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Copy pathRxn_CaPKA_I1PP1.xml
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Rxn_CaPKA_I1PP1.xml
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<ReactionScheme>
<!-- You can specify the units of the diffusion constant. If they are not
specified they are assumed to be micron^2/second, (microns written "mu" here).
It should understand microns, mm, and m for distances and seconds and ms for times. -->
<Specie name="Epac1" id="Epac1" kdiff="10" kdiffunit="mu2/s"/>
<Specie name="Epac1cAMP" id="Epac1cAMP" kdiff="10" kdiffunit="mu2/s"/>
<Specie name="L" id="L" kdiff="111.3" kdiffunit="mu2/s"/>
<Specie name="LOut" id="LOut" kdiff="111.3" kdiffunit="mu2/s"/>
<Specie name="cAMP" id="cAMP" kdiff="86.4" kdiffunit="mu2/s"/>
<Specie name="ATP" id="ATP" kdiff="74.7" kdiffunit="mu2/s"/>
<Specie name="AMP" id="AMP" kdiff="85.5" kdiffunit="mu2/s"/>
<Specie name="R" id="R" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Gs" id="Gs" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="GsR" id="GsR" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="LR" id="LR" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="LRGs" id="LRGs" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKAcLRGs" id="PKAcLRGs" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pLRGs" id="pLRGs" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="GasGTP" id="GasGTP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="GasGDP" id="GasGDP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Gbg" id="Gbg" kdiff="0" kdiffunit="mu2/s"/>
<!-- calcium stuff -->
<Specie name="Ca" id="Ca" kdiff="174.3" kdiffunit="mu2/s"/>
<Specie name="Calbin" id="Calbin" kdiff="9.3" kdiffunit="mu2/s"/>
<Specie name="CalbinC" id="CalbinC" kdiff="9.3" kdiffunit="mu2/s"/>
<!-- Cam and PP2B-->
<Specie name="Cam" id="Cam" kdiff="11" kdiffunit="mu2/s"/>
<Specie name="CamCa2C" id="CamCa2C" kdiff="11" kdiffunit="mu2/s"/>
<Specie name="CamCa2N" id="CamCa2N" kdiff="11" kdiffunit="mu2/s"/>
<Specie name="CamCa4" id="CamCa4" kdiff="11" kdiffunit="mu2/s"/>
<Specie name="PP2B" id="PP2B" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PP2BCam" id="PP2BCam" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PP2BCamCa2C" id="PP2BCamCa2C" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PP2BCamCa2N" id="PP2BCamCa2N" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PP2BCamCa4" id="PP2BCamCa4" kdiff="0" kdiffunit="mu2/s"/>
<!-- AC, PKA -->
<Specie name="AC1" id="AC1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC1GasGTP" id="AC1GasGTP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC1GasCamCa4" id="AC1GasCamCa4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC1GasCamCa4ATP" id="AC1GasCamCa4ATP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC1CamCa4" id="AC1CamCa4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC1CamCa4ATP" id="AC1CamCa4ATP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC5" id="AC5" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC5Gas" id="AC5Gas" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC5GasATP" id="AC5GasATP" kdiff="0" kdiffunit="mu2/s"/>
<!-- PKA -->
<Specie name="PKA" id="PKA" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKAcAMP2" id="PKAcAMP2" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKAcAMP4" id="PKAcAMP4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKAc" id="PKAc" kdiff="0.836" kdiffunit="mu2/s"/>
<Specie name="PKAr" id="PKAr" kdiff="0" kdiffunit="mu2/s"/>
<!-- PDE4 only -->
