<ReactionScheme>
<!-- Merged, tuned model, with CamKII phos of DagL.
Uses higher order reactions for CamKII phosphorylation -->
<!-- calcium stuff first -->
<Specie name="Ca" id="Ca" kdiff="174.3" kdiffunit="mu2/s"/>
<Specie name="CaOut" id="CaOut" kdiff="174.3" kdiffunit="mu2/s"/>
<Specie name="CaOutLeak" id="CaOutLeak" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Leak" id="Leak" kdiff="0" 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"/>
<Specie name="pmca" id="pmca" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="ncx" id="ncx" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pmcaCa" id="pmcaCa" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="ncxCa" id="ncxCa" kdiff="0" kdiffunit="mu2/s"/>
<!-- CaM from Gq files, with either C or N site binding first -->
<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"/>
<!-- Gs coupled Dopamine D1 Receptor; Ligand currently called L,
Dbuf is used to eliminate injected D -->
<Specie name="Da" id="Da" kdiff="10" kdiffunit="mu2/s"/>
<Specie name="Dbuf" id="Dbuf" kdiff="1" kdiffunit="mu2/s"/>
<Specie name="DaDbuf" id="DaDbuf" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="DaOut" id="DaOut" kdiff="1" kdiffunit = "mu2/s"/>
<Specie name="D1R" id="D1R" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="DaD1R" id="DaD1R" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Gsabg" id="Gsabg" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="DaD1RGs" id="DaD1RGs" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="GsD1R" id="GsD1R" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKAcDaD1RGs" id="PKAcDaD1RGs" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pDaD1RGs" id="pDaD1RGs" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pGsD1R" id="pGsD1R" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="GsaGTP" id="GsaGTP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="GsaGDP" id="GsaGDP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Gbg" id="Gbg" kdiff="0" kdiffunit="mu2/s"/>
<!-- Gi coupled m4R -->
<Specie name="ACh" id="ACh" kdiff="10" kdiffunit = "mu2/s"/>
<Specie name="m4R" id="m4R" kdiff="0" kdiffunit = "mu2/s"/>
<Specie name="AChm4R" id="AChm4R" kdiff="0" kdiffunit = "mu2/s"/>
<Specie name="Giabg" id="Giabg" kdiff="0" kdiffunit = "mu2/s"/>
<Specie name="AChm4RGi" id="AChm4RGi" kdiff="0" kdiffunit = "mu2/s"/>
<Specie name="Gim4R" id="Gim4R" kdiff="0" kdiffunit = "mu2/s"/>
<Specie name="GiaGTP" id="GiaGTP" kdiff="0" kdiffunit = "mu2/s"/>
<Specie name="GiaGDP" id="GiaGDP" kdiff="0" kdiffunit = "mu2/s"/>
<!-- Gi coupled m4R -->
<Specie name="m1R" id="m1R" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AChm1R" id="AChm1R" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="m1RGq" id="m1RGq" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AChm1RGq" id="AChm1RGq" kdiff="0" kdiffunit="mu2/s"/>
<!--m1R or m4R inhibition -->
<Specie name="telenz" id="telenz" kdiff="1" kdiffunit="mu2/s"/>
<Specie name="telenzm1R" id="telenzm1R" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="telenzm1RGq" id="telenzm1RGq" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PD1028" id="PD1028" kdiff="1" kdiffunit = "mu2/s"/>
<Specie name="PD1028m4R" id="PD1028m4R" kdiff="0" kdiffunit = "mu2/s"/>
<Specie name="PD1028m4RGi" id="PD1028m4RGi" kdiff="0" kdiffunit = "mu2/s"/>
<!-- Gq coupled mGluR or mAChR receptor; ligand currently called Glu,
GluOut is used to eliminate injected Glu -->
<Specie name="Glu" id="Glu" kdiff="0.01" kdiffunit="mu2/s"/>
<Specie name="GluGbuf" id="GluGbuf" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="GluOut" id="GluOut" kdiff="1" kdiffunit="mu2/s"/>
<Specie name="Gbuf" id="Gbuf" kdiff="1" kdiffunit="mu2/s"/>
<Specie name="MgluR" id="MgluR" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="GluMgluR" id="GluMgluR" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="GluMgluRdesens" id="GluMgluRdesens" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="MgluRGq" id="MgluRGq" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Gqabg" id="Gqabg" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="GluMgluRGq" id="GluMgluRGq" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="GqaGTP" id="GqaGTP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="GqaGDP" id="GqaGDP" kdiff="0" kdiffunit="mu2/s"/>
<!-- This is AC5, from Gs model. May need to add AC1 at some point -->
<Specie name="AC5" id="AC5" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC5Gsa" id="AC5Gsa" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC5GsaATP" id="AC5GsaATP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC5Ca" id="AC5Ca" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC5GsaCa" id="AC5GsaCa" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC5GsaCaATP" id="AC5GsaCaATP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC5Gia" id="AC5Gia" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC5GsaGia" id="AC5GsaGia" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC5GsaGiaATP" id="AC5GsaGiaATP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC1" id="AC1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC1Gsa" id="AC1Gsa" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC1GsaCamCa4" id="AC1GsaCamCa4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC1GsaCamCa4ATP" id="AC1GsaCamCa4ATP" 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"/>
<!-- cAMP, and degradation by PDEs, from Gs model -->
<!--Specie name="ATP" id="ATP" kdiff="74.8" kdiffunit="mu2/s"/-->
<Specie name="cAMP" id="cAMP" kdiff="86.4" kdiffunit="mu2/s"/>
<Specie name="AMP" id="AMP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PDE1" id="PDE1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PDE1CamCa4cAMP" id="PDE1CamCa4cAMP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PDE1CamCa4" id="PDE1CamCa4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PDE10" id="PDE10" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PDE10cAMP" id="PDE10cAMP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKAcPDE10" id="PKAcPDE10" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKAcPDE10cAMP" id="PKAcPDE10cAMP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pPDE10" id="pPDE10" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pPDE10cAMP" id="pPDE10cAMP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pPDE10PP2A" id="pPDE10PP2A" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pPDE10PP2Ac" id="pPDE10PP2Ac" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PDE2" id="PDE2" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PDE2cAMP" id="PDE2cAMP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PDE2cAMP2" id="PDE2cAMP2" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PDE4" id="PDE4" kdiff="6.01" kdiffunit="mu2/s"/>
<Specie name="PDE4cAMP" id="PDE4cAMP" kdiff="6.0" kdiffunit="mu2/s"/>
<Specie name="PKAcPDE4" id="PKAcPDE4" kdiff="5.4" kdiffunit="mu2/s"/>
<Specie name="PKAcPDE4cAMP" id="PKAcPDE4cAMP" kdiff="5.41" kdiffunit="mu2/s"/>
<Specie name="pPDE4" id="pPDE4" kdiff="6.01" kdiffunit="mu2/s"/>
<Specie name="pPDE4PP2A" id="pPDE4PP2A" kdiff="6.61" kdiffunit="mu2/s"/>
<Specie name="pPDE4PP2Ac" id="pPDE4PP2Ac" kdiff="6.61" kdiffunit="mu2/s"/>
<Specie name="pPDE4cAMP" id="pPDE4cAMP" kdiff="6.0" kdiffunit="mu2/s"/>
<Specie name="Pap" id="Pap" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PapPDE10" id="PapPDE10" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Roli" id="Roli" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="RoliPDE4" id="RoliPDE4" kdiff="0" kdiffunit="mu2/s"/>
<!-- Gq, PLC, Dag, IP3, PKC and 2ag are from Gq model -->
<Specie name="Plc" id="Plc" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PlcCa" id="PlcCa" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PlcCaGqa" id="PlcCaGqa" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PlcGqa" id="PlcGqa" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Pip2" id="Pip2" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PlcCaPip2" id="PlcCaPip2" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PlcCaGqaPip2" id="PlcCaGqaPip2" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Ip3" id="Ip3" kdiff="79.6" kdiffunit="mu2/s"/>
<Specie name="Dag" id="Dag" kdiff="0" kdiffunit="mu2/s"/>
<!-- degradation of Dag, 2ag and IP3 -->
<Specie name="DagK" id="DagK" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="DagKdag" id="DagKdag" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PA" id="PA" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="2agDegrad" id="2agDegrad" kdiff="88.6" kdiffunit="mu2/s"/>
<Specie name="Ip3degrad" id="Ip3degrad" kdiff="79.6" kdiffunit="mu2/s"/>
<!-- Production of endocannabinoid -->
<Specie name="Dgl" id="Dgl" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pDgl" id="pDgl" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CaDgl" id="CaDgl" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CapDgl" id="CapDgl" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="DagCaDgl" id="DagCaDgl" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="DagCapDgl" id="DagCapDgl" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="2ag" id="2ag" kdiff="88.6" kdiffunit="mu2/s"/>
