259255
units: 182067
value: 1.1E-10
type: LocalParameter

182880
local parameters: 259277
local parameters: 259276
notes: kf*Gs_slash_L*Gs_slash_R_dot_GDP_dot_Gabc-kb*Gs_slash_L_dot_R_dot_GDP_dot_Gabc
type: KineticLaw

183014
stoichiometry: 1.0
species: 899237
type: SpeciesReference

259264
units: 182067
value: 1.0E-13
type: LocalParameter

183159
local parameters: 259320
notes: k3*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx
type: KineticLaw

183099
stoichiometry: 1.0
species: 899257
type: SpeciesReference

259254
units: 182151
value: 7.5E-11
type: LocalParameter

182965
stoichiometry: 1.0
species: 899457
type: SpeciesReference

183183
stoichiometry: 1.0
species: 899297
type: SpeciesReference

259256
units: 182151
value: 7.5E-11
type: LocalParameter

182540
stoichiometry: 1.0
species: 899057
type: SpeciesReference

899477
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

259266
units: 182151
value: 4.99998E-10
type: LocalParameter

182043
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

259314
units: 182067
value: 9.0E-12
type: LocalParameter

182600
stoichiometry: 1.0
species: 899357
type: SpeciesReference

259265
units: 182067
value: 0.0
type: LocalParameter

898982
constant: true
size: 1.0E-18
spatial dimensions: 3.0
type: Compartment

182527
stoichiometry: 1.0
species: 899037
type: SpeciesReference

182333
stoichiometry: 1.0
species: 899197
type: SpeciesReference

182892
stoichiometry: 1.0
species: 899437
type: SpeciesReference

259267
units: 182067
value: 1.0E-12
type: LocalParameter

182491
stoichiometry: 1.0
species: 899177
type: SpeciesReference

182794
local parameters: 259273
local parameters: 259272
notes: kf*Gs_slash_GDP_dot_Ga*Gs_slash_Gbg-kb*Gs_slash_GDP_dot_Gabc
type: KineticLaw

899676
kinetic law: 182830
product: 182818
reactant: 182806
notes: From Brandt and Ross JBC 261(4):1656-1664, rate is 4/min and is agonist independent. I treat this as irreversible.
fast: false
reversible: true
type: Reaction

259317
units: 182151
value: 2.52E-12
type: LocalParameter

182953
stoichiometry: 1.0
species: 899417
type: SpeciesReference

259327
units: 182031
value: 20.0
type: LocalParameter

899177
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

183002
stoichiometry: 1.0
species: 899217
type: SpeciesReference

259252
units: 182151
value: 5.4E-11
type: LocalParameter

182929
local parameters: 259279
local parameters: 259278
notes: kf*Gs_slash_GDP_dot_Gabc*Gs_slash_R-kb*Gs_slash_R_dot_GDP_dot_Gabc
type: KineticLaw

182612
stoichiometry: 1.0
species: 899377
type: SpeciesReference

899636
kinetic law: 182636
product: 182624
reactant: 182612
reactant: 182600
notes: 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.
fast: false
reversible: true
type: Reaction

899337
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

182055
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

183195
stoichiometry: 1.0
species: 899317
type: SpeciesReference

182394
stoichiometry: 1.0
species: 899137
type: SpeciesReference

259268
units: 182151
value: 1.00002E-13
type: LocalParameter

182515
stoichiometry: 1.0
species: 899217
type: SpeciesReference

899277
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

182345
stoichiometry: 1.0
species: 899117
type: SpeciesReference

259326
units: 182067
value: 1.8E-11
type: LocalParameter

899437
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 898997
type: Species

259253
units: 182067
value: 3.3E-11
type: LocalParameter

182868
stoichiometry: 1.0
species: 899457
type: SpeciesReference

182091
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

899377
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

259269
units: 182067
value: 1.0E-13
type: LocalParameter

899077
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

182418
stoichiometry: 1.0
species: 899137
type: SpeciesReference

182163
exponent: 2.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

259259
units: 182151
value: 1.8E-11
type: LocalParameter

183075
local parameters: 259314
notes: k3*PKA_minus_active_slash_phosph_minus_PDE_slash_phosph_minus_PDE_cplx
type: KineticLaw

899037
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.25
initial amount: NaN
in compartment: 898997
type: Species

