<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : curien_model_2003.xml
CREATED : 22nd December 2003
LAST MODIFIED : 22nd December 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 16/1/02 CellML Metadata 1.0 Specification.
DESCRIPTION : This file contains a CellML description of Curien et al.'s 2003 kinetic model of the branch-point between methionine and threonine biosynthesis pathways in Arabidopsis thaliana.
CHANGES:
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="curien_ravanel_dumas_2003_version01" name="curien_ravanel_dumas_2003_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>A Kinetic Model of the Branch-Point between the Methionine and Threonine Biosynthesis Pathways in Arabidopsis thaliana</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 model contains no ODEs, and as such can not currently be solved by any of the available CellML tools.
</para>
<para>
ValidateCellMl verifies this model as valid CellML with full unit consistency.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Metabolic branch-points are highly diverse in terms of the enzymes involved, the kinetic mechanisms of the competing enzymes, and the nature of the allosteric controls. How such diversity in organisation affects variation in branch-point kinetics is not well understood. In the Curien <emphasis>et al.</emphasis> 2003 publication described here, the authors present a kinetic model of the branch-point between the methionine and threonine biosynthesis pathway in <emphasis>Arabidopsis thaliana</emphasis> (see the figure below).
</para>
<para>
The pathway branch-point involves two enzymes: cystathionine gamma-synthase (CGS), and threonine synthase (TS). These two enzymes compete for the substrate phosphohomoserine (Phser), in chloroplasts. CGS catalyses the formation of cystathionine, the precursor of methionine (Met) and S-adenosylmethionine (AdoMet). In the competing branch, TS catalyses the synthesis of threonine. TS is stimulated by AdoMet, and both TS and CGS are inhibited by inorganic phosphate (Pi). In addition, TS is inhibited by AMP, which competes with AdoMet for its binding site on the enzyme.
</para>
<para>
The model has been described here in CellML and showed partial agreement when simulation results were compared with <emphasis>in vitro</emphasis> experimental results.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
A Kinetic Model of the Branch-Point between the Methionine and Threonine Biosynthesis Pathways in <emphasis>Arabidopsis thaliana</emphasis>
, Gilles Curien, Stephane Ravanel and Renaud Dumas, 2003,
<emphasis>European Journal of Biochemistry </emphasis>
, 270, 4615-4627. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/14622248">PubMed ID: 14622248</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>reaction diagram</title>
</objectinfo>
<imagedata fileref="curien_2003.png"/>
</imageobject>
</mediaobject>
<caption>Schematic diagram of the Phser branch-point in the aspartate-derived amino acid biosynthetic pathway in plants.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
<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="micromolar2">
<unit units="micromolar" exponent="2"/>
</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>
<component name="environment">
<variable units="second" public_interface="out" name="time"/>
</component>
<component name="v_cystathionine">
<variable units="flux" public_interface="out" name="v_cystathionine"/>
<variable units="micromolar" public_interface="in" name="Cys"/>
<variable units="micromolar" public_interface="in" name="CGS"/>
<variable units="micromolar" public_interface="in" name="Pi"/>
<variable units="micromolar" public_interface="in" name="Phser"/>
<variable units="micromolar" name="Km_CGS_Cys" initial_value="460.0"/>
<variable units="first_order_rate_constant" name="kcat_CGS" initial_value="30.0"/>
<variable units="first_order_rate_constant" name="kcat_CGS_Cys"/>
<variable units="micromolar" name="Km_CGS_Phser" initial_value="2500.0"/>
<variable units="micromolar" name="km_CGS_Cys"/>
<variable units="micromolar" name="Ki_CGS_Pi" initial_value="2500.0"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="v_cystathionine_calculation">
<eq/>
<ci> v_cystathionine </ci>
<apply>
<divide/>
<apply>
<times/>
<ci> kcat_CGS_Cys </ci>
<ci> CGS </ci>
<ci> Cys </ci>
</apply>
<apply>
<plus/>
<ci> Km_CGS_Cys </ci>
<ci> Cys </ci>
</apply>
</apply>
</apply>
<apply id="kcat_CGS_Cys_calculation">
<eq/>
<ci> kcat_CGS_Cys </ci>
<apply>
<divide/>
<ci> kcat_CGS </ci>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<times/>
<apply>
<divide/>
<ci> Km_CGS_Phser </ci>
<ci> Phser </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> Pi </ci>
<ci> Ki_CGS_Pi </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="Km_CGS_Cys_calculation">
<eq/>
<ci> Km_CGS_Cys </ci>
<apply>
<divide/>
<ci> km_CGS_Cys </ci>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<times/>
<apply>
<divide/>
<ci> Km_CGS_Phser </ci>
<ci> Phser </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> Pi </ci>
<ci> Ki_CGS_Pi </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="v_Thr">
<variable units="flux" public_interface="out" name="v_Thr"/>
<variable units="micromolar" public_interface="in" name="TS"/>
<variable units="micromolar" public_interface="in" name="AdoMet"/>
<variable units="micromolar" public_interface="in" name="Pi"/>
<variable units="micromolar" public_interface="in" name="Phser"/>
<variable units="micromolar" name="Km_TS"/>
<variable units="first_order_rate_constant" name="kcat_TS_noAdoMet" initial_value="0.42"/>
<variable units="first_order_rate_constant" name="kcat_TS_AdoMet" initial_value="3.5"/>
<variable units="first_order_rate_constant" name="kcat_TS"/>
