//genesis // kkit Version 7 dumpfile // Saved on Mon Aug 7 21:53:53 2000 include kkit {argv 1} FASTDT = 0.001 SIMDT = 0.001 CONTROLDT = 1 PLOTDT = 1 MAXTIME = 1000 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 kreac A B kf kb is_active oldmsgmode notes editfunc xtree_fg_req \ xtree_textfg_req plotfield manageclass simundump group /kinetics/PKA 0 \ "General ref: Taylor et al Ann Rev Biochem 1990 59:971-1005\n" edit_group \ blue blue x group 0 0 simundump kpool /kinetics/PKA/R2C2 0 0.5 0.5 0.5 8.1847e-19 3e+05 3e+05 3e+05 \ 0 6e+05 0 \ "This is the R2C2 complex, consisting of 2 catalytic (C)\nsubunits, and the R-dimer. See Taylor et al Ann Rev Biochem\n1990 59:971-1005 for a review.\nThe Doskeland and Ogreid review is better for numbers.\nAmount of PKA is about .5 uM." \ white blue simundump kreac /kinetics/PKA/cAMP-bind-site-B1 0 7.7373e+05 7.7373e+05 9e-05 \ 33 1 0 \ "Hasler et al FASEB J 6:2734-2741 1992 say Kd =1e-7M\nfor type II, 5.6e-8 M for type I. Take mean\nwhich comes to 2e-13 #/cell\nSmith et al PNAS USA 78:3 1591-1595 1981 have better data.\nFirst kf/kb=2.1e7/M = 3.5e-5 (#/cell).\nOgreid and Doskeland Febs Lett 129:2 287-292 1981 have figs\nsuggesting time course of complete assoc is < 1 min." \ edit_reac white blue A group simundump kreac /kinetics/PKA/cAMP-bind-site-B2 1 93546 93546 9e-05 33 1 0 \ "For now let us set this to the same Km (1e-7M) as\nsite B. This gives kf/kb = .7e-7M * 1e6 / (6e5^2) : 1/(6e5^2)\n= 2e-13:2.77e-12\nSmith et al have better values. They say that this is\ncooperative, so the consts are now kf/kb =8.3e-4" \ edit_reac white blue A group simundump kreac /kinetics/PKA/cAMP-bind-site-A1 1 15708 15708 0.000125 110 1 \ 0 "" edit_reac white blue A group simundump kreac /kinetics/PKA/cAMP-bind-site-A2 1 791.35 791.33 0.000125 32.5 \ 1 0 "" edit_reac white blue A group simundump kreac /kinetics/PKA/Release-C1 1 1461 1460.9 60 3e-05 1 0 \ "This has to be fast, as the activation of PKA by cAMP\nis also fast.\nkf was 10\n" \ edit_reac white blue A group simundump kreac /kinetics/PKA/Release-C2 1 82694 82694 60 3e-05 1 0 "" \ edit_reac white blue A group simundump kpool /kinetics/PKA/PKA-inhibitor 1 1 0.25 0.25 4.3745e-18 1.5e+05 \ 1.5e+05 6e+05 0 6e+05 0 \ "About 25% of PKA C subunit is dissociated in resting cells without\nhaving any noticable activity.\nDoskeland and Ogreid Int J biochem 13 pp1-19 suggest that this is\nbecause there is a corresponding amount of inhibitor protein." \ cyan blue simundump kreac /kinetics/PKA/inhib-PKA 1 1.1691e+05 1.1691e+05 1e-04 1 1 0 \ "This has to be set to zero for matching the expts in vitro.\nIn vivo we need to consider the inhibition though.