Location: Biophysical Characteristics of the Pig Kidney Na/Glucose Cotransporter SGLT2 Reveal a Common Mechanism for SGLT1 and SGLT2, Mackenzie, Loo, Panayotova-Heiermann and Wright, 1996 @ 2f750bf5ebed / model / MacKenzie_1996.rdf

Author:
AnandR <a.rampadarath@auckland.ac.nz>
Date:
2019-09-11 12:10:19+12:00
Desc:
added .omex files
Permanent Source URI:
http://models.cellml.org/workspace/598/rawfile/2f750bf5ebed3a930bd535e0fb2ac4c3214b42d1/model/MacKenzie_1996.rdf
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<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
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    <dcterms:description>Rate constant for release of glucose from internal CNaS</dcterms:description>
  </rdf:Description>
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  </rdf:Description>
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    <dcterms:description>Rate constant for release of Sodium from internal Na bound cotransporter</dcterms:description>
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    <dcterms:description>Rate for external CNa to internal CNa reaction step.</dcterms:description>
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    <dcterms:description>Rate for external CNa to internal CNa reaction step.</dcterms:description>
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    <semsim:modelName>mackenzie_1996</semsim:modelName>
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    <semsim:hasCellMLdocumentation>&lt;documentation xmlns="http://cellml.org/tmp-documentation"&gt;&#xD;
  &lt;article&gt;&#xD;
    &lt;articleinfo&gt;&#xD;
      &lt;title&gt;Biophysical Characteristics of the Pig Kidney Na/Glucose Cotransporter SGLT2 Reveal a Common Mechanism for SGLT1 and SGLT2&lt;/title&gt;&#xD;
      &lt;author&gt;&#xD;
        &lt;firstname&gt;Jonna&lt;/firstname&gt;&#xD;
        &lt;surname&gt;Terkildsen&lt;/surname&gt;&#xD;
        &lt;affiliation&gt;&#xD;
          &lt;shortaffil&gt;Auckland Bioengineering Institute, University of Auckland&lt;/shortaffil&gt;&#xD;
        &lt;/affiliation&gt;&#xD;
      &lt;/author&gt;&#xD;
    &lt;/articleinfo&gt;&#xD;
    &lt;sect1 id="sec_status"&gt;&#xD;
      &lt;title&gt;Model Status&lt;/title&gt;&#xD;
      &lt;para&gt;This CellML model has been curated, the units are consistent and the model runs in COR and PCEnv. This model recreates the published results.&lt;/para&gt;&#xD;
    &lt;/sect1&gt;&#xD;
    &lt;sect1 id="sec_structure"&gt;&#xD;
      &lt;title&gt;Model Structure&lt;/title&gt;&#xD;
      &lt;para&gt;Abstract: The Na-dependent, low affinity glucose transporter SGLT2 cloned from pig kidney is 76% identical (at the amino acid level) to its high affinity homologue SGLT1. Using two-microelectrode voltage clamp, we have characterized the presteady-state and steady-state kinetics of SGLT2 expressed in Xenopus oocytes. The kinetic properties of the steady-state sugar-evoked currents as a function of external Na and a-methyl-D-glucopyranoside (aMG) concentrations were consistent with an ordered, simultaneous transport model in which Na binds first. Na binding was voltage-dependent and saturated with hyperpolarizing voltages. Phlorizin was a potent inhibitor of the sugar-evoked currents (Ki ~10 mM) and blocked an inward Na current in the absence of sugar. SGLT2 exhibited Na-dependent presteadystate currents with time constants 3-7 ms. Charge movements were described by Boltzmann relations with apparent valence ~1 and maximal charge transfer ~11 nC, and were reduced by the addition of sugar or phlorizin. The differences between SGLT1 and SGLT2 were that (i) the apparent affinity constant (K0.5) for aMG (~3 mM) was an order of magnitude higher for SGLT2; (ii) SGLT2 excluded galactose, suggesting discrete sugar binding; (iii) K0.5 for Na was lower in SGLT2; and (iv) the Hill coefficient for Na was 1 for SGLT2 but 2 for SGLT1. Simulations of the six-state kinetic model previously proposed for SGLT1 indicated that many of the kinetic properties observed in SGLT2 are expected by simply reducing the Na/glucose coupling from 2 to 1.&lt;/para&gt;&#xD;