<Specie name="PDE4" id="PDE4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PDE4cAMP" id="PDE4cAMP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKAcPDE4" id="PKAcPDE4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pPDE4" id="pPDE4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pPDE4cAMP" id="pPDE4cAMP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pPDE4PP1" id="pPDE4PP1" kdiff="0" kdiffunit="mu2/s"/>
<!-- non-specific phosphoprotein X -->
<Specie name="X" id="X" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKAcX" id="PKAcX" kdiff="0" kdiffunit="mu2/s" />
<Specie name="pX" id="pX" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pXPP1" id="pXPP1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="I1" id="I1" kdiff="10.6" kdiffunit="mu2/s"/>
<Specie name="I1PKAc" id="I1PKAc" kdiff="10.6" kdiffunit="mu2/s"/>
<Specie name="Ip35" id="Ip35" kdiff="10.6" kdiffunit="mu2/s"/>
<Specie name="PP1" id="PP1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Ip35PP1" id="Ip35PP1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Ip35PP1PP2BCamCa4" id="Ip35PP1PP2BCaMCa4" kdiff="0" kdiffunit="mu2/s"/>
<!-- ###################### Reactions, parameters ##########################-->
<!-- vii: Ca Buffer Ca + Calbindin <-> calbinC SAME-->
<Reaction name = "Ca_buffer" id="Ca_Buffer">
<Reactant specieID="Ca"/>
<Reactant specieID="Calbin"/>
<Product specieID="CalbinC"/>
<forwardRate>0.028e-3</forwardRate>
<reverseRate>19.6</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--1A) Cam + 2Ca <-> CamCa2C GQ RXN FILE, C or N can bind first-->
<Reaction name = "CamC_bind" id="CamC_bind">
<Reactant specieID="Cam"/>
<Reactant specieID="Ca" n="2"/>
<Product specieID="CamCa2C"/>
<forwardRate>6e-6</forwardRate>
<reverseRate>9.1e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--2A) CamCa2C + 2Ca <-> CamCa4 GQ RXN FILE, C or N can bind first-->
<Reaction name = "CamCa2C_bind" id="CamCa2C_bind">
<Reactant specieID="CamCa2C"/>
<Reactant specieID="Ca" n="2"/>
<Product specieID="CamCa4"/>
<forwardRate>0.1e-3</forwardRate>
<reverseRate>1000e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--1B) Cam + 2Ca <-> CamCa2N GQ RXN FILE, C or N can bind first-->
<Reaction name = "CamN_bind" id="CamN_bind">
<Reactant specieID="Cam"/>
<Reactant specieID="Ca" n="2"/>
<Product specieID="CamCa2N"/>
<forwardRate>0.1e-3</forwardRate>
<reverseRate>1000e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--2B) CamCa2N + 2Ca <-> CamCa4 GQ RXN FILE, C or N can bind first-->
<Reaction name = "CamCa2N_bind" id="CamCa2N_bind">
<Reactant specieID="CamCa2N"/>
<Reactant specieID="Ca" n="2"/>
<Product specieID="CamCa4"/>
<forwardRate>6e-6</forwardRate>
<reverseRate>9.1e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- L Buffer- L <-> LOut -->
<!--
<Reaction name = "L_buffer" id="L_Buffer">
<Reactant specieID="L"/>
<Product specieID="LOut"/>
<forwardRate>2e-3</forwardRate>
<reverseRate>2e-8</reverseRate>
<Q10>0.2</Q10>
</Reaction>
-->
<!-- 1) L + R <-> LR -->
<Reaction name = "LR_bind" id="LR_bind">
<Reactant specieID="L"/>
<Reactant specieID="R"/>
<Product specieID="LR"/>
<forwardRate>0.005555e-3</forwardRate>
<reverseRate>5e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- 2) LR + Gs <-> LRGs -->
<Reaction name = "LRGs_bind" id="LRGs_bind">
<Reactant specieID="LR"/>
<Reactant specieID="Gs"/>
<Product specieID="LRGs"/>
<forwardRate>0.0006e-3</forwardRate>
<reverseRate>0.001e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- 3) Gs + R <-> GsR -->
<Reaction name = "GsR_bind" id="GsR_bind">
<Reactant specieID="Gs"/>
<Reactant specieID="R"/>
<Product specieID="GsR"/>
<forwardRate>0.00004e-3</forwardRate>
<reverseRate>0.0003e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- 4) GsR + L <-> LRGs -->