899637
kinetic law: 182685
product: 182673
reactant: 182660
reactant: 182648
notes: Ligand binding to receptor. From Gether et al JBC 270:28268-28275 (1995) the binding to the purified receptor is at about 1 uM, but the conformational change only happens at 30 uM. We\'ll take 1 uM for this, since it is already much weaker binding than to the R.Gs complex. The time-course from this paper appears remarkably slow, based on physiological data I estimate more like 10 sec.
fast: false
reversible: true
type: Reaction

182941
stoichiometry: 1.0
species: 899437
type: SpeciesReference

899017
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 898997
type: Species

183207
local parameters: 259324
local parameters: 259321
notes: k1*cAMP*AC_slash_cAMP_minus_PDE_star_-k2*AC_slash_cAMP_minus_PDE_star__slash_PDE_star__slash_PDE_star__cplx
type: KineticLaw

899657
kinetic law: 182794
product: 182782
reactant: 182770
reactant: 182758
notes: Negligible back-reaction.
fast: false
reversible: true
type: Reaction

898997
constant: true
size: 1.0E-12
spatial dimensions: 3.0
type: Compartment

259325
units: 182067
value: 2.0E-11
type: LocalParameter

259279
units: 182067
value: 1.0E-13
type: LocalParameter

899616
kinetic law: 182552
product: 182540
reactant: 182527
reactant: 182515
notes: This has to be set to zero for matching the expts in vitro. In vivo we need to consider the inhibition though.
fast: false
reversible: true
type: Reaction

899397
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0833333333333333
initial amount: NaN
in compartment: 898997
type: Species

899237
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

899716
kinetic law: 183026
product: 183014
reactant: 183002
reactant: 182990
notes: 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).
fast: false
reversible: true
type: Reaction

899057
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

259311
units: 182067
value: 3.6E-11
type: LocalParameter

899697
kinetic law: 182977
product: 182965
reactant: 182953
reactant: 182941
notes: See Fay et al Biochem 30 5066-5075 1991. kf is 0.01/sec but does not account for Gs levels. kb is 0.0001/sec. The fraction of RG is about 50%, so we can estimate Kd at about the same as for Gs basal levels. This rate has to be faster since it has to feed GTP.Ga into the system faster than the GTPase. Waldhoer et al Mol Pharmacol 53:808-818 1988 say affinity for A1adenosine/Gi is 10 nM.
fast: false
reversible: true
type: Reaction

182503
local parameters: 259261
local parameters: 259260
notes: kf*PKA_slash_cAMP4_dot_R2C-kb*PKA_minus_active*PKA_slash_cAMP4_dot_R2
type: KineticLaw

259304
units: 182151
value: 1.00002E-11
type: LocalParameter

899776
kinetic law: 183291
modifier: 183279
product: 183267
reactant: 183255
notes: See Feinstein et al PNAS 88:10173-10177, Jacobowitz et al JBC 286(6):3829-3832 Smigel, JBC 261(4):1976-1982 (1986)
fast: false
reversible: false
type: Reaction

259324
units: 182067
value: 8.0E-11
type: LocalParameter

182211
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

182842
stoichiometry: 1.0
species: 899537
type: SpeciesReference

899677
kinetic law: 182880
product: 182868
reactant: 182855
reactant: 182842
notes: From Seifert et al Mol. Pharmacol 56:348-358 (1999) The EC50 for ISO is about 20 nM.
fast: false
reversible: true
type: Reaction

182576
stoichiometry: 1.0
species: 899257
type: SpeciesReference

899696
kinetic law: 182929
product: 182916
reactant: 182904
reactant: 182892
notes: Receptor binding to Gs. Scale it to the same slow rates described by Fay et al for L.R to L.R.G. From detailed balance, Kd is 50.
fast: false
reversible: true
type: Reaction

899717
kinetic law: 183075
product: 183062
product: 183050
reactant: 183038
fast: false
reversible: false
type: Reaction

182564
stoichiometry: 1.0
species: 899297
type: SpeciesReference

182855
stoichiometry: 1.0
species: 899516
type: SpeciesReference

183087
stoichiometry: 1.0
species: 899197
type: SpeciesReference

182406
local parameters: 259257
local parameters: 259256
notes: kf*cAMP*PKA_slash_cAMP3_dot_R2C2-kb*PKA_slash_cAMP4_dot_R2C2
type: KineticLaw

