<?xml version="1.0" encoding="UTF-8"?>
<!--
   DOQCS : http://doqcs.ncbs.res.in/ 
   Accession Name = PLCbeta1 
   Accession Number = 13 
   Transcriber = Sridhar Hariharaputran, NCBS 
   Developer = Sridhar Hariharputran, NCBS 
   Species = Bovine; Mammalian 
   Tissue = Brain - Neuronal; expressed in E.coli 
   Cell Compartment = Cell Membrane 
   Notes =  This is a model of PLCbeta1 in the bovine brain membranes as stimulated by Ca, Gq and PA. <br>The primary data sources are <a href= http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10869178 >Irene Litosch Biochemistry (2000) 39(26):7736-43</a>, <br><a href= http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1351294 >Sternweis PC et al. Philos Trans R Soc Lond B Biol Sci. (1992) 336(1276):35-41</a> and <br><a href= http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1846707 >Smrcka AV et al. Science (1991) 251(4995):804-7</a>. 
 
    Note: All the concentrations are in micro Mole (uM)
-->
<sbml xmlns="http://www.sbml.org/sbml/level2" level="2" version="1">
  <model id="testid" name="PLCbeta1putran">
    <notes>
      <body xmlns="http://www.w3.org/1999/xhtml">
	     This is a model of PLCbeta1 in the bovine brain membranes as stimulated by Ca, Gq and PA. &lt;br"""&gt;The primary data sources are &lt;a href = "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=pubmed&amp;dopt=Abstract&amp;list_uids=10869178&gt;Irene Litosch Biochemistry (2000) 39(26):7736-43&lt;/a&gt;, &lt;br&gt;&lt;a href = "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=pubmed&amp;dopt=Abstract&amp;list_uids=1351294&gt;Sternweis PC et al. Philos Trans R Soc Lond B Biol Sci. (1992) 336(1276):35-41&lt;/a&gt; and &lt;br&gt;&lt;a href = "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=pubmed&amp;dopt=Abstract&amp;list_uids=1846707&gt;Smrcka AV et al. Science 251(4995):804-7&lt;/a&gt;.
          </body>
    </notes>
    <annotation xmlns:doqcs="http://www.doqcs.ncbs.res.in">
      <doqcs:timestamp>Thu Nov  9 14:53:14 2006</doqcs:timestamp>
      <doqcs:accesstype>pathway</doqcs:accesstype>
      <doqcs:transcriber>Sridhar Hariharaputran, NCBS</doqcs:transcriber>
      <doqcs:developer>Sridhar Hariharputran, NCBS</doqcs:developer>
      <doqcs:species>Bovine ; Mammalian</doqcs:species>
      <doqcs:tissue>Brain - Neuronal; expressed in E.coli</doqcs:tissue>
      <doqcs:cellcompartment>Cell Membrane</doqcs:cellcompartment>
      <doqcs:methodology>Qualitative</doqcs:methodology>
      <doqcs:model_implementation>Exact GENESIS implementation</doqcs:model_implementation>
      <doqcs:model_validation>Approximates original data </doqcs:model_validation>
    </annotation>
    <listOfUnitDefinitions>
     <unitDefinition id="uM1">
      <listOfUnits>
       <unit kind="litre" exponent="-1" multiplier="1" offset="0"/>
       <unit kind="mole" scale="-6" multiplier="1" offset="0"/>
      </listOfUnits>
     </unitDefinition>
     <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="PLCbeta_slash_PLCbeta" compartment="geometry" initialConcentration="0.12"/>
      <species id="PLCbeta_slash_Ca_dot_PLCbeta" compartment="geometry" initialConcentration="0"/>
      <species id="PLCbeta_slash_PA_dot_Ca_dot_PLCbeta" compartment="geometry" initialConcentration="0"/>
      <species id="PLCbeta_slash_Gq" compartment="geometry" initialConcentration="0"/>
      <species id="PLCbeta_slash_PA" compartment="geometry" initialConcentration="1"/>
      <species id="PLCbeta_slash_DAG" compartment="geometry" initialConcentration="0"/>
      <species id="PLCbeta_slash_IP3" compartment="geometry" initialConcentration="0"/>
      <species id="PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta" compartment="geometry" initialConcentration="0"/>
      <species id="PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_cplx" compartment="geometry" initialConcentration="0"/>
      <species id="PLCbeta_slash_PIP2" compartment="geometry" initialConcentration="25" boundaryCondition="true" constant="true">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
	     12 Jul 2001 The PIP2 concentration is fixed to 25uM and is buffered to maitain the same level of substrate. I. Liotsch, Biochem., 2000, 7736-7743.