<variable units="micromolar2" name="K1K2" initial_value="73.0"/>
<variable units="micromolar" name="Ki_TS_Pi" initial_value="1000.0"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="v_Thr_calculation">
<eq/>
<ci> v_Thr </ci>
<apply>
<divide/>
<apply>
<times/>
<ci> TS </ci>
<ci> kcat_TS </ci>
<ci> Phser </ci>
</apply>
<apply>
<plus/>
<ci> Km_TS </ci>
<ci> Phser </ci>
</apply>
</apply>
</apply>
<apply id="kcat_TS_calculation">
<eq/>
<ci> kcat_TS </ci>
<apply>
<divide/>
<apply>
<plus/>
<ci> kcat_TS_noAdoMet </ci>
<apply>
<times/>
<ci> kcat_TS_AdoMet </ci>
<apply>
<divide/>
<apply>
<power/>
<ci> AdoMet </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<ci> K1K2 </ci>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<apply>
<power/>
<ci> AdoMet </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<ci> K1K2 </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="Km_TS_calculation">
<eq/>
<ci> Km_TS </ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="micromolar"> 250.0 </cn>
<apply>
<divide/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> AdoMet </ci>
<cn cellml:units="micromolar"> 0.5 </cn>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> AdoMet </ci>
<cn cellml:units="micromolar"> 1.1 </cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<apply>
<power/>
<ci> AdoMet </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<cn cellml:units="micromolar2"> 140.0 </cn>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> Pi </ci>
<ci> Ki_TS_Pi </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="J_Phser">
<variable units="flux" name="J_Phser" initial_value="1.0"/>
<variable units="flux" public_interface="in" name="v_cystathionine"/>
<variable units="flux" public_interface="in" name="v_Thr"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="J_Phser_calculation">
<eq/>
<ci> J_Phser </ci>
<apply>
<plus/>
<ci> v_cystathionine </ci>
<ci> v_Thr </ci>
</apply>
</apply>
</math>
</component>
<component name="CGS" cmeta:id="CGS">
<rdf:RDF>
<rdf:Description rdf:about="CGS">
<dc:title>CGS</dc:title>
<dcterms:alternative>cystathionine gamma-synthase</dcterms:alternative> </rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="CGS" initial_value="0.7"/>
</component>
<component name="Phser" cmeta:id="Phser">
<rdf:RDF>
<rdf:Description rdf:about="Phser">
<dc:title>Phser</dc:title>
<dcterms:alternative>phosphohomoserine</dcterms:alternative> </rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="Phser"/>
</component>
<component name="AdoMet" cmeta:id="AdoMet">
<rdf:RDF>
<rdf:Description rdf:about="AdoMet">
<dc:title>AdoMet</dc:title>
<dcterms:alternative>S-adenosylmethionine</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="AdoMet" initial_value="20.0"/>
</component>
<component name="Cys" cmeta:id="Cys">
<rdf:RDF>
<rdf:Description rdf:about="Cys">
<dc:title>Cys</dc:title>
<dcterms:alternative>cysteine</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="Cys" initial_value="15.0"/>
</component>
<component name="Pi" cmeta:id="Pi">
<rdf:RDF>
<rdf:Description rdf:about="Pi">
<dc:title>Pi</dc:title>
<dcterms:alternative>inorganic phosphate</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="millimolar" public_interface="out" name="Pi" initial_value="10.0"/>
</component>
<component name="TS" cmeta:id="TS">
<rdf:RDF>
<rdf:Description rdf:about="TS">
<dc:title>TS</dc:title>
<dcterms:alternative>threonine synthase</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="TS" initial_value="5.0"/>
</component>
<connection>
<map_components component_2="CGS" component_1="v_cystathionine"/>
<map_variables variable_2="CGS" variable_1="CGS"/>
</connection>
<connection>
<map_components component_2="Cys" component_1="v_cystathionine"/>
<map_variables variable_2="Cys" variable_1="Cys"/>
</connection>
<connection>
<map_components component_2="Phser" component_1="v_cystathionine"/>
<map_variables variable_2="Phser" variable_1="Phser"/>
</connection>
<connection>
<map_components component_2="Pi" component_1="v_cystathionine"/>
<map_variables variable_2="Pi" variable_1="Pi"/>
</connection>
<connection>
<map_components component_2="TS" component_1="v_Thr"/>
<map_variables variable_2="TS" variable_1="TS"/>
</connection>
<connection>
<map_components component_2="Phser" component_1="v_Thr"/>
<map_variables variable_2="Phser" variable_1="Phser"/>
</connection>
<connection>
<map_components component_2="AdoMet" component_1="v_Thr"/>
<map_variables variable_2="AdoMet" variable_1="AdoMet"/>
</connection>
<connection>
<map_components component_2="Pi" component_1="v_Thr"/>
<map_variables variable_2="Pi" variable_1="Pi"/>
</connection>
<connection>
<map_components component_2="v_Thr" component_1="J_Phser"/>
<map_variables variable_2="v_Thr" variable_1="v_Thr"/>
</connection>
<connection>
<map_components component_2="v_cystathionine" component_1="J_Phser"/>
<map_variables variable_2="v_cystathionine" variable_1="v_cystathionine"/>
</connection>
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Curien et al.'s 2003 kinetic model of the branch-point between
methionine and threonine biosynthesis pathways in Arabidopsis thaliana.
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<dcterms:W3CDTF>2003-12</dcterms:W3CDTF>
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removed reference link in documentation</rdf:value>
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of the branch-point between methionine and threonine biosynthesis
pathways in Arabidopsis thaliana.</rdf:value>
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<vCard:FN>Catherine Lloyd</vCard:FN>
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<dc:title>European Journal of Biochemistry</dc:title>
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