      &lt;para&gt;The original paper reference is cited below:&lt;/para&gt;&#xD;
      &lt;para&gt;&#xD;
        Biophysical Characteristics of the Pig Kidney Na/Glucose Cotransporter SGLT2 Reveal a Common Mechanism for SGLT1 and SGLT2, M. Mackenzie, D.D.F. Loo, M. Panayotova-Heiermann, and E. M. Wright, 1996,&#xD;
        &lt;emphasis&gt;Journal of Biological Chemistry&lt;/emphasis&gt;&#xD;
        , 271, 32678-32683.&#xD;
        &lt;ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&amp;amp;cmd=Retrieve&amp;amp;dopt=AbstractPlus&amp;amp;list_uids=8955098&amp;amp;query_hl=1&amp;amp;itool=pubmed_docsum"&gt;PubMed ID: 8955098&lt;/ulink&gt;&#xD;
      &lt;/para&gt;&#xD;
      &lt;informalfigure float="0" id="fig_reaction_diagram"&gt;&#xD;
        &lt;mediaobject&gt;&#xD;
          &lt;imageobject&gt;&#xD;
            &lt;objectinfo&gt;&#xD;
              &lt;title&gt;model diagram&lt;/title&gt;&#xD;
            &lt;/objectinfo&gt;&#xD;
            &lt;imagedata fileref="mackenzie_1996.png" /&gt;&#xD;
          &lt;/imageobject&gt;&#xD;
        &lt;/mediaobject&gt;&#xD;
        &lt;caption&gt;Schematic diagram of the Mackenzie et al 1996 SGLT2 model. C' represents the external-facing carrier. C'' represents the internal-facing carrier.&lt;/caption&gt;&#xD;
      &lt;/informalfigure&gt;&#xD;
    &lt;/sect1&gt;&#xD;
  &lt;/article&gt;&#xD;
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  <rdf:Description rdf:about="./MacKenzie_1996.cellml#parameters.k0_61">
    <dcterms:description>Rate constant for internal unbound cotransporter binding site to external unbound cotransporter binding site reaction step</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#entity_9">
    <bqbiol:isPartOf rdf:resource="./MacKenzie_1996.cellml#entity_10"/>
    <bqbiol:is rdf:resource="http://identifiers.org/chebi/CHEBI:29101"/>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#NBC_current.F">
    <dcterms:description>Faraday constant</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#phenomonological_constants.k_25">
    <dcterms:description>Rate for external CNa to internal CNa reaction step.</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#rate_constants.k_23">
    <dcterms:description>Rate for binding of glucose to external CNa binding site</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#rate_constants.glucose_i">
    <bqbiol:isPropertyOf rdf:resource="./MacKenzie_1996.cellml#entity_13"/>
    <bqbiol:isVersionOf rdf:resource="https://identifiers.org/opb/OPB_00340"/>
    <dcterms:description>Intracellular glucose concentration</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#kinetic_equations.C_5">
    <bqbiol:isPropertyOf rdf:resource="./MacKenzie_1996.cellml#entity_7"/>
    <bqbiol:isVersionOf rdf:resource="https://identifiers.org/opb/OPB_00425"/>
    <dcterms:description>Pre-steady state internal CNa concentration</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#king_altman_states.k_43">
    <dcterms:description>Rate for internal CNaS to external CNaS reaction step</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#rate_constants.k0_54">
    <dcterms:description>Rate constant for binding of glucose to internal CNa binding site</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#parameters.z_c">
    <dcterms:description>Empty transporter valence</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#kinetic_equations.k_43">
    <dcterms:description>Rate for internal CNaS to external CNaS reaction step</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#rate_constants.z_Na">
    <dcterms:description>Na valence</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#king_altman_states.C2">
    <dcterms:description>Steady state external Na bound cotransporter concentration</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#entity_6">
    <bqbiol:isPartOf rdf:resource="./MacKenzie_1996.cellml#entity_0"/>
    <semsim:name>External Na Bound SGLT2 Cotransporter</semsim:name>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#NBC_current.C6">
    <dcterms:description>Steady state internal unbound cotransporter concentration</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#rate_constants.alpha_p">
