_P_g" />
    <variable units="dimensionless" public_interface="in" name="Keq_TIM" />
    <variable units="micromolar" public_interface="in" name="DHAP_g" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <ci>GA_3_P_g</ci>
        <apply>
          <times />
          <ci>Keq_TIM</ci>
          <ci>DHAP_g</ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="triose_P" cmeta:id="triose_P">
    <rdf:RDF>
      <rdf:Description rdf:about="triose_P">
        <dc:title>triose_P</dc:title>
        <dcterms:alternative>total concentration of three carbon phopshates</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="micromolar" public_interface="out" name="triose_P" />
    <variable units="flux" public_interface="in" name="V_ALD" />
    <variable units="flux" public_interface="in" name="V_GAPDH" />
    <variable units="flux" public_interface="in" name="V_GDH" />
    <variable units="flux" public_interface="in" name="V_GPO" />
    <variable units="second" public_interface="in" name="time" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>triose_P</ci>
        </apply>
        <apply>
          <minus />
          <apply>
            <plus />
            <apply>
              <times />
              <cn cellml:units="dimensionless"> 2.0 </cn>
              <ci>V_ALD</ci>
            </apply>
            <ci>V_GPO</ci>
          </apply>
          <apply>
            <plus />
            <ci>V_GAPDH</ci>
            <ci>V_GDH</ci>
          </apply>
        </apply>
      </apply>
    </math>
  </component>

