MODEL9079740062
type: SBMLModel
reaction: 931514
volume units: 679943
units def: 202139
species: 930734
reaction: 931334
reaction: 931234
reaction: 931374
reaction: 931474
reaction: 931274
species: 930774
reaction: 931574
species: 930594
time units: 131570
name: Bhalla2004_PKA_2003
reaction: 931534
species: 930914
area units: area
reaction: 931354
reaction: 931154
reaction: 931394
species: 930674
length unit: length
units def: 202090
notes: This model consists of receptor-ligand interaction, G-protein activation, Adenylyl cyclase mediated formation of cAMP and activation of PKA in the neuron. Demonstration programs using this model described in Bhalla US. (2004) Biophys J. 87(2):733-44 to generate a dose-response curve using stochastic calculations are available here. 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.
reaction: 931314
species: 930794
units def: 202016
species: 931094
substance units: 202187
compartment: 930554
species: 931114
species: 930854
reaction: 931254
species: 931014
is described by: http://identifiers.org/pubmed/15298882
species: 930634
species: 931054
species: 930974
reaction: 931194
reaction: 931434
units def: 202053
species: 931074
species: 930694
reaction: 931214
species: 930754
species: 930574
reaction: 931294
species: 930934
species: 930834
species: 931134
compartment: 930536
species: 930874
species: 930814
units def: 202187
species: 930894
reaction: 931174
reaction: 931414
species: 931034
species: 930654
species: 930954
species: 930714
species: 930994
reaction: 931594
reaction: 931554
species: 930614
reaction: 931494
reaction: 931454
curated: false

931514
type: Reaction
kinetic law: 203109
product: 203097
reactant: 203085
reactant: 203073
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

203109
type: KineticLaw
local parameters: 298034
local parameters: 298033
notes: k1*cAMP*AC_slash_cAMP_minus_PDE-k2*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx

298034
type: LocalParameter
units: 202053
value: 4.0E-11

202078
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND

202066
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE

298033
type: LocalParameter
units: 202139
value: 2.52E-12

202175
type: SBMLUnit
exponent: -1.0
scale: 0
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kind: SECOND

202163
type: SBMLUnit
exponent: -1.0
scale: -6
multipler: 1.0
kind: MOLE

202151
type: SBMLUnit
exponent: 2.0
scale: 0
multipler: 1.0
kind: LITRE

203097
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stoichiometry: 1.0
species: 930834

930834
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

930554
type: Compartment
constant: true
size: 1.0E-12
spatial dimensions: 3.0

203085
type: SpeciesReference
stoichiometry: 1.0
species: 930814

930814
type: Species
constant: false
boundary condition: false
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initial concentration: 0.5
initial amount: NaN
in compartment: 930554

203073
type: SpeciesReference
stoichiometry: 1.0
species: 930754

930754
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

930734
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

931334
type: Reaction
kinetic law: 202675
product: 202662
reactant: 202649
reactant: 202637
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

202675
type: KineticLaw
local parameters: 298002
local parameters: 298000
notes: kf*Gs_slash_R*Gs_slash_L-kb*Gs_slash_L_dot_R

298002
type: LocalParameter
units: 202053
value: 1.0E-13

298000
type: LocalParameter
units: 202139
value: 1.00002E-13

202662
type: SpeciesReference
stoichiometry: 1.0
species: 930974

930974
type: Species
constant: false
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has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

202649
type: SpeciesReference
stoichiometry: 1.0
species: 931134

931134
type: Species
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: 0.0
initial amount: NaN
in compartment: 930554

202637
type: SpeciesReference
stoichiometry: 1.0
species: 930954

930954
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0833333333333333
initial amount: NaN
in compartment: 930554

931234
type: Reaction
kinetic law: 202441
product: 202429
product: 202417
reactant: 202405
notes: This has to be fast, as the activation of PKA by cAMP is also fast. kf was 10
fast: false
reversible: true

202441
type: KineticLaw
local parameters: 297989
local parameters: 297988
notes: kf*PKA_slash_cAMP4_dot_R2C2-kb*PKA_minus_active*PKA_slash_cAMP4_dot_R2C

297989
type: LocalParameter
units: 202139
value: 1.8E-11

297988
type: LocalParameter
units: 202053
value: 6.0E-11

202429
type: SpeciesReference
stoichiometry: 1.0
species: 930714

930714
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

202417
type: SpeciesReference
stoichiometry: 1.0
species: 930774

930774
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

202405
type: SpeciesReference
stoichiometry: 1.0
species: 930694

930694
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

931374
type: Reaction
kinetic law: 202783
product: 202771
reactant: 202759
reactant: 202747
notes: Negligible back-reaction.
fast: false
reversible: true