<Specie name="Dgl_CKCamCa4" id="Dgl_CKCamCa4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Dgl_CKpCamCa4" id="Dgl_CKpCamCa4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CaDgl_CKCamCa4" id="CaDgl_CKCamCa4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CaDgl_CKpCamCa4" id="CaDgl_CKpCamCa4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Dgl_CKp" id="Dgl_CKp" kdiff="0" kdiffunit="mu2/s"/>
<!-- Kinases and Phosphatases -->
<Specie name="PIkinase" id="PIkinase" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Ip3degPIk" id="Ip3degPIk" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Pkc" id="Pkc" kdiff="6.61" kdiffunit="mu2/s"/>
<Specie name="PkcCa" id="PkcCa" kdiff="6.61" kdiffunit="mu2/s"/>
<Specie name="PkcCaDag" id="PkcCaDag" kdiff="0" kdiffunit="mu2/s"/>
<!-- PP1, PP2B, PP2A, CaMKII, PKA, Darpp32 from Gs, since Gq didn't have them -->
<!-- PP1, PP2B, PP2A are non-diffusible? -->
<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"/>
<Specie name="PP1" id="PP1" kdiff="0" kdiffunit="mu2/s"/>
<!-- PP2A -->
<Specie name="PP2ABPR72" id="PP2ABPR72" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PP2AB56d" id="PP2AB56d" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKAcPP2AB56d" id="PKAcPP2AB56d" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pPP2A" id="pPP2A" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PP2Acal" id="PP2Acal" kdiff="0" kdiffunit="mu2/s"/>
<!-- CaMKII: delete Complex and pComplex and re-do rate constants when using new NeuroRD version -->
<Specie name="CK" id="CK" kdiff="3.6" kdiffunit="mu2/s"/>
<Specie name="CKCamCa4" id="CKCamCa4" kdiff="3.6" kdiffunit="mu2/s"/>
<Specie name="CKpCamCa4" id="CKpCamCa4" kdiff="3.6" kdiffunit="mu2/s"/>
<Specie name="CKp" id="CKp" kdiff="3.6" kdiffunit="mu2/s"/>
<Specie name="CKpPP1" id="CKpPP1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CKpCamCa4PP1" id="CKpCamCa4PP1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CKCam_block" id="CKCam_block" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AIP" id="AIP" kdiff="1" 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"/>
<Specie name="Epac1" id="Epac1" kdiff="10" kdiffunit="mu2/s"/>
<Specie name="Epac1cAMP" id="Epac1cAMP" kdiff="10" kdiffunit="mu2/s"/>
<!-- Use the updated reactions from Asia's hippocampal model -->
<!-- D32,D32p34 -->
<Specie name="D32" id="D32" kdiff="8.9" kdiffunit="mu2/s"/>
<Specie name="D32PKAc" id="D32PKAc" kdiff="6.8" kdiffunit="mu2/s"/>
<Specie name="D32p34" id="D32p34" kdiff="8.8" kdiffunit="mu2/s"/>
<Specie name="D32p34PP1" id="D32p34PP1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="D32p34PP2BCamCa4" id="D32p34PP2BCamCa4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="D32p34PP1PP2BCamCa4" id="D32p34PP1PP2BCamCa4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="D32p34PP1PP2BCamCa2C" id="D32p34PP1PP2BCamCa2C" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="D32p34PP2ABPR72" id="D32p34PP2ABPR72" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="D32p34PP2AB56d" id="D32p34PP2AB56d" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="D32p34PP1PP2ABPR72" id="D32p34PP1PP2ABPR72" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="D32p34PP1PP2AB56d" id="D32p34PP1PP2AB56d" kdiff="0" kdiffunit="mu2/s"/>
<!-- D32p75 -->
<Specie name="Cdk5" id="Cdk5" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Cdk5D32" id="Cdk5D32" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="D32p75" id="D32p75" kdiff="8.8" kdiffunit="mu2/s"/>
<Specie name="D32p75PKAc" id="D32p75PKAc" kdiff="6.8" kdiffunit="mu2/s"/>
<Specie name="D32p75PP2ABPR72" id="D32p75PP2ABPR72" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="D32p75PP2AB56d" id="D32p75PP2AB56d" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="D32p75PP2Acal" id="D32p75PP2Acal" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="D32p75pPP2A" id="D32p75pPP2A" kdiff="0" kdiffunit="mu2/s"/>
<!-- AKAR -->
<Specie name="AKAR3" id="AKAR3" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pAKAR3" id="pAKAR3" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKAcAKAR3" id="PKAcAKAR3" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PP1pAKAR3" id="PP1pAKAR3" kdiff="0" kdiffunit="mu2/s"/>
<!-- blockers -->
<Specie name="OkadaicAcid" id="OA" kdiff="1" kdiffunit="mu2/s"/>
<Specie name="CyclosporinA" id="CyA" kdiff="1" kdiffunit="mu2/s"/>
<Specie name="OA_PP2ABPR72" id="OA_PP2ABPR72" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="OA_PP2AB56d" id="OA_PP2AB56d" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="OA_pPP2A" id="OA_pPP2A" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="OA_PP2Acal" id="OA_PP2Acal" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="OA_PP1" id="OA_PP1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CyA_PP2B" id="CyA_PP2B" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CyA_PP2BCa2C" id="CyA_PP2BCa2C" kdiff="0" kdiffunit="mu2/s"/>
<!-- For now, no GluA1 receptors -->
<!--*************************************************************************
Now, the reactions themselves SAME means params are same in both files
**************************************************************************-->
<!--I. *********** Ca pump and buffer rxns ************* -->
<!-- i: Ca pump high affinity - Ca + pmca <-> pmcaCa SAME-->
<Reaction name = "Ca_pump1a" id="Ca_pump1a">
<Reactant specieID="Ca"/>
<Reactant specieID="pmca"/>
<Product specieID="pmcaCa"/>
<forwardRate>0.05e-3</forwardRate>
<reverseRate>9e-3</reverseRate>
</Reaction>
<!-- ii: Ca pump high affinity - pmcaCa <-> pmca + CaOut SAME-->
<Reaction name = "Ca_pump1b" id="Ca_pump1b">
<Reactant specieID="pmcaCa"/>
<Product specieID="pmca"/>
<Product specieID="CaOut"/>
<forwardRate>3.0e-3</forwardRate>
<reverseRate>0</reverseRate>
</Reaction>
<!-- iii: Ca pump low affinity - Ca + ncx <-> ncxCa SAME-->
<Reaction name = "Ca_pump2a" id="Ca_pump2a">
<Reactant specieID="Ca"/>
<Reactant specieID="ncx"/>
<Product specieID="ncxCa"/>
<forwardRate>0.011e-3</forwardRate>
<reverseRate>11.2e-3</reverseRate>
</Reaction>
<!-- iv: Ca pump low affinity - ncxCa <-> ncx + CaOut SAME-->
<Reaction name = "Ca_pump2b" id="Ca_pump2b">
<Reactant specieID="ncxCa"/>
<Product specieID="ncx"/>
<Product specieID="CaOut"/>
<forwardRate>5.6e-3</forwardRate>
<reverseRate>0</reverseRate>
</Reaction>
<!-- v: Ca leak - CaOut + Leak <-> CaOutLeak GQ RXN FILE, Leak is sm only-->
<Reaction name = "Ca_leak" id="Ca_leak">
<Reactant specieID="CaOut"/>
<Reactant specieID="Leak"/>
<Product specieID="CaOutLeak"/>
<forwardRate>0.01e-6</forwardRate>
<reverseRate>1.1e-3</reverseRate>
</Reaction>
<!-- vi: Ca leak - CaOutLeak <-> Ca (inside) + Leak -->
<Reaction name = "Ca_leak" id="Ca_leak">
<Reactant specieID="CaOutLeak"/>
<Product specieID="Ca"/>
<Product specieID="Leak"/>
<forwardRate>1.1e-3</forwardRate>
<reverseRate>0</reverseRate>
</Reaction>
<!-- 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>
</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>0.006e-3</forwardRate>
<reverseRate>9.1e-3</reverseRate>
</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>
</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>
</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>0.006e-3</forwardRate>
<reverseRate>9.1e-3</reverseRate>
</Reaction>
<!--II. *********** Gs coupled receptor, from GS RXN FILE *************-->
<!--0a. Injected DaDbuf dissociates to Dbuf (external) and Da: DaDbuf -> Da + Dbuf -->
<Reaction name = "DaDbuf--Da+Dbuf" id="DaDbuf--Da+Dbuf">
<Reactant specieID="DaDbuf" />
<Product specieID="Dbuf" />
<Product specieID="Da" />
<forwardRate> 20e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--0b. Da or Da Agonist is extruded -->
<Reaction name = "Da--DaOut" id="Da--DaOut">
<Reactant specieID="Da"/>
<Product specieID="DaOut" />
<forwardRate> 1.0e-3 </forwardRate>
<reverseRate> 0.055e-6 </reverseRate>
</Reaction>
<!--0c. excess DaOut eliminated to prevent baseline shift: DaOut + Dbuf <-> DaOutbuf -->
<Reaction name = "DaOut+Dbuf--NULL" id="DaOut_buf--NULL">
<Reactant specieID="DaOut" />
<Reactant specieID="Dbuf" />
<forwardRate> 1e-06 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--1a. Da + D1R <-> DaD1R Kd=3000 source: Sunahara et al. Nature 1991-->
<Reaction name = "Da+D1R--DaD1R" id="Da+D1R--DaD1R">
<Reactant specieID="Da" />
<Reactant specieID="D1R" />
<Product specieID="DaD1R" />
<forwardRate> 0.00166667e-03 </forwardRate>
<reverseRate> 5e-03 </reverseRate>
</Reaction>
<!-- 2a. DaD1R + Gsabg <-> DaD1RGs Kd=11.666667 source: Zhuang J Neurosci 2000-->
<Reaction name = "DaD1R+Gs--DaD1RGs" id="DaD1R+Gs--DaD1RGs">
<Reactant specieID="DaD1R" />
<Reactant specieID="Gsabg" />
<Product specieID="DaD1RGs" />
<forwardRate> 0.03e-03 </forwardRate>
<reverseRate> 0.4e-03 </reverseRate>
</Reaction>
<!-- 1b. Gsabg + D1R <-> GsD1R Kd=35 source: PMR-->
<Reaction name = "Gsabg+D1R--GsD1R" id="Gsabg+D1R--GsD1R">
<Reactant specieID="Gsabg" />
<Reactant specieID="D1R" />
<Product specieID="GsD1R" />
<forwardRate> 0.01e-03 </forwardRate>
<reverseRate> 0.4e-03 </reverseRate>
</Reaction>
<!-- 2b. GsD1R + Da < - > DaD1RGs Kd=1000 source: Falkenburger J Gen Phys off-rate, Dreyer J Neurosci-->
<Reaction name = "GsD1R+Da--DaD1RGs" id="GD1R+Da--DaD1RGs">
<Reactant specieID="GsD1R" />
<Reactant specieID="Da" />
<Product specieID="DaD1RGs" />
<forwardRate> 0.005e-03 </forwardRate>
<reverseRate> 5e-03 </reverseRate>
</Reaction>
<!-- 3. DaD1RGs <-> DaD1R + GsaGTP +Gbg-->
<Reaction name = "DaD1RGs-DaD1R+GsaGTP+Gbg reac" id="DaD1RGs-DaD1R+GsaGTP+Gbg_id">
