- Author:
- Hanne <Hanne@hanne-nielsens-macbook.local>
- Date:
- 2010-04-07 17:29:42+12:00
- Desc:
- Added images in ai, svg and png format
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/albert_haanstra_hannaert_vanroy_opperdoes_bakker_michels_2005/rawfile/59e1b44482fd120c92d4ccdc5c1a5749b3678772/albert_2005.cellml
<?xml version="1.0" encoding="utf-8"?>
<!--
This CellML file was generated on 6/04/2010 at 3:58:55 at p.m. using:
COR (0.9.31.1371)
Copyright 2002-2010 Dr Alan Garny
http://cor.physiol.ox.ac.uk/ - cor@physiol.ox.ac.uk
CellML 1.0 was used to generate this model
http://www.cellml.org/
-->
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<article>
<articleinfo>
<title>Experimental and <emphasis>in Silico</emphasis> Analyses of Glycolytic Flux Control in
Bloodstream Form <emphasis>Trypanosoma brucei</emphasis></title>
<author>
<firstname>Geoffrey</firstname>
<surname>Nunns</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model runs in PCenv, COR and OpenCell and the units are consistent throughout. It is unclear at this stage at to whether it recreates the published results. It was adapted from the Biomodels Database with the help of Lukas Endler (available: http://www.ebi.ac.uk/biomodels-main/BIOMD0000000211).
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: A mathematical model of glycolysis in bloodstream form Trypanosoma brucei was developed previously on the basis of all available enzyme kinetic data (Bakker, B. M., Michels, P. A. M., Opperdoes, F. R., and Westerhoff, H. V. (1997) J. Biol. Chem. 272, 3207-3215). The model predicted correctly the fluxes and cellular metabolite concentrations as measured in non-growing trypanosomes and the major contribution to the flux control exerted by the plasma membrane glucose transporter. Surprisingly, a large overcapacity was predicted for hexokinase (HXK), phosphofructokinase (PFK), and pyruvate kinase (PYK). Here, we present our further analysis of the control of glycolytic flux in bloodstream form T. brucei. First, the model was optimized and extended with recent information about the kinetics of enzymes and their activities as measured in lysates of in vitro cultured growing trypanosomes. Second, the concentrations of five glycolytic enzymes (HXK, PFK, phosphoglycerate mutase, enolase, and PYK) in trypanosomes were changed by RNA interference. The effects of the knockdown of these enzymes on the growth, activities, and levels of various enzymes and glycolytic flux were studied and compared with model predictions. Data thus obtained support the conclusion from the in silico analysis that HXK, PFK, and PYK are in excess, albeit less than predicted. Interestingly, depletion of PFK and enolase had an effect on the activity (but not, or to a lesser extent, expression) of some other glycolytic enzymes. Enzymes located both in the glycosomes (the peroxisome-like organelles harboring the first seven enzymes of the glycolytic pathway of trypanosomes) and in the cytosol were affected. These data suggest the existence of novel regulatory mechanisms operating in trypanosome glycolysis.
</para>
<para>
The original paper reference is cited below:
</para>
<para>
Experimental and in silico analyses of glycolytic flux control in bloodstream form Trypanosoma brucei, Marie-Astrid Albert, Jurgen R. Haanstra, Veronique Hannaert, Joris Van Roy, Fred R. Opperdoes, Barbara M. Bakker, and Paul A. M. Michels, 2005, <emphasis>Journal of Biological Chemistry</emphasis>, volume 280, 28306-28315. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15955817&query_hl=1&itool=pubmed_docsum">PubMed ID: 15955817</ulink>
</para>
</sect1>
</article>
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<variable name="glyceraldehyde3phosphate_gly" units="mM" public_interface="in"/>
<variable name="nad_gly" units="mM" public_interface="in"/>
<variable name="nadh_gly" units="mM" public_interface="in"/>
<variable name="bisphosphoglycerate_gly" units="mM" public_interface="in"/>
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<ci>v_GAPDH</ci>
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<divide/>
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<minus/>
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<divide/>
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<variable name="nadh_gly" units="mM" public_interface="in"/>
<variable name="glycerol3phosphate_gly" units="mM" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
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<divide/>
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<minus/>
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<plus/>
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<apply>
<divide/>
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<eq/>
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<eq/>
<ci>v_PT</ci>
<apply>
<divide/>
<apply>
<times/>
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<apply>
<plus/>
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<variable name="adp_gly" units="mM" public_interface="in"/>
<variable name="bisphosphoglycerate_gly" units="mM" public_interface="in"/>
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<minus/>
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<divide/>
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<plus/>
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<divide/>
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<divide/>
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<divide/>
