- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2009-06-17 12:21:53+12:00
- Desc:
- committing version03 of aon_cortassa_2002
- Permanent Source URI:
- https://models.cellml.org/workspace/aon_cortassa_2002/rawfile/ff0581984d61fdcd4a3f20657172bf873e637ccd/aon_cortassa_2002.cellml
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This CellML file was generated on 31/12/2007 at 1:46:57 at p.m. using:
COR (0.9.31.833)
Copyright 2002-2007 Dr Alan Garny
http://COR.physiol.ox.ac.uk/ - COR@physiol.ox.ac.uk
CellML 1.0 was used to generate this cellular model
http://www.CellML.org/
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<title>Modulation of a Metabolic Network by Cytoskeletal Organisation and Dynamics</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 CellML model runs in both PCENv and COR. The units have been checked and are consistent and correct. Unfortunately this version of the CellML model does not recreate the published results of the original model. We are unsure why as the full set of equations and parameters are included and the simulation tools produce no error messages.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
The spatio-temporal coordination of cellular processes is a challenge which is faced by many biological systems, including cell growth, proliferation, differentiation, and functional adaptation. Such coordination is apparent in processes such as signal transduction, gene expression, and metabolism. Over the past few decades, two main theories concerning the organisation of metabolism have evolved:
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<para>The concept of metabolic channelling, where reactions are facilitated by substrate transfer between closely associated enzymes; and</para>
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<para>The idea of cytoskeletal driven control of enzyme fluxes.</para>
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Although these two theories are not mutually exclusive, there are cases where one mechanism will be favoured over the other, for example, channelling would not be favoured on the surface of a supramolecular structure.
</para>
<para>
The microtubular protein enhancement of metabolic flux depends on several factors, including:
</para>
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<para>The concentration of the microtubular protein;</para>
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<para>The presence of microtubule associated proteins (MAPs);</para>
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<para>The polymerisation state of the cytoskeletal proteins; and</para>
</listitem>
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<para>The type of cytoskeletal protein present.</para>
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<para>
The cellular metabolic response to hormones such as insulin and glucagon depends on cell volume: turgid cells synthesise protein and glycogen, whereas flaccid cells break down these substances. Cytoskeletal dynamics play an essential role in sensing and responding to osmotic stress. It is likely that the spatial organisation and orientation of cytoskeletal proteins are modulating gene expression, signal transduction, and metabolic fluxes. Microtubules, actin microfilaments, and intermediate filaments represent a large surface area in the cell (estimated to be 3000 micrometres square per mammalian cell). This large surface area provides an interface for enzyme and other protein binding.
</para>
<para>
Although much is known about the interactions between glycolytic enzymes and cytoskeletal proteins, much less is understood about the consequences of these interactions. In their 2002 mathematical model of cytoskeletal modulation of a metabolic network, Miguel Aon and Sonia Cortassa look to determine the influence of cytoskeletal organisation and dynamics on cellular biochemistry. Specifically, they address the question of whether the degree of microtubule polymerisation affects the metabolic flux through the glycolytic pathway and/or it branches towards the pentose phosphate cycle, the tricarboxylic acid (TCA) cycle, and ethanol fermentation. Their model (see the figure below) is based on experimental data from yeast.
</para>
<para>
The main observation taken from the model simulations was that the cytoskeleton provides the modulation of metabolism with coherence (the integration of diverse elements and activities to produce a consistent response) and robustness (enhanced stability in the steady state dynamic behaviour of the metabolic network when parameters are varied).