202783
type: KineticLaw
local parameters: 298010
local parameters: 298008
notes: kf*Gs_slash_GDP_dot_Ga*Gs_slash_Gbg-kb*Gs_slash_GDP_dot_Gabc

298010
type: LocalParameter
units: 202053
value: 0.0

298008
type: LocalParameter
units: 202139
value: 6.0E-12

202771
type: SpeciesReference
stoichiometry: 1.0
species: 930994

930994
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 930554

202759
type: SpeciesReference
stoichiometry: 1.0
species: 931054

931054
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

202747
type: SpeciesReference
stoichiometry: 1.0
species: 931034

931034
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

931474
type: Reaction
kinetic law: 203012
product: 203000
reactant: 202988
reactant: 202976
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

203012
type: KineticLaw
local parameters: 298030
local parameters: 298028
notes: k1*AC_slash_cAMP_minus_PDE*PKA_minus_active-k2*PKA_minus_active_slash_phosph_minus_PDE_slash_phosph_minus_PDE_cplx

298030
type: LocalParameter
units: 202053
value: 3.6E-11

298028
type: LocalParameter
units: 202139
value: 6.0E-12

203000
type: SpeciesReference
stoichiometry: 1.0
species: 930794

930794
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

202988
type: SpeciesReference
stoichiometry: 1.0
species: 930774

202976
type: SpeciesReference
stoichiometry: 1.0
species: 930814

931274
type: Reaction
kinetic law: 202539
product: 202526
reactant: 202514
reactant: 202502
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

202539
type: KineticLaw
local parameters: 297993
local parameters: 297992
notes: kf*PKA_minus_active*PKA_slash_PKA_minus_inhibitor-kb*PKA_slash_inhibited_minus_PKA

297993
type: LocalParameter
units: 202053
value: 1.0E-12

297992
type: LocalParameter
units: 202139
value: 6.0E-11

202526
type: SpeciesReference
stoichiometry: 1.0
species: 930614

930614
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

202514
type: SpeciesReference
stoichiometry: 1.0
species: 930594

930594
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.25
initial amount: NaN
in compartment: 930554

202502
type: SpeciesReference
stoichiometry: 1.0
species: 930774

931574
type: Reaction
kinetic law: 203229
product: 203217
reactant: 203205
fast: false
reversible: false

203229
type: KineticLaw
local parameters: 298038
notes: k3*AC_slash_cAMP_minus_PDE_star__slash_PDE_star__slash_PDE_star__cplx

298038
type: LocalParameter
units: 202053
value: 2.0E-11

203217
type: SpeciesReference
stoichiometry: 1.0
species: 930854

930854
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

203205
type: SpeciesReference
stoichiometry: 1.0
species: 930874

930874
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

931534
type: Reaction
kinetic law: 203145
product: 203133
reactant: 203121
fast: false
reversible: false

203145
type: KineticLaw
local parameters: 298035
notes: k3*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx

298035
type: LocalParameter
units: 202053
value: 1.0E-11

203133
type: SpeciesReference
stoichiometry: 1.0
species: 930814

203121
type: SpeciesReference
stoichiometry: 1.0
species: 930834

930914
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.015
initial amount: NaN
in compartment: 930554

931354
type: Reaction
reactant: 202687
kinetic law: 202735
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.
reversible: true
product: 202711
product: 202699
fast: false
product: 202723

202687
type: SpeciesReference
stoichiometry: 1.0
species: 931014

931014
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

202735
type: KineticLaw
local parameters: 298006
local parameters: 298004
notes: kf*Gs_slash_L_dot_R_dot_GDP_dot_Gabc-kb*Gs_slash_Gbg*Gs_slash_L_dot_R*GTP_dot_Ga

298006
type: LocalParameter
units: 202090
value: 0.0

202127
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND

202114
type: SBMLUnit
exponent: -2.0
scale: -6
multipler: 1.0
kind: MOLE

202102
type: SBMLUnit
exponent: 3.0
scale: 0
multipler: 1.0
kind: LITRE

298004
type: LocalParameter
units: 202053
value: 2.5E-14

202711
type: SpeciesReference
stoichiometry: 1.0
species: 930974

202699
type: SpeciesReference
stoichiometry: 1.0
species: 931054

202723
type: SpeciesReference
stoichiometry: 1.0
species: 930934

930934
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

931154
type: Reaction
kinetic law: 202247
product: 202235
reactant: 202223
reactant: 202211
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

202247
type: KineticLaw
local parameters: 297981
local parameters: 297980
notes: kf*PKA_slash_R2C2*cAMP-kb*PKA_slash_cAMP_dot_R2C2