  <component name="one_three_BPGA_g" cmeta:id="one_three_BPGA_g">
    <rdf:RDF>
      <rdf:Description rdf:about="one_three_BPGA_g">
        <dc:title>one_three_BPGA_g</dc:title>
        <dcterms:alternative>glycosomal 1,3-bisphosphoglycerate</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="micromolar" public_interface="out" name="one_three_BPGA_g" />
    <variable units="flux" public_interface="in" name="V_GAPDH" />
    <variable units="flux" public_interface="in" name="V_PGK" />
    <variable units="second" public_interface="in" name="time" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>one_three_BPGA_g</ci>
        </apply>
        <apply>
          <minus />
          <ci>V_GAPDH</ci>
          <ci>V_PGK</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="three_PGA" cmeta:id="three_PGA">
    <rdf:RDF>
      <rdf:Description rdf:about="three_PGA">
        <dc:title>three_PGA</dc:title>
        <dcterms:alternative>3-phosphoglycerate</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="micromolar" public_interface="out" name="three_PGA" />
    <variable units="micromolar" public_interface="in" name="N" />
    <variable units="microlitre" public_interface="in" name="Vg" />
    <variable units="microlitre" public_interface="in" name="Vc" />
    <variable units="dimensionless" public_interface="out" name="Keq_PGM" initial_value="0.187" />
    <variable units="dimensionless" public_interface="out" name="Keq_ENO" initial_value="6.7" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <ci>three_PGA</ci>
        <apply>
          <divide />
          <apply>
            <times />
            <ci>N</ci>
            <apply>
              <plus />
              <cn cellml:units="dimensionless"> 1.0 </cn>
              <apply>
                <divide />
                <ci>Vc</ci>
                <ci>Vg</ci>
              </apply>
            </apply>
          </apply>
          <apply>
            <plus />
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <times />
              <apply>
                <plus />
                <cn cellml:units="dimensionless"> 1.0 </cn>
                <ci>Keq_PGM</ci>
                <apply>
                  <times />
                  <ci>Keq_PGM</ci>
                  <ci>Keq_ENO</ci>
                </apply>
              </apply>
              <apply>
                <divide />
                <ci>Vc</ci>
                <ci>Vg</ci>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="two_PGA_c" cmeta:id="two_PGA_c">
    <rdf:RDF>
      <rdf:Description rdf:about="two_PGA_c">
        <dc:title>two_PGA_c</dc:title>
        <dcterms:alternative>cytosolic 2-phosphoglycerate</dcterms:alternative>        </rdf:Description>
    </rdf:RDF> 
    <variable units="micromolar" public_interface="out" name="two_PGA_c" />
    <variable units="micromolar" public_interface="in" name="three_PGA" />
    <variable units="dimensionless" public_interface="in" name="Keq_PGM" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <ci>two_PGA_c</ci>
        <apply>
          <times />
          <ci>Keq_PGM</ci>
          <ci>three_PGA</ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="N" cmeta:id="N">
    <rdf:RDF>
      <rdf:Description rdf:about="N">
        <dc:title>N</dc:title>
        <dcterms:alternative>the sum of 3-phosphoglycerate, 2-phosphoglycerate, and phosphoenolpyruvate</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="micromolar" public_interface="out" name="N" />
    <variable units="flux" public_interface="in" name="V_PGK" />
    <variable units="flux" public_interface="in" name="V_PYK" />
    <variable units="second" public_interface="in" name="time" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>N</ci>
        </apply>
        <apply>
          <minus />
          <ci>V_PGK</ci>
          <ci>V_PYK</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="PEP_c" cmeta:id="PEP_c">
    <rdf:RDF>
      <rdf:Description rdf:about="PEP_c">
        <dc:title>PEP_c</dc:title>
        <dcterms:alternative>cytosolic phosphoenolpyruvate</dcterms:alternative>       </rdf:Description>
    </rdf:RDF>
    <variable units="micromolar" public_interface="out" name="PEP_c" />
    <variable units="micromolar" public_interface="in" name="two_PGA_c" />
    <variable units="dimensionless" public_interface="in" name="Keq_ENO" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <ci>PEP_c</ci>
        <apply>
          <times />
          <ci>Keq_ENO</ci>
          <ci>two_PGA_c</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="PYR_c" cmeta:id="PYR_c">
    <rdf:RDF>
      <rdf:Description rdf:about="PYR_c">
        <dc:title>PYR_c</dc:title>
        <dcterms:alternative>cytosolic pyruvate</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="micromolar" public_interface="out" name="PYR_c" />
    <variable units="flux" public_interface="in" name="V_PYK" />
    <variable units="flux" public_interface="in" name="V_pyruvate_transport" />
    <variable units="second" public_interface="in" name="time" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>PYR_c</ci>
        </apply>
        <apply>
          <minus />
          <ci>V_PYK</ci>
          <ci>V_pyruvate_transport</ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="pyruvate_o" cmeta:id="pyruvate_o">
    <rdf:RDF>
      <rdf:Description rdf:about="pyruvate_o">
        <dc:title>pyruvate_o</dc:title>
        <dcterms:alternative>extracellular pyruvate</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF>
    <variable units="micromolar" public_interface="out" name="pyruvate_o" /> 
  </component>

  <component name="glycerol_g">
    <variable units="micromolar" public_interface="out" name="glycerol_g" />
  </component>

  <component name="DHAP_c" cmeta:id="DHAP_c">
   <rdf:RDF>
      <rdf:Description rdf:about="DHAP_c">
        <dc:title>DHAP_c</dc:title>
        <dcterms:alternative>cytosolic dihydroxyacetone phosphate</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
    <variable units="micromolar" public_interface="out" name="DHAP_c" />
    <variable units="micromolar" public_interface="in" name="triose_P" />
    <variable units="micromolar" public_interface="in" name="Q" />
    <variable units="micromolar" public_interface="in" name="C5" />
    <variable units="microlitre" public_interface="in" name="Vg" />
    <variable units="microlitre" public_interface="in" name="Vc" />
    <variable units="dimensionless" public_interface="out" name="Keq_TIM" initial_value="0.045" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <ci>DHAP_c</ci>
        <apply>
          <divide />
          <apply>
            <plus />
            <apply>
              <minus />
              <apply>
                <minus />
                <apply>
                  <plus />
                  <apply>
                    <times />
                    <ci>Q</ci>
                    <apply>
                      <plus />
                      <cn cellml:units="dimensionless"> 1.0 </cn>
                      <ci>Keq_TIM</ci>
                    </apply>
                  </apply>
                  <apply>
                    <times />
                    <apply>
                      <divide />