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TFB-45R7WBF-3&_user=140507&_coverDate=06%2F19%2F2002&_alid=108052762&_rdoc=1&_fmt=summary&_orig=search&_qd=1&_cdi=5222&_sort=d&_docanchor=&view=c&_acct=C000011498&_version=1&_urlVersion=0&_userid=140507&md5=f721a3270481db2b2560eb6f3781f295">Coherent and robust modulation of a metabolic network by cytoskeletal organization and dynamics</ulink>, Miguel A. Aon and Sonia Cortassa, 2002, <ulink url="http://www.sciencedirect.com/science?_ob=JournalURL&_cdi=5222&_auth=y&_acct=C000011498&_version=1&_urlVersion=0&_userid=140507&md5=7d06a1ef3b4293bc0633b8269aa54192">
<emphasis>Biophysical Chemistry</emphasis>
</ulink>, 97, 213-231. (<ulink url="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TFB-45R7WBF-3&_coverDate=06%2F19%2F2002&_alid=108052762&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=5222&_sort=d&view=c&_acct=C000011498&_version=1&_urlVersion=0&_userid=140507&md5=1c7c67cd16a36773e5073a16450ae963">Full text (HTML)</ulink> and PDF versions of the article are available on the <emphasis>Biophysical Chemistry</emphasis> website.) <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12050011&dopt=Abstract">PubMed ID: 12050011</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
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<caption>A schematic diagram of the metabolic network, the cycle of assembly-disassembly of microtubular proteins, and their interactions, upon which the Aon-Cortassa model is based.</caption>
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<variable units="dimensionless" name="cAMP" initial_value="0.019"/>
<variable units="dimensionless" name="cG6P" initial_value="0.0005"/>
<variable units="dimensionless" name="Lo" initial_value="25000"/>
<variable units="dimensionless" name="gr" initial_value="10"/>
<variable units="dimensionless" name="n1" initial_value="2"/>
<variable units="flux" name="V_PFK_max" initial_value="30"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_PFK</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>V_PFK_max</ci>
<ci>gr</ci>
<ci>G6P</ci>
</apply>
<ci>KG6P_r</ci>
</apply>
<ci>ATP</ci>
</apply>
<ci>KATP_r</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>G6P</ci>
<ci>KG6P_r</ci>
</apply>
<apply>
<divide/>
<ci>ATP</ci>
<ci>KATP_r</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>gr</ci>
<ci>G6P</ci>
</apply>
<ci>KG6P_r</ci>
</apply>
<ci>ATP</ci>
</apply>
<ci>KATP_r</ci>
</apply>
</apply>
<apply>
<minus/>
<ci>n1</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
<apply>
<plus/>
<apply>
<power/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>G6P</ci>
<ci>KG6P_r</ci>
</apply>
<apply>
<divide/>
<ci>ATP</ci>
<ci>KATP_r</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>gr</ci>
<ci>G6P</ci>
</apply>
<ci>KG6P_r</ci>
</apply>
<ci>ATP</ci>
</apply>
<ci>KATP_r</ci>
</apply>
</apply>
<ci>n1</ci>
</apply>
<apply>
<times/>
<ci>Lo</ci>
<apply>
<power/>
<apply>
<divide/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>cAMP</ci>
<ci>AMP</ci>
</apply>
<ci>KAMP_r</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>AMP</ci>
<ci>KAMP_r</ci>
</apply>
</apply>
</apply>
<ci>n1</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>cG6P</ci>
<ci>G6P</ci>
</apply>
<ci>KG6P_r</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>cATP</ci>
<ci>ATP</ci>
</apply>
<ci>KATP_r</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>gr</ci>
<ci>cG6P</ci>
<ci>G6P</ci>
</apply>
<ci>KG6P_r</ci>
</apply>
<ci>cATP</ci>
<ci>ATP</ci>
</apply>
<ci>KATP_r</ci>
</apply>
</apply>
<ci>n1</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_G6PDH">
<variable units="flux" public_interface="out" name="V_G6PDH"/>
<variable units="millimolar" public_interface="in" name="G6P"/>
<variable units="millimolar" public_interface="in" name="NADP"/>
<variable units="millimolar" public_interface="in" name="CT"/>
<variable units="millimolar" public_interface="in" name="CD"/>