297981
type: LocalParameter
units: 202053
value: 3.3E-11

297980
type: LocalParameter
units: 202139
value: 5.4E-11

202235
type: SpeciesReference
stoichiometry: 1.0
species: 930634

930634
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

202223
type: SpeciesReference
stoichiometry: 1.0
species: 930754

202211
type: SpeciesReference
stoichiometry: 1.0
species: 930574

930574
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 930554

931394
type: Reaction
kinetic law: 202820
product: 202808
reactant: 202795
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

202820
type: KineticLaw
local parameters: 298014
local parameters: 298012
notes: kf*GTP_dot_Ga-kb*Gs_slash_GDP_dot_Ga

298014
type: LocalParameter
units: 202053
value: 0.0

298012
type: LocalParameter
units: 202053
value: 6.6667E-14

202808
type: SpeciesReference
stoichiometry: 1.0
species: 931034

202795
type: SpeciesReference
stoichiometry: 1.0
species: 930934

930674
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

931314
type: Reaction
kinetic law: 202624
product: 202612
reactant: 202600
reactant: 202588
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

202624
type: KineticLaw
local parameters: 297998
local parameters: 297996
notes: kf*AC_slash_AC*GTP_dot_Ga-kb*AC_slash_Gs_dot_AC

297998
type: LocalParameter
units: 202053
value: 1.0E-12

297996
type: LocalParameter
units: 202139
value: 4.99998E-10

202612
type: SpeciesReference
stoichiometry: 1.0
species: 930894

930894
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

202600
type: SpeciesReference
stoichiometry: 1.0
species: 930934

202588
type: SpeciesReference
stoichiometry: 1.0
species: 930914

202040
type: SBMLUnit
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE

202028
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE

931094
type: Species
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: 930554

202199
type: SBMLUnit
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE

931114
type: Species
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: 930554

931254
type: Reaction
kinetic law: 202489
product: 202477
product: 202465
reactant: 202453
fast: false
reversible: true

202489
type: KineticLaw
local parameters: 297991
local parameters: 297990
notes: kf*PKA_slash_cAMP4_dot_R2C-kb*PKA_minus_active*PKA_slash_cAMP4_dot_R2

297991
type: LocalParameter
units: 202139
value: 1.8E-11

297990
type: LocalParameter
units: 202053
value: 6.0E-11

202477
type: SpeciesReference
stoichiometry: 1.0
species: 930734

202465
type: SpeciesReference
stoichiometry: 1.0
species: 930774

202453
type: SpeciesReference
stoichiometry: 1.0
species: 930714

931194
type: Reaction
kinetic law: 202345
product: 202333
reactant: 202321
reactant: 202308
fast: false
reversible: true

202345
type: KineticLaw
local parameters: 297985
local parameters: 297984
notes: kf*PKA_slash_cAMP2_dot_R2C2*cAMP-kb*PKA_slash_cAMP3_dot_R2C2

297985
type: LocalParameter
units: 202053
value: 1.1E-10

297984
type: LocalParameter
units: 202139
value: 7.5E-11

202333
type: SpeciesReference
stoichiometry: 1.0
species: 930674

202321
type: SpeciesReference
stoichiometry: 1.0
species: 930754

202308
type: SpeciesReference
stoichiometry: 1.0
species: 930654

930654
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

931434
type: Reaction
kinetic law: 202916
product: 202904
reactant: 202892
reactant: 202880
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

202916
type: KineticLaw
local parameters: 298022
local parameters: 298020
notes: kf*Gs_slash_GDP_dot_Gabc*Gs_slash_R-kb*Gs_slash_R_dot_GDP_dot_Gabc

298022
type: LocalParameter
units: 202053
value: 1.0E-13

298020
type: LocalParameter
units: 202139
value: 1.99998E-13

202904
type: SpeciesReference
stoichiometry: 1.0
species: 931074

931074
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 930554

202892
type: SpeciesReference
stoichiometry: 1.0
species: 930954

202880
type: SpeciesReference
stoichiometry: 1.0
species: 930994

931214
type: Reaction
kinetic law: 202393
product: 202381
reactant: 202369
reactant: 202357
fast: false
reversible: true

202393
type: KineticLaw
local parameters: 297987
local parameters: 297986
notes: kf*cAMP*PKA_slash_cAMP3_dot_R2C2-kb*PKA_slash_cAMP4_dot_R2C2

297987
type: LocalParameter
units: 202053
value: 3.25E-11

297986
type: LocalParameter
units: 202139
value: 7.5E-11

202381
type: SpeciesReference
stoichiometry: 1.0
species: 930694

202369
type: SpeciesReference
stoichiometry: 1.0
species: 930674

202357
type: SpeciesReference
stoichiometry: 1.0
species: 930754

931294
type: Reaction
kinetic law: 202575
product: 202563
reactant: 202551
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

202575
type: KineticLaw
local parameters: 297995
local parameters: 297994
notes: kf*AC_slash_cAMP_minus_PDE_star_-kb*AC_slash_cAMP_minus_PDE