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<times/>
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<minus/>
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<variable name="threephosphoglycerate_cyt" units="mM" public_interface="in"/>
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<eq/>
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<divide/>
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<minus/>
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<times/>
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<minus/>
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<times/>
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<variable name="adp_gly" units="mM" public_interface="in"/>
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<minus/>
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<variable name="threephosphoglycerate_gly" units="mM" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
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<eq/>
<ci>v_PGT</ci>
<apply>
<minus/>
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<times/>
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<variable name="dihydroxyacetonephosphate_cyt" units="mM" public_interface="in"/>
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<variable name="dihydroxyacetonephosphate_gly" units="mM" public_interface="in"/>
<variable name="glycerol3phosphate_gly" units="mM" public_interface="in"/>
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<eq/>
<ci>v_ANTI</ci>
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<minus/>
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<times/>
<ci>k1</ci>
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<ci>glycerol3phosphate_cyt</ci>
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<variable name="k1" units="ul_per_mg_per_minute" initial_value="1000000"/>
<variable name="k2" units="ul_per_mg_per_minute" initial_value="1000000"/>
<variable name="glycerol_gly" units="mM" public_interface="in"/>
<variable name="glycerol_ext" units="mM" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>v_GlyT</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>k1</ci>
<ci>glycerol_gly</ci>
</apply>
<apply>
<times/>
<ci>k2</ci>
<ci>glycerol_ext</ci>
</apply>
</apply>
</apply>
</math>
</component>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="environment" component_2="cytosolic_species"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="cytosolic_volume" variable_2="cytosolic_volume"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="environment" component_2="glycosomal_species"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="glycosomal_volume" variable_2="glycosomal_volume"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="environment" component_2="extracellular_species"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_GT" component_2="extracellular_species"/>
<map_variables variable_1="glucose_external" variable_2="glucose_external"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_GT" component_2="glycosomal_species"/>
<map_variables variable_1="glucose_gly" variable_2="glucose_gly"/>
<map_variables variable_1="v_GT" variable_2="v_GT"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_HK" component_2="glycosomal_species"/>
<map_variables variable_1="glucose_gly" variable_2="glucose_gly"/>
<map_variables variable_1="atp_gly" variable_2="atp_gly"/>
<map_variables variable_1="adp_gly" variable_2="adp_gly"/>
<map_variables variable_1="glucose6phosphate_gly" variable_2="glucose6phosphate_gly"/>
<map_variables variable_1="v_HK" variable_2="v_HK"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_PGI" component_2="glycosomal_species"/>
<map_variables variable_1="glucose6phosphate_gly" variable_2="glucose6phosphate_gly"/>
<map_variables variable_1="fructose6phosphate_gly" variable_2="fructose6phosphate_gly"/>
<map_variables variable_1="v_PGI" variable_2="v_PGI"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_PFK" component_2="glycosomal_species"/>
<map_variables variable_1="fructose16bisphosphate_gly" variable_2="fructose16bisphosphate_gly"/>
<map_variables variable_1="fructose6phosphate_gly" variable_2="fructose6phosphate_gly"/>
<map_variables variable_1="atp_gly" variable_2="atp_gly"/>
<map_variables variable_1="v_PFK" variable_2="v_PFK"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_ALD" component_2="glycosomal_species"/>
<map_variables variable_1="fructose16bisphosphate_gly" variable_2="fructose16bisphosphate_gly"/>
<map_variables variable_1="glyceraldehyde3phosphate_gly" variable_2="glyceraldehyde3phosphate_gly"/>
<map_variables variable_1="dihydroxyacetonephosphate_gly" variable_2="dihydroxyacetonephosphate_gly"/>
<map_variables variable_1="atp_gly" variable_2="atp_gly"/>
<map_variables variable_1="adp_gly" variable_2="adp_gly"/>
<map_variables variable_1="amp_gly" variable_2="amp_gly"/>
<map_variables variable_1="v_ALD" variable_2="v_ALD"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_TPI" component_2="glycosomal_species"/>
<map_variables variable_1="dihydroxyacetonephosphate_gly" variable_2="dihydroxyacetonephosphate_gly"/>
<map_variables variable_1="glyceraldehyde3phosphate_gly" variable_2="glyceraldehyde3phosphate_gly"/>
<map_variables variable_1="v_TPI" variable_2="v_TPI"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_GAPDH" component_2="glycosomal_species"/>
<map_variables variable_1="glyceraldehyde3phosphate_gly" variable_2="glyceraldehyde3phosphate_gly"/>