<Reactant specieID="DaD1RGs" />
<Product specieID="DaD1R" />
<Product specieID="GsaGTP" />
<Product specieID="Gbg" />
<forwardRate> 0.15e-03 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!--*****************PKAc phosphorylation of DaD1R *******************************-->
<!--4. PKAc + DaD1RGs -> PKAcDaD1RGs Km= 125nM-->
<Reaction name = "DaD1RGs phosp1" id="phospDaD1RGs1">
<Reactant specieID="PKAc" />
<Reactant specieID="DaD1RGs" />
<Product specieID="PKAcDaD1RGs" />
<forwardRate> 0.006e-03 </forwardRate>
<reverseRate> 0.6e-03 </reverseRate>
</Reaction>
<!--5. PKAcDaD1RGs -> PKAc + phosphoDaD1RGs -->
<Reaction name = "DaD1RGs phosp2" id="phospDaD1RGs2">
<Reactant specieID="PKAcDaD1RGs" />
<Product specieID="pDaD1RGs" />
<Product specieID="PKAc" />
<forwardRate> 0.15e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--6a. pDaD1RGs -> pD1RGs - Da dissociation 1 uM-->
<Reaction name = "Da_dissoc" id="Da_dissoc">
<Reactant specieID="pDaD1RGs" />
<Product specieID="pGsD1R" />
<Product specieID="Da" />
<forwardRate> 0.1 </forwardRate>
<reverseRate> 0.1e-3 </reverseRate>
</Reaction>
<!--6b. pD1RGs -> D1RGs - fast dephos of unbound receptor -->
<Reaction name = "Da_dissoc" id="Da_dissoc">
<Reactant specieID="pGsD1R" />
<Product specieID="GsD1R" />
<forwardRate> 0.02e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--6c. pDaD1RGs -> DaD1RGs -->
<Reaction name = "dephosD1R" id="dphospD1R">
<Reactant specieID="pDaD1RGs" />
<Product specieID="Gsabg" />
<Product specieID="D1R" />
<Product specieID="Da" />
<forwardRate> 0.0002e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--III. *********** Gq coupled receptor, from GQ RXN FILE *************-->
<!--0a. Glu or Glu Agonist is extruded -->
<!--0a. Injected DaDbuf dissociates to Dbuf (external) and Da: DaDbuf -> Da + Dbuf -->
<Reaction name = "Glubuf--Glu+Gbuf" id="GluGbuf--Glu+Gbuf">
<Reactant specieID="GluGbuf" />
<Product specieID="Gbuf" />
<Product specieID="Glu" />
<forwardRate> 20e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--0b. GluOut Glu <-> GluOut> -->
<Reaction name = "Glu--GluOut" id="Glu--GluOut">
<Reactant specieID="Glu"/>
<Product specieID="GluOut"/>
<forwardRate>1.2e-3</forwardRate>
<reverseRate>0.06e-6</reverseRate>
</Reaction>
<!--0c. GluOut eliminated to prevent baseline shift: GluOut + Gbuf <-> Null -->
<Reaction name = "GluOut-buf reac" id="Glu-buf_id">
<Reactant specieID="GluOut" />
<Reactant specieID="Gbuf" />
<forwardRate> 1e-6 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--0c. GluMgluR <==> Desensitized, needed for prolonged DHPG application -->
<Reaction name = "Glu+MgluR--GluMgluRdesens" id="Glu+MgluR--GluMgluRdesens">
<Reactant specieID="GluMgluR" />
<Product specieID="GluMgluRdesens" />
<forwardRate> 0.0625e-03 </forwardRate>
<reverseRate> 0.001e-03 </reverseRate>
</Reaction>
<!--1a. Glu or Glu agonist Dhpg: Glu + MgluR <==> GluMgluR
1st set of rates is for Dhpg, 2nd set of rates for Glu -->
<Reaction name = "Glu+MgluR--GluMgluR" id="Glu+MgluR--GluMgluR">
<Reactant specieID="Glu" />
<Reactant specieID="MgluR" />
<Product specieID="GluMgluR" />
<forwardRate> 0.001e-03 </forwardRate>
<!--reverseRate> 13.2e-03 </reverseRate-->
<!-- uncomment below and comment above for Glu (opposite for Dhpg) -->
<reverseRate> 0.5e-03 </reverseRate>
</Reaction>
<!--2a. Gqabg + GluMgluR <-> GluMgluRGq -->
<Reaction name = "Gqabg+GluMgluR--GluMgluRGq" id="Gqabg+GluMgluR--GluMgluRGq">
<Reactant specieID="Gqabg" />
<Reactant specieID="GluMgluR" />
<Product specieID="GluMgluRGq" />
<forwardRate> 0.009e-03 </forwardRate>
<reverseRate> 1.36e-03 </reverseRate>
</Reaction>
<!--1b. Gqabg + MgluR <-> MgluRGq -->
<Reaction name = "Gqabg+MgluR- -MgluRGq" id="Gqabg+MgluR- -MgluRGq">
<Reactant specieID="Gqabg" />
<Reactant specieID="MgluR" />
<Product specieID="MgluRGq" />
<forwardRate> 0.00225e-06 </forwardRate>
<reverseRate> 0.68e-03 </reverseRate>
</Reaction>
<!--2b. Glu + MgluRGq <-> GluMgluRGq -->
<Reaction name = "Glu+MgluRGq- -GluMgluRGq" id="Glu+MgluRGq- -GluMgluRGq">
<Reactant specieID="Glu" />
<Reactant specieID="MgluRGq" />
<Product specieID="GluMgluRGq" />
<forwardRate> 0.004e-03 </forwardRate>
<!--reverseRate> 26.4e-03 </reverseRate-->
<!-- uncomment below and comment above for Glu (opposite for Dhpg) -->
<reverseRate> 1e-03 </reverseRate>
</Reaction>
<!--3. GabgGluMglu <-> GqaGTP + GluMgluRGbg -->
<Reaction name = "GluMgluRGq--GqaGTP+GluMgluRGbg" id="GluMgluRGq--GqaGTP+GluMgluRGbg">
<Reactant specieID="GluMgluRGq" />
<Product specieID="GqaGTP" />
<Product specieID="GluMgluR" />
<Product specieID="Gbg" />
<forwardRate> 1.5e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- *********** Gq coupled m1 ACh receptor ***************-->
<!--1a. ACh binding to m1R: ACh + m1R <=> AChm1R -->
<Reaction name = "ACh+m1R--AChm1R" id="ACh+m1R--AChm1R">
<Reactant specieID="ACh" />
<Reactant specieID="m1R" />
<Product specieID="AChm1R" />
<forwardRate> 0.095e-06 </forwardRate>
<reverseRate> 2.5e-03 </reverseRate>
</Reaction>
<!--2a. Gqabg + AChm1R <-> AChm1RGq - make lower than for mGluR, to decrease basal Gq -->
<Reaction name = "Gqabg+AChm1R--AChm1RGq" id="Gqabg+AChm1R--AChm1RGq">
<Reactant specieID="Gqabg" />
<Reactant specieID="AChm1R" />
<Product specieID="AChm1RGq" />
<forwardRate> 0.024e-03 </forwardRate>
<reverseRate> 0.42e-03 </reverseRate>
</Reaction>
<!--1b. Gqabg + m1R <-> m1RGq -->
<Reaction name = "Gqabg+m1R- -m1RGq" id="Gqabg+m1R- -m1RGq">
<Reactant specieID="Gqabg" />
<Reactant specieID="m1R" />
<Product specieID="m1RGq" />
<forwardRate> 0.000576e-03 </forwardRate>
<reverseRate> 0.42e-03 </reverseRate>
</Reaction>
<!--2b. ACh + m1RGq <-> AChm1RGq: 20x higher affinity than Glu binding mGluR-->
<Reaction name = "ACh+m1RGq- -AChm1RGq" id="ACh+m1RGq- -AChm1RGq">
<Reactant specieID="ACh" />
<Reactant specieID="m1RGq" />
<Product specieID="AChm1RGq" />
<forwardRate> 0.00396e-03 </forwardRate>
<reverseRate> 2.5e-03 </reverseRate>
</Reaction>
<!--3. GabgAChMglu <-> GqaGTP + AChm1RGbg -->
<Reaction name = "AChm1RGq--GqaGTP+AChm1RGbg" id="AChm1RGq--GqaGTP+AChm1RGbg">
<Reactant specieID="AChm1RGq" />
<Product specieID="GqaGTP" />
<Product specieID="AChm1R" />
<Product specieID="Gbg" />
<forwardRate> 0.5e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- *********** Gi coupled m4 receptor ***************-->
<!--0. ACh -> null -->
<Reaction name = "ACh--null" id="ACh--null">
<Reactant specieID="ACh" />
<forwardRate> 6e-03 </forwardRate>
</Reaction>
<!-- ACh or ACh agonist: ACh + m4R <==> AChm4R Kd = 7.4uM: low affinity Leach 2010 -->
<Reaction name = "ACh+m4R--AChm4R" id="ACh+m4R--AChm4R">
<Reactant specieID="ACh" />
<Reactant specieID="m4R" />
<Product specieID="AChm4R" />
<forwardRate> 0.000338e-03 </forwardRate>
<reverseRate> 2.5e-03 </reverseRate>
</Reaction>
<!-- Giabg + AChm4R <-> GiabgAChm4R Kd = 17.5 source: sengeles JBiolChem 265 -->
<Reaction name = "Giabg+AChm4R--AChm4RGi" id="Giabg+AChm4R--AChm4RGi">
<Reactant specieID="AChm4R" />
<Reactant specieID="Giabg" />
<Product specieID="AChm4RGi" />
<forwardRate> 0.192e-03 </forwardRate>
<reverseRate> 3.36e-03 </reverseRate>
</Reaction>
<!-- Gi + m4R <-> Gim4R Kd = 236 source: PMR, Hein et al. JBC 2006: Gi dissoc tau=14s -->
<Reaction name = "Giabg+m4R--Gim4R" id="Giabg+m4R--Gim4R">
<Reactant specieID="Giabg" />
<Reactant specieID="m4R" />
<Product specieID="Gim4R" />
<forwardRate> 0.00178e-03 </forwardRate>
<reverseRate> 0.42e-03 </reverseRate>
</Reaction>
<!-- Gim4R + ACh <-> AChm4RGi Kd = 548 nM: high affinity (4x greater than measured)-->
<Reaction name = "Gim4R+ACh--AChm4RGi" id="Gm4R+ACh--AChm4RGi">
<Reactant specieID="Gim4R" />
<Reactant specieID="ACh" />
<Product specieID="AChm4RGi" />
<forwardRate> 0.0365e-03 </forwardRate>
<reverseRate> 20.0e-03 </reverseRate>
</Reaction>
<!-- AChm4RGiabg <-> GiaGTP + AChm4R +Gbg -->
<Reaction name = "AChm4RGi--GiaGTP+AChm4R+Gbg" id="AChm4RGi--GiaGTP+AChm4R+Gbg">
<Reactant specieID="AChm4RGi" />
<Product specieID="GiaGTP" />
<Product specieID="AChm4R" />
<Product specieID="Gbg" />
<forwardRate> 8.0e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--IV. *************** G protein hydrolysis and regeneration *******************-->
<!--1. hydrolysis: GsaGTP <-> GsaGDP -->
<Reaction name = "GsaGTP--GsaGDP reac" id="GsaGTP--GsaGDP_id">
<Reactant specieID="GsaGTP" />
<Product specieID="GsaGDP" />
<forwardRate> 0.01e-03 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!-- slow this down if depletion is significant, or to match regen of Gqa -->
<!--2. regen: GsaGDP + Gbg <-> Gsabg (in xpp: k5=100), Kd=? -->
<Reaction name = "GsaGDP+Gbg--Gs reac" id="GsaGDP+Gbg--Gs_id">
<Reactant specieID="GsaGDP" />
<Reactant specieID="Gbg" />
<Product specieID="Gsabg" />
<forwardRate> 2e-03 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!-- Hydrolysis of GqaGTP - slower than with GAP activity -->
<!--3. GqaGTP <-> GqaGDP -->
<Reaction name = "GqaGTP--GqaGDP" id="GqaGTP--GqaGDP">
<Reactant specieID="GqaGTP" />
<Product specieID="GqaGDP" />
<forwardRate> 0.1e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- 2nd order (was 1st order in Gq files) regeneration of Gqabg -->
<!--4. GqaGDP + Gbg <-> Gqabg -->
<Reaction name = "GqaGDP+Gbg--Gqabg" id="GqaGDP+Gbg--Gqabg">
<Reactant specieID="GqaGDP" />
<Reactant specieID="Gbg" />
<Product specieID="Gqabg" />
