// DOQCS : http://doqcs.ncbs.res.in/ // Accession Name = NonOsc_Ca_IP3metabolism // Accession Number = 31 // Transcriber = Jyoti Mishra, NCBS // Developer = Jyoti Mishra, NCBS // Species = Generic mammalian // Tissue = Brain - Neuronal // Cell Compartment = Cytosol // Notes = This network models detailed metabolism of Ins(145)P3, integrated with GPCR mediated PLCbeta activation and Ca release by the InsP3 receptor in the neuron. It is similar to the NonOsc_Ca_IP3metab model (accession 23) except that some enzymes have been modified to have reversible kinetics rather than Michaelis-Menten kinetics. These modified enzymes belong to the groups: IP4-system, IP3-3K, 145_dephos and 134_dephos. Mishra J, Bhalla US. 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/kinetics/1345_dephos/145-inhib-3pase 0 1.6667e-06 1.75 "" \ white purple -17.337 -17.336 0 simundump kreac /kinetics/1345_dephos/IP4-inhib-3pase 0 1.6667e-06 0.5 "" \ white purple -12.739 -16.297 0 simundump kreac /kinetics/1345_dephos/134-inhib-3pase 0 1.6667e-06 2 "" white \ purple -10.842 -18.194 0 simundump kpool /kinetics/1345_dephos/IP4-3pase-cmplx 0 0 0 0 0 0 0 0 \ 5.9999e+05 0 /kinetics/geometry[1] 21 purple -18.609 -19.821 0 simundump kpool /kinetics/1345_dephos/IP3(145)-3pase-cmplx 0 0 0 0 0 0 0 0 \ 5.9999e+05 0 /kinetics/geometry[1] 21 purple -20.684 -22.193 0 simundump kpool /kinetics/1345_dephos/IP3(134)-3pase-cmplx 0 0 0 0 0 0 0 0 \ 5.9999e+05 0 /kinetics/geometry[1] 21 purple -9.8935 -21.244 0 simundump kpool /kinetics/1345_dephos/IP6-inhib-3pase-cmplx 0 0 0 0 0 0 0 0 \ 6e+05 0 /kinetics/geometry[1] 21 purple -19.996 -17.371 0 simundump kpool /kinetics/1345_dephos/1345_3pase 0 0 0.1 0.1 59999 59999 0 0 \ 5.9999e+05 0 /kinetics/geometry[1] white purple -13.19 -12.582 0 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Biophys J. 2002 Sep;83(3):1298-316. ( peer-reviewed publication )" \ "Exact GENESIS implementation" "Approximates original data " 10 27 0 simundump xgraph /graphs/conc1 0 0 1000 1.5607 53.863 0 simundump xgraph /graphs/conc2 0 0 1000 0.27212 59.151 0 simundump xplot /graphs/conc1/bisPP-IP4.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 7 0 0 1 simundump xplot /graphs/conc1/PP-IP5.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 52 0 0 1 simundump xplot /graphs/conc1/PP-IP4.Co 3 524288 \ "delete_plot.w ; edit_plot.D " pink 0 0 1 simundump xplot /graphs/conc1/IP6.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 39 0 0 1 simundump xplot /graphs/conc1/IP5(13456).Co 3 524288 \ "delete_plot.w ; edit_plot.D " 0 0 0 1 simundump xplot /graphs/conc1/Ca-sequester.Co 3 524288 \ "delete_plot.w ; edit_plot.D " red 0 0 1 simundump xplot /graphs/conc2/IP4(1345).Co 3 524288 \ "delete_plot.w ; edit_plot.D " 46 0 0 1 simundump xplot /graphs/conc2/IP4(3456).Co 3 524288 \ "delete_plot.w ; edit_plot.D " 61 0 0 1 simundump xplot 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524288 \ "delete_plot.w ; edit_plot.D " 7 0 0 1 simundump xplot /moregraphs/conc4/IP1(1).Co 3 524288 \ "delete_plot.w ; edit_plot.D " 1 0 0 1 simundump xcoredraw /edit/draw 0 -45.762 32.171 -42.695 36.894 simundump xtree /edit/draw/tree 0 \ /kinetics/#[],/kinetics/#[]/#[],/kinetics/#[]/#[]/#[][TYPE!=proto],/kinetics/#[]/#[]/#[][TYPE!=linkinfo]/##[] \ "edit_elm.D ; drag_from_edit.w " auto 0.6 simundump xtext /file/notes 0 1 xtextload /file/notes \ "" addmsg /kinetics/MIPP/MIPP/ip6_pase /kinetics/MIPP/IP6_ER REAC sA B addmsg /kinetics/MIPP/ip6_trp /kinetics/MIPP/IP6_ER REAC B A addmsg /kinetics/MIPP/MIPP/ip6_pase /kinetics/MIPP/IP5(12456)_ER MM_PRD pA addmsg /kinetics/MIPP/ip5(12456)_trp /kinetics/MIPP/IP5(12456)_ER REAC A B addmsg /kinetics/MIPP/MIPP/ip6_pase /kinetics/MIPP/IP5(13456)_ER MM_PRD pA addmsg /kinetics/MIPP/MIPP/ip5_3pase /kinetics/MIPP/IP5(13456)_ER REAC sA B addmsg /kinetics/MIPP/ip5(13456)_trp /kinetics/MIPP/IP5(13456)_ER REAC A B addmsg /kinetics/MIPP/ip4(1456)_trp /kinetics/MIPP/IP4(1456)_ER REAC A B addmsg /kinetics/MIPP/MIPP/ip5_3pase /kinetics/MIPP/IP4(1456)_ER MM_PRD pA addmsg /kinetics/MIPP/MIPP/ip4_3pase /kinetics/MIPP/IP3(145)_ER MM_PRD pA addmsg /kinetics/MIPP/ip3(145)_trp /kinetics/MIPP/IP3(145)_ER REAC A B addmsg /kinetics/MIPP/MIPP/ip4_3pase /kinetics/MIPP/IP4(1345)_ER REAC sA B addmsg /kinetics/MIPP/ip4(1345)_trp /kinetics/MIPP/IP4(1345)_ER REAC B A addmsg /kinetics/MIPP/IP6_ER /kinetics/MIPP/ip6_trp PRODUCT n addmsg /kinetics/IHP-system/IP6 /kinetics/MIPP/ip6_trp SUBSTRATE n addmsg /kinetics/MIPP/IP5(12456)_ER /kinetics/MIPP/ip5(12456)_trp SUBSTRATE n addmsg /kinetics/MIPP/IP5(12456) /kinetics/MIPP/ip5(12456)_trp PRODUCT n addmsg /kinetics/MIPP/IP5(13456)_ER /kinetics/MIPP/ip5(13456)_trp SUBSTRATE n addmsg /kinetics/IP4-system/IP5(13456) /kinetics/MIPP/ip5(13456)_trp PRODUCT n addmsg /kinetics/MIPP/IP4(1456)_ER /kinetics/MIPP/ip4(1456)_trp SUBSTRATE n addmsg /kinetics/IP4-system/IP4(1456) /kinetics/MIPP/ip4(1456)_trp PRODUCT n addmsg /kinetics/MIPP/IP4(1345)_ER /kinetics/MIPP/ip4(1345)_trp PRODUCT n addmsg /kinetics/IP3-3K/IP4(1345) /kinetics/MIPP/ip4(1345)_trp SUBSTRATE n addmsg /kinetics/MIPP/IP3(145)_ER /kinetics/MIPP/ip3(145)_trp SUBSTRATE n addmsg /kinetics/IP3-3K/IP3(145) /kinetics/MIPP/ip3(145)_trp PRODUCT n addmsg /kinetics/MIPP/MIPP/ip6_pase /kinetics/MIPP/MIPP REAC eA B addmsg /kinetics/MIPP/MIPP/ip5_3pase /kinetics/MIPP/MIPP REAC eA B addmsg /kinetics/MIPP/MIPP/ip4_3pase /kinetics/MIPP/MIPP REAC eA B addmsg /kinetics/MIPP/MIPP /kinetics/MIPP/MIPP/ip5_3pase ENZYME n addmsg /kinetics/MIPP/IP5(13456)_ER /kinetics/MIPP/MIPP/ip5_3pase SUBSTRATE n addmsg /kinetics/MIPP/MIPP /kinetics/MIPP/MIPP/ip4_3pase ENZYME n addmsg /kinetics/MIPP/IP4(1345)_ER /kinetics/MIPP/MIPP/ip4_3pase SUBSTRATE n addmsg /kinetics/MIPP/MIPP /kinetics/MIPP/MIPP/ip6_pase ENZYME n addmsg /kinetics/MIPP/IP6_ER /kinetics/MIPP/MIPP/ip6_pase SUBSTRATE n addmsg /kinetics/MIPP/ip5(12456)_trp /kinetics/MIPP/IP5(12456) REAC B A addmsg /kinetics/CaMKII/CaMKII-bind-CaM /kinetics/CaMKII/CaMKII REAC A B addmsg /kinetics/CaMKII/PP1-active/Deph-thr306 /kinetics/CaMKII/CaMKII MM_PRD pA addmsg /kinetics/CaMKII/PP1-active/Deph_thr286b /kinetics/CaMKII/CaMKII MM_PRD pA addmsg /kinetics/CaMKII/basal-activity /kinetics/CaMKII/CaMKII REAC A B addmsg /kinetics/CaMKII/CaMKII-bind-CaM /kinetics/CaMKII/CaMKII-CaM REAC B A addmsg /kinetics/CaMKII/PP1-active/Deph-thr286 /kinetics/CaMKII/CaMKII-CaM MM_PRD pA addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286 /kinetics/CaMKII/CaMKII-CaM REAC sA B addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286 /kinetics/CaMKII/CaMKII-CaM REAC sA B addmsg /kinetics/CaMKII/CaMK-thr286-bind-CaM /kinetics/CaMKII/CaMKII-thr286*-CaM REAC B A addmsg /kinetics/CaMKII/PP1-active/Deph-thr286 /kinetics/CaMKII/CaMKII-thr286*-CaM REAC sA B addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286 /kinetics/CaMKII/CaMKII-thr286*-CaM MM_PRD pA addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286 /kinetics/CaMKII/CaMKII-thr286*-CaM MM_PRD pA addmsg /kinetics/CaMKII/PP1-active/Deph-thr305 /kinetics/CaMKII/CaMKII*** REAC sA B addmsg /kinetics/CaMKII/PP1-active/Deph-thr286c /kinetics/CaMKII/CaMKII*** REAC sA B addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305 /kinetics/CaMKII/CaMKII*** MM_PRD pA addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305 /kinetics/CaMKII/CaMKII*** MM_PRD pA addmsg /kinetics/CaM/CaM-Ca4 /kinetics/CaMKII/CaMKII-bind-CaM SUBSTRATE n addmsg /kinetics/CaMKII/CaMKII /kinetics/CaMKII/CaMKII-bind-CaM SUBSTRATE n addmsg /kinetics/CaMKII/CaMKII-CaM /kinetics/CaMKII/CaMKII-bind-CaM PRODUCT n addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/CaMKII/CaMK-thr286-bind-CaM SUBSTRATE n addmsg /kinetics/CaM/CaM-Ca4 /kinetics/CaMKII/CaMK-thr286-bind-CaM SUBSTRATE n addmsg /kinetics/CaMKII/CaMKII-thr286*-CaM /kinetics/CaMKII/CaMK-thr286-bind-CaM PRODUCT n addmsg /kinetics/CaMKII/CaMK-thr286-bind-CaM /kinetics/CaMKII/CaMKII-thr286 REAC A B addmsg /kinetics/CaMKII/PP1-active/Deph-thr305 /kinetics/CaMKII/CaMKII-thr286 MM_PRD pA addmsg /kinetics/CaMKII/PP1-active/Deph_thr286b /kinetics/CaMKII/CaMKII-thr286 REAC sA B addmsg /kinetics/CaMKII/basal-activity /kinetics/CaMKII/CaMKII-thr286 REAC B A addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305 /kinetics/CaMKII/CaMKII-thr286 REAC sA B addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305 /kinetics/CaMKII/CaMKII-thr286 REAC sA B addmsg /kinetics/CaMKII/PP1-active/Deph-thr306 /kinetics/CaMKII/CaMK-thr306 REAC sA B addmsg /kinetics/CaMKII/PP1-active/Deph-thr286c /kinetics/CaMKII/CaMK-thr306 MM_PRD pA addmsg /kinetics/CaMKII/CaMKII /kinetics/CaMKII/basal-activity SUBSTRATE n addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/CaMKII/basal-activity PRODUCT n addmsg /kinetics/CaMKII/CaMKII-CaM /kinetics/CaMKII/tot_CaM_CaMKII SUMTOTAL n nInit addmsg /kinetics/CaMKII/CaMKII-thr286*-CaM /kinetics/CaMKII/tot_CaM_CaMKII SUMTOTAL n nInit addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305 /kinetics/CaMKII/tot_CaM_CaMKII REAC eA B addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286 /kinetics/CaMKII/tot_CaM_CaMKII REAC eA B addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM-CaMK-phos /kinetics/CaMKII/tot_CaM_CaMKII REAC eA B addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM-CaMK-phos1 /kinetics/CaMKII/tot_CaM_CaMKII REAC eA B addmsg /kinetics/CaMKII/tot_CaM_CaMKII /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305 ENZYME n addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305 SUBSTRATE n addmsg /kinetics/CaMKII/total-CaMKII /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305 INTRAMOL n addmsg /kinetics/CaMKII/tot_CaM_CaMKII /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286 ENZYME n addmsg /kinetics/CaMKII/CaMKII-CaM /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286 SUBSTRATE n addmsg /kinetics/CaMKII/total-CaMKII /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286 INTRAMOL n addmsg /kinetics/CaMKII/tot_CaM_CaMKII /kinetics/CaMKII/tot_CaM_CaMKII/CaM-CaMK-phos ENZYME n addmsg /kinetics/IP3-3K/IP3_3K /kinetics/CaMKII/tot_CaM_CaMKII/CaM-CaMK-phos SUBSTRATE n addmsg /kinetics/CaMKII/tot_CaM_CaMKII /kinetics/CaMKII/tot_CaM_CaMKII/CaM-CaMK-phos1 ENZYME n addmsg /kinetics/IP3-3K/IP3_3K_CaM /kinetics/CaMKII/tot_CaM_CaMKII/CaM-CaMK-phos1 SUBSTRATE n addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/CaMKII/tot_autonomous_CaMKII SUMTOTAL n nInit addmsg /kinetics/CaMKII/CaMKII*** /kinetics/CaMKII/tot_autonomous_CaMKII SUMTOTAL n nInit addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305 /kinetics/CaMKII/tot_autonomous_CaMKII REAC eA B addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286 /kinetics/CaMKII/tot_autonomous_CaMKII REAC eA B addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/CaMK-phos /kinetics/CaMKII/tot_autonomous_CaMKII REAC eA B addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/CaMK-phos1 /kinetics/CaMKII/tot_autonomous_CaMKII REAC eA B addmsg /kinetics/CaMKII/tot_autonomous_CaMKII /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305 ENZYME n addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305 SUBSTRATE n addmsg /kinetics/CaMKII/total-CaMKII /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305 INTRAMOL n addmsg /kinetics/CaMKII/tot_autonomous_CaMKII /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286 ENZYME n addmsg /kinetics/CaMKII/CaMKII-CaM /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286 SUBSTRATE n addmsg /kinetics/CaMKII/total-CaMKII /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286 INTRAMOL n addmsg /kinetics/CaMKII/tot_autonomous_CaMKII /kinetics/CaMKII/tot_autonomous_CaMKII/CaMK-phos ENZYME n addmsg /kinetics/IP3-3K/IP3_3K /kinetics/CaMKII/tot_autonomous_CaMKII/CaMK-phos SUBSTRATE n addmsg /kinetics/CaMKII/tot_autonomous_CaMKII /kinetics/CaMKII/tot_autonomous_CaMKII/CaMK-phos1 ENZYME n addmsg /kinetics/IP3-3K/IP3_3K_CaM /kinetics/CaMKII/tot_autonomous_CaMKII/CaMK-phos1 SUBSTRATE n addmsg /kinetics/CaMKII/PP1-active/Deph-thr286 /kinetics/CaMKII/PP1-active REAC eA B addmsg /kinetics/CaMKII/PP1-active/Deph-thr305 /kinetics/CaMKII/PP1-active REAC eA B addmsg /kinetics/CaMKII/PP1-active/Deph-thr306 /kinetics/CaMKII/PP1-active REAC eA B addmsg /kinetics/CaMKII/PP1-active/Deph_thr286b /kinetics/CaMKII/PP1-active REAC eA B addmsg /kinetics/CaMKII/PP1-active/Deph-thr286c /kinetics/CaMKII/PP1-active REAC eA B addmsg /kinetics/CaMKII/PP1-active /kinetics/CaMKII/PP1-active/Deph-thr286 ENZYME n addmsg /kinetics/CaMKII/CaMKII-thr286*-CaM /kinetics/CaMKII/PP1-active/Deph-thr286 SUBSTRATE n addmsg /kinetics/CaMKII/PP1-active /kinetics/CaMKII/PP1-active/Deph-thr305 ENZYME n addmsg /kinetics/CaMKII/CaMKII*** /kinetics/CaMKII/PP1-active/Deph-thr305 SUBSTRATE n addmsg /kinetics/CaMKII/PP1-active /kinetics/CaMKII/PP1-active/Deph-thr306 ENZYME n addmsg /kinetics/CaMKII/CaMK-thr306 /kinetics/CaMKII/PP1-active/Deph-thr306 SUBSTRATE n addmsg /kinetics/CaMKII/PP1-active /kinetics/CaMKII/PP1-active/Deph-thr286c ENZYME n addmsg /kinetics/CaMKII/CaMKII*** /kinetics/CaMKII/PP1-active/Deph-thr286c SUBSTRATE n addmsg /kinetics/CaMKII/PP1-active /kinetics/CaMKII/PP1-active/Deph_thr286b ENZYME n addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/CaMKII/PP1-active/Deph_thr286b SUBSTRATE n addmsg /kinetics/CaM/CaM-TR2-bind-Ca /kinetics/CaM/CaM REAC A B addmsg /kinetics/CaM/CaM /kinetics/CaM/CaM-TR2-bind-Ca SUBSTRATE n addmsg /kinetics/CaM/CaM-TR2-Ca2 /kinetics/CaM/CaM-TR2-bind-Ca PRODUCT n addmsg /kinetics/CaRegulation/Ca /kinetics/CaM/CaM-TR2-bind-Ca SUBSTRATE n addmsg /kinetics/CaRegulation/Ca /kinetics/CaM/CaM-TR2-bind-Ca SUBSTRATE n addmsg /kinetics/CaM/CaM-TR2-Ca2 /kinetics/CaM/CaM-TR2-Ca2-bind-Ca SUBSTRATE n addmsg /kinetics/CaRegulation/Ca /kinetics/CaM/CaM-TR2-Ca2-bind-Ca SUBSTRATE n addmsg /kinetics/CaM/CaM-Ca3 /kinetics/CaM/CaM-TR2-Ca2-bind-Ca PRODUCT n addmsg /kinetics/CaM/CaM-Ca3 /kinetics/CaM/CaM-Ca3-bind-Ca SUBSTRATE n addmsg /kinetics/CaRegulation/Ca /kinetics/CaM/CaM-Ca3-bind-Ca SUBSTRATE n addmsg /kinetics/CaM/CaM-Ca4 /kinetics/CaM/CaM-Ca3-bind-Ca PRODUCT n addmsg /kinetics/IP3-3K/3K-bind-CaM /kinetics/CaM/CaM-Ca4 REAC A B addmsg /kinetics/CaMKII/CaMKII-bind-CaM /kinetics/CaM/CaM-Ca4 REAC A B addmsg /kinetics/CaMKII/CaMK-thr286-bind-CaM /kinetics/CaM/CaM-Ca4 REAC A B addmsg /kinetics/CaM/CaM-Ca3-bind-Ca /kinetics/CaM/CaM-Ca4 REAC B A addmsg /kinetics/IP3-3K/3K*-bind-CaM /kinetics/CaM/CaM-Ca4 REAC A B addmsg /kinetics/CaM/CaM-TR2-Ca2-bind-Ca /kinetics/CaM/CaM-Ca3 REAC B A addmsg /kinetics/CaM/CaM-Ca3-bind-Ca /kinetics/CaM/CaM-Ca3 REAC A B addmsg /kinetics/CaM/CaM-TR2-bind-Ca /kinetics/CaM/CaM-TR2-Ca2 REAC B A addmsg /kinetics/CaM/CaM-TR2-Ca2-bind-Ca /kinetics/CaM/CaM-TR2-Ca2 REAC A B addmsg /kinetics/PKC/PKC-cytosolic /kinetics/PKC/PKC-act-by-Ca SUBSTRATE n addmsg /kinetics/CaRegulation/Ca /kinetics/PKC/PKC-act-by-Ca SUBSTRATE n addmsg /kinetics/PKC/PKC-Ca /kinetics/PKC/PKC-act-by-Ca PRODUCT n addmsg /kinetics/PLCbeta/DAG /kinetics/PKC/PKC-act-by-DAG SUBSTRATE n addmsg /kinetics/PKC/PKC-Ca /kinetics/PKC/PKC-act-by-DAG SUBSTRATE n addmsg /kinetics/PKC/PKC-Ca-DAG /kinetics/PKC/PKC-act-by-DAG PRODUCT n addmsg /kinetics/PKC/PKC-Ca /kinetics/PKC/PKC-Ca-to-memb SUBSTRATE n addmsg /kinetics/PKC/PKC-Ca-memb* /kinetics/PKC/PKC-Ca-to-memb PRODUCT n addmsg /kinetics/PKC/PKC-Ca-DAG /kinetics/PKC/PKC-DAG-to-memb SUBSTRATE n addmsg /kinetics/PKC/PKC-DAG-memb* /kinetics/PKC/PKC-DAG-to-memb PRODUCT n addmsg /kinetics/PKC/PKC-Ca /kinetics/PKC/PKC-act-by-Ca-AA SUBSTRATE n addmsg /kinetics/PKC/AA /kinetics/PKC/PKC-act-by-Ca-AA SUBSTRATE n addmsg /kinetics/PKC/PKC-Ca-AA* /kinetics/PKC/PKC-act-by-Ca-AA PRODUCT n addmsg /kinetics/PKC/PKC-DAG-AA* /kinetics/PKC/PKC-act-by-DAG-AA PRODUCT n addmsg /kinetics/PKC/PKC-DAG-AA /kinetics/PKC/PKC-act-by-DAG-AA SUBSTRATE n addmsg /kinetics/PKC/PKC-act-by-DAG-AA /kinetics/PKC/PKC-DAG-AA* REAC B A addmsg /kinetics/PKC/PKC-act-by-Ca-AA /kinetics/PKC/PKC-Ca-AA* REAC B A addmsg /kinetics/PKC/PKC-Ca-to-memb /kinetics/PKC/PKC-Ca-memb* REAC B A addmsg /kinetics/PKC/PKC-DAG-to-memb /kinetics/PKC/PKC-DAG-memb* REAC B A addmsg /kinetics/PKC/PKC-basal-act /kinetics/PKC/PKC-basal* REAC B A addmsg /kinetics/PKC/PKC-cytosolic /kinetics/PKC/PKC-basal-act SUBSTRATE n addmsg /kinetics/PKC/PKC-basal* /kinetics/PKC/PKC-basal-act PRODUCT n addmsg /kinetics/PKC/PKC-act-by-AA /kinetics/PKC/PKC-AA* REAC B A addmsg /kinetics/PKC/AA /kinetics/PKC/PKC-act-by-AA SUBSTRATE n addmsg /kinetics/PKC/PKC-AA* /kinetics/PKC/PKC-act-by-AA PRODUCT n addmsg /kinetics/PKC/PKC-cytosolic /kinetics/PKC/PKC-act-by-AA SUBSTRATE n addmsg /kinetics/PKC/PKC-act-by-DAG /kinetics/PKC/PKC-Ca-DAG REAC B A addmsg /kinetics/PKC/PKC-DAG-to-memb /kinetics/PKC/PKC-Ca-DAG REAC A B addmsg /kinetics/PKC/PKC-cytosolic /kinetics/PKC/PKC-n-DAG SUBSTRATE n addmsg /kinetics/PLCbeta/DAG /kinetics/PKC/PKC-n-DAG SUBSTRATE n addmsg /kinetics/PKC/PKC-DAG /kinetics/PKC/PKC-n-DAG PRODUCT n addmsg /kinetics/PKC/PKC-n-DAG /kinetics/PKC/PKC-DAG REAC B A addmsg /kinetics/PKC/PKC-n-DAG-AA /kinetics/PKC/PKC-DAG REAC A B addmsg /kinetics/PKC/PKC-DAG /kinetics/PKC/PKC-n-DAG-AA SUBSTRATE n addmsg /kinetics/PKC/AA /kinetics/PKC/PKC-n-DAG-AA SUBSTRATE n addmsg /kinetics/PKC/PKC-DAG-AA /kinetics/PKC/PKC-n-DAG-AA PRODUCT n addmsg /kinetics/PKC/PKC-n-DAG-AA /kinetics/PKC/PKC-DAG-AA REAC B A addmsg /kinetics/PKC/PKC-act-by-DAG-AA /kinetics/PKC/PKC-DAG-AA REAC A B addmsg /kinetics/PKC/PKC-act-by-Ca /kinetics/PKC/PKC-cytosolic REAC A B addmsg /kinetics/PKC/PKC-basal-act /kinetics/PKC/PKC-cytosolic REAC A B addmsg /kinetics/PKC/PKC-act-by-AA /kinetics/PKC/PKC-cytosolic REAC A B addmsg /kinetics/PKC/PKC-n-DAG /kinetics/PKC/PKC-cytosolic REAC A B addmsg /kinetics/PKC/PKC-act-by-Ca-AA /kinetics/PKC/AA REAC A B addmsg /kinetics/PKC/PKC-act-by-AA /kinetics/PKC/AA REAC A B addmsg /kinetics/PKC/PKC-n-DAG-AA /kinetics/PKC/AA REAC A B addmsg /kinetics/PKC/PKC-act-by-Ca /kinetics/PKC/PKC-Ca REAC B A addmsg /kinetics/PKC/PKC-act-by-DAG /kinetics/PKC/PKC-Ca REAC A B addmsg /kinetics/PKC/PKC-Ca-to-memb /kinetics/PKC/PKC-Ca REAC A B addmsg /kinetics/PKC/PKC-act-by-Ca-AA /kinetics/PKC/PKC-Ca REAC A B addmsg /kinetics/PKC/PKC-DAG-AA* /kinetics/PKC/PKC-active SUMTOTAL n nInit addmsg /kinetics/PKC/PKC-Ca-memb* /kinetics/PKC/PKC-active SUMTOTAL n nInit addmsg /kinetics/PKC/PKC-Ca-AA* /kinetics/PKC/PKC-active SUMTOTAL n nInit addmsg /kinetics/PKC/PKC-DAG-memb* /kinetics/PKC/PKC-active SUMTOTAL n nInit addmsg /kinetics/PKC/PKC-basal* /kinetics/PKC/PKC-active SUMTOTAL n nInit addmsg /kinetics/PKC/PKC-AA* /kinetics/PKC/PKC-active SUMTOTAL n nInit addmsg /kinetics/PKC/PKC-active/PKC-phos /kinetics/PKC/PKC-active REAC eA B addmsg /kinetics/PKC/PKC-active /kinetics/PKC/PKC-active/PKC-phos ENZYME n addmsg /kinetics/IP3-3K/IP3_3K /kinetics/PKC/PKC-active/PKC-phos SUBSTRATE n addmsg /kinetics/IP3-3K/IP3_3K/ip3-3k /kinetics/IP3-3K/IP3_3K REAC eA B addmsg /kinetics/IP3-3K/3K-bind-CaM /kinetics/IP3-3K/IP3_3K REAC A B addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM-CaMK-phos /kinetics/IP3-3K/IP3_3K REAC sA B addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/CaMK-phos /kinetics/IP3-3K/IP3_3K REAC sA B addmsg /kinetics/PKC/PKC-active/PKC-phos /kinetics/IP3-3K/IP3_3K REAC sA B addmsg /kinetics/IP3-3K/IP3_3K /kinetics/IP3-3K/IP3_3K/ip3-3k ENZYME n addmsg /kinetics/IP3-3K/IP3(145) /kinetics/IP3-3K/IP3_3K/ip3-3k SUBSTRATE n addmsg /kinetics/IP3-3K/IP3_3K*1/ip3-3k*1 /kinetics/IP3-3K/IP3_3K*1 REAC eA B addmsg /kinetics/PKC/PKC-active/PKC-phos /kinetics/IP3-3K/IP3_3K*1 MM_PRD pA addmsg /kinetics/IP3-3K/IP3_3K*1 /kinetics/IP3-3K/IP3_3K*1/ip3-3k*1 ENZYME n addmsg /kinetics/IP3-3K/IP3(145) /kinetics/IP3-3K/IP3_3K*1/ip3-3k*1 SUBSTRATE n addmsg /kinetics/IP3-3K/IP3_3K*/ip3-3k* /kinetics/IP3-3K/IP3_3K* REAC eA B addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM-CaMK-phos /kinetics/IP3-3K/IP3_3K* MM_PRD pA addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/CaMK-phos /kinetics/IP3-3K/IP3_3K* MM_PRD pA addmsg /kinetics/IP3-3K/3K*-bind-CaM /kinetics/IP3-3K/IP3_3K* REAC A B addmsg /kinetics/IP3-3K/IP3_3K* /kinetics/IP3-3K/IP3_3K*/ip3-3k* ENZYME n addmsg /kinetics/IP3-3K/IP3(145) /kinetics/IP3-3K/IP3_3K*/ip3-3k* SUBSTRATE n addmsg /kinetics/IP3-3K/3K*-bind-CaM /kinetics/IP3-3K/IP3_3K_CaM* REAC B A addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM-CaMK-phos1 /kinetics/IP3-3K/IP3_3K_CaM* MM_PRD pA addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/CaMK-phos1 /kinetics/IP3-3K/IP3_3K_CaM* MM_PRD pA addmsg /kinetics/IP3-3K/3k-CaM*-on /kinetics/IP3-3K/IP3_3K_CaM* REAC A B addmsg /kinetics/IP3-3K/3k-CaM*-off /kinetics/IP3-3K/IP3_3K_CaM* REAC B A addmsg /kinetics/IP3-3K/3K-bind-CaM /kinetics/IP3-3K/IP3_3K_CaM REAC B A addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM-CaMK-phos1 /kinetics/IP3-3K/IP3_3K_CaM REAC sA B addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/CaMK-phos1 /kinetics/IP3-3K/IP3_3K_CaM REAC sA B addmsg /kinetics/IP3-3K/3k-CaM-off /kinetics/IP3-3K/IP3_3K_CaM REAC B A addmsg /kinetics/IP3-3K/3k-CaM-on /kinetics/IP3-3K/IP3_3K_CaM REAC A B addmsg /kinetics/IP3-3K/IP3_3K /kinetics/IP3-3K/3K-bind-CaM SUBSTRATE n addmsg /kinetics/CaM/CaM-Ca4 /kinetics/IP3-3K/3K-bind-CaM SUBSTRATE n addmsg /kinetics/IP3-3K/IP3_3K_CaM /kinetics/IP3-3K/3K-bind-CaM PRODUCT n addmsg /kinetics/IP3-3K/IP3_3K* /kinetics/IP3-3K/3K*-bind-CaM SUBSTRATE n addmsg /kinetics/IP3-3K/IP3_3K_CaM* /kinetics/IP3-3K/3K*-bind-CaM PRODUCT n addmsg /kinetics/CaM/CaM-Ca4 /kinetics/IP3-3K/3K*-bind-CaM SUBSTRATE n addmsg /kinetics/145_dephos/IP_5pase1/ip3_5pase1 /kinetics/IP3-3K/IP3(145) REAC sA B addmsg /kinetics/145_dephos/IP3_5pase2/ip3_5pase2 /kinetics/IP3-3K/IP3(145) REAC sA B addmsg /kinetics/MIPP/ip3(145)_trp /kinetics/IP3-3K/IP3(145) REAC B A addmsg /kinetics/1345_dephos/1345_3pase/ip4_3pase /kinetics/IP3-3K/IP3(145) MM_PRD pA addmsg /kinetics/1345_dephos/145-inhib-3pase /kinetics/IP3-3K/IP3(145) REAC A B addmsg /kinetics/IP3-3K/IP3_3K/ip3-3k /kinetics/IP3-3K/IP3(145) REAC sA B addmsg /kinetics/IP3-3K/IP3_3K*/ip3-3k* /kinetics/IP3-3K/IP3(145) REAC sA B addmsg /kinetics/IP3-3K/IP3_3K*1/ip3-3k*1 /kinetics/IP3-3K/IP3(145) REAC sA B addmsg /kinetics/PLCbeta/PLC-Gq/PLC-Gq /kinetics/IP3-3K/IP3(145) MM_PRD pA addmsg /kinetics/PLCbeta/PLC-Ca-Gq/PLCb-Ca-Gq /kinetics/IP3-3K/IP3(145) MM_PRD pA addmsg /kinetics/PLCbeta/PLC/PLC /kinetics/IP3-3K/IP3(145) MM_PRD pA addmsg /kinetics/PLCbeta/PLC-Ca/PLC-Ca /kinetics/IP3-3K/IP3(145) MM_PRD pA addmsg /kinetics/IP4-system/ip4-6pase /kinetics/IP3-3K/IP3(145) REAC B A addmsg /kinetics/PLCbeta/basal /kinetics/IP3-3K/IP3(145) REAC B A addmsg /kinetics/IP3-3K/3k-CaM*-on /kinetics/IP3-3K/IP3(145) REAC A B addmsg /kinetics/IP3-3K/3k-CaM-on /kinetics/IP3-3K/IP3(145) REAC A B addmsg /kinetics/IP3-3K/IP3(145) /kinetics/IP3-3K/3k-CaM*-on SUBSTRATE n addmsg /kinetics/IP3-3K/IP3_3K_CaM* /kinetics/IP3-3K/3k-CaM*-on SUBSTRATE n addmsg /kinetics/IP3-3K/3kCaM*_ip3_cmplx /kinetics/IP3-3K/3k-CaM*-on PRODUCT n addmsg /kinetics/IP3-3K/3kCaM*_ip3_cmplx /kinetics/IP3-3K/3k-CaM*-off SUBSTRATE n addmsg /kinetics/IP3-3K/IP4(1345) /kinetics/IP3-3K/3k-CaM*-off PRODUCT n addmsg /kinetics/IP3-3K/IP3_3K_CaM* /kinetics/IP3-3K/3k-CaM*-off PRODUCT n addmsg /kinetics/IP3-3K/3k-CaM*-on /kinetics/IP3-3K/3kCaM*_ip3_cmplx REAC B A addmsg /kinetics/IP3-3K/3k-CaM*-off /kinetics/IP3-3K/3kCaM*_ip3_cmplx REAC A B addmsg /kinetics/IP3-3K/3k-CaM-off /kinetics/IP3-3K/3kCaM_ip3_cmplx REAC A B addmsg /kinetics/IP3-3K/3k-CaM-on /kinetics/IP3-3K/3kCaM_ip3_cmplx REAC B A addmsg /kinetics/IP3-3K/IP3_3K_CaM /kinetics/IP3-3K/3k-CaM-on SUBSTRATE n addmsg /kinetics/IP3-3K/IP3(145) /kinetics/IP3-3K/3k-CaM-on SUBSTRATE n addmsg /kinetics/IP3-3K/3kCaM_ip3_cmplx /kinetics/IP3-3K/3k-CaM-on PRODUCT n addmsg /kinetics/IP3-3K/3kCaM_ip3_cmplx /kinetics/IP3-3K/3k-CaM-off SUBSTRATE n addmsg /kinetics/IP3-3K/IP4(1345) /kinetics/IP3-3K/3k-CaM-off PRODUCT n addmsg /kinetics/IP3-3K/IP3_3K_CaM /kinetics/IP3-3K/3k-CaM-off PRODUCT n addmsg /kinetics/IP4-system/5kinase /kinetics/IP3-3K/IP4(1345) REAC B A addmsg /kinetics/145_dephos/IP_5pase1/ip4_5pase /kinetics/IP3-3K/IP4(1345) REAC sA B addmsg /kinetics/MIPP/ip4(1345)_trp /kinetics/IP3-3K/IP4(1345) REAC A B addmsg /kinetics/1345_dephos/1345_3pase/ip4_3pase /kinetics/IP3-3K/IP4(1345) REAC sA B addmsg /kinetics/IP3-3K/IP3_3K/ip3-3k /kinetics/IP3-3K/IP4(1345) MM_PRD pA addmsg /kinetics/IP3-3K/IP3_3K*/ip3-3k* /kinetics/IP3-3K/IP4(1345) MM_PRD pA addmsg /kinetics/IP3-3K/IP3_3K*1/ip3-3k*1 /kinetics/IP3-3K/IP4(1345) MM_PRD pA addmsg /kinetics/IP3-3K/3k-CaM*-off /kinetics/IP3-3K/IP4(1345) REAC B A addmsg /kinetics/IP3-3K/3k-CaM-off /kinetics/IP3-3K/IP4(1345) REAC B A addmsg /kinetics/CaRegulation/CaTransp-2Ca /kinetics/CaRegulation/CaTraspATPase SUBSTRATE n addmsg /kinetics/CaRegulation/CaTransp /kinetics/CaRegulation/CaTraspATPase PRODUCT n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/CaTraspATPase PRODUCT n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/CaTraspATPase PRODUCT n addmsg /kinetics/CaRegulation/CaTraspATPase /kinetics/CaRegulation/Ca-sequester REAC B A addmsg /kinetics/CaRegulation/IP3R*/IP3chan /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca-leak-to-cytoplasm/Ca-leak-chan /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/CaTraspATPase /kinetics/CaRegulation/Ca-sequester REAC B A addmsg /kinetics/CaRegulation/inactivate_cap_Ca /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/inactivate_cap_Ca /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca5-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca5-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca5-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca5-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca5-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca10-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca10-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca10-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca10-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca10-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca15-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca15-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca15-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca15-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca15-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca20-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca20-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca20-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca20-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca20-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca25-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca25-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca25-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca25-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca25-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca35-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca40-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca35-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca35-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca35-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca35-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca40-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca40-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca40-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca40-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca30-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca30-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca30-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca30-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca30-bind-Cal /kinetics/CaRegulation/Ca-sequester REAC A B addmsg /kinetics/CaRegulation/Ca-leak-to-cytoplasm /kinetics/CaRegulation/Ca-leak-to-cytoplasm/Ca-leak-chan NUMCHAN n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca-leak-to-cytoplasm/Ca-leak-chan SUBSTRATE n vol addmsg /kinetics/CaRegulation/Ca /kinetics/CaRegulation/Ca-leak-to-cytoplasm/Ca-leak-chan PRODUCT n vol addmsg /kinetics/CaRegulation/CaTraspATPase /kinetics/CaRegulation/CaTransp-2Ca REAC A B addmsg /kinetics/CaRegulation/Ca-bind-to-Transp /kinetics/CaRegulation/CaTransp-2Ca REAC B A addmsg /kinetics/CaRegulation/CaTransp /kinetics/CaRegulation/CaTransp-2Ca CONSERVE n nInit addmsg /kinetics/CaRegulation/Ca-bind-to-Transp /kinetics/CaRegulation/CaTransp REAC A B addmsg /kinetics/CaRegulation/CaTraspATPase /kinetics/CaRegulation/CaTransp REAC B A addmsg /kinetics/CaRegulation/Ca /kinetics/CaRegulation/Ca-bind-to-Transp SUBSTRATE n addmsg /kinetics/CaRegulation/CaTransp /kinetics/CaRegulation/Ca-bind-to-Transp SUBSTRATE n addmsg /kinetics/CaRegulation/Ca /kinetics/CaRegulation/Ca-bind-to-Transp SUBSTRATE n addmsg /kinetics/CaRegulation/CaTransp-2Ca /kinetics/CaRegulation/Ca-bind-to-Transp PRODUCT n addmsg /kinetics/CaRegulation/IP3Rbind /kinetics/CaRegulation/IP3R REAC A B addmsg /kinetics/CaRegulation/IP3R* /kinetics/CaRegulation/IP3Rbind PRODUCT n addmsg /kinetics/CaRegulation/IP3R /kinetics/CaRegulation/IP3Rbind SUBSTRATE n addmsg /kinetics/CaRegulation/IP3 /kinetics/CaRegulation/IP3Rbind SUBSTRATE n addmsg /kinetics/CaRegulation/IP3 /kinetics/CaRegulation/IP3Rbind SUBSTRATE n addmsg /kinetics/CaRegulation/IP3 /kinetics/CaRegulation/IP3Rbind SUBSTRATE n addmsg /kinetics/CaRegulation/IP3Rbind /kinetics/CaRegulation/IP3R* REAC B A addmsg /kinetics/CaRegulation/IP3R* /kinetics/CaRegulation/IP3R*/IP3chan NUMCHAN n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/IP3R*/IP3chan SUBSTRATE n vol addmsg /kinetics/CaRegulation/Ca /kinetics/CaRegulation/IP3R*/IP3chan PRODUCT n vol addmsg /kinetics/CaRegulation/CaEPump/Ca-pump-out /kinetics/CaRegulation/CaEPump REAC eA B addmsg /kinetics/CaRegulation/CaEPump/Ca-pump-out /kinetics/CaRegulation/CaEPump CONSERVE nComplex nComplexInit addmsg /kinetics/CaRegulation/CaEPump /kinetics/CaRegulation/CaEPump/Ca-pump-out ENZYME n addmsg /kinetics/CaRegulation/Ca /kinetics/CaRegulation/CaEPump/Ca-pump-out SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-leak-from-extracell/Ca-leak-chan /kinetics/CaRegulation/Ca-ext REAC A B addmsg /kinetics/CaRegulation/CaEPump/Ca-pump-out /kinetics/CaRegulation/Ca-ext MM_PRD pA addmsg /kinetics/CaRegulation/capacitive_Ca_entry*/Cap_entry_chan /kinetics/CaRegulation/Ca-ext REAC A B addmsg /kinetics/CaRegulation/Ca-leak-from-extracell /kinetics/CaRegulation/Ca-leak-from-extracell/Ca-leak-chan NUMCHAN n addmsg /kinetics/CaRegulation/Ca-ext /kinetics/CaRegulation/Ca-leak-from-extracell/Ca-leak-chan SUBSTRATE n vol addmsg /kinetics/CaRegulation/Ca /kinetics/CaRegulation/Ca-leak-from-extracell/Ca-leak-chan PRODUCT n vol addmsg /kinetics/CaRegulation/inactivate_cap_Ca /kinetics/CaRegulation/capacitive_Ca_entry* REAC A B addmsg /kinetics/CaRegulation/capacitive_Ca_entry* /kinetics/CaRegulation/capacitive_Ca_entry*/Cap_entry_chan NUMCHAN n addmsg /kinetics/CaRegulation/Ca-ext /kinetics/CaRegulation/capacitive_Ca_entry*/Cap_entry_chan SUBSTRATE n vol addmsg /kinetics/CaRegulation/Ca /kinetics/CaRegulation/capacitive_Ca_entry*/Cap_entry_chan PRODUCT n vol addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/inactivate_cap_Ca SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/inactivate_cap_Ca SUBSTRATE n addmsg /kinetics/CaRegulation/capacitive_Ca_entry* /kinetics/CaRegulation/inactivate_cap_Ca SUBSTRATE n addmsg /kinetics/CaRegulation/inact_cap_entry /kinetics/CaRegulation/inactivate_cap_Ca PRODUCT n addmsg /kinetics/CaRegulation/inactivate_cap_Ca /kinetics/CaRegulation/inact_cap_entry REAC B A addmsg /kinetics/IP3-3K/IP3(145) /kinetics/CaRegulation/IP3 SUMTOTAL n nInit addmsg /kinetics/CaRegulation/IP3Rbind /kinetics/CaRegulation/IP3 REAC A B addmsg /kinetics/CaRegulation/IP3Rbind /kinetics/CaRegulation/IP3 REAC A B addmsg /kinetics/CaRegulation/IP3Rbind /kinetics/CaRegulation/IP3 REAC A B addmsg /kinetics/145_dephos/Ca-inhib-1pase /kinetics/CaRegulation/Ca REAC A B addmsg /kinetics/CaM/CaM-TR2-bind-Ca /kinetics/CaRegulation/Ca REAC A B addmsg /kinetics/CaM/CaM-TR2-bind-Ca /kinetics/CaRegulation/Ca REAC A B addmsg /kinetics/CaM/CaM-TR2-Ca2-bind-Ca /kinetics/CaRegulation/Ca REAC A B addmsg /kinetics/CaM/CaM-Ca3-bind-Ca /kinetics/CaRegulation/Ca REAC A B addmsg /kinetics/PKC/PKC-act-by-Ca /kinetics/CaRegulation/Ca REAC A B addmsg /kinetics/CaRegulation/Ca-bind-to-Transp /kinetics/CaRegulation/Ca REAC A B addmsg /kinetics/CaRegulation/Ca-bind-to-Transp /kinetics/CaRegulation/Ca REAC A B addmsg /kinetics/CaRegulation/IP3R*/IP3chan /kinetics/CaRegulation/Ca REAC B A addmsg /kinetics/CaRegulation/Ca-leak-to-cytoplasm/Ca-leak-chan /kinetics/CaRegulation/Ca REAC B A addmsg /kinetics/CaRegulation/Ca-leak-from-extracell/Ca-leak-chan /kinetics/CaRegulation/Ca REAC B A addmsg /kinetics/CaRegulation/CaEPump/Ca-pump-out /kinetics/CaRegulation/Ca REAC sA B addmsg /kinetics/CaRegulation/capacitive_Ca_entry*/Cap_entry_chan /kinetics/CaRegulation/Ca REAC B A addmsg /kinetics/PLCbeta/Act-PLC-Ca /kinetics/CaRegulation/Ca REAC A B addmsg /kinetics/PLCbeta/PLC-Gq-bind-Ca /kinetics/CaRegulation/Ca REAC A B addmsg /kinetics/CaRegulation/Ca5-bind-Cal /kinetics/CaRegulation/Calseq REAC A B addmsg /kinetics/CaRegulation/Calseq /kinetics/CaRegulation/Ca5-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca5-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca5-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca5-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca5-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca5-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca5-Cal /kinetics/CaRegulation/Ca5-bind-Cal PRODUCT n addmsg /kinetics/CaRegulation/Ca5-bind-Cal /kinetics/CaRegulation/Ca5-Cal REAC B A addmsg /kinetics/CaRegulation/Ca10-bind-Cal /kinetics/CaRegulation/Ca5-Cal REAC A B addmsg /kinetics/CaRegulation/Ca5-Cal /kinetics/CaRegulation/Ca10-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca10-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca10-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca10-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca10-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca10-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca10-Cal /kinetics/CaRegulation/Ca10-bind-Cal PRODUCT n addmsg /kinetics/CaRegulation/Ca10-Cal /kinetics/CaRegulation/Ca15-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca15-Cal /kinetics/CaRegulation/Ca15-bind-Cal PRODUCT n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca15-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca15-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca15-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca15-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca15-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca10-bind-Cal /kinetics/CaRegulation/Ca10-Cal REAC B A addmsg /kinetics/CaRegulation/Ca15-bind-Cal /kinetics/CaRegulation/Ca10-Cal REAC A B addmsg /kinetics/CaRegulation/Ca15-bind-Cal /kinetics/CaRegulation/Ca15-Cal REAC B A addmsg /kinetics/CaRegulation/Ca20-bind-Cal /kinetics/CaRegulation/Ca15-Cal REAC A B addmsg /kinetics/CaRegulation/Ca15-Cal /kinetics/CaRegulation/Ca20-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca20-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca20-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca20-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca20-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca20-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca20-Cal /kinetics/CaRegulation/Ca20-bind-Cal PRODUCT n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca25-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca25-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca25-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca25-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca25-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca20-Cal /kinetics/CaRegulation/Ca25-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca25-Cal /kinetics/CaRegulation/Ca25-bind-Cal PRODUCT n addmsg /kinetics/CaRegulation/Ca25-Cal /kinetics/CaRegulation/Ca30-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca30-Cal /kinetics/CaRegulation/Ca30-bind-Cal PRODUCT n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca30-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca30-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca30-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca30-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca30-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca35-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca35-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca35-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca35-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca35-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca30-Cal /kinetics/CaRegulation/Ca35-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca35-Cal /kinetics/CaRegulation/Ca35-bind-Cal PRODUCT n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca40-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca40-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca40-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca40-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca-sequester /kinetics/CaRegulation/Ca40-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca35-Cal /kinetics/CaRegulation/Ca40-bind-Cal SUBSTRATE n addmsg /kinetics/CaRegulation/Ca40-Cal /kinetics/CaRegulation/Ca40-bind-Cal PRODUCT n addmsg /kinetics/CaRegulation/Ca30-bind-Cal /kinetics/CaRegulation/Ca25-Cal REAC A B addmsg /kinetics/CaRegulation/Ca25-bind-Cal /kinetics/CaRegulation/Ca25-Cal REAC B A addmsg /kinetics/CaRegulation/Ca30-bind-Cal /kinetics/CaRegulation/Ca30-Cal REAC B A addmsg /kinetics/CaRegulation/Ca35-bind-Cal /kinetics/CaRegulation/Ca30-Cal REAC A B addmsg /kinetics/CaRegulation/Ca35-bind-Cal /kinetics/CaRegulation/Ca35-Cal REAC B A addmsg /kinetics/CaRegulation/Ca40-bind-Cal /kinetics/CaRegulation/Ca35-Cal REAC A B addmsg /kinetics/CaRegulation/Ca40-bind-Cal /kinetics/CaRegulation/Ca40-Cal REAC B A addmsg /kinetics/CaRegulation/Ca20-bind-Cal /kinetics/CaRegulation/Ca20-Cal REAC B A addmsg /kinetics/CaRegulation/Ca25-bind-Cal /kinetics/CaRegulation/Ca20-Cal REAC A B addmsg /kinetics/Gq/mGluR /kinetics/Gq/RecLigandBinding SUBSTRATE n addmsg /kinetics/Gq/Glu /kinetics/Gq/RecLigandBinding SUBSTRATE n addmsg /kinetics/Gq/Rec-Glu /kinetics/Gq/RecLigandBinding PRODUCT n addmsg /kinetics/Gq/Trimerize-G /kinetics/Gq/G-GDP REAC B A addmsg /kinetics/Gq/Basal-Act-G /kinetics/Gq/G-GDP REAC A B addmsg /kinetics/Gq/Rec-Glu-bind-Gq /kinetics/Gq/G-GDP REAC A B addmsg /kinetics/Gq/Rec-bind-Gq /kinetics/Gq/G-GDP REAC A B addmsg /kinetics/Gq/G-GDP /kinetics/Gq/Basal-Act-G SUBSTRATE n addmsg /kinetics/Gq/G*GTP /kinetics/Gq/Basal-Act-G PRODUCT n addmsg /kinetics/Gq/BetaGamma /kinetics/Gq/Basal-Act-G PRODUCT n addmsg /kinetics/Gq/G*GDP /kinetics/Gq/Trimerize-G SUBSTRATE n addmsg /kinetics/Gq/BetaGamma /kinetics/Gq/Trimerize-G SUBSTRATE n addmsg /kinetics/Gq/G-GDP /kinetics/Gq/Trimerize-G PRODUCT n addmsg /kinetics/Gq/G*GTP /kinetics/Gq/Inact-G SUBSTRATE n addmsg /kinetics/Gq/G*GDP /kinetics/Gq/Inact-G PRODUCT n addmsg /kinetics/Gq/RecLigandBinding /kinetics/Gq/mGluR REAC A B addmsg /kinetics/Gq/Rec-Glu /kinetics/Gq/mGluR CONSERVE n nInit addmsg /kinetics/Gq/Rec-Glu-Gq /kinetics/Gq/mGluR CONSERVE n nInit addmsg /kinetics/Gq/Rec-Gq /kinetics/Gq/mGluR CONSERVE n nInit addmsg /kinetics/Gq/Rec-bind-Gq /kinetics/Gq/mGluR REAC A B addmsg /kinetics/Gq/Blocked-rec-Gq /kinetics/Gq/mGluR CONSERVE n nInit addmsg /kinetics/Gq/RecLigandBinding /kinetics/Gq/Rec-Glu REAC B A addmsg /kinetics/Gq/Rec-Glu-bind-Gq /kinetics/Gq/Rec-Glu REAC A B addmsg /kinetics/Gq/Activate-Gq /kinetics/Gq/Rec-Glu REAC B A addmsg /kinetics/Gq/Glu-bind-Rec-Gq /kinetics/Gq/Rec-Gq REAC A B addmsg /kinetics/Gq/Rec-bind-Gq /kinetics/Gq/Rec-Gq REAC B A addmsg /kinetics/Gq/Antag-bind-Rec-Gq /kinetics/Gq/Rec-Gq REAC A B addmsg /kinetics/Gq/G-GDP /kinetics/Gq/Rec-Glu-bind-Gq SUBSTRATE n addmsg /kinetics/Gq/Rec-Glu /kinetics/Gq/Rec-Glu-bind-Gq SUBSTRATE n addmsg /kinetics/Gq/Rec-Glu-Gq /kinetics/Gq/Rec-Glu-bind-Gq PRODUCT n addmsg /kinetics/Gq/Glu /kinetics/Gq/Glu-bind-Rec-Gq SUBSTRATE n addmsg /kinetics/Gq/Rec-Glu-Gq /kinetics/Gq/Glu-bind-Rec-Gq PRODUCT n addmsg /kinetics/Gq/Rec-Gq /kinetics/Gq/Glu-bind-Rec-Gq SUBSTRATE n addmsg /kinetics/Gq/Rec-Glu-bind-Gq /kinetics/Gq/Rec-Glu-Gq REAC B A addmsg /kinetics/Gq/Glu-bind-Rec-Gq /kinetics/Gq/Rec-Glu-Gq REAC B A addmsg /kinetics/Gq/Activate-Gq /kinetics/Gq/Rec-Glu-Gq REAC A B addmsg /kinetics/Gq/Rec-Glu-Gq /kinetics/Gq/Activate-Gq SUBSTRATE n addmsg /kinetics/Gq/G*GTP /kinetics/Gq/Activate-Gq PRODUCT n addmsg /kinetics/Gq/BetaGamma /kinetics/Gq/Activate-Gq PRODUCT n addmsg /kinetics/Gq/Rec-Glu /kinetics/Gq/Activate-Gq PRODUCT n addmsg /kinetics/Gq/G-GDP /kinetics/Gq/Rec-bind-Gq SUBSTRATE n addmsg /kinetics/Gq/mGluR /kinetics/Gq/Rec-bind-Gq SUBSTRATE n addmsg /kinetics/Gq/Rec-Gq /kinetics/Gq/Rec-bind-Gq PRODUCT n addmsg /kinetics/Gq/Antag-bind-Rec-Gq /kinetics/Gq/mGluRAntag REAC A B addmsg /kinetics/Gq/Rec-Gq /kinetics/Gq/Antag-bind-Rec-Gq SUBSTRATE n addmsg /kinetics/Gq/mGluRAntag /kinetics/Gq/Antag-bind-Rec-Gq SUBSTRATE n addmsg /kinetics/Gq/Blocked-rec-Gq /kinetics/Gq/Antag-bind-Rec-Gq PRODUCT n addmsg /kinetics/Gq/Antag-bind-Rec-Gq /kinetics/Gq/Blocked-rec-Gq REAC B A addmsg /kinetics/Gq/Inact-G /kinetics/Gq/G*GDP REAC B A addmsg /kinetics/Gq/Trimerize-G /kinetics/Gq/G*GDP REAC A B addmsg /kinetics/PLCbeta/Inact-PLC-Gq /kinetics/Gq/G*GDP REAC B A addmsg /kinetics/Gq/Inact-G /kinetics/Gq/G*GTP REAC A B addmsg /kinetics/Gq/Basal-Act-G /kinetics/Gq/G*GTP REAC B A addmsg /kinetics/Gq/Activate-Gq /kinetics/Gq/G*GTP REAC B A addmsg /kinetics/PLCbeta/PLC-bind-Gq /kinetics/Gq/G*GTP REAC A B addmsg /kinetics/PLCbeta/Act-PLC-by-Gq /kinetics/Gq/G*GTP REAC A B addmsg /kinetics/Gq/Trimerize-G /kinetics/Gq/BetaGamma REAC A B addmsg /kinetics/Gq/Basal-Act-G /kinetics/Gq/BetaGamma REAC B A addmsg /kinetics/Gq/Activate-Gq /kinetics/Gq/BetaGamma REAC B A addmsg /kinetics/Gq/RecLigandBinding /kinetics/Gq/Glu REAC A B addmsg /kinetics/Gq/Glu-bind-Rec-Gq /kinetics/Gq/Glu REAC A B addmsg /kinetics/PLCbeta/PLC-bind-Gq /kinetics/PLCbeta/PLC-Gq REAC B A addmsg /kinetics/PLCbeta/PLC-Gq-bind-Ca /kinetics/PLCbeta/PLC-Gq REAC A B addmsg /kinetics/PLCbeta/PLC-Gq/PLC-Gq /kinetics/PLCbeta/PLC-Gq REAC eA B addmsg /kinetics/PLCbeta/PLC-Gq /kinetics/PLCbeta/PLC-Gq/PLC-Gq ENZYME n addmsg /kinetics/PLCbeta/PIP2 /kinetics/PLCbeta/PLC-Gq/PLC-Gq SUBSTRATE n addmsg /kinetics/PLCbeta/PLC-Ca/PLC-Ca /kinetics/PLCbeta/PLC-Ca REAC eA B addmsg /kinetics/PLCbeta/Act-PLC-Ca /kinetics/PLCbeta/PLC-Ca REAC B A addmsg /kinetics/PLCbeta/Inact-PLC-Gq /kinetics/PLCbeta/PLC-Ca REAC B A addmsg /kinetics/PLCbeta/Act-PLC-by-Gq /kinetics/PLCbeta/PLC-Ca REAC A B addmsg /kinetics/PLCbeta/PLC-Ca /kinetics/PLCbeta/PLC-Ca/PLC-Ca ENZYME n addmsg /kinetics/PLCbeta/PIP2 /kinetics/PLCbeta/PLC-Ca/PLC-Ca SUBSTRATE n addmsg /kinetics/PLCbeta/Degrade-DAG /kinetics/PLCbeta/PC REAC B A addmsg /kinetics/PLCbeta/PLC-Ca-Gq/PLCb-Ca-Gq /kinetics/PLCbeta/PLC-Ca-Gq REAC eA B addmsg /kinetics/PLCbeta/PLC-Gq-bind-Ca /kinetics/PLCbeta/PLC-Ca-Gq REAC B A addmsg /kinetics/PLCbeta/Inact-PLC-Gq /kinetics/PLCbeta/PLC-Ca-Gq REAC A B addmsg /kinetics/PLCbeta/Act-PLC-by-Gq /kinetics/PLCbeta/PLC-Ca-Gq REAC B A addmsg /kinetics/PLCbeta/PLC-Ca-Gq /kinetics/PLCbeta/PLC-Ca-Gq/PLCb-Ca-Gq ENZYME n addmsg /kinetics/PLCbeta/PIP2 /kinetics/PLCbeta/PLC-Ca-Gq/PLCb-Ca-Gq SUBSTRATE n addmsg /kinetics/PLCbeta/Act-PLC-Ca /kinetics/PLCbeta/PLC REAC A B addmsg /kinetics/PLCbeta/PLC-bind-Gq /kinetics/PLCbeta/PLC REAC A B addmsg /kinetics/PLCbeta/PLC/PLC /kinetics/PLCbeta/PLC REAC eA B addmsg /kinetics/PLCbeta/PLC /kinetics/PLCbeta/PLC/PLC ENZYME n addmsg /kinetics/PLCbeta/PIP2 /kinetics/PLCbeta/PLC/PLC SUBSTRATE n addmsg /kinetics/CaRegulation/Ca /kinetics/PLCbeta/Act-PLC-Ca SUBSTRATE n addmsg /kinetics/PLCbeta/PLC /kinetics/PLCbeta/Act-PLC-Ca SUBSTRATE n addmsg /kinetics/PLCbeta/PLC-Ca /kinetics/PLCbeta/Act-PLC-Ca PRODUCT n addmsg /kinetics/PLCbeta/PLC /kinetics/PLCbeta/PLC-bind-Gq SUBSTRATE n addmsg /kinetics/Gq/G*GTP /kinetics/PLCbeta/PLC-bind-Gq SUBSTRATE n addmsg /kinetics/PLCbeta/PLC-Gq /kinetics/PLCbeta/PLC-bind-Gq PRODUCT n addmsg /kinetics/PLCbeta/PLC-Gq /kinetics/PLCbeta/PLC-Gq-bind-Ca SUBSTRATE n addmsg /kinetics/CaRegulation/Ca /kinetics/PLCbeta/PLC-Gq-bind-Ca SUBSTRATE n addmsg /kinetics/PLCbeta/PLC-Ca-Gq /kinetics/PLCbeta/PLC-Gq-bind-Ca PRODUCT n addmsg /kinetics/PLCbeta/PLC-Ca-Gq /kinetics/PLCbeta/Inact-PLC-Gq SUBSTRATE n addmsg /kinetics/PLCbeta/PLC-Ca /kinetics/PLCbeta/Inact-PLC-Gq PRODUCT n addmsg /kinetics/Gq/G*GDP /kinetics/PLCbeta/Inact-PLC-Gq PRODUCT n addmsg /kinetics/PLCbeta/PLC-Ca /kinetics/PLCbeta/Act-PLC-by-Gq SUBSTRATE n addmsg /kinetics/PLCbeta/PLC-Ca-Gq /kinetics/PLCbeta/Act-PLC-by-Gq PRODUCT n addmsg /kinetics/Gq/G*GTP /kinetics/PLCbeta/Act-PLC-by-Gq SUBSTRATE n addmsg /kinetics/PLCbeta/DAG /kinetics/PLCbeta/Degrade-DAG SUBSTRATE n addmsg /kinetics/PLCbeta/PC /kinetics/PLCbeta/Degrade-DAG PRODUCT n addmsg /kinetics/PLCbeta/PIP2 /kinetics/PLCbeta/basal SUBSTRATE n addmsg /kinetics/PLCbeta/DAG /kinetics/PLCbeta/basal PRODUCT n addmsg /kinetics/IP3-3K/IP3(145) /kinetics/PLCbeta/basal PRODUCT n addmsg /kinetics/PKC/PKC-act-by-DAG /kinetics/PLCbeta/DAG REAC A B addmsg /kinetics/PKC/PKC-n-DAG /kinetics/PLCbeta/DAG REAC A B addmsg /kinetics/PLCbeta/PLC-Ca/PLC-Ca /kinetics/PLCbeta/DAG MM_PRD pA addmsg /kinetics/PLCbeta/PLC-Ca-Gq/PLCb-Ca-Gq /kinetics/PLCbeta/DAG MM_PRD pA addmsg /kinetics/PLCbeta/Degrade-DAG /kinetics/PLCbeta/DAG REAC A B addmsg /kinetics/PLCbeta/PLC/PLC /kinetics/PLCbeta/DAG MM_PRD pA addmsg /kinetics/PLCbeta/PLC-Gq/PLC-Gq /kinetics/PLCbeta/DAG MM_PRD pA addmsg /kinetics/PLCbeta/basal /kinetics/PLCbeta/DAG REAC B A addmsg /kinetics/PLCbeta/PLC-Ca/PLC-Ca /kinetics/PLCbeta/PIP2 REAC sA B addmsg /kinetics/PLCbeta/PLC-Ca-Gq/PLCb-Ca-Gq /kinetics/PLCbeta/PIP2 REAC sA B addmsg /kinetics/PLCbeta/PLC/PLC /kinetics/PLCbeta/PIP2 REAC sA B addmsg /kinetics/PLCbeta/PLC-Gq/PLC-Gq /kinetics/PLCbeta/PIP2 REAC sA B addmsg /kinetics/PLCbeta/basal /kinetics/PLCbeta/PIP2 REAC A B addmsg /kinetics/134_dephos/IP2_3pase2/ip2_3pase2 /kinetics/134_dephos/IP2_3pase2 REAC eA B addmsg /kinetics/134_dephos/IP2_3pase2 /kinetics/134_dephos/IP2_3pase2/ip2_3pase2 ENZYME n addmsg /kinetics/134_dephos/IP2(13) /kinetics/134_dephos/IP2_3pase2/ip2_3pase2 SUBSTRATE n addmsg /kinetics/134_dephos/IP1(3) /kinetics/134_dephos/IP1(3)_deg SUBSTRATE n addmsg /kinetics/145_dephos/inositol /kinetics/134_dephos/IP1(3)_deg PRODUCT n addmsg /kinetics/134_dephos/IP_4pase/ip2_4pase /kinetics/134_dephos/IP1(3) MM_PRD pA addmsg /kinetics/134_dephos/IP1(3)_deg /kinetics/134_dephos/IP1(3) REAC A B addmsg /kinetics/134_dephos/IP2_3pase1/ip2_3pase1 /kinetics/134_dephos/IP2_3pase1 REAC eA B addmsg /kinetics/134_dephos/IP2_3pase1 /kinetics/134_dephos/IP2_3pase1/ip2_3pase1 ENZYME n addmsg /kinetics/134_dephos/IP2(13) /kinetics/134_dephos/IP2_3pase1/ip2_3pase1 SUBSTRATE n addmsg /kinetics/145_dephos/IP_1pase/ip3_1pase /kinetics/134_dephos/IP2(34) MM_PRD pA addmsg /kinetics/134_dephos/IP_4pase/ip2_4pase /kinetics/134_dephos/IP2(34) REAC sA B addmsg /kinetics/134_dephos/IP_4pase /kinetics/134_dephos/IP_4pase-inact SUBSTRATE n addmsg /kinetics/134_dephos/IP_4pase_inact /kinetics/134_dephos/IP_4pase-inact PRODUCT n addmsg /kinetics/IHP-system/IP6 /kinetics/134_dephos/IP_4pase-inact SUBSTRATE n addmsg /kinetics/134_dephos/IP_4pase-inact /kinetics/134_dephos/IP_4pase_inact REAC B A addmsg /kinetics/134_dephos/IP_4pase/ip3_4pase /kinetics/134_dephos/IP_4pase REAC eA B addmsg /kinetics/134_dephos/IP_4pase/ip2_4pase /kinetics/134_dephos/IP_4pase REAC eA B addmsg /kinetics/134_dephos/IP_4pase-inact /kinetics/134_dephos/IP_4pase REAC A B addmsg /kinetics/134_dephos/IP_4pase /kinetics/134_dephos/IP_4pase/ip3_4pase ENZYME n addmsg /kinetics/IP4-system/IP3(134) /kinetics/134_dephos/IP_4pase/ip3_4pase SUBSTRATE n addmsg /kinetics/134_dephos/IP_4pase /kinetics/134_dephos/IP_4pase/ip2_4pase ENZYME n addmsg /kinetics/134_dephos/IP2(34) /kinetics/134_dephos/IP_4pase/ip2_4pase SUBSTRATE n addmsg /kinetics/134_dephos/IP_4pase/ip3_4pase /kinetics/134_dephos/IP2(13) MM_PRD pA addmsg /kinetics/134_dephos/IP2_3pase1/ip2_3pase1 /kinetics/134_dephos/IP2(13) REAC sA B addmsg /kinetics/134_dephos/IP2_3pase2/ip2_3pase2 /kinetics/134_dephos/IP2(13) REAC sA B addmsg /kinetics/134_dephos/IP2_3pase1/ip2_3pase1 /kinetics/134_dephos/IP1(1) MM_PRD pA addmsg /kinetics/134_dephos/IP2_3pase2/ip2_3pase2 /kinetics/134_dephos/IP1(1) MM_PRD pA addmsg /kinetics/134_dephos/1pase-on /kinetics/134_dephos/IP1(1) REAC A B addmsg /kinetics/134_dephos/ip1_syn /kinetics/134_dephos/IP1(1) REAC B A addmsg /kinetics/134_dephos/1pase-on /kinetics/134_dephos/ip1_1pase_cmplx REAC B A addmsg /kinetics/134_dephos/1pase-off /kinetics/134_dephos/ip1_1pase_cmplx REAC A B addmsg /kinetics/134_dephos/IP1(1) /kinetics/134_dephos/1pase-on SUBSTRATE n addmsg /kinetics/145_dephos/IP1_pase /kinetics/134_dephos/1pase-on SUBSTRATE n addmsg /kinetics/134_dephos/ip1_1pase_cmplx /kinetics/134_dephos/1pase-on PRODUCT n addmsg /kinetics/134_dephos/ip1_1pase_cmplx /kinetics/134_dephos/1pase-off SUBSTRATE n addmsg /kinetics/145_dephos/inositol /kinetics/134_dephos/1pase-off PRODUCT n addmsg /kinetics/145_dephos/IP1_pase /kinetics/134_dephos/1pase-off PRODUCT n addmsg /kinetics/145_dephos/inositol /kinetics/134_dephos/ip1_syn SUBSTRATE n addmsg /kinetics/134_dephos/IP1(1) /kinetics/134_dephos/ip1_syn PRODUCT n addmsg /kinetics/145_dephos/IP3_5pase2/ip3_5pase2 /kinetics/145_dephos/IP3_5pase2 REAC eA B addmsg /kinetics/145_dephos/IP3_5pase2 /kinetics/145_dephos/IP3_5pase2/ip3_5pase2 ENZYME n addmsg /kinetics/IP3-3K/IP3(145) /kinetics/145_dephos/IP3_5pase2/ip3_5pase2 SUBSTRATE n addmsg /kinetics/145_dephos/IP_5pase1/ip3_5pase1 /kinetics/145_dephos/IP_5pase1 REAC eA B addmsg /kinetics/145_dephos/IP_5pase1/ip4_5pase /kinetics/145_dephos/IP_5pase1 REAC eA B addmsg /kinetics/145_dephos/IP5-inhib-5pase /kinetics/145_dephos/IP_5pase1 REAC A B addmsg /kinetics/145_dephos/IP6-inhib-5pase /kinetics/145_dephos/IP_5pase1 REAC A B addmsg /kinetics/145_dephos/IP_5pase1 /kinetics/145_dephos/IP_5pase1/ip3_5pase1 ENZYME n addmsg /kinetics/IP3-3K/IP3(145) /kinetics/145_dephos/IP_5pase1/ip3_5pase1 SUBSTRATE n addmsg /kinetics/145_dephos/IP_5pase1 /kinetics/145_dephos/IP_5pase1/ip4_5pase ENZYME n addmsg /kinetics/IP3-3K/IP4(1345) /kinetics/145_dephos/IP_5pase1/ip4_5pase SUBSTRATE n addmsg /kinetics/145_dephos/IP_5pase1/ip3_5pase1 /kinetics/145_dephos/IP2(14) MM_PRD pA addmsg /kinetics/145_dephos/IP3_5pase2/ip3_5pase2 /kinetics/145_dephos/IP2(14) MM_PRD pA addmsg /kinetics/145_dephos/IP_1pase/ip2_1pase /kinetics/145_dephos/IP2(14) REAC sA B addmsg /kinetics/145_dephos/IP5-5pase-cmplx /kinetics/145_dephos/IP5-inhib-5pase PRODUCT n addmsg /kinetics/IP4-system/IP5(13456) /kinetics/145_dephos/IP5-inhib-5pase SUBSTRATE n addmsg /kinetics/145_dephos/IP_5pase1 /kinetics/145_dephos/IP5-inhib-5pase SUBSTRATE n addmsg /kinetics/145_dephos/IP5-inhib-5pase /kinetics/145_dephos/IP5-5pase-cmplx REAC B A addmsg /kinetics/145_dephos/IP6-inhib-5pase /kinetics/145_dephos/IP6-5pase-inhib REAC B A addmsg /kinetics/145_dephos/IP6-5pase-inhib /kinetics/145_dephos/IP6-inhib-5pase PRODUCT n addmsg /kinetics/IHP-system/IP6 /kinetics/145_dephos/IP6-inhib-5pase SUBSTRATE n addmsg /kinetics/145_dephos/IP_5pase1 /kinetics/145_dephos/IP6-inhib-5pase SUBSTRATE n addmsg /kinetics/145_dephos/IP_1pase/ip2_1pase /kinetics/145_dephos/IP_1pase REAC eA B addmsg /kinetics/145_dephos/IP_1pase/ip3_1pase /kinetics/145_dephos/IP_1pase REAC eA B addmsg /kinetics/145_dephos/Ca-inhib-1pase /kinetics/145_dephos/IP_1pase REAC A B addmsg /kinetics/145_dephos/IP_1pase /kinetics/145_dephos/IP_1pase/ip2_1pase ENZYME n addmsg /kinetics/145_dephos/IP2(14) /kinetics/145_dephos/IP_1pase/ip2_1pase SUBSTRATE n addmsg /kinetics/145_dephos/IP_1pase /kinetics/145_dephos/IP_1pase/ip3_1pase ENZYME n addmsg /kinetics/IP4-system/IP3(134) /kinetics/145_dephos/IP_1pase/ip3_1pase SUBSTRATE n addmsg /kinetics/145_dephos/IP_1pase/ip2_1pase /kinetics/145_dephos/IP1(4) MM_PRD pA addmsg /kinetics/145_dephos/4pase-on /kinetics/145_dephos/IP1(4) REAC A B addmsg /kinetics/145_dephos/4pase-on /kinetics/145_dephos/IP1_pase REAC A B addmsg /kinetics/145_dephos/4pase-off /kinetics/145_dephos/IP1_pase REAC B A addmsg /kinetics/134_dephos/1pase-on /kinetics/145_dephos/IP1_pase REAC A B addmsg /kinetics/134_dephos/1pase-off /kinetics/145_dephos/IP1_pase REAC B A addmsg /kinetics/145_dephos/Ca-inhib-1pase /kinetics/145_dephos/Ca-1pase-cmplx REAC B A addmsg /kinetics/134_dephos/IP1(3)_deg /kinetics/145_dephos/inositol REAC B A addmsg /kinetics/145_dephos/4pase-off /kinetics/145_dephos/inositol REAC B A addmsg /kinetics/134_dephos/1pase-off /kinetics/145_dephos/inositol REAC B A addmsg /kinetics/134_dephos/ip1_syn /kinetics/145_dephos/inositol REAC A B addmsg /kinetics/145_dephos/Ca-1pase-cmplx /kinetics/145_dephos/Ca-inhib-1pase PRODUCT n addmsg /kinetics/145_dephos/IP_1pase /kinetics/145_dephos/Ca-inhib-1pase SUBSTRATE n addmsg /kinetics/CaRegulation/Ca /kinetics/145_dephos/Ca-inhib-1pase SUBSTRATE n addmsg /kinetics/145_dephos/4pase-on /kinetics/145_dephos/ip1_4pase_cmplx REAC B A addmsg /kinetics/145_dephos/4pase-off /kinetics/145_dephos/ip1_4pase_cmplx REAC A B addmsg /kinetics/145_dephos/IP1(4) /kinetics/145_dephos/4pase-on SUBSTRATE n addmsg /kinetics/145_dephos/IP1_pase /kinetics/145_dephos/4pase-on SUBSTRATE n addmsg /kinetics/145_dephos/ip1_4pase_cmplx /kinetics/145_dephos/4pase-on PRODUCT n addmsg /kinetics/145_dephos/ip1_4pase_cmplx /kinetics/145_dephos/4pase-off SUBSTRATE n addmsg /kinetics/145_dephos/IP1_pase /kinetics/145_dephos/4pase-off PRODUCT n addmsg /kinetics/145_dephos/inositol /kinetics/145_dephos/4pase-off PRODUCT n addmsg /kinetics/IP4-system/6kinase /kinetics/IP4-system/IP4(1346) REAC B A addmsg /kinetics/IP4-system/ip4-5K /kinetics/IP4-system/IP4(1346) REAC A B addmsg /kinetics/1345_dephos/IP4-inhib-3pase /kinetics/IP4-system/IP4(3456) REAC A B addmsg /kinetics/IP4-system/ip4-1k-on /kinetics/IP4-system/IP4(3456) REAC A B addmsg /kinetics/IP4-system/ip5_1pase /kinetics/IP4-system/IP4(3456) REAC B A addmsg /kinetics/MIPP/ip4(1456)_trp /kinetics/IP4-system/IP4(1456) REAC B A addmsg /kinetics/IP4-system/ip4-6pase /kinetics/IP4-system/IP4(1456) REAC A B addmsg /kinetics/IP4-system/ip5_3pase /kinetics/IP4-system/IP4(1456) REAC B A addmsg /kinetics/IP4-system/ip4-3k-on /kinetics/IP4-system/IP4(1456) REAC A B addmsg /kinetics/IP4-system/IP4(1456) /kinetics/IP4-system/ip4-6pase SUBSTRATE n addmsg /kinetics/IP3-3K/IP3(145) /kinetics/IP4-system/ip4-6pase PRODUCT n addmsg /kinetics/IP4-system/IP5(13456) /kinetics/IP4-system/ip5_3pase SUBSTRATE n addmsg /kinetics/IP4-system/IP4(1456) /kinetics/IP4-system/ip5_3pase PRODUCT n addmsg /kinetics/IP4-system/IP3(134) /kinetics/IP4-system/IP3-Kcmplx-on SUBSTRATE n addmsg /kinetics/IP4-system/IP3-56Kcmplx /kinetics/IP4-system/IP3-Kcmplx-on PRODUCT n addmsg /kinetics/IP4-system/IP3-56K_IP4-1K /kinetics/IP4-system/IP3-Kcmplx-on SUBSTRATE n addmsg /kinetics/IP4-system/IP3-56Kcmplx /kinetics/IP4-system/6kinase SUBSTRATE n addmsg /kinetics/IP4-system/IP4(1346) /kinetics/IP4-system/6kinase PRODUCT n addmsg /kinetics/IP4-system/IP3-56K_IP4-1K /kinetics/IP4-system/6kinase PRODUCT n addmsg /kinetics/IP4-system/IP3-56Kcmplx /kinetics/IP4-system/5kinase SUBSTRATE n addmsg /kinetics/IP3-3K/IP4(1345) /kinetics/IP4-system/5kinase PRODUCT n addmsg /kinetics/IP4-system/IP3-56K_IP4-1K /kinetics/IP4-system/5kinase PRODUCT n addmsg /kinetics/IP4-system/IP4(1346) /kinetics/IP4-system/ip4-5K SUBSTRATE n addmsg /kinetics/IP4-system/IP5(13456) /kinetics/IP4-system/ip4-5K PRODUCT n addmsg /kinetics/IP4-system/ip4-3k-on /kinetics/IP4-system/IP4-3K REAC A B addmsg /kinetics/IP4-system/ip4-3k-off /kinetics/IP4-system/IP4-3K REAC B A addmsg /kinetics/IP4-system/6kinase /kinetics/IP4-system/IP3-56Kcmplx REAC A B addmsg /kinetics/IP4-system/5kinase /kinetics/IP4-system/IP3-56Kcmplx REAC A B addmsg /kinetics/IP4-system/IP3-Kcmplx-on /kinetics/IP4-system/IP3-56Kcmplx REAC B A addmsg /kinetics/IHP-system/ip5-kinase-pase /kinetics/IP4-system/IP5(13456) REAC A B addmsg /kinetics/IP4-system/ip4-5K /kinetics/IP4-system/IP5(13456) REAC B A addmsg /kinetics/IHP-system/IP6_K2/ip5_k2 /kinetics/IP4-system/IP5(13456) REAC sA B addmsg /kinetics/IHP-system/IP6-K/ip5_k1 /kinetics/IP4-system/IP5(13456) REAC sA B addmsg /kinetics/IHP-system/IP5-dipp-inhib /kinetics/IP4-system/IP5(13456) REAC A B addmsg /kinetics/1345_dephos/IP5-inhib-3pase /kinetics/IP4-system/IP5(13456) REAC A B addmsg /kinetics/145_dephos/IP5-inhib-5pase /kinetics/IP4-system/IP5(13456) REAC A B addmsg /kinetics/MIPP/ip5(13456)_trp /kinetics/IP4-system/IP5(13456) REAC B A addmsg /kinetics/IHP-system/dipp_ip6 /kinetics/IP4-system/IP5(13456) REAC B A addmsg /kinetics/IP4-system/ip5_3pase /kinetics/IP4-system/IP5(13456) REAC A B addmsg /kinetics/IP4-system/ip4-3k-off /kinetics/IP4-system/IP5(13456) REAC B A addmsg /kinetics/IP4-system/ip4-1k-off /kinetics/IP4-system/IP5(13456) REAC B A addmsg /kinetics/IP4-system/ip5_1pase /kinetics/IP4-system/IP5(13456) REAC A B addmsg /kinetics/IP4-system/ip4-3k-on /kinetics/IP4-system/ip4_3k_cmplx REAC B A addmsg /kinetics/IP4-system/ip4-3k-off /kinetics/IP4-system/ip4_3k_cmplx REAC A B addmsg /kinetics/IP4-system/IP4(1456) /kinetics/IP4-system/ip4-3k-on SUBSTRATE n addmsg /kinetics/IP4-system/ip4_3k_cmplx /kinetics/IP4-system/ip4-3k-on PRODUCT n addmsg /kinetics/IP4-system/IP4-3K /kinetics/IP4-system/ip4-3k-on SUBSTRATE n addmsg /kinetics/IP4-system/ip4_3k_cmplx /kinetics/IP4-system/ip4-3k-off SUBSTRATE n addmsg /kinetics/IP4-system/IP4-3K /kinetics/IP4-system/ip4-3k-off PRODUCT n addmsg /kinetics/IP4-system/IP5(13456) /kinetics/IP4-system/ip4-3k-off PRODUCT n addmsg /kinetics/IP4-system/ip4-1k-on /kinetics/IP4-system/ip4_1k_cmplx REAC B A addmsg /kinetics/IP4-system/ip4-1k-off /kinetics/IP4-system/ip4_1k_cmplx REAC A B addmsg /kinetics/IP4-system/IP4(3456) /kinetics/IP4-system/ip4-1k-on SUBSTRATE n addmsg /kinetics/IP4-system/ip4_1k_cmplx /kinetics/IP4-system/ip4-1k-on PRODUCT n addmsg /kinetics/IP4-system/IP3-56K_IP4-1K /kinetics/IP4-system/ip4-1k-on SUBSTRATE n addmsg /kinetics/IP4-system/ip4_1k_cmplx /kinetics/IP4-system/ip4-1k-off SUBSTRATE n addmsg /kinetics/IP4-system/IP5(13456) /kinetics/IP4-system/ip4-1k-off PRODUCT n addmsg /kinetics/IP4-system/IP3-56K_IP4-1K /kinetics/IP4-system/ip4-1k-off PRODUCT n addmsg /kinetics/IP4-system/IP3-Kcmplx-on /kinetics/IP4-system/IP3(134) REAC A B addmsg /kinetics/145_dephos/IP_5pase1/ip4_5pase /kinetics/IP4-system/IP3(134) MM_PRD pA addmsg /kinetics/145_dephos/IP_1pase/ip3_1pase /kinetics/IP4-system/IP3(134) REAC sA B addmsg /kinetics/134_dephos/IP_4pase/ip3_4pase /kinetics/IP4-system/IP3(134) REAC sA B addmsg /kinetics/1345_dephos/134-inhib-3pase /kinetics/IP4-system/IP3(134) REAC A B addmsg /kinetics/IP4-system/IP3-Kcmplx-on /kinetics/IP4-system/IP3-56K_IP4-1K REAC A B addmsg /kinetics/IP4-system/6kinase /kinetics/IP4-system/IP3-56K_IP4-1K REAC B A addmsg /kinetics/IP4-system/5kinase /kinetics/IP4-system/IP3-56K_IP4-1K REAC B A addmsg /kinetics/IP4-system/ip4-1k-on /kinetics/IP4-system/IP3-56K_IP4-1K REAC A B addmsg /kinetics/IP4-system/ip4-1k-off /kinetics/IP4-system/IP3-56K_IP4-1K REAC B A addmsg /kinetics/IP4-system/IP5(13456) /kinetics/IP4-system/ip5_1pase SUBSTRATE n addmsg /kinetics/IP4-system/IP4(3456) /kinetics/IP4-system/ip5_1pase PRODUCT n addmsg /kinetics/IHP-system/PP-IP4 /kinetics/IHP-system/dipp_ip6 SUBSTRATE n addmsg /kinetics/IP4-system/IP5(13456) /kinetics/IHP-system/dipp_ip6 PRODUCT n addmsg /kinetics/IHP-system/IP6_K2/ip5_k2 /kinetics/IHP-system/PP-IP4 MM_PRD pA addmsg /kinetics/IHP-system/IP6-K/ip5_k1 /kinetics/IHP-system/PP-IP4 MM_PRD pA addmsg /kinetics/IHP-system/IP6_K2/pp-ip4-k2 /kinetics/IHP-system/PP-IP4 REAC sA B addmsg /kinetics/IHP-system/IP6-K/pp-ip4-k1 /kinetics/IHP-system/PP-IP4 REAC sA B addmsg /kinetics/IHP-system/dipp_ip6 /kinetics/IHP-system/PP-IP4 REAC A B addmsg /kinetics/IHP-system/IP6_K2/ip6_k2 /kinetics/IHP-system/IP6_K2 REAC eA B addmsg /kinetics/IHP-system/IP6_K2/ip5_k2 /kinetics/IHP-system/IP6_K2 REAC eA B addmsg /kinetics/IHP-system/IP6_K2/pp-ip4-k2 /kinetics/IHP-system/IP6_K2 REAC eA B addmsg /kinetics/IHP-system/IP6_K2 /kinetics/IHP-system/IP6_K2/ip6_k2 ENZYME n addmsg /kinetics/IHP-system/IP6 /kinetics/IHP-system/IP6_K2/ip6_k2 SUBSTRATE n addmsg /kinetics/IHP-system/IP6_K2 /kinetics/IHP-system/IP6_K2/ip5_k2 ENZYME n addmsg /kinetics/IP4-system/IP5(13456) /kinetics/IHP-system/IP6_K2/ip5_k2 SUBSTRATE n addmsg /kinetics/IHP-system/IP6_K2 /kinetics/IHP-system/IP6_K2/pp-ip4-k2 ENZYME n addmsg /kinetics/IHP-system/PP-IP4 /kinetics/IHP-system/IP6_K2/pp-ip4-k2 SUBSTRATE n addmsg /kinetics/IHP-system/IP6_K2/pp-ip4-k2 /kinetics/IHP-system/bisPP-IP3 MM_PRD pA addmsg /kinetics/IHP-system/IP6-K/pp-ip4-k1 /kinetics/IHP-system/bisPP-IP3 MM_PRD pA addmsg /kinetics/IHP-system/IP6cmplx-on /kinetics/IHP-system/ATP REAC A B addmsg /kinetics/IHP-system/PP-IP5cmplx-on /kinetics/IHP-system/ATP REAC A B addmsg /kinetics/IHP-system/IP6cmplx-off /kinetics/IHP-system/ADP REAC B A addmsg /kinetics/IHP-system/PP-IP5cmplx-off /kinetics/IHP-system/ADP REAC B A addmsg /kinetics/IHP-system/IP6cmplx-on /kinetics/IHP-system/IP6 REAC A B addmsg /kinetics/IHP-system/IP6_K2/ip6_k2 /kinetics/IHP-system/IP6 REAC sA B addmsg /kinetics/IHP-system/ip5-kinase-pase /kinetics/IHP-system/IP6 REAC B A addmsg /kinetics/134_dephos/IP_4pase-inact /kinetics/IHP-system/IP6 REAC A B addmsg /kinetics/MIPP/ip6_trp /kinetics/IHP-system/IP6 REAC A B addmsg /kinetics/IHP-system/DIPP1/dipp_ip7 /kinetics/IHP-system/IP6 MM_PRD pA addmsg /kinetics/IHP-system/IP6-dipp-inhib /kinetics/IHP-system/IP6 REAC A B addmsg /kinetics/1345_dephos/IP6-inhib-3pase /kinetics/IHP-system/IP6 REAC A B addmsg /kinetics/145_dephos/IP6-inhib-5pase /kinetics/IHP-system/IP6 REAC A B addmsg /kinetics/IP4-system/IP5(13456) /kinetics/IHP-system/ip5-kinase-pase SUBSTRATE n addmsg /kinetics/IHP-system/IP6 /kinetics/IHP-system/ip5-kinase-pase PRODUCT n addmsg /kinetics/IHP-system/IP6cmplx-off /kinetics/IHP-system/PP-IP5 REAC B A addmsg /kinetics/IHP-system/PP-IP5cmplx-on /kinetics/IHP-system/PP-IP5 REAC A B addmsg /kinetics/IHP-system/IP6_K2/ip6_k2 /kinetics/IHP-system/PP-IP5 MM_PRD pA addmsg /kinetics/IHP-system/DIPP1/dipp_ip8 /kinetics/IHP-system/PP-IP5 MM_PRD pA addmsg /kinetics/IHP-system/DIPP1/dipp_ip7 /kinetics/IHP-system/PP-IP5 REAC sA B addmsg /kinetics/IHP-system/PP-IP5cmplx-off /kinetics/IHP-system/bisPP-IP4 REAC B A addmsg /kinetics/IHP-system/DIPP1/dipp_ip8 /kinetics/IHP-system/bisPP-IP4 REAC sA B addmsg /kinetics/IHP-system/DIPP1/dipp_ip7 /kinetics/IHP-system/DIPP1 REAC eA B addmsg /kinetics/IHP-system/DIPP1/dipp_ip8 /kinetics/IHP-system/DIPP1 REAC eA B addmsg /kinetics/IHP-system/IP6-dipp-inhib /kinetics/IHP-system/DIPP1 REAC A B addmsg /kinetics/IHP-system/IP5-dipp-inhib /kinetics/IHP-system/DIPP1 REAC A B addmsg /kinetics/IHP-system/DIPP1 /kinetics/IHP-system/DIPP1/dipp_ip8 ENZYME n addmsg /kinetics/IHP-system/bisPP-IP4 /kinetics/IHP-system/DIPP1/dipp_ip8 SUBSTRATE n addmsg /kinetics/IHP-system/DIPP1 /kinetics/IHP-system/DIPP1/dipp_ip7 ENZYME n addmsg /kinetics/IHP-system/PP-IP5 /kinetics/IHP-system/DIPP1/dipp_ip7 SUBSTRATE n addmsg /kinetics/IHP-system/DIPP1 /kinetics/IHP-system/IP5-dipp-inhib SUBSTRATE n addmsg /kinetics/IP4-system/IP5(13456) /kinetics/IHP-system/IP5-dipp-inhib SUBSTRATE n addmsg /kinetics/IHP-system/IP5-DIPPcmplx /kinetics/IHP-system/IP5-dipp-inhib PRODUCT n addmsg /kinetics/IHP-system/IP6 /kinetics/IHP-system/IP6-dipp-inhib SUBSTRATE n addmsg /kinetics/IHP-system/DIPP1 /kinetics/IHP-system/IP6-dipp-inhib SUBSTRATE n addmsg /kinetics/IHP-system/IP6-DIPPcmplx /kinetics/IHP-system/IP6-dipp-inhib PRODUCT n addmsg /kinetics/IHP-system/IP6-dipp-inhib /kinetics/IHP-system/IP6-DIPPcmplx REAC B A addmsg /kinetics/IHP-system/IP5-dipp-inhib /kinetics/IHP-system/IP5-DIPPcmplx REAC B A addmsg /kinetics/IHP-system/ATP /kinetics/IHP-system/PP-IP5cmplx-on SUBSTRATE n addmsg /kinetics/IHP-system/PP-IP5 /kinetics/IHP-system/PP-IP5cmplx-on SUBSTRATE n addmsg /kinetics/IHP-system/PP-IP5-K /kinetics/IHP-system/PP-IP5cmplx-on SUBSTRATE n addmsg /kinetics/IHP-system/PP-IP5-K-complex /kinetics/IHP-system/PP-IP5cmplx-on PRODUCT n addmsg /kinetics/IHP-system/PP-IP5-K-complex /kinetics/IHP-system/PP-IP5cmplx-off SUBSTRATE n addmsg /kinetics/IHP-system/ADP /kinetics/IHP-system/PP-IP5cmplx-off PRODUCT n addmsg /kinetics/IHP-system/bisPP-IP4 /kinetics/IHP-system/PP-IP5cmplx-off PRODUCT n addmsg /kinetics/IHP-system/PP-IP5-K /kinetics/IHP-system/PP-IP5cmplx-off PRODUCT n addmsg /kinetics/IHP-system/PP-IP5cmplx-on /kinetics/IHP-system/PP-IP5-K-complex REAC B A addmsg /kinetics/IHP-system/PP-IP5cmplx-off /kinetics/IHP-system/PP-IP5-K-complex REAC A B addmsg /kinetics/IHP-system/IP6cmplx-on /kinetics/IHP-system/IP6-K-complex REAC B A addmsg /kinetics/IHP-system/IP6cmplx-off /kinetics/IHP-system/IP6-K-complex REAC A B addmsg /kinetics/IHP-system/IP6-K-complex /kinetics/IHP-system/IP6cmplx-off SUBSTRATE n addmsg /kinetics/IHP-system/PP-IP5 /kinetics/IHP-system/IP6cmplx-off PRODUCT n addmsg /kinetics/IHP-system/ADP /kinetics/IHP-system/IP6cmplx-off PRODUCT n addmsg /kinetics/IHP-system/IP6-K /kinetics/IHP-system/IP6cmplx-off PRODUCT n addmsg /kinetics/IHP-system/IP6 /kinetics/IHP-system/IP6cmplx-on SUBSTRATE n addmsg /kinetics/IHP-system/ATP /kinetics/IHP-system/IP6cmplx-on SUBSTRATE n addmsg /kinetics/IHP-system/IP6-K /kinetics/IHP-system/IP6cmplx-on SUBSTRATE n addmsg /kinetics/IHP-system/IP6-K-complex /kinetics/IHP-system/IP6cmplx-on PRODUCT n addmsg /kinetics/IHP-system/PP-IP5cmplx-on /kinetics/IHP-system/PP-IP5-K REAC A B addmsg /kinetics/IHP-system/PP-IP5cmplx-off /kinetics/IHP-system/PP-IP5-K REAC B A addmsg /kinetics/IHP-system/IP6cmplx-on /kinetics/IHP-system/IP6-K REAC A B addmsg /kinetics/IHP-system/IP6cmplx-off /kinetics/IHP-system/IP6-K REAC B A addmsg /kinetics/IHP-system/IP6-K/ip5_k1 /kinetics/IHP-system/IP6-K REAC eA B addmsg /kinetics/IHP-system/IP6-K/pp-ip4-k1 /kinetics/IHP-system/IP6-K REAC eA B addmsg /kinetics/IHP-system/IP6-K /kinetics/IHP-system/IP6-K/ip5_k1 ENZYME n addmsg /kinetics/IP4-system/IP5(13456) /kinetics/IHP-system/IP6-K/ip5_k1 SUBSTRATE n addmsg /kinetics/IHP-system/IP6-K /kinetics/IHP-system/IP6-K/pp-ip4-k1 ENZYME n addmsg /kinetics/IHP-system/PP-IP4 /kinetics/IHP-system/IP6-K/pp-ip4-k1 SUBSTRATE n addmsg /kinetics/1345_dephos/1345_3pase /kinetics/1345_dephos/IP5-inhib-3pase SUBSTRATE n addmsg /kinetics/1345_dephos/IP5-3pase-cmplx /kinetics/1345_dephos/IP5-inhib-3pase PRODUCT n addmsg /kinetics/IP4-system/IP5(13456) /kinetics/1345_dephos/IP5-inhib-3pase SUBSTRATE n addmsg /kinetics/1345_dephos/IP5-inhib-3pase /kinetics/1345_dephos/IP5-3pase-cmplx REAC B A addmsg /kinetics/1345_dephos/1345_3pase /kinetics/1345_dephos/IP6-inhib-3pase SUBSTRATE n addmsg /kinetics/1345_dephos/IP6-inhib-3pase-cmplx /kinetics/1345_dephos/IP6-inhib-3pase PRODUCT n addmsg /kinetics/IHP-system/IP6 /kinetics/1345_dephos/IP6-inhib-3pase SUBSTRATE n addmsg /kinetics/1345_dephos/1345_3pase /kinetics/1345_dephos/145-inhib-3pase SUBSTRATE n addmsg /kinetics/IP3-3K/IP3(145) /kinetics/1345_dephos/145-inhib-3pase SUBSTRATE n addmsg /kinetics/1345_dephos/IP3(145)-3pase-cmplx /kinetics/1345_dephos/145-inhib-3pase PRODUCT n addmsg /kinetics/IP4-system/IP4(3456) /kinetics/1345_dephos/IP4-inhib-3pase SUBSTRATE n addmsg /kinetics/1345_dephos/1345_3pase /kinetics/1345_dephos/IP4-inhib-3pase SUBSTRATE n addmsg /kinetics/1345_dephos/IP4-3pase-cmplx /kinetics/1345_dephos/IP4-inhib-3pase PRODUCT n addmsg /kinetics/1345_dephos/1345_3pase /kinetics/1345_dephos/134-inhib-3pase SUBSTRATE n addmsg /kinetics/IP4-system/IP3(134) /kinetics/1345_dephos/134-inhib-3pase SUBSTRATE n addmsg /kinetics/1345_dephos/IP3(134)-3pase-cmplx /kinetics/1345_dephos/134-inhib-3pase PRODUCT n addmsg /kinetics/1345_dephos/IP4-inhib-3pase /kinetics/1345_dephos/IP4-3pase-cmplx REAC B A addmsg /kinetics/1345_dephos/145-inhib-3pase /kinetics/1345_dephos/IP3(145)-3pase-cmplx REAC B A addmsg /kinetics/1345_dephos/134-inhib-3pase /kinetics/1345_dephos/IP3(134)-3pase-cmplx REAC B A addmsg /kinetics/1345_dephos/IP6-inhib-3pase /kinetics/1345_dephos/IP6-inhib-3pase-cmplx REAC B A addmsg /kinetics/1345_dephos/134-inhib-3pase /kinetics/1345_dephos/1345_3pase REAC A B addmsg /kinetics/1345_dephos/145-inhib-3pase /kinetics/1345_dephos/1345_3pase REAC A B addmsg /kinetics/1345_dephos/IP4-inhib-3pase /kinetics/1345_dephos/1345_3pase REAC A B addmsg /kinetics/1345_dephos/IP5-inhib-3pase /kinetics/1345_dephos/1345_3pase REAC A B addmsg /kinetics/1345_dephos/IP6-inhib-3pase /kinetics/1345_dephos/1345_3pase REAC A B addmsg /kinetics/1345_dephos/1345_3pase/ip4_3pase /kinetics/1345_dephos/1345_3pase REAC eA B addmsg /kinetics/1345_dephos/1345_3pase /kinetics/1345_dephos/1345_3pase/ip4_3pase ENZYME n addmsg /kinetics/IP3-3K/IP4(1345) /kinetics/1345_dephos/1345_3pase/ip4_3pase SUBSTRATE n addmsg /kinetics/IHP-system/bisPP-IP4 /graphs/conc1/bisPP-IP4.Co PLOT Co *bisPP-IP4.Co *7 addmsg /kinetics/IHP-system/PP-IP5 /graphs/conc1/PP-IP5.Co PLOT Co *PP-IP5.Co *52 addmsg /kinetics/IHP-system/PP-IP4 /graphs/conc1/PP-IP4.Co PLOT Co *PP-IP4.Co *pink addmsg /kinetics/IHP-system/IP6 /graphs/conc1/IP6.Co PLOT Co *IP6.Co *39 addmsg /kinetics/IP4-system/IP5(13456) /graphs/conc1/IP5(13456).Co PLOT Co *IP5(13456).Co *0 addmsg /kinetics/CaRegulation/Ca-sequester /graphs/conc1/Ca-sequester.Co PLOT Co *Ca-sequester.Co *red addmsg /kinetics/IP3-3K/IP4(1345) /graphs/conc2/IP4(1345).Co PLOT Co *IP4(1345).Co *46 addmsg /kinetics/IP4-system/IP4(3456) /graphs/conc2/IP4(3456).Co PLOT Co *IP4(3456).Co *61 addmsg /kinetics/IP4-system/IP4(1456) /graphs/conc2/IP4(1456).Co PLOT Co *IP4(1456).Co *1 addmsg /kinetics/IP4-system/IP4(1346) /graphs/conc2/IP4(1346).Co PLOT Co *IP4(1346).Co *34 addmsg /kinetics/IP3-3K/IP3(145) /moregraphs/conc3/IP3(145).Co PLOT Co *IP3(145).Co *53 addmsg /kinetics/IP4-system/IP3(134) /moregraphs/conc3/IP3(134).Co PLOT Co *IP3(134).Co *62 addmsg /kinetics/134_dephos/IP2(13) /moregraphs/conc3/IP2(13).Co PLOT Co *IP2(13).Co *cyan addmsg /kinetics/134_dephos/IP2(34) /moregraphs/conc3/IP2(34).Co PLOT Co *IP2(34).Co *26 addmsg /kinetics/145_dephos/IP2(14) /moregraphs/conc3/IP2(14).Co PLOT Co *IP2(14).Co *18 addmsg /kinetics/CaRegulation/Ca /moregraphs/conc4/Ca.Co PLOT Co *Ca.Co *61 addmsg /kinetics/145_dephos/IP1(4) /moregraphs/conc4/IP1(4).Co PLOT Co *IP1(4).Co *34 addmsg /kinetics/134_dephos/IP1(3) /moregraphs/conc4/IP1(3).Co PLOT Co *IP1(3).Co *7 addmsg /kinetics/134_dephos/IP1(1) /moregraphs/conc4/IP1(1).Co PLOT Co *IP1(1).Co *1 enddump // End of dump call /kinetics/MIPP/notes LOAD \ "Model for Multiple Inositol Polyphosphate Phosphatase. Primary refs:" \ "Nogimori et al, JBC 266, 1991: 16499-506; Chi et al, MCB 20, 2000:" \ "6496-507" call /kinetics/MIPP/ip6_trp/notes LOAD \ "InsP6 ER-cytosol transport. Rate based on cytosolic levels of " \ "InsP6. ER-cytosol transport for other inositol phosphates are" \ "assigned the same rate as of now, as exact transport rates are " \ "not known." call /kinetics/MIPP/ip5(12456)_trp/notes LOAD \ "Ins(12456)P5 ER-cytosol transport" call /kinetics/MIPP/ip5(13456)_trp/notes LOAD \ "Ins(13456)P5 ER-cytosol transport" call /kinetics/MIPP/ip4(1456)_trp/notes LOAD \ "Ins(1456)P4 ER-cytosol transport" call /kinetics/MIPP/ip4(1345)_trp/notes LOAD \ "Ins(1345)P4 ER-cytosol transport" call /kinetics/MIPP/ip3(145)_trp/notes LOAD \ "Ins(145)P3 ER-cytosol transport" call /kinetics/MIPP/MIPP/notes LOAD \ "Multiple Inositol Polyphosphate Phosphatase" \ "from Nogimori et al, JBC 266(25); 1991: 16499-506" \ "" \ "MIPP clustered in ER. Distinct transporters present for cytosolic " \ "substrates. Accounts for 30-45% of total 3-phosphatase activity " \ "against substrates, hence cytosolic counterparts of this enzyme " \ "must be present (as per Chi et al, MCB 20; 2000: 6496-507) " call /kinetics/MIPP/MIPP/ip5_3pase/notes LOAD \ "Ins(13456)P5 3-phosphatase" \ "from Nogimori et al, JBC 266; 1991" call /kinetics/MIPP/MIPP/ip4_3pase/notes LOAD \ "Ins(1345)P4 3-phosphatase" \ "from Nogimori et al, JBC 266; 1991" call /kinetics/MIPP/MIPP/ip6_pase/notes LOAD \ "InsP6 2/3-phosphatase" \ "from Nogimori et al, JBC 266; 1991" call /kinetics/MIPP/IP5(12456)/notes LOAD \ "Inositol(12456)pentakisphosphate" \ "Conc = 4% of total InsP5" call /kinetics/CaMKII/notes LOAD \ "Main reference here is the review by Hanson and Schulman, Ann Rev Biochem" \ "1992 vol 61 pp 559-601. Most of the mechanistic details and a few constants" \ "are derived from there. Many kinetics are from Hanson and Schulman JBC" \ "267:24 17216-17224 1992." \ "The enzymes look a bit complicated." \ "Actually it is just 3 reactions for different sites," \ "by 4 states of CaMKII, defined by the phosphorylation state." \ "This model approximates the fact that the enzyme is actually present as" \ "a decamer/dodecamer. It does so by treating the autophosphorylation reactions" \ "as being independent of the concentration of CaMKII. Also the rates for" \ "the autophosphorylation steps have been scaled to fit this " \ "approximation. " call /kinetics/CaMKII/CaMKII/notes LOAD \ "Huge concentration of CaMKII. In PSD it is 20-40% of protein," \ " so we assume it is around" \ "2.5% of protein in spine as a whole. This level is so high it is unlikely to" \ " matter much if we are off a bit. This comes to about 70 uM." \ "Seen the review:" \ "Hanson and Schulman 1992 Ann. Rev. Biuochem 60:559-601" call /kinetics/CaMKII/CaMKII-CaM/notes LOAD \ "This is the regular, CaM-activated form of CaMKII." \ "See the review" \ "Hanson and Schulman 1992 Ann. Rev. Biochem 60:559-601" call /kinetics/CaMKII/CaMKII-thr286*-CaM/notes LOAD \ "From Hanson and Schulman, the thr286 is responsible for autonomous activation" \ "of CaMKII." call /kinetics/CaMKII/CaMKII***/notes LOAD \ "From Hanson and Schulman, the CaMKII does a lot of autophosphorylation" \ "just after the CaM is released. This prevents further CaM binding and renders" \ "the enzyme quite independent of Ca." call /kinetics/CaMKII/CaMKII-bind-CaM/notes LOAD \ "This is tricky. There is some cooperativity here arising from interactions" \ "between the subunits of the CAMKII holoenzyme. However, the" \ "stoichiometry is 1. " \ "Kd = 0.1 uM. Rate is fast (see Hanson et al Neuron 12 943-956 1994)" \ "Hanson and Schulman 1992 AnnRev Biochem 61:559-601" \ "give tau for dissoc as 0.2 sec at low Ca, 0.4 at high." \ "Low Ca = 100 nM = physiol." call /kinetics/CaMKII/CaMK-thr286-bind-CaM/notes LOAD \ "Affinity is up 1000X over the unphosphorylated CaMKII, which makes the" \ "Kd of 0.1 nM. See Hanson et al 1994 Neuron 12:943-956." \ "Time to release is about 20 sec, so the kb is OK at 0.1/sec." \ "as tested by a few runs." \ "" call /kinetics/CaMKII/CaMKII-thr286/notes LOAD \ "The threonine-286 phosphorylated form of CaMKII. It is likely" \ "to be a short-lived intermediate, since it will be phosphorylated further" \ "as soon as the CAM falls off." call /kinetics/CaMKII/CaMK-thr306/notes LOAD \ "This forms due to basal autophosphorylation, but I think it has to be" \ "considered as a pathway even if some CaM is floating around. In either" \ "case it will tend to block further binding of CaM, and will not display any" \ "enzyme activity. See Hanson and Schulman JBC 267:24 pp17216-17224 1992" call /kinetics/CaMKII/total-CaMKII/notes LOAD \ "This pool is purely here to provide a single, fixed number," \ "which is the total amount of CaMKII. This is used by the" \ "autophosphorylation steps to scale down the rates so that the" \ "autophosphorylation reactions are independent of CaMKII levels." call /kinetics/CaMKII/basal-activity/notes LOAD \ "This reaction represents one of the unknowns in CaMK-II" \ "biochemistry: what maintains the basal level of phosphorylation" \ "on thr 286 ? See Hanson and Schulman Ann Rev Biochem 1992" \ "61:559-601, specially pg 580, for review. I have not been able to" \ "find any compelling mechanism in the literature, but fortunately" \ "the level of basal activity is well documented. " \ "Lisman et al propose that the levels of PP1 are very low in the " \ "postsynaptic density, and PP2A is excluded from the PSD, and this would" \ "lead to autophosphorylation at a sustained level." call /kinetics/CaMKII/tot_CaM_CaMKII/notes LOAD \ "This pool sums the levels of the CaM-bound forms of CaMKII:" \ "CaMKII-CaM + CaMKII-thr286*-CaM. Although their phosphorylation states" \ "are different, the level of activity is about the same so it makes sense" \ "to sum the levels." \ "Hanson et al 1994 Neuron 12:943-956" call /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305/notes LOAD \ "Rates from autocamtide phosphorylation, from " \ "Hanson and Schulman JBC 267:24 17216-17224 1992. See especially Fig 5." call /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286/notes LOAD \ "See Hanson and Schulman 1992 JBC 267(24):17216-17224" call /kinetics/CaMKII/tot_CaM_CaMKII/CaM-CaMK-phos/notes LOAD \ "rates referred from standard CaM-CaMKII phosphorylation rates" call /kinetics/CaMKII/tot_CaM_CaMKII/CaM-CaMK-phos1/notes LOAD \ "rates referred from standard CaM-CaMKII phosphorylation rates" call /kinetics/CaMKII/tot_autonomous_CaMKII/notes LOAD \ "This is the sum total of the various CaM-independent forms of the " \ "kinase. There are actually several possible states here, but I only" \ "consider the forms thr-286 phosphorylated form and the doubly/triply" \ "phosphorylated form including the thr305/306, represented here" \ "as CaMKII***" \ "" call /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305/notes LOAD \ "See Hanson and Schulman 1992 JBC 267(24):17216-17224" \ "for afterburst rates of phosphorylation" call /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286/notes LOAD \ "The autonomous rate has a slightly higher Km than the CaM-bound rate," \ "but Vmax is the same." \ "Hanson and Schulman 1992 Ann Rev Biochem 61:559-601" \ "and " \ "Hanson and Schulman 1992 JBC 267(24):17216-17224" call /kinetics/CaMKII/tot_autonomous_CaMKII/CaMK-phos/notes LOAD \ "rates referred from standard CaMKII phosphorylation rates" call /kinetics/CaMKII/tot_autonomous_CaMKII/CaMK-phos1/notes LOAD \ "rates referred from standard CaMKII phosphorylation rates" call /kinetics/CaMKII/PP1-active/notes LOAD \ "Cohen et al Meth Enz 159 390-408 is main source of info" \ "concentration of enzyme = 1.8 uM" call /kinetics/CaMKII/PP1-active/Deph-thr286/notes LOAD \ "The rates are from Stralfors et al Eur J Biochem 149 295-303 giving" \ "Vmax = 5.7 umol/min giving k3 = 3.5/sec and k2 = 14." \ "Foulkes et al Eur J Biochem 132 309-313 1983 give Km = 5.1 uM so" \ "k1 becomes 5.72e-6" \ "Simonelli 1984 (Grad Thesis, CUNY) showed that other substrates" \ "are about 1/10 rate of phosphorylase a, so we reduce k1,k2,k3 by 10" \ "to 5.72e-7, 1.4, 0.35. " \ "This gives the final Km of 5.1, and Vmax of 0.35/sec." call /kinetics/CaMKII/PP1-active/Deph-thr305/notes LOAD \ "Dephosphorylation tempkin are assumed to be the same for all" \ "phosphorylation sites on CaMKII. " \ "The rates are from Stralfors et al Eur J Biochem 149 295-303 giving" \ "Vmax = 5.7 umol/min giving k3 = 3.5/sec and k2 = 14." \ "Foulkes et al Eur J Biochem 132 309-313 1983 give Km = 5.1 uM so" \ "k1 becomes 5.72e-6" \ "Simonelli 1984 (Grad Thesis, CUNY) showed that other substrates" \ "are about 1/10 rate of phosphorylase a, so we reduce k1,k2,k3 by 10" \ "to 5.72e-7, 1.4, 0.35. " \ "This gives the final Km of 5.1, and Vmax of 0.35/sec." call /kinetics/CaMKII/PP1-active/Deph-thr306/notes LOAD \ "Dephosphorylation tempkin are assumed to be the same for all" \ "phosphorylation sites on CaMKII. " \ "The rates are from Stralfors et al Eur J Biochem 149 295-303 giving" \ "Vmax = 5.7 umol/min giving k3 = 3.5/sec and k2 = 14." \ "Foulkes et al Eur J Biochem 132 309-313 1983 give Km = 5.1 uM so" \ "k1 becomes 5.72e-6" \ "Simonelli 1984 (Grad Thesis, CUNY) showed that other substrates" \ "are about 1/10 rate of phosphorylase a, so we reduce k1,k2,k3 by 10" \ "to 5.72e-7, 1.4, 0.35. " \ "This gives the final Km of 5.1, and Vmax of 0.35/sec." call /kinetics/CaMKII/PP1-active/Deph-thr286c/notes LOAD \ "Dephosphorylation tempkin are assumed to be the same for all" \ "phosphorylation sites on CaMKII. " \ "The rates are from Stralfors et al Eur J Biochem 149 295-303 giving" \ "Vmax = 5.7 umol/min giving k3 = 3.5/sec and k2 = 14." \ "Foulkes et al Eur J Biochem 132 309-313 1983 give Km = 5.1 uM so" \ "k1 becomes 5.72e-6" \ "Simonelli 1984 (Grad Thesis, CUNY) showed that other substrates" \ "are about 1/10 rate of phosphorylase a, so we reduce k1,k2,k3 by 10" \ "to 5.72e-7, 1.4, 0.35. " \ "This gives the final Km of 5.1, and Vmax of 0.35/sec." call /kinetics/CaMKII/PP1-active/Deph_thr286b/notes LOAD \ "Rates are assumed to be the same for all phosphorylation sites" \ "on CaMKII. " \ "The rates are from Stralfors et al Eur J Biochem 149 295-303 giving" \ "Vmax = 5.7 umol/min giving k3 = 3.5/sec and k2 = 14." \ "Foulkes et al Eur J Biochem 132 309-313 1983 give Km = 5.1 uM so" \ "k1 becomes 5.72e-6" \ "Simonelli 1984 (Grad Thesis, CUNY) showed that other substrates" \ "are about 1/10 rate of phosphorylase a, so we reduce k1,k2,k3 by 10" \ "to 5.72e-7, 1.4, 0.35. " \ "This gives the final Km of 5.1, and Vmax of 0.35/sec." call /kinetics/CaM/notes LOAD \ "This is the basic Ca-binding-to-CaM model." \ "Main data sources are " \ "Forsen et al 1986 Calcium and Cell funciton VI 113_157" \ "Drabikowski and Brzeska 1982 JBC 257(19):11584-11590" \ "Martin et al 1985 Eur J Biochem 151(3):543-550" \ "Stemmer and Klee 1994 Biochem 33:6859-6866" \ "Data is pretty thorough." call /kinetics/CaM/CaM/notes LOAD \ "LOT of this present in the cell: upto 1% of total protein mass. " \ "(Alberts et al, Mol Biol of the Cell, Garland Publishers) says " \ "25 uM. Meyer et al, Science 256; 1992: 1199-1202 refer to " \ "studies saying it is comparable to CaMK levels." \ "(Kakiuchi et al, J Biochem 92; 1982; 1041-48) say conc in " \ "cerebral cortex & cerebellum homogenates: 20-30uM" \ "Lower conc in other tissues: lung, adrenal gland, liver, " \ "kidney, spleen = 6,5,5,3,2 uM respectively" call /kinetics/CaM/CaM-TR2-bind-Ca/notes LOAD \ "We use the Martin et al 1985 Eur J Biochem 151(3):543-550 rates here, " \ "plus the Drabikowski and Brzeska 1982 JBC 257(19):11584-11590 binding consts." \ "All are scaled by 3X to cell temperature." \ "kf = 2e-10 kb = 72" \ "Stemmer & Klee 1994 Biochem 33:6859-6866 have values of : K1=.9, K2=1.1." \ "Assume 1.0uM