259257
units: 182067
value: 3.25E-11
type: LocalParameter

259276
units: 182151
value: 4.99998E-12
type: LocalParameter

259277
units: 182067
value: 1.0E-13
type: LocalParameter

899137
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

182990
stoichiometry: 1.0
species: 899257
type: SpeciesReference

183219
stoichiometry: 1.0
species: 899317
type: SpeciesReference

182139
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

259258
units: 182067
value: 6.0E-11
type: LocalParameter

182758
stoichiometry: 1.0
species: 899477
type: SpeciesReference

182552
local parameters: 259263
local parameters: 259262
notes: kf*PKA_minus_active*PKA_slash_PKA_minus_inhibitor-kb*PKA_slash_inhibited_minus_PKA
type: KineticLaw

182588
local parameters: 259265
local parameters: 259264
notes: kf*AC_slash_cAMP_minus_PDE_star_-kb*AC_slash_cAMP_minus_PDE
type: KineticLaw

259278
units: 182151
value: 1.99998E-13
type: LocalParameter

182079
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

183231
stoichiometry: 1.0
species: 899297
type: SpeciesReference

183171
stoichiometry: 1.0
species: 899197
type: SpeciesReference

182734
stoichiometry: 1.0
species: 899377
type: SpeciesReference

183243
local parameters: 259325
notes: k3*AC_slash_cAMP_minus_PDE_star__slash_PDE_star__slash_PDE_star__cplx
type: KineticLaw

182235
stoichiometry: 1.0
species: 899197
type: SpeciesReference

899457
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

182115
exponent: 3.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

899617
kinetic law: 182588
product: 182576
reactant: 182564
notes: 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.
fast: false
reversible: true
type: Reaction

259274
units: 182067
value: 6.6667E-14
type: LocalParameter

182467
stoichiometry: 1.0
species: 899157
type: SpeciesReference

182673
stoichiometry: 1.0
species: 899417
type: SpeciesReference

182709
stoichiometry: 1.0
species: 899497
type: SpeciesReference

899317
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

259309
units: 182151
value: 6.0E-12
type: LocalParameter

182272
stoichiometry: 1.0
species: 899077
type: SpeciesReference

183050
stoichiometry: 1.0
species: 899297
type: SpeciesReference

183147
stoichiometry: 1.0
species: 899257
type: SpeciesReference

183026
local parameters: 259311
local parameters: 259309
notes: k1*AC_slash_cAMP_minus_PDE*PKA_minus_active-k2*PKA_minus_active_slash_phosph_minus_PDE_slash_phosph_minus_PDE_cplx
type: KineticLaw

899497
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

259275
units: 182067
value: 0.0
type: LocalParameter

182916
stoichiometry: 1.0
species: 899516
type: SpeciesReference

182187
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

182320
stoichiometry: 1.0
species: 899097
type: SpeciesReference

182127
exponent: -2.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

899737
kinetic law: 183159
product: 183147
reactant: 183135
fast: false
reversible: false
type: Reaction

899357
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.015
initial amount: NaN
in compartment: 898997
type: Species

182648
stoichiometry: 1.0
species: 899397
type: SpeciesReference

183255
stoichiometry: 1.0
species: 899517
type: SpeciesReference

182746
local parameters: 259271
local parameters: 259270
notes: kf*Gs_slash_L_dot_R_dot_GDP_dot_Gabc-kb*Gs_slash_Gbg*Gs_slash_L_dot_R*GTP_dot_Ga
type: KineticLaw

182223
stoichiometry: 1.0
species: 899017
type: SpeciesReference

182830
local parameters: 259275
local parameters: 259274
notes: kf*GTP_dot_Ga-kb*Gs_slash_GDP_dot_Ga
type: KineticLaw

183062
stoichiometry: 1.0
species: 899217
type: SpeciesReference

259272
units: 182151
value: 6.0E-12
type: LocalParameter

183291
local parameters: 259327
local parameters: 259326
notes: kcat*AC_slash_Gs_dot_AC*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

899157
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

182479
stoichiometry: 1.0
species: 899217
type: SpeciesReference

899757
kinetic law: 183243
product: 183231
reactant: 183219
fast: false
reversible: false
type: Reaction

