<?xml version="1.0" encoding="UTF-8"?>
<!--
   DOQCS : http://doqcs.ncbs.res.in/ 
   Accession Name = NOHArginine 
   Accession Number = 75 
   Transcriber = Sharat J. Vayttaden and Prasoon Agarwal, NCBS 
   Developer = Abu-Soud HM, Wang J, Rousseau DL, and Stuehr DJ 
   Species = human 
   Tissue = Kidney cell expressing the rat brain nNOS 
   Cell Compartment = Cytosol 
   Notes = This model is taken from the <a href=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10493814&query_hl=10&itool=pubmed_docsum>Abu-Soud HM et al. Biochemistry. 1999 Sep 21;38(38):12446-51</a>. This model shows kinetic binding of NOHArginine to neuronal nitric oxide synthase. <br>Model shows the substrate (NOH-Arginine) binding to nNOS in a two-step reversible fashion. First there is rapid binding equilibrium between Im-nNOS and NOH-Arginine to form an intermediate that contains bound imidazole and NOH-arginine. This is followed by a slower conformational change in the Im-enzyme-substrate complex that is associated with release of bound imidazole and generation of a modified enzyme-substrate complex which is detected due to spectral change. Rates approximated based on data in Table 2. The rates for first reaction are not exact since only Kd known and appropriate graphs do not exist for matching the kinetic profile.
 
 
    Note: All the concentrations are in micro Mole (uM)
-->
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  <model id="testid" name="NOHArginine">
    <notes>
      <body xmlns="http://www.w3.org/1999/xhtml">
	     This model is taken from the &lt;a href = "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&amp;cmd=Retrieve&amp;dopt=AbstractPlus&amp;list_uids=10493814&amp;query_hl=10&amp;itool=pubmed_docsum"&gt;Abu-Soud HM et al. Biochemistry. 1999 Sep 21;38(38):12446-51&lt;/a&gt;. This model shows kinetic binding of NOHArginine to neuronal nitric oxide synthase. Model shows the substrate (NOH-Arginine) binding to nNOS in a two-step reversible fashion. First there is rapid binding equilibrium between Im-nNOS and NOH-Arginine to form an intermediate that contains bound imidazole and NOH-arginine. This is followed by a slower conformational change in the Im-enzyme-substrate complex that is associated with release of bound imidazole and generation of a modified enzyme-substrate complex which is detected due to spectral change. Rates approximated based on data in Table 2. The rates for first reaction are not exact since only Kd known and appropriate graphs do not exist for matching the profile.
          </body>
    </notes>
    <annotation xmlns:doqcs="http://www.doqcs.ncbs.res.in">
      <doqcs:timestamp>Wed Oct 18 16:58:47 2006</doqcs:timestamp>
      <doqcs:accesstype>pathway</doqcs:accesstype>
      <doqcs:transcriber>Sharat J. Vayttaden and Prasoon Agarwal, NCBS</doqcs:transcriber>
      <doqcs:developer>Abu-Soud HM, Wang J, Rousseau DL, and Stuehr DJ</doqcs:developer>
      <doqcs:species>Human</doqcs:species>
      <doqcs:tissue>Kidney cell expressing the rat brain nNOS</doqcs:tissue>
      <doqcs:cellcompartment>Cytosol</doqcs:cellcompartment>
      <doqcs:methodology>Quantitative match to experiments</doqcs:methodology>
      <doqcs:model_implementation>Exact GENESIS implementation</doqcs:model_implementation>
      <doqcs:model_validation>Approximates original data </doqcs:model_validation>
    </annotation>
    <listOfUnitDefinitions>
     <unitDefinition id="vol_secINV">
      <listOfUnits>
       <unit kind="litre" multiplier="1" offset="0"/>
       <unit kind="second" exponent="-1" multiplier="1" offset="0"/>
      </listOfUnits>
     </unitDefinition>
     <unitDefinition id="vol_uMINVsecINV">
      <listOfUnits>
       <unit kind="litre" exponent="2" multiplier="1" offset="0"/>
       <unit kind="mole" exponent="-1" scale="-6" multiplier="1" offset="0"/>
       <unit kind="second" exponent="-1" multiplier="1" offset="0"/>
      </listOfUnits>
     </unitDefinition>