          </body>
        </notes>
      </species>
      <species id="PLCbeta_slash_Ca" compartment="geometry" initialConcentration="0.09" boundaryCondition="true" constant="true">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
	     21 Jul 2001 Concn varies betwn 0.001 to 10 uM. The Concentration of Ca is obtained from I. Litosch, Biochem., 2000, 39,7736-7743. The concentration of Ca is buffered to different levels and rate of binding of enzyme is noted.But here it is set to 0.09uM which is the basal level Calcium.
          </body>
        </notes>
      </species>
    </listOfSpecies>
    <listOfReactions>
      <reaction id="PLCbeta_slash_Gq_minus_bind_minus_Ca_dot_PLCbeta">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
	     6 Nov 2001 The Kf and Kb values were fixed according to the response curves obtained from I. Litosch, Biochem., 2000, 7736-7743.
          </body>
        </notes>
        <listOfReactants>
          <speciesReference species="PLCbeta_slash_Gq"/>
          <speciesReference species="PLCbeta_slash_Ca_dot_PLCbeta"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta"/>
        </listOfProducts>
        <kineticLaw>
          <notes>
            <body xmlns="http://www.w3.org/1999/xhtml">
		kf*PLCbeta_slash_Gq*PLCbeta_slash_Ca_dot_PLCbeta-kb*PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta
	    </body>
          </notes>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <minus/>
              <apply>
                <times/>
                <ci> kf </ci>
                <ci> PLCbeta_slash_Gq </ci>
                <ci> PLCbeta_slash_Ca_dot_PLCbeta </ci>
              </apply>
              <apply>
                <times/>
                <ci> kb </ci>
                <ci> PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="kf" value="8.33333333333333e-17" units="vol_uMINVsecINV"/>
            <parameter id="kb" value="1.66666666666667e-18" units="vol_secINV"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
      <reaction id="PLCbeta_slash_Ca_bind_PLCbeta">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
	     6 Nov 2001 The Kf and Kb values were fixed according to the dose response curves obtained from I.Litosch, Biochem., 2000, 7736-7743.
          </body>
        </notes>
        <listOfReactants>
          <speciesReference species="PLCbeta_slash_Ca"/>
          <speciesReference species="PLCbeta_slash_PLCbeta"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="PLCbeta_slash_Ca_dot_PLCbeta"/>
        </listOfProducts>
        <kineticLaw>
          <notes>
            <body xmlns="http://www.w3.org/1999/xhtml">
		kf*PLCbeta_slash_Ca*PLCbeta_slash_PLCbeta-kb*PLCbeta_slash_Ca_dot_PLCbeta
	    </body>
          </notes>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <minus/>
              <apply>
                <times/>
                <ci> kf </ci>
                <ci> PLCbeta_slash_Ca </ci>
                <ci> PLCbeta_slash_PLCbeta </ci>
              </apply>
              <apply>
                <times/>
                <ci> kb </ci>
                <ci> PLCbeta_slash_Ca_dot_PLCbeta </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="kf" value="1.66666666666667e-18" units="vol_uMINVsecINV"/>
            <parameter id="kb" value="1.66666666666667e-18" units="vol_secINV"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
      <reaction id="PLCbeta_slash_PA_minus_bind_minus_Ca_dot_PLCbeta">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
	     6 Nov 2001 The Kf and Kb values were fixed according to the dose response curves obtained from I. Litosch, Biochem., 2000, 7736-7743.
