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Molecule Parameter List for cAMP | The statistics table lists the distribution of a molecule acting either as a substrate, product, enzyme or as a molecule within the network.
The text color of a molecule is highlighted by  color. | | Statistics |
Accession and Pathway Details | |
| Accession Name | Accession No. | Accession Type | Pathway Link | AMPAR_traff_
model1 | 60 | Network |
Shared_Object_AMPAR_traff_model1, CaMKII, CaM,
PP1, PP2B, PP1_PSD,
PKA, AC, AMPAR,
AMPAR_memb | | This is the basic model of AMPAR trafficking bistability. It is based on Hayer and Bhalla, PLoS Comput. Biol. 2005. It includes the degradation and turnover of AMPARs. The CaMKII portion of the model is not bistable. |
cAMP acting as a Molecule in AMPAR_traff_model1 Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | cAMP | AMPAR_traff_
model1
Accession No. : 60 | AC
Pathway No. : 251 | 0 | 0.09 | No | | The conc of this has been a problem. Schaecter and Benowitz use 50 uM, but Shinomura et al have < 5. So I have altered the cAMP-dependent rates in the PKA model to reflect this. |
cAMP acting as a Substrate for an Enzyme in AMPAR_traff_model1 Network
| | Enzyme Molecule /
Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | | 1 | cAMP-PDE /
PDE | AMPAR_traff_
model1
Accession No. : 60 | AC
Pathway No. : 251 | 19.8411 | 10 | 4 | explicit E-S complex | Substrate
cAMP
Product
AMP
| | | 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 | | 2 | cAMP-PDE* /
PDE* | AMPAR_traff_
model1
Accession No. : 60 | AC
Pathway No. : 251 | 19.8413 | 20 | 4 | explicit E-S complex | Substrate
cAMP
Product
AMP
| | | 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. | | 3 | PDE1 /
PDE1 | AMPAR_traff_
model1
Accession No. : 60 | AC
Pathway No. : 251 | 39.6999 | 1.667 | 4.0012 | explicit E-S complex | Substrate
cAMP
Product
AMP
| | | Rate is 1/6 of the CaM stim form. We'll just reduce all lf k1, k2, k3 so that the Vmax goes down 1/6. | | 4 | CaM.PDE1 /
CaM.PDE1 | AMPAR_traff_
model1
Accession No. : 60 | AC
Pathway No. : 251 | 39.6831 | 10 | 4 | explicit E-S complex | Substrate
cAMP
Product
AMP
| | | Max activity ~10umol/min/mg in presence of lots of CaM. Affinity is low, 40 uM. k3 = 10, k2 = 40, k1 = (50/40) / 6e5. |
cAMP acting as a Product of an Enzyme in AMPAR_traff_model1 Network
| | Enzyme Molecule /
Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | | 1 | AC1-CaM /
kenz | AMPAR_traff_
model1
Accession No. : 60 | AC
Pathway No. : 251 | 299.998 | 4.5 | 4 | Classical Michaelis-Menten
V = Etot.S.Kcat/Km+S | Substrate
ATP
Product
cAMP
| | | 17 Feb 2005 Halved Vmax as the amount of enzyme has been doubled to get an integer value in the spine. 18 Feb 2005. Updated Km from BRENDA: EC No 4.6.1.1 Rat Km: 0.95 mM Turnover 12/sec. Human Km: 0.3 mM 12 umol/min/mg for mammalia, turnover is 12/sec See PMID 8663304 by Dessauer and Gilman JBC 271 1996 Unfortunately turnover range is from 34 down to 0.1 in different studies, according to BRENDA. | | 2 | AC2* /
kenz | AMPAR_traff_
model1
Accession No. : 60 | AC
Pathway No. : 251 | 300.002 | 2 | 4 | Classical Michaelis-Menten
V = Etot.S.Kcat/Km+S | Substrate
ATP
Product
cAMP
| | | Reduced Km to match expt data for basal activation of AC2 by PKC. Now k1 = 2.9e-6, k2 = 72, k3 = 18 18 Feb: Raised Km to 300 based on BRENDA data. Unlikely to make much difference, given the vast amount of ATP. |
cAMP acting as a Substrate in a reaction in AMPAR_traff_model1 Network
| Kd is calculated only for second order reactions, like nA+nB <->nC or nA<->nC+nD, where n is number and A,B,C,D are molecules, where as for first order reactions Keq is calculated.
Kd for higher order reaction are not consider. |
| | Name | Accession Name | Pathway Name | Kf | Kb | Kd | tau | Reagents | | 1 | cAMP-bind-site-B
1 | AMPAR_traff_
model1
Accession No. : 60 | PKA
Pathway No. : 250 | 54
(uM^-1 s^-1) | 33
(s^-1) | Kd(bf) = 0.6111(uM) | - | Substrate
R2C2
cAMP
Product
R2C2-cAMP
| | | 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. | | 2 | cAMP-bind-site-B
2 | AMPAR_traff_
model1
Accession No. : 60 | PKA
Pathway No. : 250 | 54
(uM^-1 s^-1) | 33
(s^-1) | Kd(bf) = 0.6111(uM) | - | Substrate
R2C2-cAMP
cAMP
Product
R2C2-cAMP2
| | | 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 | | 3 | cAMP-bind-site-A
1 | AMPAR_traff_
model1
Accession No. : 60 | PKA
Pathway No. : 250 | 75.0006
(uM^-1 s^-1) | 110
(s^-1) | Kd(bf) = 1.4667(uM) | - | Substrate
R2C2-cAMP2
cAMP
Product
R2C2-cAMP3
| | 4 | cAMP-bind-site-A
2 | AMPAR_traff_
model1
Accession No. : 60 | PKA
Pathway No. : 250 | 75.0006
(uM^-1 s^-1) | 32.5
(s^-1) | Kd(bf) = 0.4333(uM) | - | Substrate
R2C2-cAMP3
cAMP
Product
R2C2-cAMP4
| | 5 | cAMP_diffusion | AMPAR_traff_
model1
Accession No. : 60 | AC
Pathway No. : 251 | 300
(s^-1) | 5.4
(s^-1) | Not applicable** | - | Substrate
cAMP
Product
cAMP_in_dend
| | | Represents diffusion, from a volume of 9e-20 to 5e-18. Assuming neck dimensions of 0.1 x 0.1 microns, this works out to a diffusion const of about 270 um^2/sec, which is pretty conservative. It is what cAMP does in frog cilia. |
** This is a trasport reation between compartments of different volumes. Therefore Kd is not applicable. Please Note Kf, Kb units are in number of molecules instead of concentration
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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