     <unitDefinition id="substance">
      <listOfUnits>
       <unit kind="mole" scale="-6" multiplier="1" offset="0"/>
      </listOfUnits>
     </unitDefinition>
    </listOfUnitDefinitions>
    <listOfCompartments>
      <compartment id="default_compartment" size="1e-18"/>
      <compartment id="geometry" size="1.6667e-18"/>
    </listOfCompartments>
    <listOfSpecies>
      <species id="Im_minus_nNOS" compartment="geometry" initialConcentration="1"/>
      <species id="Imidazole" compartment="geometry" initialConcentration="0"/>
      <species id="NOH_minus_Arginine" compartment="geometry" initialConcentration="6000"/>
      <species id="Im_minus_nNOS_minus_NOH_minus_Arginine" compartment="geometry" initialConcentration="0"/>
      <species id="nNOS_minus_NOH_minus_Arginine" compartment="geometry" initialConcentration="0"/>
    </listOfSpecies>
    <listOfReactions>
      <reaction id="Imidazole_release">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
	     Release of Imidazole from complex of NOH-Arginine and Imidazole bound rat brain neuronal Nitric Oxide Synthase. Abu-Soud HM et al. Biochemistry. 1999 21;38(38):12446-51.
          </body>
        </notes>
        <listOfReactants>
          <speciesReference species="Im_minus_nNOS_minus_NOH_minus_Arginine"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="nNOS_minus_NOH_minus_Arginine"/>
          <speciesReference species="Imidazole"/>
        </listOfProducts>
        <kineticLaw>
          <notes>
            <body xmlns="http://www.w3.org/1999/xhtml">
		kf*Im_minus_nNOS_minus_NOH_minus_Arginine-kb*nNOS_minus_NOH_minus_Arginine*Imidazole
	    </body>
          </notes>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <minus/>
              <apply>
                <times/>
                <ci> kf </ci>
                <ci> Im_minus_nNOS_minus_NOH_minus_Arginine </ci>
              </apply>
              <apply>
                <times/>
                <ci> kb </ci>
                <ci> nNOS_minus_NOH_minus_Arginine </ci>
                <ci> Imidazole </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="kf" value="9.5e-17" units="vol_secINV"/>
            <parameter id="kb" value="1.16666666666667e-19" units="vol_uMINVsecINV"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
      <reaction id="NOH_minus_Arginine_binding">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
	     Binding of NOH-Arginine to Imidazole bound rat brain neuronal Nitric Oxide Synthase. Only Kd is known, Kf and Kb need to be approximated accordingly to match kinetic profiles. Due to lack of appropriate graphs the choice of Kf and Kb here is arbitrary and matches only the Kd. Kd = 2.7mM = 2700uM Abu-Soud HM et al. Biochemistry. 1999 21;38(38):12446-51.
          </body>
        </notes>
        <listOfReactants>
          <speciesReference species="NOH_minus_Arginine"/>
          <speciesReference species="Im_minus_nNOS"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="Im_minus_nNOS_minus_NOH_minus_Arginine"/>
        </listOfProducts>
        <kineticLaw>
          <notes>
            <body xmlns="http://www.w3.org/1999/xhtml">
		kf*NOH_minus_Arginine*Im_minus_nNOS-kb*Im_minus_nNOS_minus_NOH_minus_Arginine
	    </body>
          </notes>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <minus/>
              <apply>
                <times/>
                <ci> kf </ci>
                <ci> NOH_minus_Arginine </ci>
                <ci> Im_minus_nNOS </ci>
              </apply>
              <apply>
                <times/>
                <ci> kb </ci>
                <ci> Im_minus_nNOS_minus_NOH_minus_Arginine </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="kf" value="4.16666666666667e-17" units="vol_uMINVsecINV"/>
            <parameter id="kb" value="1.125e-13" units="vol_secINV"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
    </listOfReactions>
  </model>
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