          </body>
        </notes>
        <listOfReactants>
          <speciesReference species="PLCbeta_slash_PA"/>
          <speciesReference species="PLCbeta_slash_Ca_dot_PLCbeta"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="PLCbeta_slash_PA_dot_Ca_dot_PLCbeta"/>
        </listOfProducts>
        <kineticLaw>
          <notes>
            <body xmlns="http://www.w3.org/1999/xhtml">
		kf*PLCbeta_slash_PA*PLCbeta_slash_Ca_dot_PLCbeta-kb*PLCbeta_slash_PA_dot_Ca_dot_PLCbeta
	    </body>
          </notes>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <minus/>
              <apply>
                <times/>
                <ci> kf </ci>
                <ci> PLCbeta_slash_PA </ci>
                <ci> PLCbeta_slash_Ca_dot_PLCbeta </ci>
              </apply>
              <apply>
                <times/>
                <ci> kb </ci>
                <ci> PLCbeta_slash_PA_dot_Ca_dot_PLCbeta </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="kf" value="1.66666666666667e-18" units="vol_uMINVsecINV"/>
            <parameter id="kb" value="1.33333333333333e-17" units="vol_secINV"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
      <reaction id="PLCbeta_slash_Basal">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
	     6 Nov 2001 The basal reaction rates are fixed according to the respomse curves obtained from I. Litosch, Biochem.,2000, 7736-7743.
          </body>
        </notes>
        <listOfReactants>
          <speciesReference species="PLCbeta_slash_PIP2"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="PLCbeta_slash_DAG"/>
          <speciesReference species="PLCbeta_slash_IP3"/>
        </listOfProducts>
        <kineticLaw>
          <notes>
            <body xmlns="http://www.w3.org/1999/xhtml">
		kf*PLCbeta_slash_PIP2-kb*PLCbeta_slash_DAG*PLCbeta_slash_IP3
	    </body>
          </notes>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <minus/>
              <apply>
                <times/>
                <ci> kf </ci>
                <ci> PLCbeta_slash_PIP2 </ci>
              </apply>
              <apply>
                <times/>
                <ci> kb </ci>
                <ci> PLCbeta_slash_DAG </ci>
                <ci> PLCbeta_slash_IP3 </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="kf" value="1.5e-20" units="vol_secINV"/>
            <parameter id="kb" value="0" units="vol_uMINVsecINV"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
      <reaction id="PLCbeta_slash_Ca_dot_PLCbeta_slash_Ca_dot_PLCbeta" reversible="false">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
	     3 Nov 2001 Sternweis et al Phil Trans Soc R Lond B Biol Sci 1992 Apr 29; 336(1276);35-41;discussion 41-2. The Km and Vmax values according to Sternweis et al. The Km is fixed to 10uM since there is absence of Gq and so is the Vmax values which is fixed at 7uM since the Km obtained varies between 5 and 20uM and Vmax between 7 and 23umol/min/mg depending on the presence and absence Gq.
          </body>
        </notes>
        <listOfReactants>
          <speciesReference species="PLCbeta_slash_PIP2"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="PLCbeta_slash_DAG"/>
          <speciesReference species="PLCbeta_slash_IP3"/>
        </listOfProducts>
        <listOfModifiers>
          <modifierSpeciesReference species="PLCbeta_slash_Ca_dot_PLCbeta"/>
        </listOfModifiers>
        <kineticLaw>
          <notes>
            <body xmlns="http://www.w3.org/1999/xhtml">
		kcat*PLCbeta_slash_Ca_dot_PLCbeta*PLCbeta_slash_PIP2/(Km+PLCbeta_slash_PIP2)
	    </body>
          </notes>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <divide/>
              <apply>
                <times/>
                <ci> kcat </ci>
                <ci> PLCbeta_slash_Ca_dot_PLCbeta </ci>
                <ci> PLCbeta_slash_PIP2 </ci>
              </apply>
              <apply>
                <plus/>
                <ci> Km </ci>
                <ci> PLCbeta_slash_PIP2 </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="kcat" value="1.16666666666667e-17" units="vol_secINV"/>
            <parameter id="Km" value="10" units="uM1"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
      <reaction id="PLCbeta_slash_PA_dot_Ca_dot_PLCbeta_slash_PA_dot_Ca_dot_PLCbeta" reversible="false">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
	     3 Nov 2001 The Km and Vmax were fixed relatively to the Km and Vmax values of Ca.PLCbeta and Gq.Ca.PLCbeta which were obtained from the works of Sternweis et al and Smrcka et al where the Km varied between 5 and 20uM and Vmax between 7 and 23 umol/min/mg depending on the presence and absence Gq.