<variable units="millimolar" name="TUB"/>
<variable units="millimolar" name="KG6P" initial_value="0.05"/>
<variable units="millimolar" name="KNADP" initial_value="0.05"/>
<variable units="millimolar" name="KNADP_" initial_value="0.05"/>
<variable units="millimolar" name="KTUB" initial_value="0.4"/>
<variable units="flux" name="V_G6PDH_max" initial_value="1.6"/>
<variable units="flux" name="V_G6PDH_max_II" initial_value="1"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_G6PDH</ci>
<apply>
<plus/>
<apply>
<divide/>
<ci>V_G6PDH_max</ci>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<ci>KG6P</ci>
<ci>KNADP</ci>
</apply>
<apply>
<times/>
<ci>G6P</ci>
<ci>NADP</ci>
</apply>
</apply>
<apply>
<divide/>
<ci>KG6P</ci>
<ci>G6P</ci>
</apply>
<apply>
<divide/>
<ci>KNADP</ci>
<ci>NADP</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
<apply>
<divide/>
<ci>V_G6PDH_max_II</ci>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<ci>KG6P</ci>
<ci>KNADP_</ci>
<ci>KTUB</ci>
</apply>
<apply>
<times/>
<ci>G6P</ci>
<ci>NADP</ci>
<ci>TUB</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>KG6P</ci>
<ci>KNADP_</ci>
</apply>
<apply>
<times/>
<ci>G6P</ci>
<ci>NADP</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>KNADP_</ci>
<ci>KTUB</ci>
</apply>
<apply>
<times/>
<ci>NADP</ci>
<ci>TUB</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>KG6P</ci>
<ci>KTUB</ci>
</apply>
<apply>
<times/>
<ci>G6P</ci>
<ci>TUB</ci>
</apply>
</apply>
<apply>
<divide/>
<ci>KTUB</ci>
<ci>TUB</ci>
</apply>
<apply>
<divide/>
<ci>KG6P</ci>
<ci>G6P</ci>
</apply>
<apply>
<divide/>
<ci>KNADP_</ci>
<ci>NADP</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>TUB</ci>
<apply>
<plus/>
<ci>CT</ci>
<ci>CD</ci>
</apply>
</apply>
</math>
</component>
<component name="V_ALD">
<variable units="flux" public_interface="out" name="V_ALD"/>
<variable units="millimolar" public_interface="in" name="G3P"/>
<variable units="millimolar" public_interface="in" name="FDP"/>
<variable units="millimolar" name="KG3P_m" initial_value="20"/>
<variable units="millimolar" name="KFDP_m" initial_value="0.5"/>
<variable units="flux" name="V_ALD_max" initial_value="2.5"/>
<variable units="flux" name="V_ALD_max_r" initial_value="1"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_ALD</ci>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>V_ALD_max</ci>
<ci>FDP</ci>
</apply>
<ci>KFDP_m</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>V_ALD_max_r</ci>
<ci>G3P</ci>
</apply>
<ci>KG3P_m</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>FDP</ci>
<ci>KFDP_m</ci>
</apply>
<apply>
<divide/>
<ci>G3P</ci>
<ci>KG3P_m</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_GAPDH">
<variable units="flux" public_interface="out" name="V_GAPDH"/>
<variable units="millimolar" public_interface="in" name="G3P"/>
<variable units="millimolar" public_interface="in" name="NAD"/>
<variable units="millimolar" public_interface="in" name="NADH"/>
<variable units="millimolar" public_interface="in" name="ATP"/>
<variable units="millimolar" public_interface="in" name="AMP"/>
<variable units="millimolar" public_interface="in" name="ADP"/>
<variable units="millimolar" name="K1" initial_value="1.1"/>
<variable units="millimolar" name="K2" initial_value="1.5"/>
<variable units="millimolar" name="K3" initial_value="2.5"/>
<variable units="millimolar" name="KG3P" initial_value="0.0025"/>
<variable units="millimolar" name="KNAD" initial_value="0.18"/>
<variable units="millimolar" name="KNADH_i" initial_value="0.0003"/>
<variable units="flux" name="V_GAPDH_max" initial_value="10"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_GAPDH</ci>
<apply>
<divide/>
<ci>V_GAPDH_max</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>KG3P</ci>
<ci>G3P</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<ci>KNAD</ci>
<ci>NAD</ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>AMP</ci>
<ci>K1</ci>
</apply>
<apply>
<divide/>