for both" \ "" call /kinetics/CaM/CaM-TR2-Ca2-bind-Ca/notes LOAD \ "Stemmer and Klee 1994 Biochem 33:6859-6866" \ "K3 = 21.5, K4 = 2.8. Assuming that the K4 step happens first, we get" \ "kb/kf = 2.8 uM = 1.68e6 so kf =6e-6 assuming kb = 10" \ "" call /kinetics/CaM/CaM-Ca3-bind-Ca/notes LOAD \ "Use K3 = 21.5 uM here from Stemmer and Klee table 3." \ "Stemmer and Klee 1994 Biochem 33:6859-6866" \ "kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10" call /kinetics/CaM/CaM-Ca4/notes LOAD \ "The four-calcium-bound form of CaM. It is the active form for most" \ "reactions." call /kinetics/CaM/CaM-Ca3/notes LOAD \ "The TR1 end now begins to bind Ca. This form has 2 Ca's on the" \ "TR2 end, and one on the TR1." call /kinetics/CaM/CaM-TR2-Ca2/notes LOAD \ "This is the intermediate where the TR2 end (the high-affinity end) has" \ "bound the Ca but the TR1 end has not." call /kinetics/PKC/notes LOAD \ "Protein Kinase C. This module represents a weighted average of" \ "the alpha, beta and gamma isoforms. It takes inputs from" \ "Ca, DAG (Diacyl Glycerol) and AA (arachidonic acid)." \ "Regulation parameters are largely from Schaechter and Benowitz" \ "1993 J Neurosci 13(10):4361 who use synaptosomes from" \ "mammalian brain and in one paper look at all three inputs." \ "Shinomura et al 1991 PNAS 88:5149-5153 is also a useful source" \ "of data and helps to tighten the DAG inputs. " \ "General reviews include Azzi et al 1992 Eur J Bioch 208:541" \ "and Nishizuka 1988, Nature 334:661" \ "Concentration info from Kikkawa et al 1982 JBC 257(22):13341" \ "The process of parameterization is described in detail" \ "in several places. See Supplementary notes to " \ "Bhalla and Iyengar 1999 Science 284:92-96, available at the site" \ "http://www.ncbs.res.in/~bhalla/ltploop/pkc_example.html" \ "The parameterization is also described in a book chapter:" \ "Bhalla, 2000: Simulations of Biochemical Signaling in" \ "Computational Neuroscience: Realistic Modeling for Experimentalists." \ "Ed. E. De Schutter. CRC Press." \ "" call /kinetics/PKC/PKC-act-by-Ca/notes LOAD \ "This Kd is a straightforward result from the Schaechter and Benowitz" \ "1993 J Neurosci 13(10):4361 curves. The time-course is based on the" \ "known rapid activation of PKC and also the fact that Ca association" \ "with proteins is typically quite fast. My guess is that this tau of" \ "2 sec is quite conservative and the actualy rate may be much faster." \ "The parameter is quite insensitive for most stimuli." \ "" \ "" call /kinetics/PKC/PKC-act-by-DAG/notes LOAD \ "Ca.PKC interaction with DAG is modeled by this reaction." \ "Kf based on Shinomura et al PNAS 88 5149-5153 1991 and" \ "Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and uses" \ "the constraining procedure referred to in the general" \ "notes for PKC." call /kinetics/PKC/PKC-Ca-to-memb/notes LOAD \ "Membrane translocation is a standard step in PKC activation." \ "It also turns out to be necessary to replicate the curves" \ "from Schaechter and Benowitz 1993 J Neurosci 13(10):4361" \ "and Shonomura et al 1991 PNAS 88:5149-5153. These rates" \ "are constrained by matching the curves in the above papers and" \ "by fixing a rather fast (sub-second) tau for PKC activation." call /kinetics/PKC/PKC-DAG-to-memb/notes LOAD \ "membrane translocation step for Ca.DAG.PKC complex." \ "Rates constrained from Shinomura et al 1991 PNAS 88:5149-5153" \ " and Schaechter and Benowitz 1993 J Neurosci 13(10):4361" \ "as derived in the references cited in PKC general notes." call /kinetics/PKC/PKC-act-by-Ca-AA/notes LOAD \ "Ca-dependent AA activation of PKC." \ "Note that this step combines the AA activation and also the " \ "membrane translocation." \ "From Schaechter and Benowitz 1993 J Neurosci 13(10):4361" call /kinetics/PKC/PKC-act-by-DAG-AA/notes LOAD \ "Membrane translocation step for PKC-DAG-AA complex." \ "Rates from matching concentration-effect data in our" \ "two main references:" \ "Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and" \ "Shinomura et al 1988 PNAS 88: 5149-5153" call /kinetics/PKC/PKC-DAG-AA*/notes LOAD \ "Membrane translocated form of PKC-DAG-AA complex." call /kinetics/PKC/PKC-Ca-AA*/notes LOAD \ "Membrane bound and active complex of PKC, Ca and AA." call /kinetics/PKC/PKC-Ca-memb*/notes LOAD \ "This is the direct Ca-stimulated activity of PKC." call /kinetics/PKC/PKC-DAG-memb*/notes LOAD \ "Active, membrane attached form of Ca.DAG.PKC complex." call /kinetics/PKC/PKC-basal*/notes LOAD \ "This is the basal PKC activity which contributes about" \ "2% to the maximum." call /kinetics/PKC/PKC-basal-act/notes LOAD \ "Basal activity of PKC is quite high, about 10% of max." \ "See Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and" \ "Shinomura et al 1991 PNAS 88:5149-5153. This is partly due to" \ "basal levels of DAG, AA and Ca, but even when these are taken" \ "into account (see the derivations as per the PKC general notes)" \ "there is a small basal activity still to be accounted for. This" \ "reaction handles it by giving a 2% activity at baseline." call /kinetics/PKC/PKC-AA*/notes LOAD \ "This is the membrane-bound and active form of the PKC-AA complex." \ "" call /kinetics/PKC/PKC-act-by-AA/notes LOAD \ "AA stimulates PKC activity even at rather low Ca." \ "Schaechter and Benowitz 1993 J Neurosci 13(10):4361" \ "Note that this one reaction combines the initial interaction" \ "and also membrane translocation." call /kinetics/PKC/PKC-Ca-DAG/notes LOAD \ "This is the active PKC form involving Ca and DAG." \ "It has to translocate to the membrane." call /kinetics/PKC/PKC-n-DAG/notes LOAD \ "Binding of PKC to DAG, non-Ca dependent." \ "" \ "Kf based on Shinomura et al PNAS 88 5149-5153 1991" \ "Tau estimated as fast and here it is about the same time-course" \ "as the formation of DAG so it will not be rate-limiting." call /kinetics/PKC/PKC-DAG/notes LOAD \ "This is a DAG-bound intermediate used in synergistic activation" \ "of PKC by DAG and AA." call /kinetics/PKC/PKC-n-DAG-AA/notes LOAD \ "This is one of the more interesting steps. Mechanistically" \ "it does not seem necessary at first glance. Turns out that" \ "one needs this step to quantitatively match the curves" \ "in Schaechter and Benowitz 1993 J Neurosci 13(10):4361" \ "and Shinomura et al 1991 PNAS 88:5149-5153. There is" \ "a synergy between DAG and AA activation even at low" \ "Ca levels, which is most simply represented by this reaction." \ "Tau is assumed to be fast." \ "Kd comes from matching the experimental curves." call /kinetics/PKC/PKC-DAG-AA/notes LOAD \ "Complex of PKC, DAG and AA giving rise to synergistic" \ "activation of PKC by DAG and AA at resting Ca." \ "" call /kinetics/PKC/PKC-cytosolic/notes LOAD \ "Marquez et al J. Immun 149,2560(92) est 1e6/cell for chromaffin cells" \ "" \ "Kikkawa et al 1982 JBC 257(22):13341 have PKC levels in brain at " \ "about 1 uM." \ "" \ "The cytosolic form is the inactive PKC. This is really a composite" \ "of three isoforms: alpha, beta and gamma which have slightly" \ "different properties and respond to different combinations of" \ "Ca, AA and DAG." call /kinetics/PKC/AA/notes LOAD \ "Arachidonic Acid. This messenger diffuses through membranes" \ "as well as cytosolically, has been suggested as a possible" \ "retrograde messenger at synapses. " call /kinetics/PKC/PKC-Ca/notes LOAD \ "This intermediate is strongly indicated by the synergistic" \ "activation of PKC by combinations of DAG and Ca, as well" \ "as AA and Ca. PKC by definition also has a direct Ca-activation," \ "to which this also contributes." call /kinetics/PKC/PKC-active/notes LOAD \ "This is the total active PKC. It is the sum of the respective" \ "activities of " \ "PKC-basal*" \ "PKC-Ca-memb*" \ "PKC-DAG-memb*" \ "PKC-Ca-AA*" \ "PKC-DAG-AA*" \ "PKC-AA*" \ "I treat PKC here in a two-state manner: Either it is in an active" \ "state (any one of the above list) or it is inactive. No matter what " \ "combination of stimuli activate the PKC, I treat it as having the same" \ "activity. The scaling comes in through the relative amounts of PKC" \ "which bind to the respecive stimuli." \ "The justification for this is the mode of action of PKC, which like" \ "most Ser/Thr kinases has a kinase domain normally bound to and blocked" \ "by a regulatory domain. I assume that all the activators simply free" \ "up the kinase domain." \ "A more general model would incorporate a different enzyme activity for" \ "each combination of activating inputs, as well as for each substrate." \ "The current model seems to be a decent and much simpler approximation" \ "for the available data." \ "One caveat of this way of representing PKC is that the summation" \ "procedure assumes that PKC does not saturate with its substrates. " \ "If this assumption fails, then the contributing PKC complexes would" \ "experience changes in availability which would affect their " \ "balance. Given the relatively low percentage of PKC usually activated," \ "and its high throughput as an enzyme, this is a safe assumption under" \ "physiological conditions." \ "" call /kinetics/PKC/PKC-active/PKC-phos/notes LOAD \ "rates referred from standard PKC phosphorylation rates" call /kinetics/IP3-3K/notes LOAD \ "Model for Ins(145)P3 3-kinase. This includes enzyme activation by Ca-CaM" \ "and CaMKII and inactivation by PKC. We dont include PKA phosphorylation" \ "or enzyme dimerization effects. Primary refs: Johanson et al, JBC 263, 1988:" \ "7465-71; Communi et al, EMBOJ 16, 1997: 1943-52; Erneux et al, Biochem 214, " \ "1993: 497-501; Sim et al, JBC 265, 1990: 10367-72 " call /kinetics/IP3-3K/IP3_3K/notes LOAD \ "from Johanson et al, JBC, 1988, Vol. 263, No.16, pp 7465-7471" \ "" \ "this is the predominant isoform in brain ie IP3-3kinaseA:" \ "BiochemJ, 1995, 306, 429-435" call /kinetics/IP3-3K/IP3_3K/ip3-3k/notes LOAD \ "from Johanson et al, JBC 263; 1988" \ "Original Vmax scaled up by 50% to obtain value at 37C, as " \ "enzyme assay was done at 30C" \ "Km increased from 0.2 to 1.4 as per various other reports " \ "(Shears Review, BiochemJ 260; 1989)" call /kinetics/IP3-3K/IP3_3K*1/notes LOAD \ "Sim et al; JBC 265(18) June 25; 1990: pp 10367-10372" \ "Phos. at 2 major sites = Ser109 & Ser 175; but there is a possibility " \ "that inactivation is due to combined effect of multiple phosphorylations" \ "activity suppressed by 75%" \ "" call /kinetics/IP3-3K/IP3_3K*1/ip3-3k*1/notes LOAD \ "from Sim et al, JBC 265; 1990" call /kinetics/IP3-3K/IP3_3K*/notes LOAD \ "phosphorylation at thr311" \ "" \ "Communi et al, EMBO J 16; 1997" call /kinetics/IP3-3K/IP3_3K*/ip3-3k*/notes LOAD \ "from Communi et al, EMBO J 16; 1997" \ "" \ "In absence of CaM binding, activity same as that of " \ "non-phosphorylated enzyme" call /kinetics/IP3-3K/IP3_3K_CaM*/notes LOAD \ "8-10 fold activation with both CaM bound and CaMKII phosphorylation" \ "(phos at thr311)" \ "" \ "Communi et al; EMBO J 16 (8), pp 1943-1952, 1997" call /kinetics/IP3-3K/IP3_3K_CaM/notes LOAD \ "2-2.5 fold increase in enzyme activity due to CaM binding" \ "CaM binding involves Trp165" \ "" \ "Erneux et al; Biochem 214, 497-501 (1993)" call /kinetics/IP3-3K/3K-bind-CaM/notes LOAD \ "Communi et al, EMBO J 16; 1997" \ "" \ "non-phosphorylated 3kinase with low sensitivity to CaM binding" \ "(Kd = 52nM)" call /kinetics/IP3-3K/3K*-bind-CaM/notes LOAD \ "Communi et al, EMBO J 16; 1997" \ "" \ "phosphorylated 3kinase has 25 fold greater sensitivity to CaM" \ "binding than the non-phosphorylated enzyme (Kd of 2nM)" call /kinetics/IP3-3K/IP3(145)/notes LOAD \ "Inositol (145)trisphosphate" call /kinetics/IP3-3K/3k-CaM*-on/notes LOAD \ "Rates from Km of enzyme" \ "Communi et al, EMBO J 16(8)" call /kinetics/IP3-3K/3k-CaM*-off/notes LOAD \ "Kf = Vmax for enzyme (Communi et al, EMBO J 16(8)) " \ "Vmax is such that enzyme activity is 9 fold above basal." \ "Kb derived from Keq value when reaction free energy = " \ "-10 kJ/mol" call /kinetics/IP3-3K/3kCaM*_ip3_cmplx/notes LOAD \ "Enzyme complex exclusively modeled as M-M kinetics do not hold." \ "Enzyme is reversible as per free energy calculations that yield a" \ "a significant back flux." call /kinetics/IP3-3K/3kCaM_ip3_cmplx/notes LOAD \ "Enzyme complex exclusively modeled because enzymes is reversible," \ "unlike M-M enzymes. Reversibility determined from dG " \ "calculations." call /kinetics/IP3-3K/3k-CaM-on/notes LOAD \ "rates from Km for enzyme: Erneux et al, Biochem 214; 1993" \ "Enzyme is 2-2.5 fold more active than ip3-3k, but Km is " \ "doubled." \ "" call /kinetics/IP3-3K/3k-CaM-off/notes LOAD \ "Kf = Vmax for enzyme: Erneux et al, Biochem 214; 1993" \ "Enzyme is 2-2.5 fold more active than basal enzyme." \ "Kb derived from equilibrium conditions for dG = -10 kJ/mol" call /kinetics/IP3-3K/IP4(1345)/notes LOAD \ "Inositol(1345)tetrakisphosphate" call /kinetics/CaRegulation/notes LOAD \ "Ca Regulation model used for the IP3metabolism network. It includes 3 " \ "compartments: extracellular, intracellular and the Ca stores. Ca pumps " \ "that pump out Ca from cytoplasm to extracellular space and into stores, " \ "are balanced by leak channels from the stores and extracellular space." \ "The IP3 receptor and capacitative entry channels drive Ca under influence of" \ "different stimuli. Model includes the Ca buffer - Calsequestrin in the stores." \ "The model is a little artificial on IP3R kinetics, and does not include the " \ "influence of Ca on IP3R." \ "" call /kinetics/CaRegulation/CaTraspATPase/notes LOAD \ "kCa3 = 2 * Ca transporter rate since each step has 2 Ca++. " \ "= 0.5 uM/sec from Lauffenburger and Linderman 1993 Receptors pg200" \ "The amount of the activated transporter is about 0.01 uM = 6e3#. " \ "from runs. So 0.01uM * kf * 2 = 0.5 uM/sec (no back reaction) so " \ "kf = 25, kb = 0" \ "Alternatively, 6e3 * kf = 0.25 * 6e5, giving the same kf" call /kinetics/CaRegulation/Ca-sequester/notes LOAD \ "Sequestered Ca pool" \ "The vol is 0.16 * the vol of the cell as a whole. " call /kinetics/CaRegulation/Ca-leak-to-cytoplasm/notes LOAD \ "represents the channels that leak Ca into the cytoplasm. Effects " \ "of membrane potential are not considered. The amount and total " \ "flux are constrained by the need to balance Ca flux and keep " \ "basal Ca around 80 nM." call /kinetics/CaRegulation/Ca-leak-to-cytoplasm/Ca-leak-chan/notes LOAD \ "The permeability is low to keep the Ca flow rate reasonable" call /kinetics/CaRegulation/CaTransp-2Ca/notes LOAD \ "equivalent to the enzyme-substrate complex. 