<Reaction name = "GsRL_bind" id="GsRL_bind">
<Reactant specieID="GsR"/>
<Reactant specieID="L"/>
<Product specieID="LRGs"/>
<forwardRate>0.0025e-3</forwardRate>
<reverseRate>0.5e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- 5a) LRGs -> LRGbg + GasGTP -->
<Reaction name = "GasGTP_bind" id="GasGTP_bind">
<Reactant specieID="LRGs"/>
<Product specieID="LR"/>
<Product specieID="Gbg"/>
<Product specieID="GasGTP"/>
<forwardRate>2e-3</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- Above reactions are fine - thermodynamically balanced.-->
<!--*****************PKAc phosphorylation of LRGs *******************************-->
<!--1a. PKAc + LRGs -> PKAcLRGs Km=120 nM -->
<Reaction name = "LRGs phosp1" id="phospLRGs1">
<Reactant specieID="PKAc" />
<Reactant specieID="LRGs" />
<Product specieID="PKAcLRGs" />
<forwardRate> 0.00125e-03 </forwardRate>
<reverseRate> 0.16e-03 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!--2a. PKAcLRGs -> PKAc + pLRGs -->
<Reaction name = "LRGs phosp2" id="phospLRGs2">
<Reactant specieID="PKAcLRGs" />
<Product specieID="pLRGs" />
<Product specieID="PKAc" />
<forwardRate> 0.04e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!--3. pLRGs -> LRGs -->
<Reaction name = "dephosD1R" id="dphospD1R">
<Reactant specieID="pLRGs" />
<Product specieID="LRGs" />
<forwardRate> 0.003e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- 6a) GasGTP -> GasGDP -->
<Reaction name = "GasGTP_disso" id="GasGTP_disso">
<Reactant specieID="GasGTP"/>
<Product specieID="GasGDP"/>
<forwardRate>0.5e-3</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- 7a) GasGDP + Gbg -> Gs -->
<Reaction name = "Gs_form" id="Gs_form">
<Reactant specieID="GasGDP"/>
<Reactant specieID="Gbg"/>
<Product specieID="Gs"/>
<forwardRate>10e-3</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- AC part: AC1 activation through CamCa4 -->
<!-- 1a) GasGTP + AC1 <-> AC1GasGTP -->
<Reaction name = "GasGTP_AC1_reac" id="GasGTP_AC1_reac">
<Reactant specieID="GasGTP"/>
<Reactant specieID="AC1"/>
<Product specieID="AC1GasGTP"/>
<forwardRate>0.0385e-3</forwardRate>
<reverseRate>10e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<Reaction name = "AC1_GasGTP_hydrolysis" id="AC1_GasGTP_GAP">
<Reactant specieID="AC1GasGTP"/>
<Product specieID="AC1"/>
<Product specieID="GasGDP"/>
<forwardRate>1e-3</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- 1b) AC1GasGTP + CamCa4 <-> AC1GasCamCa4 -->
<Reaction name = "AC1GasGTP_CamCa4_Reac" id="AC1GasGTP_CamCa4_Reac">
<Reactant specieID="AC1GasGTP"/>
<Reactant specieID="CamCa4"/>
<Product specieID="AC1GasCamCa4"/>
<forwardRate>0.006e-3</forwardRate>
<reverseRate>0.9e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- all ATP binding slowed down 10x to avoid needing much smaller dt. -->
<!-- 1c) AC1GasCamCa4 + ATP <-> AC1GasCamCa4ATP -->
<Reaction name = "AC1GasCamCa4_ATP_Reac" id="AC1GasCamCa4_ATP_Reac">
<Reactant specieID="AC1GasCamCa4"/>
<Reactant specieID="ATP"/>
<Product specieID="AC1GasCamCa4ATP"/>
<forwardRate>0.001e-3</forwardRate>
<reverseRate>114e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- 1d) AC1GasCamATP -> AC1GasCam + cAMP -->
<Reaction name = "AC1GasCamCa4ATP_diss" id="AC1GasCamCa4ATP_diss">
<Reactant specieID="AC1GasCamCa4ATP"/>
<Product specieID="cAMP"/>
<Product specieID="AC1GasCamCa4"/>
<forwardRate>28.46e-3</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- 5a) AC1 + CamCa4 <-> AC1Cam -->
<Reaction name = "AC1CamCa4_Reac" id="AC1CamCa4_Reac">
<Reactant specieID="AC1"/>
<Reactant specieID="CamCa4"/>
<Product specieID="AC1CamCa4"/>
<forwardRate>0.006e-3</forwardRate>