899197
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

183038
stoichiometry: 1.0
species: 899237
type: SpeciesReference

899736
kinetic law: 183123
product: 183111
reactant: 183099
reactant: 183087
notes: 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
fast: false
reversible: true
type: Reaction

259321
units: 182151
value: 5.04E-12
type: LocalParameter

183135
stoichiometry: 1.0
species: 899277
type: SpeciesReference

182806
stoichiometry: 1.0
species: 899377
type: SpeciesReference

899656
product: 182709
reactant: 182697
notes: This step combines several stages in GTP.Galpha release. From Berstein et al activation is at .35 - 0.7/min From Fay et al Biochem 30 5066-5075 1991 kf = .01/sec. From Brandt and Ross JBC 261(4):1656-1664 (1986) and Ransan et al Biochem J 283(2):519-524 (1992) rates around 2.5/min to 1.5/min are better.
product: 182721
reversible: true
fast: false
type: Reaction
kinetic law: 182746
product: 182734

259306
units: 182067
value: 1.0E-13
type: LocalParameter

182175
exponent: -1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

899417
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

259273
units: 182067
value: 0.0
type: LocalParameter

899097
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

182660
stoichiometry: 1.0
species: 899537
type: SpeciesReference

899297
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

259320
units: 182067
value: 1.0E-11
type: LocalParameter

182904
stoichiometry: 1.0
species: 899397
type: SpeciesReference

899756
kinetic law: 183207
product: 183195
reactant: 183183
reactant: 183171
notes: 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.
fast: false
reversible: true
type: Reaction

182443
stoichiometry: 1.0
species: 899157
type: SpeciesReference

182296
stoichiometry: 1.0
species: 899097
type: SpeciesReference

259250
units: 182151
value: 5.4E-11
type: LocalParameter

182697
stoichiometry: 1.0
species: 899457
type: SpeciesReference

259260
units: 182067
value: 6.0E-11
type: LocalParameter

182357
local parameters: 259255
local parameters: 259254
notes: kf*PKA_slash_cAMP2_dot_R2C2*cAMP-kb*PKA_slash_cAMP3_dot_R2C2
type: KineticLaw

MODEL9077438479
species: 899497
species: 899217
volume units: 679943
species: 899157
reaction: 899597
reaction: 899616
reaction: 899776
reaction: 899756
species: 899257
units def: 182151
species: 899437
species: 899536
species: 899377
reaction: 899657
species: 899137
reaction: 899736
time units: 131570
type: SBMLModel
compartment: 898997
species: 899317
reaction: 899596
species: 899077
species: 899097
reaction: 899617
reaction: 899637
reaction: 899696
species: 899457
species: 899197
reaction: 899717
reaction: 899577
species: 899037
species: 899337
reaction: 899636
species: 899537
species: 899516
units def: 182067
species: 899417
is described by: http://identifiers.org/pubmed/11665614
species: 899297
reaction: 899557
reaction: 899697
species: 899057
area units: area
units def: 182031
length unit: length
notes: This is a model of the canonical cAMP signaling pathway:<br">Ligand->Receptor->G-protein->Cyclase->cAMP->PKA. It also includes phosphodiesterases to balance out cAMP formation.Bhalla US Methods Enzymol. 2002;345:3-23 This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
species: 899237
species: 899177
reaction: 899677
units def: 182103
name: Bhalla2002_cAMP_pathway
reaction: 899716
species: 899017
reaction: 899757
species: 899117
reaction: 899576
species: 899517
species: 899277
species: 899477
curated: false
reaction: 899676
species: 899397
substance units: 182199
reaction: 899737
reaction: 899556
species: 899357
compartment: 898982
units def: 182199
reaction: 899656

182259
local parameters: 259251
local parameters: 259250
notes: kf*PKA_slash_R2C2*cAMP-kb*PKA_slash_cAMP_dot_R2C2
type: KineticLaw

899596
kinetic law: 182455
product: 182443
product: 182430
reactant: 182418
notes: This has to be fast, as the activation of PKA by cAMP is also fast. kf was 10
fast: false
reversible: true
type: Reaction

183267
stoichiometry: 1.0
species: 899197
type: SpeciesReference

182636
local parameters: 259267
local parameters: 259266
notes: kf*AC_slash_AC*GTP_dot_Ga-kb*AC_slash_Gs_dot_AC
type: KineticLaw