<ci>ADP</ci>
<ci>K2</ci>
</apply>
<apply>
<divide/>
<ci>ATP</ci>
<ci>K3</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>KG3P</ci>
<ci>KNAD</ci>
</apply>
<apply>
<times/>
<ci>G3P</ci>
<ci>NAD</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>NADH</ci>
<ci>KNADH_i</ci>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>AMP</ci>
<ci>K1</ci>
</apply>
<apply>
<divide/>
<ci>ADP</ci>
<ci>K2</ci>
</apply>
<apply>
<divide/>
<ci>ATP</ci>
<ci>K3</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_PGK">
<variable units="flux" public_interface="out" name="V_PGK"/>
<variable units="millimolar" public_interface="in" name="DPG"/>
<variable units="millimolar" name="KDPG_m" initial_value="0.002"/>
<variable units="flux" name="V_PGK_max" initial_value="3"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_PGK</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>V_PGK_max</ci>
<ci>DPG</ci>
</apply>
<apply>
<plus/>
<ci>KDPG_m</ci>
<ci>DPG</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_PK">
<variable units="flux" public_interface="out" name="V_PK"/>
<variable units="millimolar" public_interface="in" name="PEP"/>
<variable units="millimolar" public_interface="in" name="ADP"/>
<variable units="millimolar" public_interface="in" name="FDP"/>
<variable units="millimolar" public_interface="in" name="H"/>
<variable units="millimolar" public_interface="in" name="C_PK"/>
<variable units="millimolar" public_interface="in" name="PKp"/>
<variable units="dimensionless" name="R"/>
<variable units="dimensionless" name="T"/>
<variable units="millimolar" name="KpH" initial_value="9.5e-9"/>
<variable units="millimolar" name="KPEP_r" initial_value="1"/>
<variable units="millimolar" name="KADP_r" initial_value="0.06"/>
<variable units="millimolar" name="KFDP_r" initial_value="0.025"/>
<variable units="dimensionless" name="cADP" initial_value="1"/>
<variable units="dimensionless" name="cFDP" initial_value="0.01"/>
<variable units="dimensionless" name="cPEP" initial_value="0.02"/>
<variable units="dimensionless" name="Lo_PK" initial_value="1000"/>
<variable units="dimensionless" name="gr_PK" initial_value="0.1"/>
<variable units="dimensionless" name="gt_PK" initial_value="1"/>
<variable units="dimensionless" name="n"/>
<variable units="flux" name="V_PK_max"/>
<variable units="flux" name="V_PKt_max" initial_value="25"/>
<variable units="flux" name="V_PKp_max" initial_value="50"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_PK</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>V_PK_max</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>KpH</ci>
<ci>H</ci>
</apply>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>gr_PK</ci>
<apply>
<divide/>
<ci>PEP</ci>
<ci>KPEP_r</ci>
</apply>
<apply>
<divide/>
<ci>ADP</ci>
<ci>KADP_r</ci>
</apply>
<apply>
<power/>
<ci>R</ci>
<apply>
<minus/>
<ci>n</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>Lo_PK</ci>
<apply>
<power/>
<apply>
<divide/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>cFDP</ci>
<ci>FDP</ci>
</apply>
<ci>KFDP_r</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>FDP</ci>
<ci>KFDP_r</ci>
</apply>
</apply>
</apply>
<ci>n</ci>
</apply>
<apply>
<divide/>
<ci>FDP</ci>
<ci>KFDP_r</ci>
</apply>
<ci>gt_PK</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>cPEP</ci>
<ci>PEP</ci>
</apply>
<ci>KPEP_r</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>cADP</ci>
<ci>ADP</ci>
</apply>
<ci>KADP_r</ci>
</apply>
<apply>
<power/>
<ci>T</ci>
<apply>
<minus/>
<ci>n</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<apply>
<power/>
<ci>R</ci>
<ci>n</ci>
</apply>
<apply>
<times/>
<ci>Lo_PK</ci>
<apply>
<power/>
<apply>
<divide/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>cFDP</ci>
<ci>FDP</ci>
</apply>
<ci>KFDP_r</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>FDP</ci>
<ci>KFDP_r</ci>
</apply>
</apply>
</apply>
<ci>n</ci>
</apply>
<apply>
<power/>
<ci>T</ci>
