//genesis // kkit Version 7 dumpfile // Saved on Mon Aug 7 20:58:41 2000 include kkit {argv 1} FASTDT = 0.001 SIMDT = 0.001 CONTROLDT = 1 PLOTDT = 1 MAXTIME = 300 float TRANSIENT_TIME = 2 int VARIABLE_DT_FLAG = 0 kparms //genesis initdump -version 3 -ignoreorphans 1 simobjdump table input output alloced step_mode stepsize simobjdump xtree path script namemode sizescale simobjdump xcoredraw xmin xmax ymin ymax simobjdump xtext editable simobjdump xgraph xmin xmax ymin ymax overlay simobjdump xplot pixflags script fg ysquish do_slope wy simobjdump kpool CoTotal CoInit Co CoRemaining n nInit nTotal nMin vol \ slave_enable notes xtree_fg_req xtree_textfg_req simobjdump xtab input output alloced step_mode stepsize notes editfunc \ xtree_fg_req xtree_textfg_req plotfield manageclass baselevel last_x last_y \ is_running simobjdump group notes editfunc xtree_fg_req xtree_textfg_req plotfield \ manageclass expanded movealone simobjdump kenz CoComplexInit CoComplex nComplexInit nComplex vol sA pA eA B \ k1 k2 k3 keepconc usecomplex ksum oldmsgmode notes editfunc xtree_fg_req \ xtree_textfg_req plotfield manageclass link_to_manage simobjdump kreac A B kf kb is_active oldmsgmode notes editfunc xtree_fg_req \ xtree_textfg_req plotfield manageclass simundump group /kinetics/AC 1 "" edit_group blue blue x group 0 0 simundump kpool /kinetics/AC/ATP 1 5000 5000 5000 0 3e+09 3e+09 3e+09 0 6e+05 \ 4 \ "ATP is present in all cells between 2 and 10 mM. \nSee Lehninger. It is assumed buffered since the\nmetabolic activity will take care of its levels." \ red blue simundump kpool /kinetics/AC/AMP 1 1000 1000 1000 0 6e+08 6e+08 6e+08 0 6e+05 \ 4 "Assumed buffered to 1 mM. Value is irrelevant\nto simulation." pink blue simundump kpool /kinetics/AC/cAMP-PDE 1 0.5 0.5 0.5 0 3e+05 3e+05 3e+05 0 \ 6e+05 0 \ "The levels of the PDE are not known at this time. However,\nenough\nkinetic info and info about steady-state levels of cAMP\netc are around\nto make it possible to estimate this at about 0.5 uM." \ green blue simundump kenz /kinetics/AC/cAMP-PDE/PDE 1 0 0 0 0 6e+05 1.7408e+06 \ 4.3521e+05 2.176e+06 2.176e+06 4.2e-06 40 10 0 0 50 0 \ "Best rates are from Conti et al Biochem 34 7979-7987 1995.\nThough these\nare for the Sertoli cell form, it looks like they carry\nnicely into\nalternatively spliced brain form. See Sette et al\nJBC 269:28 18271-18274\nKm ~2 uM, Vmax est ~ 10 umol/min/mg for pure form.\nBrain protein is 93 kD but this was 67.\nSo k3 ~10, k2 ~40, k1 ~4.2e-6" \ edit_enz red green CoComplex kpool enzproto_to_pool_link simundump kpool /kinetics/AC/cAMP-PDE* 1 1.6667e-06 0 0 2.1433e-35 0 0 1 0 \ 6e+05 0 \ "This form has about 2X activity as plain PDE. See Sette et al JBC 269:28\n18271-18274 1994." \ green blue simundump kenz /kinetics/AC/cAMP-PDE*/PDE* 1 0 0 0 0 6e+05 0 0 0 0 8.4e-06 80 \ 20 0 0 100 0 \ "This form has about twice the activity of the unphosphorylated form. See\nSette et al JBC 269:28 18271-18274 1994.