<reverseRate>0.9e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- 5b) AC1Cam + ATP <-> AC1CamATP -->
<Reaction name = "AC1CamCa4ATP_bind" id="AC1CamCa4ATP_bind">
<Reactant specieID="AC1CamCa4"/>
<Reactant specieID="ATP"/>
<Product specieID="AC1CamCa4ATP"/>
<forwardRate>0.001e-3</forwardRate>
<reverseRate>114e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- 5c) AC1CamATP -> AC1Cam +cAMP -->
<Reaction name = "AC1CamCa4ATP_disso" id="AC1CamCa4ATP_disso">
<Reactant specieID="AC1CamCa4ATP"/>
<Product specieID="cAMP"/>
<Product specieID="AC1CamCa4"/>
<forwardRate>2.846e-3</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--************** V. AC5 ************** -->
<!--1a. GasGTP + AC5 <-> AC5Gas(GTP) -->
<Reaction name = "GasGTP+AC5--AC5Gas reac" id="GasGTP+AC5--AC5Gas_id">
<Reactant specieID="GasGTP" />
<Reactant specieID="AC5" />
<Product specieID="AC5Gas" />
<forwardRate> 0.00037e-03 </forwardRate>
<reverseRate> 0.1e-03 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!--2a. AC5Gas(GTP) + ATP <-> AC5Gas(GTP)ATP -->
<Reaction name = "AC5Gas+ATP--AC5GasATP reac" id="AC5Gas+ATP--AC5GasATP_id">
<Reactant specieID="AC5Gas" />
<Reactant specieID="ATP" />
<Product specieID="AC5GasATP" />
<forwardRate> 0.1276e-6 </forwardRate>
<reverseRate> 0.2612e-03 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!--3a. AC5Gas(GTP)ATP <-> AC5Gas(GTP) + cAMP -->
<Reaction name = "AC5GasATP--AC5Gas+cAMP reac" id="AC5GasATP--AC5Gas+cAMP_id">
<Reactant specieID="AC5GasATP" />
<Product specieID="AC5Gas" />
<Product specieID="cAMP" />
<forwardRate> 28.46e-03 </forwardRate>
<reverseRate> 0.2592e-6 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- PKA part. 3x faster than previous based on some FRET imaging -->
<!--1) PKA + 2cAMP <-> PKAcAMP2 -->
<Reaction name = "PKA_bind" id="PKA_bind">
<Reactant specieID="PKA"/>
<Reactant specieID="cAMP" n="2"/>
<Product specieID="PKAcAMP2"/>
<forwardRate>0.261e-6</forwardRate>
<reverseRate>0.06e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--2) PKAcAMP2 + 2cAMP <-> PKAcAMP4 -->
<Reaction name = "PKAcAMP2_bind" id="PKAcAMP2_bind">
<Reactant specieID="PKAcAMP2"/>
<Reactant specieID="cAMP" n="2"/>
<Product specieID="PKAcAMP4"/>
<forwardRate>0.346e-6</forwardRate>
<reverseRate>0.6e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--11c) PKAcAMP4 <-> PKAr + 2PKAc -->
<Reaction name = "PKAcAMP4diss2" id="PKAcAMP4diss2">
<Reactant specieID="PKAcAMP4"/>
<Product specieID="PKAr"/>
<Product specieID="PKAc" n="2"/>
<forwardRate>0.048e-3</forwardRate>
<reverseRate>0.0051e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--Epac-S^H14 EC50=4.4 uM (Polito et al. Fronteirs 2013) -->
<!--1) Epac + cAMP <-> Epac_cAMP -->
<Reaction name = "PKA_bind" id="PKA_bind">
<Reactant specieID="Epac1"/>
<Reactant specieID="cAMP"/>
<Product specieID="Epac1cAMP"/>
<forwardRate>0.033e-6</forwardRate>
<reverseRate>0.1452e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- ************** PDE Part ***************** -->
<!--6) AMP -> ATP -->
<Reaction name = "ATP_regen" id="ATP_regen">
<Reactant specieID="AMP"/>
<Product specieID="ATP"/>
<forwardRate>1e-3</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- Below PDE4B/D reactions from Rodrigo:PKAc compete with I1 and PDE4B/D -->
<!-- Current affinity with PKAc to PDE4B/D too high so nothing left binding for I1-->
<!-- Andrew 10/29/10: Condensed all PDE4B/D to PDE4 -->
<!-- 07) cAMP + PDE4 <-> PDE4cAMP -->
<Reaction name = "PDE4 enzyme1" id="PDE4bind">
<Reactant specieID="PDE4" />
<Reactant specieID="cAMP" />
<Product specieID="PDE4cAMP" />
<forwardRate> 0.02166e-03 </forwardRate>