2 Ca are bound to " \ "the transporter. ATP is ignored." call /kinetics/CaRegulation/CaTransp/notes LOAD \ "The calcium transporter levels are constrained by the resting " \ "levels of Ca in the cell. The rate of Ca sequestration depends " \ "on the amount of this pool. " call /kinetics/CaRegulation/Ca-bind-to-Transp/notes LOAD \ "Rates from Lauffenburger abd Linderman 1993 Receptors pg 200. " \ "Kd = KCa2 = 0.2 uM" call /kinetics/CaRegulation/IP3R/notes LOAD \ "The number of the IP3Rs in the cell is present only implicitly in the" \ "model, and is lumped in with the total permeability of the IP3R pool." \ "The latter is constrained by the height of the Ca transient." call /kinetics/CaRegulation/IP3Rbind/notes LOAD \ "Based on Lauffenburger and Linderman 1993 Receptors pg 200. The " \ "binding of IP3 on this reaction had a Hill coeff of 3. The eqns of " \ "Mahama and Linderman (cited in the book as 1993 a) are equivalent " \ "to the binding all occurring in a single step, so that is how I do " \ "it in this version. Their Ki1 is 0.07 uM. Lots of other data sources: " \ "Ramos-Franco et al, Biophys J 75, 1998: 834-39 have Ca sensitivity " \ "curves. At 250 nM free Ca, the EC50 for type1 is 58 nM and type 2 is " \ "194 nM. Type 3 would be about 2 uM according to Newton et al, JBC " \ "268(46), 1994: 28613-19. For the purposes of this model we use a " \ "Kd of 2.7 uM which is high but maybe OK at low calcium. The details " \ "of Ca interaction with the IP3R are not included in this model." call /kinetics/CaRegulation/IP3R*/notes LOAD \ "This is the ligand-bound form of the IP3R." call /kinetics/CaRegulation/CaEPump/notes LOAD \ "The calcium electrogenic pump: Mc Burney and Neering, TINS 10(4), 1987, " \ "164-169. We treat the pump as a simple Michaelis-Menten enzyme. Levels " \ "are constrained tightly by the need to keep resting Ca levels at 80 nM." call /kinetics/CaRegulation/CaEPump/Ca-pump-out/notes LOAD \ "From McBurney and Neering, TINS 10(4), 1987, 164-169 1987. We " \ "are using the high-affinity pump here. Their numbers exceed M&L " \ "so I am reducing the rates by 10X. Need to check. k1 = 3e-3, " \ "k2 = 288, k3 = 72, n = 1000. This comes to a Km of 0.2 for Ca, " \ "and a Vmax of 72." \ "" call /kinetics/CaRegulation/Ca-ext/notes LOAD \ "Extracell Ca conc = 4 mM Extracell vol assumed 100 X cell vol. It is anyway " \ "kept buffered for the purposes of the model, so the concentration won't change." \ "" call /kinetics/CaRegulation/Ca-leak-from-extracell/notes LOAD \ "This represents the pool of Ca leak channels. The conc gradient is so " \ "large that this pool needs only a small number of molecules." \ "For an equilibrium at 0.1 uM we need flow of 36e3/sec. With a permeability " \ "of 0.01 and a conc gradient of 4mM->0.1 uM (4e4) we get flux = N * perm * " \ "grad => N = 36e3 / (1e-2 * 4e3) = 900 if flux = 20e3, N =500, which is what we " \ "use. This works out to a concentration of 0.83 nM." call /kinetics/CaRegulation/Ca-leak-from-extracell/Ca-leak-chan/notes LOAD \ "The permeability is low to keep the Ca flow rate reasonable" call /kinetics/CaRegulation/capacitive_Ca_entry*/notes LOAD \ "This mechanism has taken a while to be more tightly confirmed as probably being " \ "the TRP channel. In this model the channel is implemented to match experimental " \ "observations about capacitative Ca entry. Levels are set by two constraints: " \ "the resting Ca levels, and the height of the response to IP3." call /kinetics/CaRegulation/inactivate_cap_Ca/notes LOAD \ "The Kd is set at about 3 uM so that at resting Ca the capacitative Ca " \ "entry is almost blocked. A 2nd order response makes the response steep." call /kinetics/CaRegulation/inact_cap_entry/notes LOAD \ "represents the portion of the capacitative-Ca entry channel which is blocked " \ "when there is lots of Ca sequestered in the stores" call /kinetics/CaRegulation/IP3/notes LOAD \ "Inositol(145)trisphosphate" call /kinetics/CaRegulation/Ca/notes LOAD \ "This pool represents intracellular calcium. Resting levels are around 80 nM, " \ "but this is subject to all sorts of influxes and pumps." call /kinetics/CaRegulation/Calseq/notes LOAD \ "This is Calsequestrin or the calcium buffer in the ER. " \ "from Cala & Jones, JBC 258(19), 1983: 11932-36" \ "Calseq is present as 4mg/g of membrane protein; membrane protein = 2% of cell " \ "mass = 0.02 * 1g/cc * (1e-9)cc = (2e-11) g" \ "Hence Calseq = 8e-14/55000 moles per (1.6e-13)l = 9.091uM " \ "As per Guidebook to the calcium-binding proteins by Celio; and Mitchell et al, JBC 263, " \ "1988: 1376-81; 1 mol of Calsequestrin binds 40 mol of Ca. This is the stoichiometry we " \ "use. System limitations do not allow us to create a 40th order reaction. Hence Calseq " \ "binding to Ca has been modeled in eight consecutive steps of 5th order each. The affinity " \ "of Calsequestrin for Ca in our model is constrained by the levels of free Ca in the stores " \ "(Ca-sequester). We use a Kd such that Ca-sequester levels remain similar to levels in the " \ "CaRegulation model without Ca buffering." call /kinetics/CaRegulation/Ca5-Cal/notes LOAD \ "Calsequestrin with 5 Ca molecules bound" call /kinetics/CaRegulation/Ca10-Cal/notes LOAD \ "Calsequestrin with 10 Ca molecules bound" call /kinetics/CaRegulation/Ca15-Cal/notes LOAD \ "Calsequestrin with 15 Ca molecules bound" call /kinetics/CaRegulation/Ca25-Cal/notes LOAD \ "Calsequestrin with 25 Ca molecules bound" call /kinetics/CaRegulation/Ca30-Cal/notes LOAD \ "Calsequestrin with 30 Ca molecules bound" call /kinetics/CaRegulation/Ca35-Cal/notes LOAD \ "Calsequestrin with 35 Ca molecules bound" call /kinetics/CaRegulation/Ca40-Cal/notes LOAD \ "Calsequestrin with 40 Ca molecules bound" call /kinetics/CaRegulation/Ca20-Cal/notes LOAD \ "Calsequestrin with 20 Ca molecules bound" call /kinetics/Gq/notes LOAD \ "The model for the Gq pathway plus its activators, here represented" \ "by the metabotropic glutamate receptor. " \ "We assume GTP is present in fixed amounts, so we leave it out" \ "of the explicit equations in this model. Normally we would expect it" \ "to associate along with the G-Receptor-ligand complex." \ "Most info is from Berstein et al JBC 267:12 8081-8088 1992" \ "Structure of receptor activation of Gq from " \ "Fay et al Biochem 30 5066-5075 1991" \ "This mGluR/Gq model lacks a mechanism for receptor desensitization. " call /kinetics/Gq/RecLigandBinding/notes LOAD \ "" \ "From Martin et al FEBS Lett 316:2 191-196 1993 we have Kd = 600 nM" \ "Assuming kb = 10/sec, we get kf = 10/(0.6 uM * 6e5) = 2.8e-5 1/sec/#" \ "The off time for Glu seems pretty slow:" \ "Nicoletti et al 1986 PNAS 83:1931-1935 and" \ "Schoepp and Johnson 1989 J Neurochem 53 1865-1870" \ "indicate it is at least 30 sec. Here we are a little faster because" \ "this is only a small part of the off rate, the rest coming from the" \ "Rec-Gq complex." call /kinetics/Gq/G-GDP/notes LOAD \ "This is the G-alpha-beta-gamma trimer in association with GDP." \ "" \ "From Pang and Sternweis JBC 265:30 18707-12 1990 we get concentration" \ "estimate of 1.6 uM to 0.8 uM. I use 1 uM which is well within this" \ "range." \ "" call /kinetics/Gq/Basal-Act-G/notes LOAD \ "This is the basal exchange of GTP for GDP. So slow as to be" \ "nearly negligible." call /kinetics/Gq/Trimerize-G/notes LOAD \ "kf == kg3 = 1e-5 /cell/sec. As usual, there is no back-reaction" \ "kb = 0" call /kinetics/Gq/Inact-G/notes LOAD \ "From Berstein et al JBC 267:12 8081-8088 1992, kcat for GTPase activity" \ "of Gq is only 0.8/min." call /kinetics/Gq/mGluR/notes LOAD \ "From Mahama and Linderman, Total # of receptors/cell = 1900" \ "However, the density is likely to be very" \ "high at the synapse." \ "Fay et al Biochem 30 5066-5075 1991 have a value of 60K receptors per" \ "cell for neutrophils which comes to 0.1 uM." \ "Here we have a situation where trying to represent the synapse by" \ "a 10 micron cube gives awkward results. I will scale up to 0.3 uM since" \ "synaptic receptor density is likely to be higher, with the caveat that I" \ "should really be using a more geometrically realistic model." call /kinetics/Gq/Rec-Glu/notes LOAD \ "Glu-Receptor complex." call /kinetics/Gq/Rec-Gq/notes LOAD \ "Turns out that a large fraction of the the receptor binds to the G-protein" \ "even in the absence of ligand. This pool represents this step." \ "Fraction of Rec-Gq is 44% of receptor, from " \ "Fay et al 1991 Biochem 30:5066-5075" \ "Since this is not the same receptor, this value is a bit doubtful. Still," \ "we adjust the rate consts in Rec-bind-Gq to match." call /kinetics/Gq/Rec-Glu-bind-Gq/notes LOAD \ "This is the k1-k2 equivalent for enzyme complex formation in the" \ "binding of Rec-Glu to Gq." \ "See Fay et al Biochem 30 5066-5075 1991." \ "Closer reading of Fay et al suggests that " \ "kb <= 0.0001, so kf = 1e-8 by detailed balance. This" \ "reaction appears to be neglible." call /kinetics/Gq/Glu-bind-Rec-Gq/notes LOAD \ "From Fay et al" \ "kb3 = kb = 1.06e-3 which is rather slow." \ "k+1 = kf = 2.8e7 /M/sec= 4.67e-5/sec use 5e-5." \ "However, the Kd from Martin et al may be more appropriate, as this" \ "is Glu not the system from Fay." \ "kf = 2.8e-5, kb = 10" \ "Let us compromise. since we have the Fay model, keep kf = k+1 = 2.8e-5." \ "But kb (k-3) is .01 * k-1 from Fay. Scaling by .01, kb = .01 * 10 = 0.1" call /kinetics/Gq/Rec-Glu-Gq/notes LOAD \ "This is the ternary complex of receptor, ligand and G protein." \ "" call /kinetics/Gq/Activate-Gq/notes LOAD \ "This reaction is the critical one for activation of Gq. It probably" \ "encapsulates multiple steps. In this approximation the receptor-ligand-" \ "Gprotein complex splits up into GTP.Galpha, rec.ligand complex, and " \ "Gbetagamma. There is a hidden step of exchange of GDP for GTP. The" \ "reaction does not take these into account since it is assumed that" \ "both GTP and GDP levels are tightly regulated by metabolic control." \ "" \ "This is the kcat==k3 stage of the Rec-Glu ezymatic activation of Gq." \ "From Berstein et al actiation is at .35 - 0.7/min" \ "From Fay et al Biochem 30 5066-5075 1991 kf = .01/sec" \ "From Nakamura et al J physiol Lond 474:1 35-41 1994 see time courses." \ "Also (Berstein) 15-40% of gprot is in GTP-bound form on stim." call /kinetics/Gq/Rec-bind-Gq/notes LOAD \ "From Berstein et al 1992 JBC 267(12):8081-8088 we know that 15-40%" \ "of Gq binds, GTP_gamma_S. Also about 20-30% of Gq is bound to GTP." \ "To get to these values the receptor-Gq amount should be similar. These" \ "rates are designed to give that steady state with a fast tau of 1 sec." \ "" call /kinetics/Gq/mGluRAntag/notes LOAD \ "I implement this as acting only on the Rec-Gq complex, based on" \ "a more complete model PLC_Gq48.g" \ "which showed that the binding to the receptor" \ "alone contributed only a small amount." call /kinetics/Gq/Antag-bind-Rec-Gq/notes LOAD \ "The rate consts give a total binding affinity of under 0.2 nM, good" \ "for a strong antagonist." call /kinetics/Gq/Blocked-rec-Gq/notes LOAD \ "This represents the blocked state of the receptor when bound" \ "to a competitive antagonist. Note that this is in the Gq bound form." \ "Simulations had shown that with the available rates, the blocking" \ "was minimal if only the unbound receptor could bind the antagonist." call /kinetics/Gq/G*GDP/notes LOAD \ "This should correctly be called GDP.G_alpha. The name is preserved for" \ "backward compatibility reasons." call /kinetics/Gq/G*GTP/notes LOAD \ "Activated G protein. Berstein et al indicate that about 20-40% of the total" \ "Gq alpha should bind GTP at steady stimulus." call /kinetics/Gq/BetaGamma/notes LOAD \ "The betagamma subunits of Gq. This is an approximation to the possible" \ "combinations of betagamma subunits. Here they are all treated as a " \ "single pool. " call /kinetics/Gq/Glu/notes LOAD \ "Varying the amount of (steady state) glu between .01 uM and up, the" \ "final amount of G*GTP complex does not change much. This means that" \ "the system should be reasonably robust wr to the amount of glu in the" \ "synaptic cleft. It would be nice to know how fast it is removed." \ "Schoepp et al 1990 TIPS 11:508-515 give a range of Glu EC50 from rat" \ "brain in the range 120 to 1000 uM." \ "Nicoletti 1986 PNAS 83:1931-1935 and" \ "Schoepp and Johnson 1989 J Neurochem 53:1865-1870 " \ "give an off time of at least 30 sec." call /kinetics/PLCbeta/notes LOAD \ "PhospholipaseC beta. This model incorporates Ca and Gq regulation of " \ "PLCbeta that generates four separate active forms of the enzyme: " \ "PLC, PLC-Gq, PLC-Ca and PLC-Ca-Gq. GAP activity of PLC has been included. " \ "Primary refs: Sternweis et al 1992 Phil Trans R Soc Lond, Smrcka et al 1991 " \ "Science 251:804-807, Biddlecome et al 1996 JBC 271: 7999-8007" \ " " call /kinetics/PLCbeta/PLC-Gq/notes LOAD \ "from Smrcka et al, 1991 Science 251: 804-807" call /kinetics/PLCbeta/PLC-Gq/PLC-Gq/notes LOAD \ "from Smrcka et al, 1991 Science 251: 804-807" call /kinetics/PLCbeta/PLC-Ca/notes LOAD \ "From Sternweis et al Phil Trans R Soc Lond 1992, also matched by Homma et al." \ "k1 = 1.5e-5, now 4.2e-6" \ "k2 = 70/sec; now 40/sec" \ "k3 = 17.5/sec; now 10/sec" \ "Note that the wording in Sternweis et al is" \ "ambiguous re the Km." \ "Also Smrcka et al; Science 251, 15.2.1991, pp804-807" call /kinetics/PLCbeta/PLC-Ca/PLC-Ca/notes LOAD \ "From Sternweis et al Phil Trans R Soc Lond 1992, also matched by Homma et al." \ "k1 = 1.5e-5, now 4.2e-6" \ "k2 = 70/sec; now 40/sec" \ "k3 = 17.5/sec; now 10/sec" \ "Note that the wording in Sternweis et al is" \ "ambiguous re the Km." \ "Also Smrcka et al; Science 251, 15.2.1991, pp804-807" call /kinetics/PLCbeta/PC/notes LOAD \ "Phosphatidylcholine is the main (around 55%) metabolic product of DAG," \ "follwed by PE (around 25%). Ref is Welsh and Cabot, JCB35:231-245(1987)" call /kinetics/PLCbeta/PLC-Ca-Gq/notes LOAD \ "This should really be labelled PLC-Ca-GTP.Gq_alpha" \ "This is the most active form of the enzyme. " call /kinetics/PLCbeta/PLC-Ca-Gq/PLCb-Ca-Gq/notes LOAD \ "Km: Sternweis et al, Phil Trans R Soc Lond 1992" \ "Vmax: Smrcka et al, Science 1991" call /kinetics/PLCbeta/PLC/notes LOAD \ "Smrcka et al; Science 251, 15.2.1991, pp804-807" call /kinetics/PLCbeta/PLC/PLC/notes LOAD \ "Smrcka et al; Science 251, 15.2.1991, pp804-807" call /kinetics/PLCbeta/Act-PLC-Ca/notes LOAD \ "Affinity for Ca = 1uM without AlF, 0.1 with:" \ " from Smrcka et al science 251 pp 804-807 1991" \ "so [Ca].kf = kb so kb/kf = 1 * 6e5 = 1/1.66e-6" \ "Assigned affinity to a Kd of 0.333 to maintain balance." call /kinetics/PLCbeta/PLC-bind-Gq/notes LOAD \ "this binding does not produce active PLC. This step was needed to" \ "implement the described (Smrcka et al) increase in affinity for Ca" \ "by PLC once Gq was bound." \ "The tempkin are the same as the binding step for Ca-PLC to Gq." \ "Kd is constrained by detailed balance." call /kinetics/PLCbeta/PLC-Gq-bind-Ca/notes LOAD \ "this step has a high affinity for Ca, from Smrcka et al. 0.1uM" \ "so kf /kb = 1/6e4 = 1.666e-5:1. See the Act-PLC-by-Gq reaction." \ "Raised kf to 5e-5 based on match to conc-eff curves from " \ "Smrcka et al." call /kinetics/PLCbeta/Inact-PLC-Gq/notes LOAD \ "Rate of 100/min to account for GAP activity of PLC:" \ "Biddlecome et al, JBC, 271, 14, 7999-8007, 1996" call /kinetics/PLCbeta/Act-PLC-by-Gq/notes LOAD \ "Affinity for Gq is > 20 nM (Smrcka et al Science251 804-807 1991)" \ "so [Gq].kf = kb so 40nM * 6e5 = kb/kf = 24e3 so kf = 4.2e-5, kb =1" \ "" call /kinetics/PLCbeta/Degrade-DAG/notes LOAD \ "Rate based on basal and activated levels of DAG" call /kinetics/PLCbeta/basal/notes LOAD \ "accounts for other PLC isoforms that contribute to basal levels of " \ "IP3" call /kinetics/PLCbeta/DAG/notes LOAD \ "Basal levels of Diacylglycerol in model are 5.06 uM." \ "DAG is pretty nasty to estimate. Data sources are many and" \ "varied and sometimes difficult to reconcile. " \ "Welsh and Cabot 1987 JCB 35:231-245: DAG degradation" \ "Bocckino et al JBC 260(26):14201-14207: " \ " hepatocytes stim with vasopressin: 190 uM." \ "Bocckino et al 1987 JBC 262(31):15309-15315:" \ " DAG rises from 70 to 200 ng/mg wet weight, approx 150 to 450 uM." \ "Prescott and Majerus 1983 JBC 258:764-769: Platelets: 6 uM." \ " Also see Rittenhouse-Simmons 1979 J Clin Invest 63." \ "Sano et al JBC 258(3):2010-2013: Report a nearly 10 fold rise." \ "Habenicht et al 1981 JBC 256(23)12329-12335: " \ " 3T3 cells with PDGF stim: 27 uM" \ "Cornell and Vance 1987 BBA 919:23-36: 10x rise from 10 to 100 uM" \ "" \ "" \ "" call /kinetics/PLCbeta/PIP2/notes LOAD \ "PIP2 conc: Willars et al; JBC 273 (9) 27.2.98; pp 5037-5046" call /kinetics/134_dephos/notes LOAD \ "Model for Ins(134)P3 dephosphorylation. Two bisphosphate intermediates" \ "[Ins(13)P2 and Ins(34)P2] and two monophosphate intermediates [Ins(1)P1 " \ "and Ins(3)P1] are formed. Primary refs: Norris et al, JBC 269, 1994:8716-20;" \ "Caldwell et al, JBC 266, 1991:18378-86, Inhorn et al, JBC 262, 1987:15946-" \ "52; Gee et al, Biochem J 249, 1988:883-89" \ "" call /kinetics/134_dephos/IP2_3pase2/notes LOAD \ "from Caldwell et al, JBC 266(27); 1991: 18378-86" \ "" \ "enzyme is a heterodimer with one catalystic subunit and one regulatory" \ "78 kDa subunit" call /kinetics/134_dephos/IP2_3pase2/ip2_3pase2/notes LOAD \ "from Caldwell et al, JBC 266; 1991" call /kinetics/134_dephos/IP1(3)_deg/notes LOAD \ "Kf and Kb based on levels of Ins(3)P1." \ "Kb necessary as energetics calculations show backflow from " \ "inositol to be significant." \ "" call /kinetics/134_dephos/IP1(3)/notes LOAD \ "Inositol (3)monophosphate = 11% of Ins(1)P1 ~ 4.8uM " \ "Ackermann et al, Biochem J 242(2), 1987: 517" call /kinetics/134_dephos/IP2_3pase1/notes LOAD \ "from Caldwell et al, JBC 266(27); 1991: 18378-86" \ "" \ "Enzyme is a homodimer with two catalytic subunits. Conc of enzyme " \ "increased 2 times from 1.9 nM to account for two monomeric subunit " \ "pools " \ "" call /kinetics/134_dephos/IP2_3pase1/ip2_3pase1/notes LOAD \ "from Caldwell et al, JBC 266; 1991" \ "enzyme activity was assayed for the monomeric form of the " \ "enzyme" call /kinetics/134_dephos/IP2(34)/notes LOAD \ "Inositol (34)bisphosphate" call /kinetics/134_dephos/IP_4pase-inact/notes LOAD \ "from Norris et al, JBC 269; 1994" call /kinetics/134_dephos/IP_4pase/notes LOAD \ "from Norris et al, JBC 269(12); 1994: 8716-20" \ "Enzyme conc increased from 9 nM to 0.9 uM to obtain appreciable enzyme " \ "activity" \ "has