    <dcterms:description>Fraction of membrane electric field between bulk solution and external face Na binding site.</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#parameters.alpha_p">
    <dcterms:description>Fraction of membrane electric field between bulk solution and external face Na binding site.</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#phenomonological_constants.k_16">
    <dcterms:description>Rate for external unbound transport site to internal unbound transport site reaction step</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#NBC_current.C_1">
    <bqbiol:isPropertyOf rdf:resource="./MacKenzie_1996.cellml#entity_5"/>
    <bqbiol:isVersionOf rdf:resource="https://identifiers.org/opb/OPB_00425"/>
    <dcterms:description>Pre-steady state external unbound cotransporter concentration</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#ion_concentrations.glucose_i">
    <bqbiol:isPropertyOf rdf:resource="./MacKenzie_1996.cellml#entity_13"/>
    <bqbiol:isVersionOf rdf:resource="https://identifiers.org/opb/OPB_00340"/>
    <dcterms:description>Intracellular glucose concentration</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#kinetic_equations.k_56">
    <dcterms:description>Rate for release of Sodium from internal Na bound cotransporter</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#kinetic_equations.C_4">
    <bqbiol:isPropertyOf rdf:resource="./MacKenzie_1996.cellml#entity_4"/>
    <bqbiol:isVersionOf rdf:resource="https://identifiers.org/opb/OPB_00425"/>
    <dcterms:description>Steady state internal CNaS concentration</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#NBC_current.k_34">
    <dcterms:description>Rate for external CNaS to internal CNas reaction step</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#king_altman_states.k_54">
    <dcterms:description>Rate for binding of glucose to internal CNa binding site</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#parameters.R">
    <dcterms:description>Boltzmann constant</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#rate_constants.k0_43">
    <dcterms:description>Rate constant for internal CNaS to external CNaS reaction step</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#environment.time">
    <dcterms:description>Time - Solution Domain</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#parameters.delta">
    <dcterms:description>Fraction of the membrane field sensed by the empty binding on the carrier durring translocation.</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#kinetic_equations.k_32">
    <dcterms:description>Rate for release of glucose from external CNaS</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#entity_7">
    <bqbiol:isPartOf rdf:resource="./MacKenzie_1996.cellml#entity_0"/>
    <semsim:name>Internal Na Bound SGLT2 Cotransporter</semsim:name>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#parameters.area">
    <bqbiol:isVersionOf rdf:resource="https://identifiers.org/opb/OPB_00295"/>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#parameters.k0_16">
    <dcterms:description>Rate constant for external unbound transport site to internal unbound transport site reaction step</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#NBC_current.C5">
    <dcterms:description>Steady state internal CNa concentration</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#king_altman_states.C1">
    <bqbiol:isVersionOf rdf:resource="https://identifiers.org/opb/OPB_00425"/>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#phenomonological_constants.Khalf_gluc">
    <dcterms:description>Experimental substrate glucose concentration for half maximal current.</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#NBC_current.k_21">
    <dcterms:description>Rate for sodium ion release from external bound cotransporter.</dcterms:description>
  </rdf:Description>
  <rdf:Description rdf:about="./MacKenzie_1996.cellml#rate_constants.k_25">
    <dcterms:description>Rate for external CNa to internal CNa reaction step.</dcterms:description>
  </rdf:Description>
</rdf:RDF>