          </body>
        </notes>
        <listOfReactants>
          <speciesReference species="PLCbeta_slash_PIP2"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="PLCbeta_slash_DAG"/>
          <speciesReference species="PLCbeta_slash_IP3"/>
        </listOfProducts>
        <listOfModifiers>
          <modifierSpeciesReference species="PLCbeta_slash_PA_dot_Ca_dot_PLCbeta"/>
        </listOfModifiers>
        <kineticLaw>
          <notes>
            <body xmlns="http://www.w3.org/1999/xhtml">
		kcat*PLCbeta_slash_PA_dot_Ca_dot_PLCbeta*PLCbeta_slash_PIP2/(Km+PLCbeta_slash_PIP2)
	    </body>
          </notes>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <divide/>
              <apply>
                <times/>
                <ci> kcat </ci>
                <ci> PLCbeta_slash_PA_dot_Ca_dot_PLCbeta </ci>
                <ci> PLCbeta_slash_PIP2 </ci>
              </apply>
              <apply>
                <plus/>
                <ci> Km </ci>
                <ci> PLCbeta_slash_PIP2 </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="kcat" value="6.33333333333333e-17" units="vol_secINV"/>
            <parameter id="Km" value="10" units="uM1"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
      <reaction id="PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_1">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
	     3 Nov 2001 The Km and Vmax values are fixed accordingly from Sternweis et al Phil Trans R Soc Lond B Bio Sci 1992 Apr 29;336(1276):35-41;discussion 41-2 and Smrcka et al Science 251 804-807 1991 where Km varied between 5 and 20uM and Vmax between 7 and 23 umol/min/mg depending on the presenece and absence Gq.
          </body>
        </notes>
        <listOfReactants>
          <speciesReference species="PLCbeta_slash_PIP2"/>
          <speciesReference species="PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_cplx"/>
        </listOfProducts>
        <kineticLaw>
          <notes>
            <body xmlns="http://www.w3.org/1999/xhtml">
		k1*PLCbeta_slash_PIP2*PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta-k2*PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_cplx
	    </body>
          </notes>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <minus/>
              <apply>
                <times/>
                <ci> k1 </ci>
                <ci> PLCbeta_slash_PIP2 </ci>
                <ci> PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta </ci>
              </apply>
              <apply>
                <times/>
                <ci> k2 </ci>
                <ci> PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_cplx </ci>
              </apply>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="k1" value="1.91666666666667e-17" units="vol_uMINVsecINV"/>
            <parameter id="k2" value="1.53333333333333e-16" units="vol_secINV"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
      <reaction id="PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_2" reversible="false">
        <listOfReactants>
          <speciesReference species="PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_cplx"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference species="PLCbeta_slash_DAG"/>
          <speciesReference species="PLCbeta_slash_IP3"/>
          <speciesReference species="PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta"/>
        </listOfProducts>
        <kineticLaw>
          <notes>
            <body xmlns="http://www.w3.org/1999/xhtml">
		k3*PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_cplx
	    </body>
          </notes>
          <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
              <times/>
              <ci> k3 </ci>
              <ci> PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_slash_Gq_dot_Ca_dot_PLCbeta_cplx </ci>
            </apply>
          </math>
          <listOfParameters>
            <parameter id="k3" value="3.83333333333333e-17" units="vol_secINV"/>
          </listOfParameters>
        </kineticLaw>
      </reaction>
    </listOfReactions>
  </model>
</sbml>