<forwardRate> 2e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- Hydrolysis of GiaGTP - slower than with GAP activity source: sengeles JBiolChem 265 -->
<Reaction name = "GiaGTP--GiaGDP" id="GiaGTP--GiaGDP">
<Reactant specieID="GiaGTP" />
<Product specieID="GiaGDP" />
<forwardRate> 4.0e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- 2nd order regeneration of Giabg source: -->
<Reaction name = "GiaGDP--Giabg" id="GiaGDP--Giabg">
<Reactant specieID="GiaGDP" />
<Reactant specieID="Gbg" />
<Product specieID="Giabg" />
<forwardRate> 2e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- ***************************************************************************-->
<!--V. AC5 to cAMP with PDEs, from Gs RXN FILE. May need to add AC1 at some point -->
<!--1. GsaGTP + AC5 <-> AC5Gsa(GTP) -->
<Reaction name = "GsaGTP+AC5--AC5Gsa reac" id="GsaGTP+AC5--AC5Gsa_id">
<Reactant specieID="GsaGTP" />
<Reactant specieID="AC5" />
<Product specieID="AC5Gsa" />
<forwardRate> 0.0148e-03 </forwardRate>
<reverseRate> 3.996e-03 </reverseRate>
</Reaction>
<!--2. AC5Gsa(GTP) + ATP <-> AC5Gsa(GTP)ATP -->
<Reaction name = "AC5Gsa+ATP--AC5GsaATP reac" id="AC5Gsa+ATP--AC5GsaATP_id">
<Reactant specieID="AC5Gsa" />
<!--Reactant specieID="ATP" /-->
<Product specieID="AC5GsaATP" />
<!--if ATP: forwardRate> 0.1276e-6 </forwardRate-->
<forwardRate> 0.2552 </forwardRate>
<reverseRate> 0.2612e-03 </reverseRate>
</Reaction>
<!--3. AC5Gsa(GTP)ATP <-> AC5Gsa(GTP) + cAMP -->
<Reaction name = "AC5GsaATP--AC5Gsa+cAMP reac" id="AC5GsaATP--AC5Gsa+cAMP_id">
<Reactant specieID="AC5GsaATP" />
<Product specieID="AC5Gsa" />
<Product specieID="cAMP" />
<forwardRate> 28.46e-03 </forwardRate>
<reverseRate> 0.2592e-6 </reverseRate>
</Reaction>
<Reaction name = "AC5GsaATP--AC5Gsa+cAMP reac" id="AC5GsaATP--AC5Gsa+cAMP_id">
<Reactant specieID="AC5GsaATP" />
<Product specieID="AC5" />
<Product specieID="cAMP" />
<Product specieID="GsaGDP" />
<forwardRate> 0.03e-03 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!-- 2a) GiaGTP + AC5 <-> AC5GiaGTP Kd=160 for AC5: Chen-Goodspeed JBC 280-1808, Nielson JBC 271-33308 1996 -->
<Reaction name = "GiaGTP_AC5_reac" id="GiaGTP_AC5_reac">
<Reactant specieID="GiaGTP"/>
<Reactant specieID="AC5"/>
<Product specieID="AC5Gia"/>
<forwardRate>0.0125e-3</forwardRate>
<reverseRate>2e-3</reverseRate>
</Reaction>
<!-- 2a) GiaGTP + AC5Gsa <-> AC5GsaGTP-GiaGTP Kd=160 for AC5: Chen-Goodspeed JBC 280-1808, Nielson JBC 271-33308 1996 -->
<Reaction name = "GiaGTP_AC5GsaGTP_reac" id="GiaGTP_AC5GsaGTP_reac">
<Reactant specieID="GiaGTP"/>
<Reactant specieID="AC5Gsa"/>
<Product specieID="AC5GsaGia"/>
<forwardRate>0.0125e-3</forwardRate>
<reverseRate>6e-3</reverseRate>
</Reaction>
<Reaction name = "GsaGTP_AC5GiaGTP_reac" id="GsaGTP_AC5GiaGTP_reac">
<Reactant specieID="GsaGTP"/>
<Reactant specieID="AC5Gia"/>
<Product specieID="AC5GsaGia"/>
<forwardRate> 0.0037e-03 </forwardRate>
<reverseRate> 2.997e-03</reverseRate>
</Reaction>
<!-- AC5GsaGia + ATP <-> AC5GsaGiaATP source: Dessauer CW, Gilman AG JBC 1997-->
<Reaction name = "AC5GsaGia+ATP--AC5GsaGiaATP" id="AC5GsaGia+ATP--AC5GsaGiaATP">
<Reactant specieID="AC5GsaGia" />
<!--Reactant specieID="ATP" /-->
<Product specieID="AC5GsaGiaATP" />
<!-- if ATP:forwardRate> 0.01276e-6 </forwardRate-->
<forwardRate> 0.02552 </forwardRate>
<reverseRate> 0.02612e-03 </reverseRate>
</Reaction>
<!-- AC5GsaGTPGiaGTP_ATP <-> AC5GsaGTPGiaGTP + CAMP source: Dessauer CW, Gilman AG JBC 1997-->
<Reaction name = "AC5GsaGiaATP--AC5GsaGia+cAMP" id="AC5GsaGiaATP--AC5GsaGia+cAMP">
<Reactant specieID="AC5GsaGiaATP" />
<Product specieID="AC5GsaGia" />
<Product specieID="cAMP" />
<forwardRate> 0.2746e-03 </forwardRate>
<reverseRate> 0.2592e-6 </reverseRate>
</Reaction>
<!-- Gap activity for part of AC5GsaGiaATP-->
<Reaction name = "AC5GsaGiaATP--AC5Gia+Gs+cAMP" id="AC5GsaGiaATP--AC5Gia+Gs+cAMP">
<Reactant specieID="AC5GsaGiaATP" />
<Product specieID="AC5Gsa" />
<Product specieID="cAMP" />
<Product specieID="GiaGDP" />
<forwardRate> 0.4e-03 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!-- Now, those involving AC5 with Ca attached: -->
<!--0b. AC5 + Ca <-> AC5Ca (in xpp: k9=0.001 k_9=0.9), 900 nM -->
<!-- <Reaction name = "AC5Ca reac" id="AC5Caid">
<Reactant specieID="AC5" />
<Reactant specieID="Ca" />
<Product specieID="AC5Ca" />
<forwardRate> 0.001e-03 </forwardRate>
<reverseRate> 0.9e-03 </reverseRate>
</Reaction>
--> <!--1b. GsaGTP + AC5Ca <-> AC5Gsa(GTP)Ca (slowed down from xpp: k6_2=0.0192, k_6_2=25) -->
<!-- <Reaction name = "AC5GsaCa reac" id="AC5GsaCaid">
<Reactant specieID="GsaGTP" />
<Reactant specieID="AC5Ca" />
<Product specieID="AC5GsaCa" />
<forwardRate> 0.00037e-03 </forwardRate>
<reverseRate> 0.1e-03 </reverseRate>
</Reaction>
--> <!--2b. AC5Gsa(GTP)Ca + ATP <-> AC5Gsa(GTP)CaATP -->
<!-- <Reaction name = "AC5GsaCaATP reac" id="AC5GsaCaATP1id">
<Reactant specieID="AC5GsaCa" />
<Reactant specieID="ATP" />
<Product specieID="AC5GsaCaATP" />
<forwardRate> 0.0638e-06 </forwardRate>
<reverseRate> 0.1306e-03 </reverseRate>
</Reaction>
--> <!--3b. AC5Gsa(GTP)CaATP <-> cAMP + AC5Gsa(GTP)Ca -->
<!-- <Reaction name = "AC5GsaCaATP<->cAMP+AC5GsaCa reac" id="AC5GsaCaATP2id">
<Reactant specieID="AC5GsaCaATP" />
<Product specieID="cAMP" />
<Product specieID="AC5GsaCa" />
<forwardRate> 14.23e-03 </forwardRate>
<reverseRate> 0.1296e-06 </reverseRate>
</Reaction>
-->
<!-- ############### AC1 activated by Gs and CamCa4 ###################-->
<!-- 1a) GsaGTP + AC1 <-> AC1GsaGTP -->
<Reaction name = "GsaGTP_AC1_reac" id="GsaGTP_AC1_reac">
<Reactant specieID="GsaGTP"/>
<Reactant specieID="AC1"/>
<Product specieID="AC1Gsa"/>
<forwardRate>0.0385e-3</forwardRate>
<reverseRate>10e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- 1b) AC1GsaGTP + CamCa4 <-> AC1GsaGTPCamCa4 -->
<Reaction name = "AC1GsaGTP_CamCa4_Reac" id="AC1GsaGTP_CamCa4_Reac">
<Reactant specieID="AC1Gsa"/>
<Reactant specieID="CamCa4"/>
<Product specieID="AC1GsaCamCa4"/>
<forwardRate>0.006e-3</forwardRate>
<reverseRate>0.9e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- 1c) AC1GsaGTPCamCa4 + ATP <-> AC1GsaGTPCamCa4ATP -->
<Reaction name = "AC1GsaGTPCamCa4_ATP_Reac" id="AC1GsaGTPCamCa4_ATP_Reac">
<Reactant specieID="AC1GsaCamCa4"/>
<!--Reactant specieID="ATP"/-->
<Product specieID="AC1GsaCamCa4ATP"/>
<!-- if ATP: forwardRate>0.01e-3</forwardRate-->
<forwardRate>20e-3</forwardRate>
<reverseRate>2273e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- 1d)AC1GsaGTPCamCa4ATP -> AC1GsaGTPCamCa4 + cAMP -->
<Reaction name = "AC1GsaGTPCamCa4ATP_diss" id="AC1GsaGTPCamCa4ATP_diss">
<Reactant specieID="AC1GsaCamCa4ATP"/>
<Product specieID="cAMP"/>
<Product specieID="AC1GsaCamCa4"/>
<forwardRate>56.84e-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"/>
<!-- if ATP:forwardRate>0.01e-3</forwardRate-->
<forwardRate>20</forwardRate>
<reverseRate>2273e-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>5.684e-3</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--VI. *****************PDE1 *******************************-->
<!--1. PDE1 + CamCa4 <-> PDE1CamCa4 (in xpp: KfpdeCam=0.1, KbpdeCam=1) -->
<Reaction name = "PDE1+CamCa4--PDE1CamCa4" id="PDE1+CamCa4--PDE1CamCa4_id">
<Reactant specieID="PDE1" />
<Reactant specieID="CamCa4" />
<Product specieID="PDE1CamCa4" />
<forwardRate> 0.01e-03 </forwardRate>
<reverseRate> 0.1e-03 </reverseRate>
</Reaction>
<!-- PDE1CamCa4 + cAMP <-> PDE1CamCa4cAMP (in xpp: KfPde1=0.0046 KbPde1=44) -->
<Reaction name = "PDE1CamCa4+cAMP--PDE1CamCa4cAMP" id="PDE1CamCa4+cAMP--PDE1CamCa4cAMP_id">
<Reactant specieID="PDE1CamCa4" />
<Reactant specieID="cAMP" />
<Product specieID="PDE1CamCa4cAMP" />
<forwardRate> 0.0046e-03 </forwardRate>
<reverseRate> 44.0e-03 </reverseRate>
</Reaction>
<!-- PDE1CamCa4cAMP -> PDE1CamCa4 + AMP (in xpp: V_Pde1=11) -->
<Reaction name = "PDE1CamCa4cAMP--PDE1CamCa4+AMP" id="PDE1CamCa4cAMP--PDE1CamCa4+AMP_id">
<Reactant specieID="PDE1CamCa4cAMP" />
<Product specieID="PDE1CamCa4" />
<Product specieID="AMP" />
<forwardRate> 11.00e-03 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!--VII. *****************PDE10 *******************************-->
<!--1. PDE10 + cAMP <-> PDE10cAMP (in xpp: KfPDE10= KbPDE10= ) -->
<Reaction name = "PDE10+cAMP--PDE10cAMP" id="PDE10+cAMP--PDE10cAMP_id">
<Reactant specieID="PDE10" />
<Reactant specieID="cAMP" />
<Product specieID="PDE10cAMP" />
<forwardRate> 0.084e-3 </forwardRate>
<reverseRate> 16.8e-3 </reverseRate>
</Reaction>
<!--2. PDE10cAMP -> PDE10 + AMP (in xpp: V_PDE10=18) -->
<Reaction name = "PDE10cAMP--PDE10+AMP" id="PDE10cAMP--PDE10+AMP_id">
<Reactant specieID="PDE10cAMP" />
<Product specieID="PDE10" />
<Product specieID="AMP" />
<forwardRate> 4.2e-3 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!--IX. *****************pPDE10 activity *******************************-->
<!--1. pPDE10 + cAMP <-> pPDE10cAMP -->
<Reaction name = "pPDE10+cAMP--pPDE10cAMP" id="pPDE10+cAMP--pPDE10cAMP_id">
<Reactant specieID="pPDE10" />
<Reactant specieID="cAMP" />
<Product specieID="pPDE10cAMP" />
<forwardRate> 0.336e-3 </forwardRate>
<reverseRate> 67.2e-3 </reverseRate>
</Reaction>
<!--2. pPDE10cAMP -> pPDE10 + AMP source: -->
<Reaction name = "pPDE10cAMP--pPDE10+AMP" id="pPDE10cAMP--pPDE10+AMP_id">
<Reactant specieID="pPDE10cAMP" />
<Product specieID="pPDE10" />
<Product specieID="AMP" />