\nWe'll ignore cGMP effects for now." \ edit_enz red green CoComplex kpool enzproto_to_pool_link simundump kreac /kinetics/AC/dephosph-PDE 1 0 0 0.1 0 1 0 \ "The rates for this are poorly constrained. In adipocytes (probably a\ndifferent PDE) the dephosphorylation is complete within 15 min, but\nthere are no intermediate time points so it could be much faster. Identity\nof phosphatase etc is still unknown." \ edit_reac white blue A group simundump kpool /kinetics/AC/Gs.AC 1 0 0 0 0 0 0 0 0 6e+05 0 \ "This is the active form of the cyclase.\n" yellow blue simundump kenz /kinetics/AC/Gs.AC/cyclase 1 0 0 0 0 6e+05 1.4265e+05 35663 \ 7.1263e+05 0 7.5e-06 72 18 0 1 90 0 \ "See Feinstein et al PNAS 88:10173-10177,\nJacobowitz et al JBC 286(6):3829-3832\nSmigel, JBC 261(4):1976-1982 (1986)" \ edit_enz red yellow CoComplex kpool enzproto_to_pool_link simundump kpool /kinetics/AC/AC 1 0.015 0.015 0.015 0 9000 9000 9000 0 6e+05 \ 0 \ "AC is present at rather low levels. Here we use\n0.015 uM which is meant to lump various isoforms.\nNone of the isoforms nor the other specific regulators\nare included here.\nJacobowitz, PhD thesis." \ yellow blue simundump kreac /kinetics/AC/Gs-bind-AC 1 1981.3 1980.9 0.00083333 1 1 0 \ "Half-max at around 3nM = kb/kf from fig 5 in \nFeinstein et al PNAS USA 88 10173-10177 1991\nkf = kb/1800 = 5.56e-4 kb\nOfer Jacobowitz thesis (Mount Sinai 1995) data indicates\nit is more like 2 nM.\n" \ edit_reac white blue A group simundump kpool /kinetics/cAMP 1 0 0 0 0 0 0 0 0 6e+05 2 \ "Key second messenger." green black simundump kpool /kinetics/PKA-active 1 1.6667e-06 0 0 2.1433e-35 0 0 1 0 \ 6e+05 0 "" yellow black simundump kenz /kinetics/PKA-active/phosph-PDE 1 0 0 0 0 6e+05 0 0 0 0 1e-05 \ 36 9 0 0 45 0 \ "See Bramson et al CRC crit rev Biochem 15:2 93-124.\nThe rates there are for peptide substrates and too fast.\nScaled down by a factor of 3 as per\nCohen et al FEBS Lett 76:182-86 (1977)." \ edit_enz red yellow CoComplex kpool enzproto_to_pool_link simundump kpool /kinetics/GTP.Ga 1 0 0 0 0 0 0 0 0 6e+05 2 "" red black simundump xgraph /graphs/conc1 0 0 300 0 4.7805 0 simundump xgraph /graphs/conc2 0 0 300 0 1 0 simundump xgraph /moregraphs/conc3 0 0 300 0 1 0 simundump xgraph /moregraphs/conc4 0 0 300 0 1 0 simundump xcoredraw /edit/draw 0 -6.8439 6.6449 -23.573 -10.084 simundump xtree /edit/draw/tree 0 /kinetics/##[] \ "edit_elm.D ; drag_from_edit.w " auto 0.6 call /edit/draw/tree ADDMSGARROW \ select all all all none -1000 0 \ "" "" "" call /edit/draw/tree ADDMSGARROW \ /kinetics/##[] /kinetics/##[TYPE=group] all all none -1001 0 \ "echo.p dragging onto group ; thing_to_group_add.p " "" "" call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=kpool] /kinetics/##[TYPE=kpool] SUMTOTAL kpool darkgreen -1002 0 \ "echo.p dragging to for sumtotal" "pool_to_pool_add_sumtot.p " "pool_to_pool_drop_sumtot.p " call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=kpool] /kinetics/##[TYPE=kpool] CONSERVE kpool blue -1003 0 \ "echo.p dragging to for conserve" "pool_to_pool_add_consv.p " "pool_to_pool_drop_consv.p " call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=kreac] /kinetics/##[TYPE=kpool] REAC kpool none -1004 0 \ "" "reac_to_pool_add.p " "reac_to_pool_drop.p " call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=kpool] /kinetics/##[TYPE=kreac] SUBSTRATE kreac green -1005 0 \ "" "pool_to_reac_add.p " "pool_to_reac_drop.p " call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=kpool] /kinetics/##[TYPE=kreac] KF kreac purple -1006 0 \ "" "" "" call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=kpool] /kinetics/##[TYPE=kreac] KB kreac hotpink -1007 0 \ "" "" "" call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=kpool] /kinetics/##[TYPE=kreac] PRODUCT kreac green -1008 1 \ "" "" "" call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=kenz] /kinetics/##[TYPE=kpool] MM_PRD kpool red -1009 0 \ "echo.p dragging to for enz product" "enz_to_pool_add.p " "enz_to_pool_drop.p " call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=kpool] /kinetics/##[TYPE=kenz] SUBSTRATE kenz red -1010 0 \ "echo.p dragging to for enz substrate" "pool_to_enz_add.p " "pool_to_enz_drop.p " call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=kenz] /kinetics/##[TYPE=kpool] SUMTOTAL kpool darkgreen -1011 0 \ "" "" "" call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=kenz] /kinetics/##[TYPE=kpool] CONSERVE kpool blue -1012 0 \ "" "" "" call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=kpool] /kinetics/##[TYPE=kenz] INTRAMOL kenz white -1013 0 \ "" "" "" call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=stim] /kinetics/##[TYPE=kpool] SLAVE kpool orange -1014 0 \ "echo.p dragging to for stimulus" "stim_to_pool_add.p " "stim_to_pool_drop.p " call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=stim] /kinetics/##[TYPE=stim] INPUT stim orange -1015 0 \ "echo.p dragging to for stim" "stim_to_stim_add.p " "stim_to_stim_drop.p " call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=xtab] /kinetics/##[TYPE=kpool] SLAVE kpool orange -1016 0 \ "echo.p dragging to for xtab" "xtab_to_pool_add.p " "xtab_to_pool_drop.p " call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=xtab] /kinetics/##[TYPE=xtab] INPUT xtab orange -1017 0 \ "echo.p dragging to for xtab" "xtab_to_xtab_add.p " "xtab_to_xtab_drop.p " call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=kpool] /kinetics/##[TYPE=xtab] INPUT xtab hotpink -1018 0 \ "echo.p dragging to for xtab" "pool_to_xtab_add.p " "pool_to_xtab_drop.p " call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=kchan] /kinetics/##[TYPE=kpool] REAC kpool none -1019 0 \ "echo.p dragging to for chan product" "chan_to_pool_add.p " "chan_to_pool_drop.p " call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=kpool] /kinetics/##[TYPE=kchan] PRODUCT kchan orange -1020 1 \ "" "" "" call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=kpool] /kinetics/##[TYPE=kchan] SUBSTRATE kchan orange -1021 0 \ "echo.p dragging to for chan substrate" "pool_to_chan_add.p " "pool_to_chan_drop.p " call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=transport] /kinetics/##[TYPE=kpool] MM_PRD