182430
stoichiometry: 1.0
species: 899217
type: SpeciesReference

182370
stoichiometry: 1.0
species: 899197
type: SpeciesReference

259270
units: 182067
value: 2.5E-14
type: LocalParameter

259251
units: 182067
value: 3.3E-11
type: LocalParameter

899217
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

259318
units: 182067
value: 4.0E-11
type: LocalParameter

259261
units: 182151
value: 1.8E-11
type: LocalParameter

182782
stoichiometry: 1.0
species: 899437
type: SpeciesReference

899257
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 898997
type: Species

259271
units: 182103
value: 0.0
type: LocalParameter

182818
stoichiometry: 1.0
species: 899477
type: SpeciesReference

183123
local parameters: 259318
local parameters: 259317
notes: k1*cAMP*AC_slash_cAMP_minus_PDE-k2*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx
type: KineticLaw

899577
kinetic law: 182406
product: 182394
reactant: 182382
reactant: 182370
fast: false
reversible: true
type: Reaction

182284
stoichiometry: 1.0
species: 899197
type: SpeciesReference

182455
local parameters: 259259
local parameters: 259258
notes: kf*PKA_slash_cAMP4_dot_R2C2-kb*PKA_minus_active*PKA_slash_cAMP4_dot_R2C
type: KineticLaw

259262
units: 182151
value: 6.0E-11
type: LocalParameter

182685
local parameters: 259269
local parameters: 259268
notes: kf*Gs_slash_R*Gs_slash_L-kb*Gs_slash_L_dot_R
type: KineticLaw

899516
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species

899536
notes: Assumed buffered to 1 mM. Value is irrelevant to simulation.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 1000.0
initial amount: NaN
in compartment: 898997
type: Species

182382
stoichiometry: 1.0
species: 899117
type: SpeciesReference

182624
stoichiometry: 1.0
species: 899337
type: SpeciesReference

182247
stoichiometry: 1.0
species: 899077
type: SpeciesReference

899557
kinetic law: 182308
product: 182296
reactant: 182284
reactant: 182272
notes: For now let us set this to the same Km (1e-7M) as site B. This gives kf/kb = .7e-7M * 1e6 / (6e5^2) : 1/(6e5^2) = 2e-13:2.77e-12 Smith et al have better values. They say that this is cooperative, so the consts are now kf/kb =8.3e-4
fast: false
reversible: true
type: Reaction

182770
stoichiometry: 1.0
species: 899497
type: SpeciesReference

182308
local parameters: 259253
local parameters: 259252
notes: kf*PKA_slash_cAMP_dot_R2C2*cAMP-kb*PKA_slash_cAMP2_dot_R2C2
type: KineticLaw

899576
kinetic law: 182357
product: 182345
reactant: 182333
reactant: 182320
fast: false
reversible: true
type: Reaction

182721
stoichiometry: 1.0
species: 899417
type: SpeciesReference

182977
local parameters: 259306
local parameters: 259304
notes: kf*Gs_slash_GDP_dot_Gabc*Gs_slash_L_dot_R-kb*Gs_slash_L_dot_R_dot_GDP_dot_Gabc
type: KineticLaw

259263
units: 182067
value: 1.0E-12
type: LocalParameter

899517
notes: 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.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 5000.0
initial amount: NaN
in compartment: 898997
type: Species

183111
stoichiometry: 1.0
species: 899277
type: SpeciesReference

899597
kinetic law: 182503
product: 182491
product: 182479
reactant: 182467
fast: false
reversible: true
type: Reaction

899537
notes: This ligand could be any of several which bind to the beta adrenergic receptor and other G-protein coupled receptors which activate AC. For the sake of argument, call it isoproterenol.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.01
initial amount: NaN
in compartment: 898997
type: Species

899556
kinetic law: 182259
product: 182247
reactant: 182235
reactant: 182223
notes: Hasler et al FASEB J 6:2734-2741 1992 say Kd =1e-7M for type II, 5.6e-8 M for type I. Take mean which comes to 2e-13 #/cell Smith et al PNAS USA 78:3 1591-1595 1981 have better data. First kf/kb=2.1e7/M = 3.5e-5 (#/cell). Ogreid and Doskeland Febs Lett 129:2 287-292 1981 have figs suggesting time course of complete assoc is < 1 min.
fast: false
reversible: true
type: Reaction

899117
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 898997
type: Species