<forwardRate> 16.8e-3 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!--3. AMP -> ATP (in xpp: katp=10) -->
<Reaction name = "AMP-ATP" id="AMP-AMP">
<Reactant specieID="AMP" />
<!--Product specieID="ATP" /-->
<!-- eliminate product if no ATP -->
<forwardRate> 0.1e-03 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!-- *****************PDE4 and pPDE4 activity *******************************-->
<!-- 15) cAMP + PDE4 <-> PDE4cAMP -->
<Reaction name = "PDE4 enzyme1" id="PDE4bind">
<Reactant specieID="PDE4" />
<Reactant specieID="cAMP" />
<Product specieID="PDE4cAMP" />
<forwardRate> 0.0216e-03 </forwardRate>
<reverseRate> 68.95e-03 </reverseRate>
</Reaction>
<!-- 16) 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>
</Reaction>
<!-- 17) cAMP + pPDE4 <-> pPDE4cAMP -->
<Reaction name = "pPDE4 enzyme1" id="pPDE4bind">
<Reactant specieID="pPDE4" />
<Reactant specieID="cAMP" />
<Product specieID="pPDE4cAMP" />
<forwardRate> 0.0864e-03 </forwardRate>
<reverseRate> 275.8e-3 </reverseRate>
</Reaction>
<!-- 18) pPDE4cAMP -> AMP + pPDE4 -->
<Reaction name = "pPDE4 actvcomp" id="pPDE4cat">
<Reactant specieID="pPDE4cAMP" />
<Product specieID="pPDE4" />
<Product specieID="AMP" />
<forwardRate> 68.932e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- extra PDE, called PDE2, requires 2 cAMP binding for activity -->
<!-- PDE2 + cAMP <-> PDE2cAMP Km=40 uM, source: WadaJBiolChem262-5139
Not allowing this single bound form to be active -->
<Reaction name = "PDE2+cAMP--PDE2cAMP" id="PDE2+cAMP--PDE2cAMP">
<Reactant specieID="PDE2" />
<Reactant specieID="cAMP" />
<Product specieID="PDE2cAMP" />
<forwardRate> 0.00002e-3 </forwardRate>
<reverseRate> 0.5e-3 </reverseRate>
</Reaction>
<!-- PDE2cGMP+cAMP <-> PDE2cGMPcAMP -> PDE2cGMP + AMP kD=1.0 uM, Kc
at=18x source: WadaJBiolChem262-5139 -->
<Reaction name = "PDE2cAMP+cAMP--PDE2cAMP2" id="PDE2cAMP+cAMP--PDE2cAMP2">
<Reactant specieID="PDE2cAMP" />
<Reactant specieID="cAMP" />
<Product specieID="PDE2cAMP2" />
<forwardRate> 0.0059e-3 </forwardRate>
<reverseRate> 0.5e-3 </reverseRate>
</Reaction>
<Reaction name = "PDE2cAMP2--PDE2cAMP+AMP" id="PDE2cAMP2--PDE2cAMP+AMP">
<Reactant specieID="PDE2cAMP2" />
<Product specieID="PDE2cAMP" />
<Product specieID="AMP" />
<forwardRate> 5.4e-3 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!--VIII. *****************PKAc phosphorylation of PDE10 and PP2A dephos*************-->
<!-- slower than previous, based on A. Chay and cAMP decay. Km=120nM-->
<!--1a. PKAc + PDE10 -> PKAcPDE10 -->
<Reaction name = "PDE10 phosp1" id="phospPDE101">
<Reactant specieID="PKAc" />
<Reactant specieID="PDE10" />
<Product specieID="PKAcPDE10" />
<forwardRate> 0.25e-06 </forwardRate>
<reverseRate> 0.024e-03 </reverseRate>
</Reaction>
<!--2a. PKAcPDE10 -> PKAc + pPDE10 -->
<Reaction name = "PDE10 phosp2" id="phospPDE102">
<Reactant specieID="PKAcPDE10" />
<Product specieID="pPDE10" />
<Product specieID="PKAc" />
<forwardRate> 0.006e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--1b. PKAc + PDE10cAMP -> PKAcPDE10cAMP -->
<Reaction name = "PDE10cAMP phosp1" id="phospPDE10cAMP1">
<Reactant specieID="PKAc" />
<Reactant specieID="PDE10cAMP" />
<Product specieID="PKAcPDE10cAMP" />
<forwardRate> 0.25e-06 </forwardRate>
<reverseRate> 0.024e-03 </reverseRate>
</Reaction>
<!--2b. PKAcPDE10cAMP -> PKAc + pPDE10cAMP -->
<Reaction name = "PDE10cAMP phosp2" id="phospPDE10cAMP2">
<Reactant specieID="PKAcPDE10cAMP" />
<Product specieID="pPDE10cAMP" />
<Product specieID="PKAc" />
<forwardRate> 0.006e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- 23,24) pPDE10 +PP2ABPR72 -> PDE10 -->
<Reaction name = "PDE10 d_phosp1" id="dphospPDE10a">
<Reactant specieID="pPDE10" />
<Reactant specieID="PP2ABPR72" />
<Product specieID="pPDE10PP2A" />
<forwardRate> 0.024e-06 </forwardRate>
<reverseRate> 0.0096e-3 </reverseRate>
</Reaction>
<Reaction name = "PDE10 d_phosp2" id="dphospPDE10b">
<Reactant specieID="pPDE10PP2A" />
<Product specieID="PDE10" />
<Product specieID="PP2ABPR72" />
<forwardRate> 0.0024e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- 25,26) pPDE10 +PP2Acal -> PDE10 -->
<Reaction name = "PDE10 d_phosp1" id="dphospPDE10a">
<Reactant specieID="pPDE10" />
<Reactant specieID="PP2Acal" />
<Product specieID="pPDE10PP2Ac" />
<forwardRate> 0.048e-06 </forwardRate>
<reverseRate> 0.0192e-3 </reverseRate>
</Reaction>
<Reaction name = "PDE10 d_phosp2" id="dphospPDE10b">
<Reactant specieID="pPDE10PP2Ac" />
<Product specieID="PDE10" />
<Product specieID="PP2Acal" />
<forwardRate> 0.0048e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- 19) PKAc + PDE4 -> PKAcPDE4 -->
<Reaction name = "PDE4 phosp1" id="phospPDE41">
<Reactant specieID="PKAc" />
<Reactant specieID="PDE4" />
<Product specieID="PKAcPDE4" />
<forwardRate> 0.25e-6 </forwardRate>
<reverseRate> 0.08e-3 </reverseRate>
</Reaction>
<!-- 20) PKAcPDE4 -> PKAc + pPDE4 -->
<Reaction name = "PDE4 phosp2" id="phospPDE42">
<Reactant specieID="PKAcPDE4" />
<Product specieID="pPDE4" />
<Product specieID="PKAc" />
<forwardRate> 0.02e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- 21) PKAc + PDE4cAMP -> PKAcPDE4cAMP -->
<Reaction name = "PDE4cAMP phosp1" id="phospPDE41cAMP">
<Reactant specieID="PKAc" />
<Reactant specieID="PDE4cAMP" />
<Product specieID="PKAcPDE4cAMP" />
<forwardRate> 0.25e-6 </forwardRate>
<reverseRate> 0.08e-3 </reverseRate>
</Reaction>
<!-- 22) PKAcPDE4cAMP -> PKAc + pPDE4cAMP -->
<Reaction name = "PDE4cAMP phosp2" id="phospPDE42cAMP">
<Reactant specieID="PKAcPDE4cAMP" />
<Product specieID="pPDE4cAMP" />
<Product specieID="PKAc" />
<forwardRate> 0.02e-3 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- 23,24) pPDE4 +PP2ABPR72 -> PDE4
Resjo Biochem J 1999, Mol Pharmacol. 2008 De Arcangelis-->
<Reaction name = "PDE4 d_phosp1" id="dphospPDE4a">
<Reactant specieID="pPDE4" />
<Reactant specieID="PP2ABPR72" />
<Product specieID="pPDE4PP2A" />
<forwardRate> 0.024e-06 </forwardRate>
<reverseRate> 0.0096e-3 </reverseRate>
</Reaction>
<Reaction name = "PDE4 d_phosp2" id="dphospPDE4b">
<Reactant specieID="pPDE4PP2A" />
<Product specieID="PDE4" />
<Product specieID="PP2ABPR72" />
<forwardRate> 0.0024e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- 25,26) pPDE4 +PP2Acal -> PDE4
Resjo Biochem J 1999, Mol Pharmacol. 2008 De Arcangelis-->
<Reaction name = "PDE4 d_phosp1" id="dphospPDE4a">
<Reactant specieID="pPDE4" />
<Reactant specieID="PP2Acal" />
<Product specieID="pPDE4PP2Ac" />
<forwardRate> 0.048e-06 </forwardRate>
<reverseRate> 0.0192e-3 </reverseRate>
</Reaction>
<Reaction name = "PDE4 d_phosp2" id="dphospPDE4b">
<Reactant specieID="pPDE4PP2Ac" />
<Product specieID="PDE4" />
<Product specieID="PP2Acal" />
<forwardRate> 0.0048e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!--X. **************************************************************************-->
<!-- PLC, Dag, IP3, 2ag and PKC, from Gq RXN FILE -->
<!-- Review these and check all molecule names -->
<!--1a. Plc+Ca <-> PlcCa 2500 nM -->
<Reaction name = "Plc+Ca--PlcCa" id="Plc+Ca--PlcCa">
<Reactant specieID="Ca" />
<Reactant specieID="Plc" />
<Product specieID="PlcCa" />
<forwardRate> 0.0004e-03 </forwardRate>
<reverseRate> 1e-03 </reverseRate>
</Reaction>
<!--2a. PlcCa + GaGTP <-> PlcCaGqa 200 nM-->
<Reaction name = "PlcCa+GqaGTP--PlcCaGqa" id="PlcCa+GqaGTP--PlcCaGqa">
<Reactant specieID="GqaGTP" />
<Reactant specieID="PlcCa" />
<Product specieID="PlcCaGqa" />
<forwardRate> 0.004375e-03 </forwardRate>
<reverseRate> 0.7e-03 </reverseRate>
</Reaction>
<!--1b. Plc + GqaGTP <-> PlcGqa 1000 nM -->
<!--AB: Falkenburger 2010 uses 0.71e-3 for reverse rate -->
<Reaction name = "Plc+GqaGTP--PlcGqa" id="Plc+GqaGTP--PlcGqa">
<Reactant specieID="GqaGTP" />
<Reactant specieID="Plc" />
<Product specieID="PlcGqa" />
<forwardRate> 0.0007e-03 </forwardRate>
<reverseRate> 0.7e-03 </reverseRate>
</Reaction>
<!--2b. PlcGqa + Ca <-> PlcCaGqa 500 nM-->
<Reaction name = "PlcGaGTP+Ca--PlcCaGqa" id="PlcGaGTP+Ca--PlcCaGqa">
<Reactant specieID="Ca" />
<Reactant specieID="PlcGqa" />
<Product specieID="PlcCaGqa" />
<forwardRate> 0.0025e-03 </forwardRate>
<reverseRate> 1.0e-03 </reverseRate>
</Reaction>
<!--3i. PlcCa + Pip2 <-> PlcCaPip2 Possibly make these two 3x-5x faster-->
<Reaction name = "PlcCa+Pip2--PlcCaPip2" id="PlcCa+Pip2--PlcCaPip2">
<Reactant specieID="PlcCa" />
<Reactant specieID="Pip2" />
<Product specieID="PlcCaPip2" />
<forwardRate> 0.03e-06 </forwardRate>
<reverseRate> 1.2e-03 </reverseRate>
</Reaction>
<!--4i. PlcCaPip2 <-> PlcCaDag + Ip3 -->
<Reaction name = "PlcCaPip2--PlcCa+Dag+Ip3" id="PlcCaPip2--PlcCa+Dag+Ip3">
<Reactant specieID="PlcCaPip2" />
<Product specieID="PlcCa" />
<Product specieID="Ip3" />
<Product specieID="Dag" />
<forwardRate> 0.3e-03 </forwardRate>
<reverseRate> 0e-03 </reverseRate>
</Reaction>
<!--3j. PlcCaGqa + Pip2 <-> PlcCaGqaPip2 Possibly make these two 3x-5x faster -->
<Reaction name = "PlcCaGqa+Pip2--PlcCaGqaPip2" id="PlcCaGqa+Pip2--PlcCaGqaPip2">
<Reactant specieID="PlcCaGqa" />
<Reactant specieID="Pip2" />
<Product specieID="PlcCaGqaPip2" />
<forwardRate> 1.665e-06 </forwardRate>
<reverseRate> 60e-03 </reverseRate>
</Reaction>
<!--4j. PlcCaGqaPip2 <-> PlcCaGqaDag + Ip3 -->
<Reaction name = "PlcCaGqaPip2--PlcCaGqaDag+Ip3" id="PlcCaGqaPip2--PlcCaGqaDag+Ip3">
<Reactant specieID="PlcCaGqaPip2" />
<Product specieID="PlcCaGqa" />
<Product specieID="Dag" />