kpool yellow -1022 0 \ "" "transport_to_pool_add.p " "transport_to_pool_drop.p " call /edit/draw/tree ADDMSGARROW \ /kinetics/##[TYPE=kpool] /kinetics/##[TYPE=transport] SUBSTRATE transport yellow -1023 0 \ "" "pool_to_transport_add.p " "pool_to_transport_drop.p " call /edit/draw/tree UNDUMP 16 \ "/kinetics/AC" 1.1996 -16.551 0 \ "/kinetics/AC/ATP" 2.767 -14.295 0 \ "/kinetics/AC/AMP" -0.03125 -14.261 0 \ "/kinetics/AC/cAMP-PDE" -2.4541 -14.124 0 \ "/kinetics/AC/cAMP-PDE/PDE" -2.4562 -15.532 0 \ "/kinetics/AC/cAMP-PDE*" -2.0655 -19.04 0 \ "/kinetics/AC/cAMP-PDE*/PDE*" -2.0446 -17.996 0 \ "/kinetics/AC/dephosph-PDE" -5.5595 -15.426 0 \ "/kinetics/AC/Gs.AC" 3.4153 -19.161 0 \ "/kinetics/AC/Gs.AC/cyclase" 3.3364 -18.153 0 \ "/kinetics/AC/AC" 6.1795 -19.161 0 \ "/kinetics/AC/Gs-bind-AC" 5.0694 -17.217 0 \ "/kinetics/cAMP" 0.78774 -19.024 0 \ "/kinetics/PKA-active" -5.3888 -19.058 0 \ "/kinetics/PKA-active/phosph-PDE" -5.7447 -17.569 0 \ "/kinetics/GTP.Ga" 5.0141 -13.11 0 simundump xtext /file/notes 0 1 xtextload /file/notes \ "Based on ac20.g. Cleaned up a bit" \ "and did some renaming." addmsg /kinetics/AC/Gs.AC/cyclase /kinetics/AC/ATP REAC sA B addmsg /kinetics/AC/cAMP-PDE*/PDE* /kinetics/AC/AMP MM_PRD pA addmsg /kinetics/AC/cAMP-PDE/PDE /kinetics/AC/AMP MM_PRD pA addmsg /kinetics/AC/cAMP-PDE/PDE /kinetics/AC/cAMP-PDE REAC eA B addmsg /kinetics/AC/dephosph-PDE /kinetics/AC/cAMP-PDE REAC B A addmsg /kinetics/PKA-active/phosph-PDE /kinetics/AC/cAMP-PDE REAC sA B addmsg /kinetics/AC/cAMP-PDE /kinetics/AC/cAMP-PDE/PDE ENZYME n addmsg /kinetics/cAMP /kinetics/AC/cAMP-PDE/PDE SUBSTRATE n addmsg /kinetics/AC/cAMP-PDE*/PDE* /kinetics/AC/cAMP-PDE* REAC eA B addmsg /kinetics/AC/dephosph-PDE /kinetics/AC/cAMP-PDE* REAC A B addmsg /kinetics/PKA-active/phosph-PDE /kinetics/AC/cAMP-PDE* MM_PRD pA addmsg /kinetics/AC/cAMP-PDE* /kinetics/AC/cAMP-PDE*/PDE* ENZYME n addmsg /kinetics/cAMP /kinetics/AC/cAMP-PDE*/PDE* SUBSTRATE n addmsg /kinetics/AC/cAMP-PDE* /kinetics/AC/dephosph-PDE SUBSTRATE n addmsg /kinetics/AC/cAMP-PDE /kinetics/AC/dephosph-PDE PRODUCT n addmsg /kinetics/AC/Gs-bind-AC /kinetics/AC/Gs.AC REAC B A addmsg /kinetics/AC/Gs.AC /kinetics/AC/Gs.AC/cyclase ENZYME n addmsg /kinetics/AC/ATP /kinetics/AC/Gs.AC/cyclase SUBSTRATE n addmsg /kinetics/AC/Gs-bind-AC /kinetics/AC/AC REAC A B addmsg /kinetics/AC/AC /kinetics/AC/Gs-bind-AC SUBSTRATE n addmsg /kinetics/AC/Gs.AC /kinetics/AC/Gs-bind-AC PRODUCT n addmsg /kinetics/GTP.Ga /kinetics/AC/Gs-bind-AC SUBSTRATE n addmsg /kinetics/AC/Gs.AC/cyclase /kinetics/cAMP MM_PRD pA addmsg /kinetics/AC/cAMP-PDE*/PDE* /kinetics/cAMP REAC sA B addmsg /kinetics/AC/cAMP-PDE/PDE /kinetics/cAMP REAC sA B addmsg /kinetics/PKA-active/phosph-PDE /kinetics/PKA-active REAC eA B addmsg /kinetics/PKA-active /kinetics/PKA-active/phosph-PDE ENZYME n addmsg /kinetics/AC/cAMP-PDE /kinetics/PKA-active/phosph-PDE SUBSTRATE n addmsg /kinetics/AC/Gs-bind-AC /kinetics/GTP.Ga REAC A B enddump // End of dump call /edit/draw/tree RESET reset