// DOQCS :http://doqcs.ncbs.res.in/
// Accession Name = cAMP_pathway
// Accession Number = 25
// Pathway Name = AC
// Pathway Number = 136
// Transcriber = Upinder S. Bhalla, NCBS
// Developer = Upinder S. Bhalla, NCBS
// Species = Generic mammalian
// Tissue = Brain - Neuronal
// Cell Compartment = Cell membrane + Cytosol
// Notes = Adenylyl cyclase, also known as adenylate cyclase. There are some ten isoforms, but here I represent only the canonical Gs-stimulated activity.
//genesis
// kkit Version 11 flat dumpfile
// Saved on Fri Dec 9 17:08:32 2005
include kkit {argv 1}
FASTDT = 0.001
SIMDT = 0.001
CONTROLDT = 1
PLOTDT = 1
MAXTIME = 300
TRANSIENT_TIME = 2
VARIABLE_DT_FLAG = 0
DEFAULT_VOL = 1.6667e-21
VERSION = 11.0
setfield /file/modpath value /home2/bhalla/scripts/modules
kparms
//genesis
initdump -version 3 -ignoreorphans 1
simobjdump doqcsinfo filename accessname accesstype transcriber developer \
citation species tissue cellcompartment methodology sources \
model_implementation model_validation x y z
simobjdump table input output alloced step_mode stepsize x y z
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 group xtree_fg_req xtree_textfg_req plotfield expanded movealone \
link savename file version md5sum mod_save_flag x y z
simobjdump geometry size dim shape outside xtree_fg_req xtree_textfg_req x y \
z
simobjdump kpool DiffConst CoInit Co n nInit mwt nMin vol slave_enable \
geomname xtree_fg_req xtree_textfg_req x y z
simobjdump kreac kf kb notes xtree_fg_req xtree_textfg_req x y z
simobjdump kenz CoComplexInit CoComplex nComplexInit nComplex vol k1 k2 k3 \
keepconc usecomplex notes xtree_fg_req xtree_textfg_req link x y z
simobjdump stim level1 width1 delay1 level2 width2 delay2 baselevel trig_time \
trig_mode notes xtree_fg_req xtree_textfg_req is_running x y z
simobjdump xtab input output alloced step_mode stepsize notes editfunc \
xtree_fg_req xtree_textfg_req baselevel last_x last_y is_running x y z
simobjdump kchan perm gmax Vm is_active use_nernst notes xtree_fg_req \
xtree_textfg_req x y z
simobjdump transport input output alloced step_mode stepsize dt delay clock \
kf xtree_fg_req xtree_textfg_req x y z
simobjdump proto x y z
simundump geometry /kinetics/geometry 0 1e-15 3 sphere "" white black 6 -11 0
simundump group /kinetics/AC 1 blue blue x 0 0 "" defaultfile defaultfile.g 0 \
0 0 1.1996 -16.551 0
simundump kpool /kinetics/AC/ATP 1 0 5000 5000 3e+09 3e+09 0 0 6e+05 4 \
/kinetics/geometry red blue 2.767 -14.295 0
simundump kpool /kinetics/AC/AMP 1 0 1000 1000 6e+08 6e+08 0 0 6e+05 4 \
/kinetics/geometry pink blue -0.03125 -14.261 0
simundump kpool /kinetics/AC/cAMP-PDE 1 0 0.5 0.5 3e+05 3e+05 0 0 6e+05 0 \
/kinetics/geometry green blue -2.4541 -14.124 0
simundump kenz /kinetics/AC/cAMP-PDE/PDE 1 0 0 0 0 6e+05 4.2e-06 40 10 0 0 "" \
red green "" -2.4562 -15.532 0
simundump kpool /kinetics/AC/cAMP-PDE* 1 0 0 0 0 0 0 0 6e+05 0 \
/kinetics/geometry green blue -2.0655 -19.04 0
simundump kenz /kinetics/AC/cAMP-PDE*/PDE* 1 0 0 0 0 6e+05 8.4e-06 80 20 0 0 \
"" red green "" -2.0446 -17.996 0
simundump kreac /kinetics/AC/dephosph-PDE 1 0.1 0 "" white blue -5.5595 \
-15.426 0
simundump kpool /kinetics/AC/Gs.AC 1 0 0 0 0 0 0 0 6e+05 0 /kinetics/geometry \
yellow blue 3.4153 -19.161 0
simundump kenz /kinetics/AC/Gs.AC/cyclase 1 0 0 0 0 6e+05 7.5e-06 72 18 0 1 \
"" red yellow "" 3.3364 -18.153 0
simundump kpool /kinetics/AC/AC 1 0 0.015 0.015 9000 9000 0 0 6e+05 0 \
/kinetics/geometry yellow blue 6.1795 -19.161 0
simundump kreac /kinetics/AC/Gs-bind-AC 1 0.00083333 1 "" white blue 5.0694 \
-17.217 0
simundump kpool /kinetics/cAMP 1 0 0 0 0 0 0 0 6e+05 2 /kinetics/geometry \
green black 0.78774 -19.024 0
simundump kpool /kinetics/PKA-active 1 0 0 0 0 0 0 0 6e+05 0 \