<Product specieID="Ip3" />
<forwardRate> 30e-03 </forwardRate>
<reverseRate> 0e-03 </reverseRate>
</Reaction>
<!-- GAP activity - only with PLC bound not to PIP2. Make slower for stronge 2AG response?-->
<!-- PlcGaGTP <-> Plc + Gabg -->
<Reaction name = "PlcGqa--Plc+GqaGDP" id="PlcGqa--Plc+GqaGDP">
<Reactant specieID="PlcGqa" />
<Product specieID="Plc" />
<Product specieID="GqaGDP" />
<forwardRate> 12e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- Gap activity of PlcCa. Make slower for stronge 2AG response?-->
<Reaction name = "PlcCaGqa--PlcCa+GaGDP" id="PlcCaGqa--Plc+GaGDP">
<Reactant specieID="PlcCaGqa" />
<Product specieID="PlcCa" />
<Product specieID="GqaGDP" />
<forwardRate> 12e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<!-- Ca + Dgl <-> CaDgl Dgl is DAG lipase, which produces 2AG -->
<!-- no source for rates. Make 400 nM affinity -->
<Reaction name = "Ca+Dlg--CaDgl" id="Ca+Dlg--CaDgl">
<Reactant specieID="Ca" />
<Reactant specieID="Dgl" />
<Product specieID="CaDgl" />
<forwardRate> 0.125e-03 </forwardRate>
<reverseRate> 50e-03 </reverseRate>
</Reaction>
<!-- Dag + CaDgl <-> DagCaDgl -->
<!--affinity dec to 2500 nM -->
<Reaction name = "Dag+CaDlg--DagCaDgl" id="Dag+CaDlg--DagCaDgl">
<Reactant specieID="Dag" />
<Reactant specieID="CaDgl" />
<Product specieID="DagCaDgl" />
<forwardRate> 0.0005e-03 </forwardRate>
<reverseRate> 1.0e-03 </reverseRate>
</Reaction>
<!-- DagCaDgl <-> CaDgl + 2ag -->
<!-- kcat from Rosenburger Lipids 2007 -->
<Reaction name = "DagCaDgl--CaDgl+2ag" id="DagCaDgl--CaDgl+2ag">
<Reactant specieID="DagCaDgl" />
<Product specieID="CaDgl" />
<Product specieID="2ag" />
<forwardRate> 0.25e-03 </forwardRate>
<reverseRate> 0e-03 </reverseRate>
</Reaction>
<!-- ************* degradation of IP3 and 2AG, implementing the enzymes? -->
<!-- Ip3 <-> Ip3degrad rate from IP3deg from Xu watras Loew J Cell science 2003 -->
<Reaction name = "Ip3--Ip3degrad" id="Ip3--Ip3degrad">
<Reactant specieID="Ip3" />
<Product specieID="Ip3degrad" />
<forwardRate> 0.1e-03 </forwardRate>
<reverseRate> 0.0e-03 </reverseRate>
</Reaction>
<!-- previously unlabeled IP3 degradation rxn -->
<Reaction name = "Ip3degrad+PIkinase--Ip3degPIk" id="PIkinase1">
<Reactant specieID="Ip3degrad" />
<Reactant specieID="PIkinase" />
<Product specieID="Ip3degPIk" />
<forwardRate> 0.0005e-3 </forwardRate>
<reverseRate> 0.4e-03 </reverseRate>
</Reaction>
<!-- rate from PIP2synth from Xu watras Loew J Cell science 2003 -->
<Reaction name = "Ip3degPIk--PIP2 + PIkinase" id="PIkinase2">
<Reactant specieID="Ip3degPIk" />
<Product specieID="PIkinase" />
<Product specieID="Pip2" />
<forwardRate> 0.1e-3 </forwardRate>
<reverseRate> 0e-3 </reverseRate>
</Reaction>
<!-- 2ag <-> 2agDegrad Degraded 2AG -->
<Reaction name = "2ag--2agDegrad" id="2ag--2agDegrad">
<Reactant specieID="2ag" />
<Product specieID="2agDegrad" />
<forwardRate> 0.25e-03 </forwardRate>
<reverseRate> 0.0e-03 </reverseRate>
</Reaction>
<!-- ************* degradation of DAG by DAG kinase -->
<!-- Dag + DagK <-> DagKdag -> PA step 1 (Km = 2 mol% Shulga et al. FEBS letters -->
<Reaction name = "DagKdag1" id="DagKdag1">
<Reactant specieID="Dag" />
<Reactant specieID="DagK" />
<Product specieID="DagKdag" />
<forwardRate> 0.00007e-03 </forwardRate>
<reverseRate> 0.8e-3 </reverseRate>
</Reaction>
<!-- Dag + DagK <-> DagKdag -> PA step 2 -->
<Reaction name = "DagKdag1" id="DagKdag1">
<Reactant specieID="DagKdag" />
<Product specieID="PA" />
<Product specieID="DagK" />
<forwardRate> 0.2e-03 </forwardRate>
<reverseRate> 0.0e-03 </reverseRate>
</Reaction>
<!-- These are values from Hellgren Kotaleski PKC paper. 2.5 uM affinity -->
<!-- Pkc + Ca <-> PkcCa -->
<Reaction name = "Pkc+Ca--PkcCa" id="Pkc+Ca--PkcCa">
<Reactant specieID="Ca" />
<Reactant specieID="Pkc" />
<Product specieID="PkcCa" />
<forwardRate> 0.020e-03 </forwardRate>
<reverseRate> 50e-03 </reverseRate>
</Reaction>
<!-- THese are values from Hellgren Kotaleski PKC paper. 10 uM affinity
MUCH slower binding compared to CaDgl -->
<!-- PkcCa + Dag <-> PkcCaDag -->
<Reaction name = "PkcCa+Dag--PkcCaDag" id="PkcCa+Dag--PkcCaDag">
<Reactant specieID="PkcCa" />
<Reactant specieID="Dag" />
<Product specieID="PkcCaDag" />
<forwardRate> 0.015e-06 </forwardRate>
<reverseRate> 0.15e-03 </reverseRate>
</Reaction>
<!-- ***************************************************************************-->
<!--XI. PP2B, PP2A, PKA, Darpp32, CaMKII from Gs RXN FILE -->
<!-- ******* PKA from Asia Hippo Model ********* -->
<!--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-06</forwardRate>
<reverseRate>0.060e-03</reverseRate>
</Reaction>
<!--2) PKAcAMP2 + 2cAMP <-> PKAcAMP4 -->
<Reaction name = "PKAcAMP2_bind" id="PKAcAMP2_bind">
<Reactant specieID="PKAcAMP2"/>
<Reactant specieID="cAMP" n="2"/>
<Product specieID="PKAcAMP4"/>
<forwardRate>0.35e-06</forwardRate>
<reverseRate>0.6e-3</reverseRate>
</Reaction>
<!--3) PKAcAMP4 <-> 2PKAr(as dimer) + 2PKAc(monomers) -->
<Reaction name = "PKAcAMP4_diss" id="PKAcAMP4_diss">
<Reactant specieID="PKAcAMP4"/>
<Product specieID="PKAr"/>
<Product specieID="PKAc" n="2"/>
<forwardRate>0.24e-03</forwardRate>
<reverseRate>0.0255e-03</reverseRate>
</Reaction>
<!--1) Epac1-camps + cAMP <-> Epac1-camps_cAMP -->
<Reaction name = "Epac_bind" id="Epac_bind">
<Reactant specieID="Epac1"/>
<Reactant specieID="cAMP"/>
<Product specieID="Epac1cAMP"/>
<forwardRate>0.033e-6</forwardRate>
<reverseRate>0.08e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- Cam or CamC2N or CamC2C or CamCa4 binding to PP2B. Check rates for microscopic reversibility -->
<!--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>
</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>
</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>
</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>
</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>
</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>
</Reaction>
<!-- PP2BCamCa2 + Ca2 <-> PP2BCamCa4, either N site or C site -->
<!--4N) N 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>
</Reaction>
<!--4C) C 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>
</Reaction>
<!--PKAc + PP2AB56d <-> PKAcPP2AB56d Km=172nM (in xpp: k27=0.0025 k_27=0.3) -->
<Reaction name = "PKAc+PP2A--PKAcPP2AB56d reac" id="PKAc+PP2A--PKAcPP2AB56d_id">
<Reactant specieID="PP2AB56d" />
<Reactant specieID="PKAc" />
<Product specieID="PKAcPP2AB56d" />
<forwardRate> 0.00125e-03 </forwardRate>
<reverseRate> 0.185e-03 </reverseRate>
</Reaction>
<!--PKAcPP2AB56d -> PKAc + pPP2A(_B56d) (in xpp: v27=0.1) -->
<Reaction name = "PKAcPP2AB56d--PKAc+pPP2A reac" id="PKAcPP2AB56d--PKAc+pPP2A_id">
<Reactant specieID="PKAcPP2AB56d" />
<Product specieID="PKAc" />
<Product specieID="pPP2A" />
<forwardRate> 0.03e-03 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!--pPP2A(_B56d) -> PP2AB56d (in xpp: v28=0.004) -->
<Reaction name = "pPP2A--PP2A reac" id="pPP2A--PP2Aid">
<Reactant specieID="pPP2A" />
<Product specieID="PP2AB56d" />
<forwardRate> 0.02e-03 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!--PP2ABPR72 + Ca -> PP2Acal(_BPR72) (in xpp: kf4=0.022, kb4=0.11) -->
<!-- binding updated from paper measuring binding -->
<Reaction name = "PP2ABPR72+Ca--PP2Acal reac" id="PP2Acal3+Ca--PP2Acal_id">
<Reactant specieID="PP2ABPR72" />
<Reactant specieID="Ca" />
<Product specieID="PP2Acal" />
<forwardRate> 0.02e-6 </forwardRate>
<reverseRate> 0.1e-3 </reverseRate>
</Reaction>
<!-- D32 + PKAc <-> D32PKAc Km=3.7uM (in xpp: k20=0.0027 k_20=8 v20=2, Kd=) -->
<Reaction name = "D32+PKAc--D32PKAc reac" id="D32+PKAc--D32PKAc_id">
<Reactant specieID="D32" />
<Reactant specieID="PKAc" />
<Product specieID="D32PKAc" />
<forwardRate> 0.0027e-03 </forwardRate>
<reverseRate> 8.0e-03 </reverseRate>
</Reaction>
<!-- D32PKAc -> PKAc + D32p34 (in xpp: v20=2) -->
<Reaction name = "D32PKAc--PKAc+D32p34 reac" id="D32PKAc--PKAc+D32p34_id">
<Reactant specieID="D32PKAc" />
<Product specieID="PKAc" />
<Product specieID="D32p34" />
<forwardRate> 2.0e-03 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!-- D32p34 + PP1 <-> D32p34PP1 (in xpp: k21=0.4 k_21=0.58, Kd=) -->
<Reaction name = "D32p34+PP1--D32p34pp1 reac" id="D32p34+PP1--D32p34pp1_id">
<Reactant specieID="D32p34" />
<Reactant specieID="PP1" />
<Product specieID="D32p34PP1" />
<forwardRate> 0.4e-03 </forwardRate>
<reverseRate> 0.58e-03 </reverseRate>
</Reaction>
<!-- ******* PP2B dephos of DARPP32 *********** -->
<!-- D32p34 + PP2BCamCa4 <-> D32p34PP2BCamCa4 King et al. 1984 Km=1.6uM -->
<Reaction name = "D32p34+PP2BCamCa4--D32p34PP2BCamCa4 reac" id="D32p34+PP2BCamCa4--D32p34PP2BCamCa4_id">
<Reactant specieID="D32p34" />
<Reactant specieID="PP2BCamCa4" />
<Product specieID="D32p34PP2BCamCa4" />
<forwardRate> 4.0e-06 </forwardRate>
<reverseRate> 4.0e-03 </reverseRate>
</Reaction>
<!-- D32p34PP2BCamCa4 -> D32 + PP2BCamCa4 King, Hemmings: Vmax =0.2-1/sec-->
<Reaction name = "D32p34PP2BCamCa4--PP2BCamCa4+D32 reac" id="D32p34PP2BCamCa4--PP2BCamCa4+D32_id">
<Reactant specieID="D32p34PP2BCamCa4" />
<Product specieID="PP2BCamCa4" />
<Product specieID="D32" />
<forwardRate> 1e-03 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!-- D32p34PP1 + PP2BCamCa4 <-> D32p34PP1PP2BCamCa4 (in xpp: k36=0.001 k_36=2, Kd=2.5 uM) -->
<Reaction name = "D32p34PP1+PP2BCamCa4--D32p34PP1PP2BCamCa4 reac" id="D32p34pp1+PP2BCamCa4--D32p34PP1PP2BCamCa4_id">