<map_variables variable_1="nad_gly" variable_2="nad_gly"/>
<map_variables variable_1="bisphosphoglycerate_gly" variable_2="bisphosphoglycerate_gly"/>
<map_variables variable_1="nadh_gly" variable_2="nadh_gly"/>
<map_variables variable_1="v_GAPDH" variable_2="v_GAPDH"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_GPDH" component_2="glycosomal_species"/>
<map_variables variable_1="dihydroxyacetonephosphate_gly" variable_2="dihydroxyacetonephosphate_gly"/>
<map_variables variable_1="nadh_gly" variable_2="nadh_gly"/>
<map_variables variable_1="nad_gly" variable_2="nad_gly"/>
<map_variables variable_1="glycerol3phosphate_gly" variable_2="glycerol3phosphate_gly"/>
<map_variables variable_1="v_GPDH" variable_2="v_GPDH"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_GPO" component_2="cytosolic_species"/>
<map_variables variable_1="glycerol3phosphate_cyt" variable_2="glycerol3phosphate_cyt"/>
<map_variables variable_1="v_GPO" variable_2="v_GPO"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_PT" component_2="cytosolic_species"/>
<map_variables variable_1="pyruvate_cyt" variable_2="pyruvate_cyt"/>
<map_variables variable_1="v_PT" variable_2="v_PT"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_PGK" component_2="glycosomal_species"/>
<map_variables variable_1="bisphosphoglycerate_gly" variable_2="bisphosphoglycerate_gly"/>
<map_variables variable_1="adp_gly" variable_2="adp_gly"/>
<map_variables variable_1="threephosphoglycerate_gly" variable_2="threephosphoglycerate_gly"/>
<map_variables variable_1="atp_gly" variable_2="atp_gly"/>
<map_variables variable_1="v_PGK" variable_2="v_PGK"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_PK" component_2="cytosolic_species"/>
<map_variables variable_1="phosphoenolpyruvate_cyt" variable_2="phosphoenolpyruvate_cyt"/>
<map_variables variable_1="atp_cyt" variable_2="atp_cyt"/>
<map_variables variable_1="adp_cyt" variable_2="adp_cyt"/>
<map_variables variable_1="v_PK" variable_2="v_PK"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_AU" component_2="cytosolic_species"/>
<map_variables variable_1="atp_cyt" variable_2="atp_cyt"/>
<map_variables variable_1="adp_cyt" variable_2="adp_cyt"/>
<map_variables variable_1="v_AU" variable_2="v_AU"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_GK" component_2="glycosomal_species"/>
<map_variables variable_1="glycerol3phosphate_gly" variable_2="glycerol3phosphate_gly"/>
<map_variables variable_1="adp_gly" variable_2="adp_gly"/>
<map_variables variable_1="glycerol_gly" variable_2="glycerol_gly"/>
<map_variables variable_1="atp_gly" variable_2="atp_gly"/>
<map_variables variable_1="v_GK" variable_2="v_GK"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_PGM" component_2="cytosolic_species"/>
<map_variables variable_1="threephosphoglycerate_cyt" variable_2="threephosphoglycerate_cyt"/>
<map_variables variable_1="twophosphoglycerate_cyt" variable_2="twophosphoglycerate_cyt"/>
<map_variables variable_1="v_PGM" variable_2="v_PGM"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_ENO" component_2="cytosolic_species"/>
<map_variables variable_1="twophosphoglycerate_cyt" variable_2="twophosphoglycerate_cyt"/>
<map_variables variable_1="phosphoenolpyruvate_cyt" variable_2="phosphoenolpyruvate_cyt"/>
<map_variables variable_1="v_ENO" variable_2="v_ENO"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_AKc" component_2="cytosolic_species"/>
<map_variables variable_1="atp_cyt" variable_2="atp_cyt"/>
<map_variables variable_1="amp_cyt" variable_2="amp_cyt"/>
<map_variables variable_1="adp_cyt" variable_2="adp_cyt"/>
<map_variables variable_1="v_AKc" variable_2="v_AKc"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_AKg" component_2="glycosomal_species"/>
<map_variables variable_1="atp_gly" variable_2="atp_gly"/>
<map_variables variable_1="amp_gly" variable_2="amp_gly"/>
<map_variables variable_1="adp_gly" variable_2="adp_gly"/>
<map_variables variable_1="v_AKg" variable_2="v_AKg"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_PGT" component_2="glycosomal_species"/>
<map_variables variable_1="threephosphoglycerate_gly" variable_2="threephosphoglycerate_gly"/>
<map_variables variable_1="v_PGT" variable_2="v_PGT"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_PGT" component_2="cytosolic_species"/>
<map_variables variable_1="threephosphoglycerate_cyt" variable_2="threephosphoglycerate_cyt"/>
<map_variables variable_1="v_PGT" variable_2="v_PGT"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_ANTI" component_2="glycosomal_species"/>
<map_variables variable_1="glycerol3phosphate_gly" variable_2="glycerol3phosphate_gly"/>
<map_variables variable_1="dihydroxyacetonephosphate_gly" variable_2="dihydroxyacetonephosphate_gly"/>
<map_variables variable_1="v_ANTI" variable_2="v_ANTI"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_ANTI" component_2="cytosolic_species"/>
<map_variables variable_1="dihydroxyacetonephosphate_cyt" variable_2="dihydroxyacetonephosphate_cyt"/>
<map_variables variable_1="glycerol3phosphate_cyt" variable_2="glycerol3phosphate_cyt"/>
<map_variables variable_1="v_ANTI" variable_2="v_ANTI"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_GlyT" component_2="glycosomal_species"/>
<map_variables variable_1="glycerol_gly" variable_2="glycerol_gly"/>
<map_variables variable_1="v_GlyT" variable_2="v_GlyT"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="v_GlyT" component_2="extracellular_species"/>
<map_variables variable_1="glycerol_ext" variable_2="glycerol_ext"/>
</connection>
</model>