\n\n" \ edit_reac white blue A group simundump kpool /kinetics/PKA/inhibited-PKA 1 1.6667e-06 0 0 0 0 0 1 0 6e+05 \ 0 "" cyan blue simundump kpool /kinetics/PKA/cAMP.R2C2 0 1 0 0 4.4487e-18 0 0 6e+05 0 6e+05 \ 0 "CoInit was .0624\n" white blue simundump kpool /kinetics/PKA/cAMP2.R2C2 1 1.6667e-06 0 0 0 0 0 1 0 6e+05 0 \ "" white blue simundump kpool /kinetics/PKA/cAMP3.R2C2 1 1.6667e-06 0 0 0 0 0 1 0 6e+05 0 \ "" white blue simundump kpool /kinetics/PKA/cAMP4.R2C2 1 1.6667e-06 0 0 0 0 0 1 0 6e+05 0 \ "" white blue simundump kpool /kinetics/PKA/cAMP4.R2C 1 1.6667e-06 0 0 0 0 0 1 0 6e+05 0 "" \ white blue simundump kpool /kinetics/PKA/cAMP4.R2 1 0.15 0 0 9.25e-20 0 0 90000 0 6e+05 \ 0 \ "Starts at 0.15 for the test of fig 6 in Smith et al, but we aren't using\nthat paper any more." \ white blue simundump kpool /kinetics/cAMP 1 10 0 0 4.5953e-17 0 0 6e+06 0 6e+05 2 \ "The conc of this has been a problem. Schaecter and Benowitz use 50 uM,\nbut Shinomura et al have < 5. So I have altered the cAMP-dependent \nrates in the PKA model to reflect this." \ green black simundump kpool /kinetics/PKA-active 0 100 0 0 4.627e-16 0 0 6e+07 0 6e+05 0 \ "Conc of PKA in brain is about 1 uM" yellow black simundump xgraph /graphs/conc1 0 0 1000 0 1 0 simundump xgraph /graphs/conc2 0 0 1000 0 1 0 simundump xgraph /moregraphs/conc3 0 0 100 0 1 0 simundump xgraph /moregraphs/conc4 0 0 100 0 1 0 simundump xcoredraw /edit/draw 0 -18.607 -1.5206 -27.012 -9.9244 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 19 \ "/kinetics/PKA" -11.636 -12.25 0 \ "/kinetics/PKA/R2C2" -16.3484 -19.3226 0 \ "/kinetics/PKA/cAMP-bind-site-B1" -13.972 -22.5977 0 \ "/kinetics/PKA/cAMP-bind-site-B2" -11.6301 -21.3501 0 \ "/kinetics/PKA/cAMP-bind-site-A1" -8.94374 -22.5353 0 \ "/kinetics/PKA/cAMP-bind-site-A2" -5.65651 -21.1041 0 \ "/kinetics/PKA/Release-C1" -5.0539 -14.46 0 \ "/kinetics/PKA/Release-C2" -9.9249 -15.738 0 \ "/kinetics/PKA/PKA-inhibitor" -14.4067 -14.8709 0 \ "/kinetics/PKA/inhib-PKA" -11.6135 -14.2476 0 \ "/kinetics/PKA/inhibited-PKA" -15.0337 -13.272 0 \ "/kinetics/PKA/cAMP.R2C2" -13.3865 -18.8548 0 \ "/kinetics/PKA/cAMP2.R2C2" -9.83918 -18.0126 0 \ "/kinetics/PKA/cAMP3.R2C2" -7.15285 -19.0731 0 \ "/kinetics/PKA/cAMP4.R2C2" -4.7663 -17.462 0 \ "/kinetics/PKA/cAMP4.R2C" -7.04952 -16.3283 0 \ "/kinetics/PKA/cAMP4.R2" -13.3865 -16.7649 0 \ "/kinetics/cAMP" -5.3828 -25.006 0 \ "/kinetics/PKA-active" -7.2906 -13.501 0 simundump xtext /file/notes 0 1 xtextload /file/notes \ "Derived from pka21.g," \ "identical except for renaming," \ "cleanups and getting rid of a " \ "couple of unused enzyme sites of" \ "PKA" addmsg /kinetics/PKA/cAMP-bind-site-B1 /kinetics/PKA/R2C2 REAC A B addmsg /kinetics/PKA/R2C2 /kinetics/PKA/cAMP-bind-site-B1 SUBSTRATE n addmsg /kinetics/PKA/cAMP.R2C2 /kinetics/PKA/cAMP-bind-site-B1 PRODUCT n addmsg /kinetics/cAMP /kinetics/PKA/cAMP-bind-site-B1 SUBSTRATE n addmsg /kinetics/PKA/cAMP.R2C2 /kinetics/PKA/cAMP-bind-site-B2 SUBSTRATE n addmsg /kinetics/cAMP /kinetics/PKA/cAMP-bind-site-B2 SUBSTRATE n addmsg /kinetics/PKA/cAMP2.R2C2 /kinetics/PKA/cAMP-bind-site-B2 PRODUCT n addmsg /kinetics/PKA/cAMP2.R2C2 /kinetics/PKA/cAMP-bind-site-A1 SUBSTRATE n addmsg /kinetics/cAMP /kinetics/PKA/cAMP-bind-site-A1 SUBSTRATE n addmsg /kinetics/PKA/cAMP3.R2C2 /kinetics/PKA/cAMP-bind-site-A1 PRODUCT n addmsg /kinetics/cAMP /kinetics/PKA/cAMP-bind-site-A2 SUBSTRATE n addmsg /kinetics/PKA/cAMP3.R2C2 /kinetics/PKA/cAMP-bind-site-A2 SUBSTRATE n addmsg /kinetics/PKA/cAMP4.R2C2 /kinetics/PKA/cAMP-bind-site-A2 PRODUCT n addmsg /kinetics/PKA/cAMP4.R2C2 /kinetics/PKA/Release-C1 SUBSTRATE n addmsg /kinetics/PKA-active /kinetics/PKA/Release-C1 PRODUCT n addmsg /kinetics/PKA/cAMP4.R2C /kinetics/PKA/Release-C1 PRODUCT n addmsg /kinetics/PKA/cAMP4.R2C /kinetics/PKA/Release-C2 SUBSTRATE n addmsg /kinetics/PKA-active /kinetics/PKA/Release-C2 PRODUCT n addmsg /kinetics/PKA/cAMP4.R2 /kinetics/PKA/Release-C2 PRODUCT n addmsg /kinetics/PKA/inhib-PKA /kinetics/PKA/PKA-inhibitor REAC A B addmsg /kinetics/PKA-active /kinetics/PKA/inhib-PKA SUBSTRATE n addmsg /kinetics/PKA/PKA-inhibitor /kinetics/PKA/inhib-PKA SUBSTRATE n addmsg /kinetics/PKA/inhibited-PKA /kinetics/PKA/inhib-PKA PRODUCT n addmsg /kinetics/PKA/inhib-PKA /kinetics/PKA/inhibited-PKA REAC B A addmsg /kinetics/PKA/cAMP-bind-site-B1 /kinetics/PKA/cAMP.R2C2 REAC B A addmsg /kinetics/PKA/cAMP-bind-site-B2 /kinetics/PKA/cAMP.R2C2 REAC A B addmsg /kinetics/PKA/cAMP-bind-site-B2 /kinetics/PKA/cAMP2.R2C2 REAC B A addmsg /kinetics/PKA/cAMP-bind-site-A1 /kinetics/PKA/cAMP2.R2C2 REAC A B addmsg /kinetics/PKA/cAMP-bind-site-A1 /kinetics/PKA/cAMP3.R2C2 REAC B A addmsg /kinetics/PKA/cAMP-bind-site-A2 /kinetics/PKA/cAMP3.R2C2 REAC A B addmsg /kinetics/PKA/cAMP-bind-site-A2 /kinetics/PKA/cAMP4.R2C2 REAC B A addmsg /kinetics/PKA/Release-C1 /kinetics/PKA/cAMP4.R2C2 REAC A B addmsg /kinetics/PKA/Release-C1 /kinetics/PKA/cAMP4.R2C REAC B A addmsg /kinetics/PKA/Release-C2 /kinetics/PKA/cAMP4.R2C REAC A B addmsg /kinetics/PKA/Release-C2 /kinetics/PKA/cAMP4.R2 REAC B A addmsg /kinetics/PKA/cAMP-bind-site-B1 /kinetics/cAMP REAC A B addmsg /kinetics/PKA/cAMP-bind-site-B2 /kinetics/cAMP REAC A B addmsg /kinetics/PKA/cAMP-bind-site-A1 /kinetics/cAMP REAC A B addmsg /kinetics/PKA/cAMP-bind-site-A2 /kinetics/cAMP REAC A B addmsg /kinetics/PKA/Release-C1 /kinetics/PKA-active REAC B A addmsg /kinetics/PKA/Release-C2 /kinetics/PKA-active REAC B A addmsg /kinetics/PKA/inhib-PKA /kinetics/PKA-active REAC A B enddump // End of dump call /edit/draw/tree RESET reset