<Reactant specieID="D32p34PP1" />
<Reactant specieID="PP2BCamCa4" />
<Product specieID="D32p34PP1PP2BCamCa4" />
<forwardRate> 4.0e-06 </forwardRate>
<reverseRate> 4.0e-03 </reverseRate>
</Reaction>
<!-- D32p34PP1PP2BCamCa4 -> PP1PP2BCamCa4 + D32 (in xpp: v36=0.5) -->
<Reaction name = "D32p34PP1PP2BCamCa4--PP1+PP2BCamCa4+D32 reac" id="D32p34PP1PP2BCamCa4--PP1+PP2BCamCa4+D32_id">
<Reactant specieID="D32p34PP1PP2BCamCa4" />
<Product specieID="PP2BCamCa4" />
<Product specieID="PP1" />
<Product specieID="D32" />
<forwardRate> 1e-03 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!--1/10th the activity compared to Ca4: Shifman ... Kennedy PNAS 2006 (for CamKII)-->
<Reaction name = "D32p34PP1+PP2BCamCa2C--D32p34PP1PP2BCamCa2C reac" id="D32p34pp1+PP2BCamCa2C--D32p34PP1PP2BCamCa2C_id">
<Reactant specieID="D32p34PP1" />
<Reactant specieID="PP2BCamCa2C" />
<Product specieID="D32p34PP1PP2BCamCa2C" />
<forwardRate> 0.10e-06 </forwardRate>
<reverseRate> 0.40e-03 </reverseRate>
</Reaction>
<!-- D32p34PP1PP2BCamCa2C -> PP1PP2BCamCa2C + D32 (in xpp: v36=0.5) -->
<Reaction name = "D32p34PP1PP2BCamCa2C--PP1+PP2BCamCa2C+D32 reac" id="D32p34PP1PP2BCamCa2C--PP1+PP2BCamCa2C+D32_id">
<Reactant specieID="D32p34PP1PP2BCamCa2C" />
<Product specieID="PP2BCamCa2C" />
<Product specieID="PP1" />
<Product specieID="D32" />
<forwardRate> 0.1e-03 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!-- ******* PP2A dephos of DARPP32 *********** -->
<!-- D32p34 + PP2ABPR72 <-> D32p34PP2ABPR72 (in xpp: k22b=0.0001 k_22b=2, Kd=) -->
<!-- these are ~15x faster than xpp model, slower than Oliveira -->
<!-- rates taken from StriatumCRCNS/StochasticSP1/PKAspace/MSPNreactionsPP2AslowPKAdiff.xml -->
<Reaction name = "D32p34+PP2ABPR72--D32p34PP2ABPR72 reac" id="D32p34+PP2ABPR72--D32p34PP2ABPR72_id">
<Reactant specieID="D32p34" />
<Reactant specieID="PP2ABPR72" />
<Product specieID="D32p34PP2ABPR72" />
<forwardRate> 1.52e-06 </forwardRate>
<reverseRate> 0.056 </reverseRate>
</Reaction>
<!-- D32p34PP2ABPR72 -> D32 + PP2ABPR72 (in xpp: v22b=0.5) -->
<Reaction name = "D32p34PP2ABPR72--PP2ABPR72+D32 reac" id="D32p34PP2ABPR72--PP2ABPR72+D32_id">
<Reactant specieID="D32p34PP2ABPR72" />
<Product specieID="PP2ABPR72" />
<Product specieID="D32" />
<forwardRate> 0.014 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!-- D32p34 + PP2AB56d <-> D32p34PP2AB56d (in xpp: k22b=0.0001 k_22b=2, Kd=) -->
<!-- these are ~15x faster than xpp model #######, slower than Oliveira -->
<!-- rates taken from StriatumCRCNS/StochasticSP1/PKAspace/MSPNreactionsPP2AslowPKAdiff.xml -->
<Reaction name = "D32p34+PP2AB56d--D32p34PP2AB56d reac" id="D32p34+PP2AB56d--D32p34PP2AB56d_id">
<Reactant specieID="D32p34" />
<Reactant specieID="PP2AB56d" />
<Product specieID="D32p34PP2AB56d" />
<forwardRate> 1.52e-06 </forwardRate>
<reverseRate> 0.056 </reverseRate>
</Reaction>
<!-- D32p34PP2AB56d -> D32 + PP2AB56d (in xpp: v22b=0.5) -->
<Reaction name = "D32p34PP2AB56d--PP2AB56d+D32 reac" id="D32p34PP2AB56d--PP2AB56d+D32_id">
<Reactant specieID="D32p34PP2AB56d" />
<Product specieID="PP2AB56d" />
<Product specieID="D32" />
<forwardRate> 0.014 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!-- D32p34pp1 + PP2ABPR72 <-> D32p34PP1PP2ABPR72 -> D32 + PP1 + PP2ABPR72 (in xpp: k36b=0.0001 k_36b=2, Kd=) -->
<Reaction name = "D32p34pp1+PP2ABPR72--D32p34PP1PP2ABPR72 reac" id="D32p34pp1+PP2ABPR72--D32p34PP1PP2ABPR72_id">
<Reactant specieID="D32p34PP1" />
<Reactant specieID="PP2ABPR72" />
<Product specieID="D32p34PP1PP2ABPR72" />
<forwardRate> 0.36e-06 </forwardRate>
<reverseRate> 0.0146 </reverseRate>
</Reaction>
<!-- D32p34PP1PP2ABPR72 -> PP1PP2ABPR72 + D32 (in xpp: v36b=0.5) -->
<Reaction name = "D32p34PP1PP2ABPR72--PP1+PP2ABPR72+D32 reac" id="D32p34PP1PP2ABPR72--PP1+PP2ABPR72+D32_id">
<Reactant specieID="D32p34PP1PP2ABPR72" />
<Product specieID="PP2ABPR72" />
<Product specieID="PP1" />
<Product specieID="D32" />
<forwardRate> 0.00336 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!-- D32p34pp1 + PP2AB56d <-> D32p34PP1PP2AB56d -> D32 + PP1 + PP2AB56d -->
<Reaction name = "D32p34pp1+PP2AB56d--D32p34PP1PP2AB56d reac" id="D32p34pp1+PP2AB56d--D32p34PP1PP2AB56d_id">
<Reactant specieID="D32p34PP1" />
<Reactant specieID="PP2AB56d" />
<Product specieID="D32p34PP1PP2AB56d" />
<forwardRate> 0.36e-06 </forwardRate>
<reverseRate> 0.0146 </reverseRate>
</Reaction>
<!-- D32p34PP1PP2AB56d -> PP1PP2AB56d + D32 (in xpp: v36b=0.5) -->
<Reaction name = "D32p34PP1PP2AB56d--PP1+PP2AB56d+D32 reac" id="D32p34PP1PP2AB56d--PP1+PP2AB56d+D32_id">
<Reactant specieID="D32p34PP1PP2AB56d" />
<Product specieID="PP2AB56d" />
<Product specieID="PP1" />
<Product specieID="D32" />
<forwardRate> 0.00336 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!-- phos D32 on T75, which then inhibits PKAc -->
<!-- Cdk5 + D32 <-> Cdk5D32 (in xpp: k23=0.00045 k_23=2) -->
<Reaction name = "Cdk5+D32--Cdk5D32 reac" id="Cdk5+D32--Cdk5D32_id">
<Reactant specieID="Cdk5" />
<Reactant specieID="D32" />
<Product specieID="Cdk5D32" />
<forwardRate> 0.0045e-03 </forwardRate>
<reverseRate> 40e-3 </reverseRate>
</Reaction>
<!-- Cdk5D32 -> D32p75 + Cdk5 (in xpp: v23=0.5) -->
<!-- rates and quantities adjusted to achieve 10 uM D32p75 at basal -->
<Reaction name = "Cdk5D32--D32p75+Cdk5 reac" id="Cdk5D32--D32p75+Cdk5_id">
<Reactant specieID="Cdk5D32" />
<Product specieID="D32p75" />
<Product specieID="Cdk5" />
<forwardRate> 10e-3 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!--D32p75 + PKAc <-> DP75PKA (in xpp: k24=0.00037 k_24=1) Kd=2.7uM -->
<Reaction name = "D32p75+PKAc--D32p75PKAc reac" id="D32p75+PKAc--D32p75PKAc_id">
<Reactant specieID="D32p75" />
<Reactant specieID="PKAc" />
<Product specieID="D32p75PKAc" />
<forwardRate> 0.00037e-03 </forwardRate>
<reverseRate> 1.0e-03 </reverseRate>
</Reaction>
<!-- dephos of D32p75 on PP2A(both BPR75 and B56d), phosphoPP2A, and Ca bound PP2A -->
<!--D32p75 + pPP2A(_B56d) <-> D32p75pPP2A(_B56d) (must faster than in xpp: k25=0.0004 k_25=12)-->
<Reaction name = "D32p75+pPP2A--D32p75pPP2A reac" id="D32p75+pPP2A--D32p75pPP2Aid">
<Reactant specieID="D32p75" />
<Reactant specieID="pPP2A" />
<Product specieID="D32p75pPP2A" />
<forwardRate> 0.015e-03 </forwardRate>
<reverseRate> 168e-3 </reverseRate>
</Reaction>
<!--D32p75pPP2A(_B56d) -> D32 + pPP2A(_B56d) (in xpp: v25=3) -->
<Reaction name = "D32p75pPP2A--D32+pPP2A reac" id="D32p75pPP2A--D32+pPP2Aid">
<Reactant specieID="D32p75pPP2A" />
<Product specieID="D32" />
<Product specieID="pPP2A" />
<forwardRate> 42e-3 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!--D32p75 + PP2ABPR72 <-> D32p75PP2ABPR72 (much faster than in xpp: k26=0.0001 k_26=6.4) -->
<Reaction name = "D32p75+PP2ABPR72--D32p75PP2ABPR72 reac" id="D32p75+PP2ABPR72--D32p75PP2ABPR72_id">
<Reactant specieID="D32p75" />
<Reactant specieID="PP2ABPR72" />
<Product specieID="D32p75PP2ABPR72" />
<forwardRate> 0.0023e-3 </forwardRate>
<reverseRate> 84e-3 </reverseRate>
</Reaction>
<!--D32p75PP2ABPR72 -> D32 + PP2ABPR72 (in xpp: v26=1.6) -->
<Reaction name = "D32p75PP2ABPR72--D32+PP2ABPR72 reac" id="D32p75PP2ABPR72--D32+PP2ABPR72_id">
<Reactant specieID="D32p75PP2ABPR72" />
<Product specieID="D32" />
<Product specieID="PP2ABPR72" />
<forwardRate> 21e-3 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!--D32p75 + PP2AB56d <-> D32p75PP2AB56d (must faster than in xpp: k26=0.0001 k_26=6.4) -->
<Reaction name = "D32p75+PP2AB56d--D32p75PP2AB56d reac" id="D32p75+PP2AB56d--D32p75PP2AB56d_id">
<Reactant specieID="D32p75" />
<Reactant specieID="PP2AB56d" />
<Product specieID="D32p75PP2AB56d" />
<forwardRate> 0.0023e-3 </forwardRate>
<reverseRate> 84e-3 </reverseRate>
</Reaction>
<!--D32p75PP2AB56d -> D32 + PP2AB56d (in xpp: v26=1.6) -->
<Reaction name = "D32p75PP2AB56d--D32+PP2AB56d reac" id="D32p75PP2AB56d--D32+PP2AB56d_id">
<Reactant specieID="D32p75PP2AB56d" />
<Product specieID="D32" />
<Product specieID="PP2AB56d" />
<forwardRate> 21e-3 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!--D32p75 + PP2Acal(_BPR72) -> D32p75PP2Acal(_BPR72) (must faster than in xpp: k25c=0.0004 k_25c=12 v25c=3) -->
<Reaction name = "D32p75+PP2Acal--D32p75PP2Acal reac" id="D32p75+PP2Acal--D32p75PP2A_id">
<Reactant specieID="D32p75" />
<Reactant specieID="PP2Acal" />
<Product specieID="D32p75PP2Acal" />
<forwardRate> 0.015e-03 </forwardRate>
<reverseRate> 168e-3 </reverseRate>
</Reaction>
<!--D32p75PP2Acal(_BPR72) -> D32 + PP2Acal(_BPR72) -->
<Reaction name = "D32p75PP2Acal-D32+PP2Acal reac" id="D32p75PP2Acal-D32+PP2Acal_id">
<Reactant specieID="D32p75PP2Acal" />
<Product specieID="PP2Acal" />
<Product specieID="D32" />
<forwardRate> 42e-3 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!--XII. *************** CamKII ************* ReDo/simplify with higher order Rxn-->
<!--1) CamCa4 + CK <-> CKCamCa4 -->
<Reaction name = "CK bind" id="CK_bind">
<Reactant specieID="CamCa4" />
<Reactant specieID="CK" />
<Product specieID="CKCamCa4" />
<forwardRate> 0.01e-3 </forwardRate>
<reverseRate> 3e-3 </reverseRate>
<!--0.8 from ode file
reverseRate> 0.8e-3 </reverseRate-->
</Reaction>
<!--2a) 3 CKCamCa4 + 1 CKCamCa4 <-> 3 CKCamCa4 + 1 CKpCamCa4-->
<Reaction name = "CKCam bind" id="CKCam_bind">
<Reactant specieID="CKCamCa4" power="4" />
<Product specieID="CKCamCa4" power="3" />
<Product specieID="CKpCamCa4" />
<forwardRate> 13.0e-18 </forwardRate>