/kinetics/geometry yellow black -5.3888 -19.058 0
simundump kenz /kinetics/PKA-active/phosph-PDE 1 0 0 0 0 6e+05 1e-05 36 9 0 0 \
"" red yellow "" -5.7447 -17.569 0
simundump kpool /kinetics/GTP.Ga 1 0 0 0 0 0 0 0 6e+05 2 /kinetics/geometry \
red black 5 -13 0
simundump doqcsinfo /kinetics/doqcsinfo 0 pdb136.g AC pathway \
"Upinder S. Bhalla, NCBS" "Upinder S. Bhalla, NCBS" "citation here" \
"Generic Mammalian" "Brain - Neuronal" "Cell membrane + Cytosol" \
"Quantitative match to experiments, Quallitative" \
"Bhalla US Methods Enzymol. 2002;345:3-23 ( Peer-reviewed publication )" \
"Exact GENESIS implementation" "Approximates original data " 4 -11 0
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 -7.7447 8.1795 -21.161 -6
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 \
"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 /kinetics/AC/ATP/notes LOAD \
"ATP is present in all cells between 2 and 10 mM. " \
"See Lehninger. It is assumed buffered since the" \
"metabolic activity will take care of its levels."
call /kinetics/AC/AMP/notes LOAD \
"Assumed buffered to 1 mM. Value is irrelevant" \
"to simulation."
call /kinetics/AC/cAMP-PDE/notes LOAD \
"The levels of the PDE are not known at this time. However," \
"enough" \
"kinetic info and info about steady-state levels of cAMP" \
"etc are around" \
"to make it possible to estimate this at about 0.5 uM."
call /kinetics/AC/cAMP-PDE/PDE/notes LOAD \
"Best rates are from Conti et al Biochem 34 7979-7987 1995." \
"Though these" \
"are for the Sertoli cell form, it looks like they carry" \
"nicely into" \
"alternatively spliced brain form. See Sette et al" \
"JBC 269:28 18271-18274" \
"Km ~2 uM, Vmax est ~ 10 umol/min/mg for pure form." \
"Brain protein is 93 kD but this was 67." \
"So k3 ~10, k2 ~40, k1 ~4.2e-6"
call /kinetics/AC/cAMP-PDE*/notes LOAD \
"This form has about 2X activity as plain PDE. See Sette et al JBC 269:28" \
"18271-18274 1994."
call /kinetics/AC/cAMP-PDE*/PDE*/notes LOAD \
"This form has about twice the activity of the unphosphorylated form. See" \
"Sette et al JBC 269:28 18271-18274 1994." \
"We'll ignore cGMP effects for now."
call /kinetics/AC/dephosph-PDE/notes LOAD \
"The rates for this are poorly constrained. In adipocytes (probably a" \
"different PDE) the dephosphorylation is complete within 15 min, but" \
"there are no intermediate time points so it could be much faster. Identity" \
"of phosphatase etc is still unknown."
call /kinetics/AC/Gs.AC/notes LOAD \
"This is the active form of the cyclase." \
""
call /kinetics/AC/Gs.AC/cyclase/notes LOAD \
"See Feinstein et al PNAS 88:10173-10177," \
"Jacobowitz et al JBC 286(6):3829-3832" \
"Smigel, JBC 261(4):1976-1982 (1986)"
call /kinetics/AC/AC/notes LOAD \
"AC is present at rather low levels. Here we use" \
"0.015 uM which is meant to lump various isoforms." \
"None of the isoforms nor the other specific regulators" \
"are included here." \
"Jacobowitz, PhD thesis."
call /kinetics/AC/Gs-bind-AC/notes LOAD \
"Half-max at around 3nM = kb/kf from fig 5 in " \
"Feinstein et al PNAS USA 88 10173-10177 1991" \
"kf = kb/1800 = 5.56e-4 kb" \
"Ofer Jacobowitz thesis (Mount Sinai 1995) data indicates" \
"it is more like 2 nM." \
""
call /kinetics/cAMP/notes LOAD \
"Key second messenger."
call /kinetics/PKA-active/phosph-PDE/notes LOAD \
"See Bramson et al CRC crit rev Biochem 15:2 93-124." \
"The rates there are for peptide substrates and too fast." \
"Scaled down by a factor of 3 as per" \
"Cohen et al FEBS Lett 76:182-86 (1977)."
call /kinetics/doqcsinfo/notes LOAD \
" Adenylyl cyclase, also known as adenylate cyclase. There are some ten isoforms, but here I represent only the canonical Gs-stimulated activity."
complete_loading