<reverseRate> 68.950e-03 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- 08) PDE4cAMP -> AMP + PDE4 -->
<Reaction name = "PDE4 actvcomp" id="PDE4cat">
<Reactant specieID="PDE4cAMP" />
<Product specieID="PDE4" />
<Product specieID="AMP" />
<forwardRate> 17.233e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- 09) PKAc + PDE4 -> PKAcPDE4 Kd=320 nM -->
<Reaction name = "PDE4 phosp1" id="phospPDE41">
<Reactant specieID="PKAc" />
<Reactant specieID="PDE4" />
<Product specieID="PKAcPDE4" />
<forwardRate> 0.214e-06 </forwardRate>
<reverseRate> 0.056e-03 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- 10) PKAcPDE4 -> PKAc + pPDE4 -->
<Reaction name = "PDE4 phosp2" id="phospPDE42">
<Reactant specieID="PKAcPDE4" />
<Product specieID="pPDE4" />
<Product specieID="PKAc" />
<forwardRate> 0.0125e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- 11) pPDE4 -> PDE4 via PP1: binding-->
<Reaction name = "PDE4 PP1 bind" id="pPDE4_PP1bind">
<Reactant specieID="pPDE4" />
<Reactant specieID="PP1" />
<Product specieID="pPDE4PP1" />
<forwardRate> 0.0001e-03 </forwardRate>
<reverseRate> 0.025e-3 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- 12) pPDE4 -> PDE4 via PP1: dephos -->
<Reaction name = "pPDE4 d_phos" id="pPDE4dephos">
<Reactant specieID="pPDE4PP1" />
<Product specieID="PP1" />
<Product specieID="PDE4" />
<forwardRate> 0.00625e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- 13) cAMP + pPDE4 <-> pPDE4cAMP, 4x rate as unphos PDE4 -->
<Reaction name = "pPDE4 enzyme1" id="pPDE4bind">
<Reactant specieID="pPDE4" />
<Reactant specieID="cAMP" />
<Product specieID="pPDE4cAMP" />
<forwardRate> 0.0866e-03 </forwardRate>
<reverseRate> 275.8e-03 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- 14) pPDE4cAMP -> AMP + pPDE4 -->
<Reaction name = "pPDE4 actvcomp" id="pPDE4cat">
<Reactant specieID="pPDE4cAMP" />
<Product specieID="pPDE4" />
<Product specieID="AMP" />
<forwardRate> 68.92e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- ******************* PP2B part ******************** -->
<!--4x) Cam + PP2B <-> PP2BCam (in xpp: k33a=1 k_33a=3) -->
<Reaction name = "Cam+PP2B--PP2BCam reac" id="Cam+PP2B--PP2BCam_id">
<Reactant specieID="Cam" />
<Reactant specieID="PP2B" />
<Product specieID="PP2BCam" />
<forwardRate> 0.0046e-3 </forwardRate>
<reverseRate> 0.0012e-3 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!--4C) CamCa2C + PP2B <-> PP2BCamCa2C (in xpp: k33c=1 k_33c=0.3) -->
<Reaction name = "CamCa2C+PP2B--PP2BCamCa2C reac" id="CamCa2C+PP2B--PP2BCamCa2C_id">
<Reactant specieID="CamCa2C" />
<Reactant specieID="PP2B" />
<Product specieID="PP2BCamCa2C" />
<forwardRate> 0.046e-3 </forwardRate>
<reverseRate> 0.0012e-3 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!--4N) CamCa2N + PP2B <-> PP2BCamCa2N (in xpp: k33c=1 k_33c=0.3) -->
<Reaction name = "CamCa2N+PP2B--PP2BCamCa2N reac" id="CamCa2N+PP2B--PP2BCamCa2N_id">
<Reactant specieID="CamCa2N" />
<Reactant specieID="PP2B" />
<Product specieID="PP2BCamCa2N" />
<forwardRate> 0.046e-3 </forwardRate>
<reverseRate> 0.0012e-3 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!--5xC) PP2BCam + Ca2 <-> PP2BCamCa2C -->
<Reaction name = "PP2BCam+Ca2--PP2BCamCa2C reac" id="PP2BCam+Ca2--PP2BCamCa2C_id">
<Reactant specieID="PP2BCam" />
<Reactant specieID="Ca" n="2" />
<Product specieID="PP2BCamCa2C" />
<forwardRate> 6.0e-06 </forwardRate>
<reverseRate> 0.91e-03 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!--5xN) PP2BCam + Ca2 <-> PP2BCamCa2N -->
<Reaction name = "PP2BCam+Ca2--PP2BCamCa2N reac" id="PP2BCam+Ca2--PP2BCamCa2N_id">
<Reactant specieID="PP2BCam" />
<Reactant specieID="Ca" n="2" />