two 4-phosphatase activities: against Ins(134)P3 and Ins(34)P2" \ "respectively" call /kinetics/134_dephos/IP_4pase/ip3_4pase/notes LOAD \ "Ins(134)P3 4-phosphatase activity of InsP 4-phosphatase" \ "from Norris et al, JBC 269; 1994. Vmax reduced from 55/sec to " \ "20/sec to maintain relative levels of Ins(134)P3 and Ins(13)P2" call /kinetics/134_dephos/IP_4pase/ip2_4pase/notes LOAD \ "Ins(34)P2 4-phosphatase activity of InsP 4-phosphatase" \ "from Norris et al, JBC 269; 1994" call /kinetics/134_dephos/IP2(13)/notes LOAD \ "Inositol (13)bisphosphate" call /kinetics/134_dephos/IP1(1)/notes LOAD \ "Inositol (1)monophsophate" \ "Basal Conc ~ 44uM : Ackermann et al, BiochemJ 1987, 242(2):" \ "517-24" \ "IP metabolism maintains only a tenth of this level while the " \ "rest is generated from PtdIns metabolism." call /kinetics/134_dephos/ip1_1pase_cmplx/notes LOAD \ "Enzyme complex exclusively modeled to accomodate enzyme " \ "reversibility as calculated from dG calculations for -5 kJ/mol." call /kinetics/134_dephos/1pase-on/notes LOAD \ "Rates derived from Km for Ins(1)P1-1phosphatase:" \ "Gee et al, Biochem J 249; 1988." call /kinetics/134_dephos/1pase-off/notes LOAD \ "Kf = Vmax for Ins(1)P1-1phosphatase: Gee et al, Biochem J 249," \ "1988." \ "Kb necessary as estimated from percent inositol backflux " \ "calculations. This contributes to maintain Ins(1)P1 at 10% of" \ "its actual pool." call /kinetics/134_dephos/ip1_syn/notes LOAD \ "This rxn. maintains levels of Ins(1)P1 at 44 uM basal. Actually, " \ "90% of Ins(1)P1 is generated from PtdIns degradation (Ackermann " \ "et al, Biochem J 242(2), 1987: 517-24) but for simplicity we " \ "use a back rxn. from Inositol to generate this conc." call /kinetics/145_dephos/notes LOAD \ "Model for Ins(145)P3 dephosphorylation. InsP3 degrades via Ins(14)P2 " \ "and Ins(4)P2 to inositol. Model incorporates enzyme inhibition from " \ "higher phosphates: InsP5 and InsP6. Primary refs: Hansen et al, JBC " \ "262, 1987: 17319-26; Hoer and Oberdisse, BiochemJ 278, 1991: 219-24;" \ "Inhorn and Majerus, JBC 262, 1987: 15946-52; Gee et al, BiochemJ 249," \ "1988: 883-89" call /kinetics/145_dephos/IP3_5pase2/notes LOAD \ "from Hansen et al, JBC 262(36), Dec 25 1987: 17319-17326 " call /kinetics/145_dephos/IP3_5pase2/ip3_5pase2/notes LOAD \ "from Hansen et al, JBC 262, 1987" \ "activity determined from pH curve. Value scaled 1.5 times to obtain " \ "activity at 37C as original experiment was performed at 30C" call /kinetics/145_dephos/IP_5pase1/notes LOAD \ "from Hansen et al, JBC 262(36); Dec 25 1987: 17319-26" \ "" \ "InsP 5phosphatase1 has two 5-phosphatase activities: against Ins(145)P3" \ "and Ins(1345)P4 respectively" call /kinetics/145_dephos/IP_5pase1/ip3_5pase1/notes LOAD \ "Ins(145)P3 5-phosphatase activity of InsP-5-phosphatase from" \ "Hansen et al, JBC 262; 1987" call /kinetics/145_dephos/IP_5pase1/ip4_5pase/notes LOAD \ "Ins(1345)P4 5-phosphatase activity of InsP 5-phosphatase1" \ "from Hansen et al, JBC 262; 1987" \ "vmax for IP4 substrate is approx 0.1 times vmax for IP3" \ "" call /kinetics/145_dephos/IP2(14)/notes LOAD \ "Inositol(1,4) bisphosphate" call /kinetics/145_dephos/IP5-inhib-5pase/notes LOAD \ "from Hoer and Oberdisse, Biochem J 278; 1991: 219-224" call /kinetics/145_dephos/IP6-inhib-5pase/notes LOAD \ "from Hoer and Oberdisse, Biochem J 278; 1991: 219-224" call /kinetics/145_dephos/IP_1pase/notes LOAD \ "from Inhorn and Majerus; JBC 262(33), 1987 pp 15946-15952" \ "InsP-1-phosphatase has two enzyme activities against Ins(14)P2 and " \ "Ins(134)P3 respectively" call /kinetics/145_dephos/IP_1pase/ip2_1pase/notes LOAD \ "from Inhorn and Majerus, JBC 1987" \ "Vmax reduced from 5.625 to 2 to maintain levels of IP2(14)" call /kinetics/145_dephos/IP_1pase/ip3_1pase/notes LOAD \ "Ins(134) 1-phosphatase activity of InsP 1-phosphatase" \ "from Inhorn and Majerus, JBC 262; 1987" call /kinetics/145_dephos/IP1(4)/notes LOAD \ "Inositol 4-monophosphate" \ "Basal levels = 10% of Ins(1)P1 ~ 4uM" \ "Ackermann et al, BiochemJ 242, 1987(2): 517" call /kinetics/145_dephos/IP1_pase/notes LOAD \ "from Gee et al, Biochem J. 1988, 249, 883-889" \ "Inositol monophosphate phosphatase; has two enzyme activities against" \ "Ins(4)P1 and Ins(1)P1 respectively" call /kinetics/145_dephos/Ca-inhib-1pase/notes LOAD \ "Ki from Inhorn & Majerus, BiochemJ 262(33); 1987: 15946-52" \ "" call /kinetics/145_dephos/ip1_4pase_cmplx/notes LOAD \ "Enzyme complex exclusively modeled to accomodate enzyme " \ "reversibility as obtained from dG = -5 kJ/mol calculations." call /kinetics/145_dephos/4pase-on/notes LOAD \ "Rates derived from Ins(4)P1 4-phosphatase Km: Gee et al, " \ "Biochem J 249; 1988" call /kinetics/145_dephos/4pase-off/notes LOAD \ "Kf = Vmax for Ins(4)P1 4-phosphatase: Gee et al, Biochem J " \ "249, 1988." \ "Kb adjusted to generate reported basal levels of Ins(4)P1 = " \ "10% of Ins(1)P1 ~ 4uM" call /kinetics/IP4-system/notes LOAD \ "This model depicts detailed dynamics of InsP4s: Ins(1456)P4, Ins(3456)P4" \ "and Ins(1346)P4. Interactions with InsP3s and InsP5 are included." \ "Ins(1345)P4 synthesis from Ins(134)P3 is also shown." \ "" call /kinetics/IP4-system/IP4(1346)/notes LOAD \ "Inositol (1346)tetrakisphosphate" call /kinetics/IP4-system/IP4(3456)/notes LOAD \ "Inositol (3456)tetrakisphosphate" \ "basal levels ~ 1.4uM" call /kinetics/IP4-system/IP4(1456)/notes LOAD \ "Inositol(1456)tetrakisphosphate" call /kinetics/IP4-system/ip4-6pase/notes LOAD \ "this step is essential to maintain flux around the network," \ "rate adjusted accordingly" call /kinetics/IP4-system/ip5_3pase/notes LOAD \ "Ins(13456)P5 3-phosphatase" \ "from Nogimori et al, JBC 266; 1991" \ "Backflux from the reversible InsP4 3-kinase is not sufficient " \ "to maintain Ins(1456)P4 levels. Hence this reaction is " \ "necessary. This reaction also maintains the flux in the " \ "network." call /kinetics/IP4-system/IP3-Kcmplx-on/notes LOAD \ "Kf and Kb are equivalent to k1 and k2 for InsP3 56-K," \ "calculated from enzyme Km and Vmax: Yang and Shears, BiochemJ" \ "2000, 351: 551-555" call /kinetics/IP4-system/6kinase/notes LOAD \ "Kf = Vmax for IP3 56-K " \ "from Yang and Shears, Biochem J 2000; 351:551-555" \ "Enzyme reversibility reported in Ho et al, Curr Biol 2002, 12:" \ "1-20. But backflow calculations do not show that Kb needs to be" \ "incorporated" call /kinetics/IP4-system/5kinase/notes LOAD \ "Kf = 0.274 times Vmax of IP3 56-K as product ratio of " \ "Ins(1345)P4 : Ins(1346)P4 is 1 : 2.3-5" \ "from Wilson and Majerus, JBC 271; 1996" \ "Kb ascertained from dG calculations for equilibrium conditions.," \ "for a dG = -10 kJ/mol" \ "Also enzyme reversibility reported in Ho et al, Curr Biol 2002," \ "12: 1-20" call /kinetics/IP4-system/ip4-5K/notes LOAD \ "Kf based on basal levels of Ins(1346)P4" \ "Kb obtained from dG calculations for equilibrium product " \ "substrate conditions." call /kinetics/IP4-system/IP4-3K/notes LOAD \ "Ins(1456)P4 3kinase" \ "from Stephens et al, Biochem J 249; 1988: 283-92" \ "" call /kinetics/IP4-system/IP3-56Kcmplx/notes LOAD \ "enzyme substrate complex of IP3 56-K and Ins(134)P3. Complex " \ "exclusively modeled as reaction generates ratio of products," \ "and because 5-kinase is reversible due to large Ins(1345)P4 " \ "backflux" call /kinetics/IP4-system/IP5(13456)/notes LOAD \ "Inositol(13456)pentakisphosphate" \ "Conc from Voglmaier et al, PNAS 93; 1996" call /kinetics/IP4-system/ip4_3k_cmplx/notes LOAD \ "Enzyme complex exclusively modeled to include reversible " \ "kinetics, as the back flux is significant for dG = -10 kJ/mol" call /kinetics/IP4-system/ip4-3k-on/notes LOAD \ "Rates derived from Km for enzyme: Stephens et al, Biochem J " \ "249; 1988." call /kinetics/IP4-system/ip4-3k-off/notes LOAD \ "Kf = Vmax for enzyme: Stephens et al, Biochem J 249; 1988." \ "Kb ascertained from dG calculations for equilibrium conditions." call /kinetics/IP4-system/ip4_1k_cmplx/notes LOAD \ "Enzyme complex exclusively modeled to accomodate reversible " \ "kinetics as opposed to M-M kinetics. Enzyme reversibility " \ "ascertained from dG calculations at -10 kJ/mol that yield a " \ "significant back flux from IP5." \ "Also IP4-1K is experimentally reversible: Ho et al, Curr Biol," \ "Mar 2002, 12: 1-20" call /kinetics/IP4-system/ip4-1k-on/notes LOAD \ "Rates derives from enzyme Km and Vmax values:" \ "Yang and Shears, Biochem J 2000, 351: 551-555." call /kinetics/IP4-system/ip4-1k-off/notes LOAD \ "Kf = enzyme Vmax : Yang and Shears, Biochem J 2000, 351, 551-5." \ "Kb ascertained from dG calculations for equilibrium product " \ "substrate conditions." \ "Ho et al, Curr Biol 2002, 12: 1-20 report a Vmax for reverse " \ "reaction of 0.0656 /sec. But this cannot be exactly incorporated " \ "unless Km for InsP5 is also known." \ "Simulations show that incorporation of this reverse reaction " \ "can maintain basal InsP4 levels but cannot achieve the " \ "stimulated InsP4 levels shown in Ho et al." \ "Hence the separate InsP5 1pase is retained." call /kinetics/IP4-system/IP3(134)/notes LOAD \ "Inositol (134)trisphosphate" \ "" call /kinetics/IP4-system/IP3-56K_IP4-1K/notes LOAD \ "Combined Ins(134)P3 5,6-kinase and Ins(3456)P4 1-kinase:" \ "from Yang and Shears, Biochem J 2000, 351: 551-555." \ "Conc from Wilson and Majerus, JBC 271(20); 1996: 11904-10" \ "5,6K Reaction products Ins(1346)P4 and Ins(1345)P4 are generated in" \ "a ratio of 2.3-5 : 1" \ "Enzyme inhibition by products, as depicted in previous versions " \ "of the model, removed because it is now shown that enzyme is " \ "multi-tasking and reversible with respect to these products:" \ "Ho et al, Curr Biol 2002, 12: 1-20. This non M-M ability has " \ "been incorporated." \ "But cycling to Ins(346)P3 by this enzyme not included because " \ "rest of Ins(346)P3 network biology is unknown in mammals." call /kinetics/IP4-system/ip5_1pase/notes LOAD \ "InsP5 1-phosphatase" \ "Reaction is necessary to generate the flux of Ins(3456)P4 seen" \ "physiologically (Ho et al Curr Biol 2002, 12:1-20), although " \ "the IP4-1K/pase can maintain basal levels of this InsP4." call /kinetics/IHP-system/notes LOAD \ "Model for interactions between Inositol High Polyphosphates. Primary " \ "refs: Voglmaier et al, PNAS 93, 1996: 4305-10; Huang et al, Biochem " \ "37, 1998: 14998-15004; Safrany et al, EMBO J 17, 1998: 6599-607;" \ "Saiardi et al, Curr Biol 9, 1999: 1323-26; Saiardi et al, JBC 275, " \ "2000: 24686-92 " call /kinetics/IHP-system/dipp_ip6/notes LOAD \ "rate based on basal levels of PP-InsP4" call /kinetics/IHP-system/PP-IP4/notes LOAD \ "Diphosphoinositol tetrakisphosphate" \ "Conc from Saiardi et al, JBC 275; 2000" call /kinetics/IHP-system/IP6_K2/notes LOAD \ "from Saiardi et al, Curr Biol 9; 1999: 1323-26" \ "" \ "has InsP5 kinase/ PP-InsP4 synthase and PP-InsP4 kinase activity " \ "apart from InsP6 kinase activity (Saiardi et al, JBC 275(32); 2000: " \ "24686-92)" \ "" \ "also referred to as PiUS (Pi Uptake Stimulator)" \ "" \ "" call /kinetics/IHP-system/IP6_K2/ip6_k2/notes LOAD \ "from Saiardi et al, Curr Biol 9; 1999" call /kinetics/IHP-system/IP6_K2/ip5_k2/notes LOAD \ "from Saiardi et al, JBC 275(32); 2000: 24686-92 " call /kinetics/IHP-system/IP6_K2/pp-ip4-k2/notes LOAD \ "from Saiardi et al, JBC 275; 2000" \ "approx Km and Vmax calculated from first order rate constants" call /kinetics/IHP-system/bisPP-IP3/notes LOAD \ "Bis(diphospho)inositol trisphosphate" \ "from Saiardi et al, JBC 275(32); 2000: 24686-92" call /kinetics/IHP-system/ATP/notes LOAD \ "Conc for mammalian brain from Huang et al, Biochem 37; 1998" call /kinetics/IHP-system/ADP/notes LOAD \ "Conc for mammaliam brain from Huang et al, Biochem 37; 1998" call /kinetics/IHP-system/IP6/notes LOAD \ "Inositol hexakisphosphate " \ "Conc from Voglmaier et al, PNAS 93; 1996" call /kinetics/IHP-system/ip5-kinase-pase/notes LOAD \ "Kf represents InsP5 2-kinase and Kb represents InsP6 2-phosphatase" \ "Although InsP5 2-kinases in yeast and plant systems have been " \ "characterized (Ives et al, JBC 275; 2000: 36575-83), the mammalian" \ "counterpart is still to be worked out." \ "Rates calculated to maintain InsP5 and InsP6 levels" call /kinetics/IHP-system/PP-IP5/notes LOAD \ "Diphosphoinositol pentakisphosphate" \ "Conc from Huang et al, Biochem 37; 1998" call /kinetics/IHP-system/bisPP-IP4/notes LOAD \ "Bis(diphospho)inositol tetrakisphosphate" \ "Conc from Huang et al, Biochem 37; 1998" call /kinetics/IHP-system/DIPP1/notes LOAD \ "Diphosphoinositol-Polyphosphate Phosphohydrolase" \ "from Safrany et al, EMBO J 17(22); 1998: 6599-607" \ "" call /kinetics/IHP-system/DIPP1/dipp_ip8/notes LOAD \ "from Safrany et al, EMBO J 17(22); 1998" \ "Vmax represents activity of human recombinant protein, which is" \ "20-50 fold greater than activity of the purified rat enzyme" call /kinetics/IHP-system/DIPP1/dipp_ip7/notes LOAD \ "from Safrany et al, EMBO J 17(22); 1998" \ "Vmax represents activity of recombinant human protein which" \ "is 20-50 fold greater than activity of the purified rat enzyme" call /kinetics/IHP-system/IP5-dipp-inhib/notes LOAD \ "IC50=1.6uM from Safrany et al, EMBO J 17(22); 1998 " call /kinetics/IHP-system/IP6-dipp-inhib/notes LOAD \ "IC50=0.2uM from Safrany et al, EMBO J 17(22); 1998" call /kinetics/IHP-system/PP-IP5cmplx-on/notes LOAD \ "from Huang et al, Biochem 37; 1998" \ "Kf calculated using Km for PP-InsP5 and ATP, and Vmax of forward and " \ "backward reactions. " \ "Kb = Vmax of backward reaction " \ "" call /kinetics/IHP-system/PP-IP5cmplx-off/notes LOAD \ "from Huang et al, Biochem 37; 1998" \ "Kf = Vmax of forward reaction" \ "Kb calculated using Km for PP-InsP5 and ATP, and Vmax of forward and " \ "backward reactions" call /kinetics/IHP-system/PP-IP5-K-complex/notes LOAD \ "enzyme substrate complex of PP-InsP5 kinase and PP-InsP5" call /kinetics/IHP-system/IP6-K-complex/notes LOAD \ "enzyme substrate complex of InsP6 kinase and InsP6" call /kinetics/IHP-system/IP6cmplx-off/notes LOAD \ "from Voglmaier et al, PNAS 93; 1996" \ "Kf = Vmax of forward reaction" \ "Kb calculated from Km for InsP6 and ATP, and Vmax of forward and " \ "backward reactions" call /kinetics/IHP-system/IP6cmplx-on/notes LOAD \ "from Voglmaier et al, PNAS 93; 1996" \ "Kf calculated from Km for InsP6 and ATP, and Vmax for forward and " \ "backward reactions" \ "Kb = Vmax of backward reaction" call /kinetics/IHP-system/PP-IP5-K/notes LOAD \ "from Huang et al, Biochem 37; 1998: 14998-15004" call /kinetics/IHP-system/IP6-K/notes LOAD \ "from Voglmaier et al, PNAS 93; 1996: 4305-10 " \ "" \ "has InsP5 kinase/ PP-InsP4 synthase and PP-InsP4 kinase apart from InsP6 " \ "kinase activity (Saiardi et al, JBC 275(32); 2000: 24686-92)" call /kinetics/IHP-system/IP6-K/ip5_k1/notes LOAD \ "from Saiardi et al, JBC 275(32); 2000: 24686-92" call /kinetics/IHP-system/IP6-K/pp-ip4-k1/notes LOAD \ "from Saiardi et al, JBC 275; 2000" \ "approx Km and Vmax calculated from first order rate constants" call /kinetics/1345_dephos/notes LOAD \ "Model for Ins(1345)P4 dephosphorylation by InsP4 3-phosphatase and" \ "InsP 5-phosphatase1. Primary refs: Hoer et al, Biochem J 270, 1990:" \ "715-19; Hoer and Oberdisse, Biochem J 278, 1991: 219-24; Hansen et al," \ "JBC 262, 1987: 17319-26" call /kinetics/1345_dephos/IP5-inhib-3pase/notes LOAD \ "from Hoer and Oberdisse, Biochem J 278; 1991: 219-224" call /kinetics/1345_dephos/IP6-inhib-3pase/notes LOAD \ "from Hoer and Oberdisse, Biochem J 278; 1991: 219-224" call /kinetics/1345_dephos/145-inhib-3pase/notes LOAD \ "from Hoer et al, Biochem J 270; 1990" call /kinetics/1345_dephos/IP4-inhib-3pase/notes LOAD \ "from Hoer et al, Biochem J 270; 1990" call /kinetics/1345_dephos/134-inhib-3pase/notes LOAD \ "from Hoer et al, Biochem J 270; 1990" call /kinetics/1345_dephos/1345_3pase/notes LOAD \ "from Hoer et al, BiochemJ 270; 1990: 715-719" call /kinetics/1345_dephos/1345_3pase/ip4_3pase/notes LOAD \ "Ins(1345)P4 3-phosphatase" \ "from Nogimori et al, JBC 266; 1991" call /kinetics/doqcsinfo/notes LOAD \ "This network models detailed metabolism of Ins(145)P3, integrated with GPCR mediated PLCbeta activation and Ca release by the InsP3 receptor in the neuron. It is similar to the NonOsc_Ca_IP3metab model (accession 23) except that some enzymes have been modified to have reversible kinetics rather than Michaelis-Menten kinetics. These modified enzymes belong to the groups: IP4-system, IP3-3K, 145_dephos and 134_dephos. Mishra J, Bhalla US. Biophys J. 2002 Sep;83(3):1298-316" complete_loading