<ci>n</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>R</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>PEP</ci>
<ci>KPEP_r</ci>
</apply>
<apply>
<divide/>
<ci>ADP</ci>
<ci>KADP_r</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>gr_PK</ci>
<ci>PEP</ci>
</apply>
<ci>KPEP_r</ci>
</apply>
<ci>ADP</ci>
</apply>
<ci>KADP_r</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>T</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>cPEP</ci>
<ci>PEP</ci>
</apply>
<ci>KPEP_r</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>cADP</ci>
<ci>ADP</ci>
</apply>
<ci>KADP_r</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>gt_PK</ci>
<ci>cPEP</ci>
<ci>PEP</ci>
</apply>
<ci>KPEP_r</ci>
</apply>
<ci>cADP</ci>
<ci>ADP</ci>
</apply>
<ci>KADP_r</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>V_PK_max</ci>
<apply>
<plus/>
<ci>V_PKt_max</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>V_PKp_max</ci>
<ci>V_PKt_max</ci>
</apply>
<ci>PKp</ci>
</apply>
<ci>C_PK</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>n</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">4</cn>
<apply>
<divide/>
<ci>PKp</ci>
<ci>C_PK</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_TCA">
<variable units="flux" public_interface="out" name="V_TCA"/>
<variable units="millimolar" public_interface="in" name="Py"/>
<variable units="millimolar" name="KPy_m" initial_value="0.329"/>
<variable units="flux" name="V_TCA_max" initial_value="10"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_TCA</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>V_TCA_max</ci>
<apply>
<power/>
<ci>Py</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<plus/>
<apply>
<power/>
<ci>KPy_m</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<apply>
<power/>
<ci>Py</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_ADH">
<variable units="flux" public_interface="out" name="V_ADH"/>
<variable units="millimolar" public_interface="in" name="Py"/>
<variable units="millimolar" name="KPy__m" initial_value="0.169"/>
<variable units="flux" name="V_ADH_max" initial_value="0.5"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_ADH</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>V_ADH_max</ci>
<ci>Py</ci>
</apply>
<apply>
<plus/>
<ci>KPy__m</ci>
<ci>Py</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_ATPase">
<variable units="flux" public_interface="out" name="V_ATPase"/>
<variable units="millimolar" public_interface="in" name="ATP"/>
<variable units="first_order_rate_constant" name="KATP" initial_value="5"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_ATPase</ci>
<apply>
<times/>
<ci>KATP</ci>
<ci>ATP</ci>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_2="V_IN" component_1="G_o"/>
<map_variables variable_2="G_o" variable_1="G_o"/>
</connection>
<connection>
<map_components component_2="V_IN" component_1="G"/>
<map_variables variable_2="G" variable_1="G"/>
<map_variables variable_2="V_IN" variable_1="V_IN"/>
</connection>
<connection>
<map_components component_2="V_HK" component_1="G"/>
<map_variables variable_2="G" variable_1="G"/>
<map_variables variable_2="V_HK" variable_1="V_HK"/>
</connection>
<connection>
<map_components component_2="V_HK" component_1="G6P"/>
<map_variables variable_2="V_HK" variable_1="V_HK"/>
</connection>
<connection>
<map_components component_2="V_PFK" component_1="G6P"/>
<map_variables variable_2="G6P" variable_1="G6P"/>
<map_variables variable_2="V_PFK" variable_1="V_PFK"/>
</connection>
<connection>
<map_components component_2="V_G6PDH" component_1="G6P"/>
<map_variables variable_2="G6P" variable_1="G6P"/>
<map_variables variable_2="V_G6PDH" variable_1="V_G6PDH"/>
</connection>
<connection>
<map_components component_2="V_PFK" component_1="FDP"/>
<map_variables variable_2="V_PFK" variable_1="V_PFK"/>
</connection>
<connection>
<map_components component_2="V_ALD" component_1="FDP"/>
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