<Product specieID="PP2BCamCa2N" />
<forwardRate> 0.1e-03 </forwardRate>
<reverseRate> 100e-03 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!--7x) CamCa4 + PP2B <-> PP2BCamCa4 -->
<Reaction name = "CamCa4+PP2B--PP2BCamCa4 reac" id="CamCa4+PP2B--PP2BCamCa4_id">
<Reactant specieID="CamCa4" />
<Reactant specieID="PP2B" />
<Product specieID="PP2BCamCa4" />
<forwardRate> 0.046e-3 </forwardRate>
<reverseRate> 0.0012e-3 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!--4C) C site binding -->
<Reaction name = "PP2BCamCa2C+Ca2--PP2BCamCa4 reac" id="PP2BCamCa2+Ca2--PP2BCamCa4_id">
<Reactant specieID="PP2BCamCa2C" />
<Reactant specieID="Ca" n="2" />
<Product specieID="PP2BCamCa4" />
<forwardRate> 0.1e-03 </forwardRate>
<reverseRate> 1000e-03 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!--4N) N site binding -->
<Reaction name = "PP2BCamCa2N+Ca2--PP2BCamCa4 reac" id="PP2BCamCa2N+Ca2--PP2BCamCa4_id">
<Reactant specieID="PP2BCamCa2N" />
<Reactant specieID="Ca" n="2" />
<Product specieID="PP2BCamCa4" />
<forwardRate> 6.0e-06 </forwardRate>
<reverseRate> 9.1e-03 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- ******************* additional target X ******************** -->
<!-- 09) PKAc + X -> PKAcX Km=250 nM-->
<Reaction name = "X phosp1" id="phospX1">
<Reactant specieID="PKAc" />
<Reactant specieID="X" />
<Product specieID="PKAcX" />
<forwardRate> 0.1e-06 </forwardRate>
<reverseRate> 0.02e-03 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- 10) PKAcX -> PKAc + pX -->
<Reaction name = "X phosp2" id="phospX2">
<Reactant specieID="PKAcX" />
<Product specieID="pX" />
<Product specieID="PKAc" />
<forwardRate> 0.005e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- 11) pX -> X via PP1: binding-->
<Reaction name = "X PP1 bind" id="pX_PP1bind">
<Reactant specieID="pX" />
<Reactant specieID="PP1" />
<Product specieID="pXPP1" />
<forwardRate> 0.00018e-03 </forwardRate>
<reverseRate> 0.08e-3 </reverseRate>
<Q10>0.2</Q10>
</Reaction>
<Reaction name = "pX d_phos" id="pXdephos">
<Reactant specieID="pXPP1" />
<Product specieID="PP1" />
<Product specieID="X" />
<forwardRate> 0.02e-03 </forwardRate>
<Q10>0.2</Q10>
</Reaction>
<!-- ********** Inhibitor 1 Phospho and Dephosphorylation ******* -->
<!--1) I1 + PKAc <-> I1PKAc -->
<Reaction name = "I1_bind" id="I1_bind">
<Reactant specieID="I1"/>
<Reactant specieID="PKAc"/>
<Product specieID="I1PKAc"/>
<forwardRate>0.0014e-3</forwardRate>
<reverseRate>5.6e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--2) I1PKAc -> Ip35 + PKAc: default kb=0 -->
<Reaction name = "I1PKAc_reac" id="I1PKAc_reac">
<Reactant specieID="I1PKAc"/>
<Product specieID="Ip35"/>
<Product specieID="PKAc"/>
<forwardRate>1.4e-3</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--3) Ip35 + PP1 <-> Ip35pp1 -->
<Reaction name = "Ip35_bind" id="Ip35_bind">
<Reactant specieID="Ip35"/>
<Reactant specieID="PP1"/>
<Product specieID="Ip35PP1"/>
<forwardRate>0.001e-3</forwardRate>
<reverseRate>0.0011e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--6) Ip35pp1 + PP2B <-> Ip35p1p2 -->
<Reaction name = "Ip35pp1_bind" id="Ip35pp1_bind">
<Reactant specieID="Ip35PP1"/>
<Reactant specieID="PP2BCamCa4"/>
<Product specieID="Ip35PP1PP2BCamCa4"/>
<forwardRate>0.00233e-3</forwardRate>
<reverseRate>11.2e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--7a) Ip35p1p2 -> I1 + PP1PP2B -->
<Reaction name = "Ip35p1p2_reac" id="Ip35p1p2_reac">
<Reactant specieID="Ip35PP1PP2BCamCa4"/>
<Product specieID="I1"/>
<Product specieID="PP1"/>
<Product specieID="PP2BCamCa4"/>
<forwardRate>2.8e-3</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
</ReactionScheme>