297995
type: LocalParameter
units: 202053
value: 0.0

297994
type: LocalParameter
units: 202053
value: 1.0E-13

202563
type: SpeciesReference
stoichiometry: 1.0
species: 930814

202551
type: SpeciesReference
stoichiometry: 1.0
species: 930854

930536
type: Compartment
constant: true
size: 1.0E-18
spatial dimensions: 3.0

931174
type: Reaction
kinetic law: 202296
product: 202284
reactant: 202272
reactant: 202260
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

202296
type: KineticLaw
local parameters: 297983
local parameters: 297982
notes: kf*PKA_slash_cAMP_dot_R2C2*cAMP-kb*PKA_slash_cAMP2_dot_R2C2

297983
type: LocalParameter
units: 202053
value: 3.3E-11

297982
type: LocalParameter
units: 202139
value: 5.4E-11

202284
type: SpeciesReference
stoichiometry: 1.0
species: 930654

202272
type: SpeciesReference
stoichiometry: 1.0
species: 930754

202260
type: SpeciesReference
stoichiometry: 1.0
species: 930634

931414
type: Reaction
kinetic law: 202868
product: 202856
reactant: 202844
reactant: 202832
notes: From Seifert et al Mol. Pharmacol 56:348-358 (1999) The EC50 for ISO is about 20 nM.
fast: false
reversible: true

202868
type: KineticLaw
local parameters: 298018
local parameters: 298016
notes: kf*Gs_slash_L*Gs_slash_R_dot_GDP_dot_Gabc-kb*Gs_slash_L_dot_R_dot_GDP_dot_Gabc

298018
type: LocalParameter
units: 202053
value: 1.0E-13

298016
type: LocalParameter
units: 202139
value: 4.99998E-12

202856
type: SpeciesReference
stoichiometry: 1.0
species: 931014

202844
type: SpeciesReference
stoichiometry: 1.0
species: 931074

202832
type: SpeciesReference
stoichiometry: 1.0
species: 931134

931594
type: Reaction
kinetic law: 203278
modifier: 203266
product: 203254
reactant: 203241
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

203278
type: KineticLaw
local parameters: 298042
local parameters: 298040
notes: kcat*AC_slash_Gs_dot_AC*AC_slash_ATP/(Km+AC_slash_ATP)

298042
type: LocalParameter
units: 202016
value: 20.0

298040
type: LocalParameter
units: 202053
value: 1.8E-11

203254
type: SpeciesReference
stoichiometry: 1.0
species: 930754

203241
type: SpeciesReference
stoichiometry: 1.0
species: 931094

931554
type: Reaction
kinetic law: 203193
product: 203181
reactant: 203169
reactant: 203157
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

203193
type: KineticLaw
local parameters: 298037
local parameters: 298036
notes: k1*cAMP*AC_slash_cAMP_minus_PDE_star_-k2*AC_slash_cAMP_minus_PDE_star__slash_PDE_star__slash_PDE_star__cplx

298037
type: LocalParameter
units: 202053
value: 8.0E-11

298036
type: LocalParameter
units: 202139
value: 5.04E-12

203181
type: SpeciesReference
stoichiometry: 1.0
species: 930874

203169
type: SpeciesReference
stoichiometry: 1.0
species: 930854

203157
type: SpeciesReference
stoichiometry: 1.0
species: 930754

931494
type: Reaction
kinetic law: 203061
product: 203048
product: 203036
reactant: 203024
fast: false
reversible: false

203061
type: KineticLaw
local parameters: 298032
notes: k3*PKA_minus_active_slash_phosph_minus_PDE_slash_phosph_minus_PDE_cplx

298032
type: LocalParameter
units: 202053
value: 9.0E-12

203048
type: SpeciesReference
stoichiometry: 1.0
species: 930774

203036
type: SpeciesReference
stoichiometry: 1.0
species: 930854

203024
type: SpeciesReference
stoichiometry: 1.0
species: 930794

931454
type: Reaction
kinetic law: 202964
product: 202952
reactant: 202940
reactant: 202928
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

202964
type: KineticLaw
local parameters: 298026
local parameters: 298024
notes: kf*Gs_slash_GDP_dot_Gabc*Gs_slash_L_dot_R-kb*Gs_slash_L_dot_R_dot_GDP_dot_Gabc

298026
type: LocalParameter
units: 202053
value: 1.0E-13

298024
type: LocalParameter
units: 202139
value: 1.00002E-11

202952
type: SpeciesReference
stoichiometry: 1.0
species: 931014

202940
type: SpeciesReference
stoichiometry: 1.0
species: 930974

202928
type: SpeciesReference
stoichiometry: 1.0
species: 930994