<reverseRate> 0e-3 </reverseRate>
</Reaction>
<!--2b) 2 CKCamCa4 + 1 CKCamCa4 <-> 2 CKCamCa4 + 1 CKpCamCa4-->
<Reaction name = "CKCam bind" id="CKCam_bind">
<Reactant specieID="CKCamCa4" power="3" />
<Product specieID="CKCamCa4" power="2" />
<Product specieID="CKpCamCa4" />
<forwardRate> 2.0e-12 </forwardRate>
<reverseRate> 0e-3 </reverseRate>
</Reaction>
<!--2c) 2 CKpCamCa4 + 2 CKCamCa4 <-> 3 CKpCamCa4 + 1 CKCamCa4-->
<Reaction name = "CKCam bind" id="CKCam_bind">
<Reactant specieID="CKpCamCa4" power="2" />
<Reactant specieID="CKCamCa4" power="2" />
<Product specieID="CKCamCa4" />
<Product specieID="CKpCamCa4" power="3" />
<forwardRate> 27.1e-18 </forwardRate>
<reverseRate> 0e-3 </reverseRate>
</Reaction>
<!-- CKpCamCamCa4 <-> CKp + CamCa4 -->
<Reaction name = "CKp auto" id="CKp_auto">
<Reactant specieID="CKpCamCa4" />
<Product specieID="CamCa4" />
<Product specieID="CKp" />
<forwardRate> 0.0008e-3 </forwardRate>
<reverseRate> 0.01e-3 </reverseRate>
</Reaction>
<!-- CKp + PP1 <-> CKpPP1 -->
<Reaction name = "CKp bind" id="CKp_bind">
<Reactant specieID="CKp" />
<Reactant specieID="PP1" />
<Product specieID="CKpPP1" />
<forwardRate> 0.009e-06 </forwardRate>
<reverseRate> 0.08e-03 </reverseRate>
</Reaction>
<!-- CKpPP1 -> PP1 + CK -->
<Reaction name = "CKpPP1 reac" id="CKpPP1_reac">
<Reactant specieID="CKpPP1" />
<Product specieID="PP1" />
<Product specieID="CK" />
<forwardRate> 0.019e-03 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!-- CKpCamCa4 + PP1 <-> CKpCamCa4PP1 -->
<Reaction name = "CKpCamCa4PP1_bind" id="CKpCamPP1_bind">
<Reactant specieID="CKpCamCa4" />
<Reactant specieID="PP1" />
<Product specieID="CKpCamCa4PP1" />
<forwardRate> 0.0045e-06 </forwardRate>
<reverseRate> 0.04e-03 </reverseRate>
</Reaction>
<!--Dephos of CKpCamCa4 by PP1 -->
<!-- CKpCamCa4PP1 -> PP1 + CKCamCa4 -->
<Reaction name = "CKpCamCa4PP1_reac" id="CKpCamPP1_reac">
<Reactant specieID="CKpCamCa4PP1" />
<Product specieID="PP1" />
<Product specieID="CKCamCa4" />
<forwardRate> 0.0095e-3 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!--2a) CKCamCa4 + AIP <-> CKCamCa4_block, affinity = 40 nM-->
<Reaction name = "CKCamblock" id="CKCamblock">
<Reactant specieID="CKCamCa4" />
<Reactant specieID="AIP" />
<Product specieID="CKCam_block" />
<forwardRate> 25e-6 </forwardRate>
<reverseRate> 1e-3 </reverseRate>
</Reaction>
<!-- ***************************************************************************-->
<!-- CaMKII phos of Dag Lipase to suppress 2ag during LTP: NOVEL REACTION -->
<!--1a) Dgl + CKCam <-> Dgl_CKCam -->
<Reaction name = "Dgl_CKCamCa4_bind" id="Dgl_CKCamCa4_bind">
<Reactant specieID="Dgl" />
<Reactant specieID="CKCamCa4" />
<Product specieID="Dgl_CKCamCa4" />
<forwardRate> 0.36e-6 </forwardRate>
<reverseRate> 0.1e-3 </reverseRate>
</Reaction>
<!-- Dgl_CKCam -> pDgl + CKCam -->
<Reaction name = "Dgl_CKCam_diss" id="Dgl_CKCam_diss">
<Reactant specieID="Dgl_CKCamCa4" />
<Product specieID="pDgl" />
<Product specieID="CKCamCa4" />
<forwardRate> 0.025e-3 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!--2a Dgl + CKpCam <-> Dgl_CKpCam -->
<Reaction name = "Dgl_CKpCamCa4_bind" id="Dgl_CKpCamCa4_bind">
<Reactant specieID="Dgl" />
<Reactant specieID="CKpCamCa4" />
<Product specieID="Dgl_CKpCamCa4" />
<forwardRate> 5.4e-6 </forwardRate>
<reverseRate> 1.5e-3 </reverseRate>
</Reaction>
<!-- Dgl_CKpCam -> pDgl + CKpCam -->
<Reaction name = "Dgl_CKpCamCa4_diss" id="Dgl_CKpCamCa4_diss">
<Reactant specieID="Dgl_CKpCamCa4" />
<Product specieID="pDgl" />
<Product specieID="CKpCamCa4" />
<forwardRate> 0.375e-3 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!--1b) CaDgl + CKCam <-> Dgl_CKCam -->
<!--Reaction name = "CaDgl_CKCamCa4_bind" id="CaDgl_CKCamCa4_bind">
<Reactant specieID="CaDgl" />
<Reactant specieID="CKCamCa4" />
<Product specieID="CaDgl_CKCamCa4" />
<forwardRate> 0.36e-6 </forwardRate>
<reverseRate> 0.1e-3 </reverseRate>
</Reaction-->
<!-- CaDgl_CKCam -> CapDgl + CKCam -->
<!--Reaction name = "CaDgl_CKCam_diss" id="CaDgl_CKCam_diss">
<Reactant specieID="CaDgl_CKCamCa4" />
<Product specieID="CapDgl" />
<Product specieID="CKCamCa4" />
<forwardRate> 0.025e-3 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction-->
<!--2b CaDgl + CKpCam <-> CaDgl_CKpCam -->
<Reaction name = "CaDgl_CKpCamCa4_bind" id="CaDgl_CKpCamCa4_bind">
<Reactant specieID="CaDgl" />
<Reactant specieID="CKpCamCa4" />
<Product specieID="CaDgl_CKpCamCa4" />
<forwardRate> 5.4e-6 </forwardRate>
<reverseRate> 1.5e-3 </reverseRate>
</Reaction>
<!-- CaDgl_CKpCam -> CapDgl + CKpCam -->
<Reaction name = "CaDgl_CKpCamCa4_diss" id="CaDgl_CKpCamCa4_diss">
<Reactant specieID="CaDgl_CKpCamCa4" />
<Product specieID="CapDgl" />
<Product specieID="CKpCamCa4" />
<forwardRate> 0.375e-3 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!-- 3)Dgl + CKp <-> Dgl_CKp -->
<Reaction name = "Dgl_CKp_bind" id="Dgl_CKp_bind">
<Reactant specieID="Dgl" />
<Reactant specieID="CKp" />
<Product specieID="Dgl_CKp" />
<forwardRate> 0.36e-6 </forwardRate>
<reverseRate> 0.1e-3 </reverseRate>
</Reaction>
<!-- Dgl_CKp -> pDgl + CKp -->
<Reaction name = "Dgl_CKp_diss" id="Dgl_CKp_diss">
<Reactant specieID="Dgl_CKp" />
<Product specieID="pDgl" />
<Product specieID="CKp" />
<forwardRate> 0.025e-3 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!-- pDgl dephosphorylation -->
<Reaction name = "pDgl_dephos" id="pDgl_dephos">
<Reactant specieID="pDgl" />
<Product specieID="Dgl" />
<forwardRate> 0.1e-3 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<!-- AKAR3 rates to allow comparison to Castro, etc. -->
<Reaction name = "AKAR3+PKAc bind" >
<Reactant specieID="AKAR3" />
<Reactant specieID="PKAc" />
<Product specieID="PKAcAKAR3" />
<forwardRate> 0.00625e-03 </forwardRate>
<reverseRate> 0.75e-03 </reverseRate>
</Reaction>
<Reaction name = "PKAcAKAR3 phos" >
<Reactant specieID="PKAcAKAR3" />
<Product specieID="PKAc" />
<Product specieID="pAKAR3" />
<forwardRate> 0.1875e-03 </forwardRate>
<reverseRate> 0e-03 </reverseRate>
</Reaction>
<Reaction name = "pAKAR3+PP1 bind" >
<Reactant specieID="pAKAR3" />
<Reactant specieID="PP1" />
<Product specieID="PP1pAKAR3" />
<forwardRate> 0.00025e-03 </forwardRate>
<reverseRate> 1.2e-03 </reverseRate>
</Reaction>
<Reaction name = "PP1pAKAR3 dephos" >
<Reactant specieID="PP1pAKAR3" />
<Product specieID="PP1" />
<Product specieID="AKAR3" />
<forwardRate> 0.312e-03 </forwardRate>
<reverseRate> 0e-03 </reverseRate>
</Reaction>
<!-- ############### Inhibition of phosphatases by specific antagonists ###################-->
<!-- cyclosporin A inhibits PP2A 32 pM (0.1-1nM according to Tocris)-->
<Reaction name="OAblockB56" id="OAblockB56">
<Reactant specieID="OA"/>
<Reactant specieID="PP2AB56d"/>
<Product specieID="OA_PP2AB56d"/>
<forwardRate>0.005e-3</forwardRate>
<reverseRate>0.00015e-3</reverseRate>
</Reaction>
<Reaction name="OAblockB56pp" id="OAblockB56p">
<Reactant specieID="OA"/>
<Reactant specieID="pPP2A"/>
<Product specieID="OA_pPP2A"/>
<forwardRate>0.005e-3</forwardRate>
<reverseRate>0.00015e-3</reverseRate>
</Reaction>
<Reaction name="OAblockBPR" id="OAblockBPR">
<Reactant specieID="OA"/>
<Reactant specieID="PP2ABPR72"/>
<Product specieID="OA_PP2ABPR72"/>
<forwardRate>0.005e-3</forwardRate>
<reverseRate>0.00015e-3</reverseRate>
</Reaction>
<Reaction name="OAblock2BPRal" id="OAblockBPRcal">
<Reactant specieID="OA"/>
<Reactant specieID="PP2Acal"/>
<Product specieID="OA_PP2Acal"/>
<forwardRate>0.005e-3</forwardRate>
<reverseRate>0.00015e-3</reverseRate>
</Reaction>
<!-- Okadaic acid inhibits PP1 150 nM Kd-->
<Reaction name="OAblock1" id="OAblock1">
<Reactant specieID="OA"/>
<Reactant specieID="PP1"/>
<Product specieID="OA_PP1"/>
<forwardRate>0.001e-3</forwardRate>
<reverseRate>0.15e-3</reverseRate>
</Reaction>
<!-- Rolipram IC50=2.0, Papaverine IC50=17nM -->
<Reaction name = "PDE4 inhib" id="PDE4inhib">
<Reactant specieID="PDE4" />
<Reactant specieID="Roli" />
<Product specieID="RoliPDE4" />
<forwardRate>0.001e-03 </forwardRate>
<reverseRate>2e-03 </reverseRate>
</Reaction>
<Reaction name = "PDE10 inhib" id="PDE10inhib">
<Reactant specieID="PDE10" />
<Reactant specieID="Pap" />
<Product specieID="PapPDE10" />
<forwardRate>0.001e-03 </forwardRate>
<reverseRate>0.017e-03 </reverseRate>
</Reaction>
<!--block of m1R IC50 is 0.94 nM -->
<Reaction name = "telenz+m1R--telenzm1R" id="telenz+m1R--telenzm1R">
<Reactant specieID="telenz" />
<Reactant specieID="m1R" />
<Product specieID="telenzm1R" />
<forwardRate> 0.95e-03 </forwardRate>
<reverseRate> 2.5e-03 </reverseRate>
</Reaction>
<Reaction name = "telenz+m1RGq- -telenzm1RGq" id="telenz+m1RGq- -telenzm1RGq">
<Reactant specieID="telenz" />
<Reactant specieID="m1RGq" />
<Product specieID="telenzm1RGq" />
<forwardRate> 39.6e-03 </forwardRate>
<reverseRate> 2.5e-03 </reverseRate>
</Reaction>
<!-- block of M4R IC50 is 91 nM -->
<Reaction name = "PD1028+m4R--PD1028m4R" id="PD1028+m4R--PD1028m4R">
<Reactant specieID="PD1028" />
<Reactant specieID="m4R" />
<Product specieID="PD1028m4R" />
<forwardRate> 0.028e-03 </forwardRate>
<reverseRate> 2.5e-03 </reverseRate>
</Reaction>
<Reaction name = "Gim4R+PD1028--PD1028m4RGi" id="Gm4R+PD1028--PD1028m4RGi">
<Reactant specieID="Gim4R" />
<Reactant specieID="PD1028" />
<Product specieID="PD1028m4RGi" />
<forwardRate> 3.024e-03 </forwardRate>
<reverseRate> 20.0e-03 </reverseRate>
</Reaction>
</ReactionScheme>