| |
Reaction
Name | Pathway Name /
Pathway No. | Kf | Kb | Kd | tau | Reagents |
| 1 | Stoch_Basal_
CaMKII_PSD | CaMKII_PSD
Pathway No. 292 | 1
(s^-1) | 1
(s^-1) | Keq = 1(uM) | 0.5sec | Substrate:
basal_CaMKII_
PSD_control
Products:
basal_CaMKII_
PSD
|
| This reaction comes into play when stochastic calculations are used. If we do not have a stochastic step here then the levels of basal_CaMKII_PSD are just a fixed number, which is probably not a good representation of stochasticity. Having a reaction for the basal activity ensures that the basal activity too exhibits some fluctuations. | | 2 | CaMKII-diss-CaM | CaMKII_PSD
Pathway No. 292 | 5
(s^-1) | 0
(uM^-1 s^-1) | - | - | Substrate:
CaMKII-CaM-PSD
Products:
CaM-Ca4-PSD
CaMKII-PSD
|
| 3 | CaMKII-bind-CaM-
PSD | CaMKII_PSD
Pathway No. 292 | 49.9998
(uM^-1 s^-1) | 0
(s^-1) | - | - | Substrate:
CaMKII-PSD
CaM-Ca4-PSD
Products:
CaMKII-CaM-PSD
|
| 4 | CaMKII-thr286-bi
nd-CaM-PSD | CaMKII_PSD
Pathway No. 292 | 1000.02
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.0001(uM) | - | Substrate:
CaMKII-thr286-PS
D
CaM-Ca4-PSD
Products:
CaMKII-thr286-Ca
M-PSD
|
| Same values as for the main compartment Can the main compartment pool of Ca/CaM be used? | | 5 | back_2 | CaMKII_PSD
Pathway No. 292 | 0.3
(s^-1) | 0
(#^-1 s^-1) | Not applicable** | - | Substrate:
CaMKII-thr305-PS
D
Products:
CaMK-thr305
NMDAR
|
| Same as for back_1 | | 6 | back_1 | CaMKII_PSD
Pathway No. 292 | 0.3
(s^-1) | 0
(#^-1 s^-1) | Not applicable** | - | Substrate:
CaMKII-PSD
Products:
CaMKII
NMDAR
|
| Rates set by the translocation experiments of Shen and Meyer, Science 1999. Note that this reaction also incorporates a translocation between compartments of different volumes. | | 7 | transloc_1 | CaMKII_PSD
Pathway No. 292 | 0
(#^-1 s^-1) | 0
(s^-1) | Not applicable** | - | Substrate:
CaMKII-CaM
NMDAR
Products:
CaMKII-CaM-PSD
|
| Rates to match curve in fig2 from Shen and Meyer, Science 284:162-166(1999), calculated for 6:1 alpha:beta CaMKII heterodimers Note that this reaction also incorporates a translocation between compartments of different volumes. | | 8 | transloc_2 | CaMKII_PSD
Pathway No. 292 | 0
(#^-1 s^-1) | 0
(s^-1) | Not applicable** | - | Substrate:
CaMKII-thr286*-C
aM
NMDAR
Products:
CaMKII-thr286-Ca
M-PSD
|
| Same as for transloc_1 | | 9 | CaM-bind-AC1 | AC
Pathway No. 289 | 49.9997
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.02(uM) | - | Substrate:
CaM-Ca4
AC1
Products:
AC1-CaM
|
| Half-max at 20 nM CaM (Tang et al JBC 266:13 8595-8603 1991 kb/kf = 20 nM = 12000 #/cell so kf = kb/12000 = kb * 8.333e-5 | | 10 | dephosph-AC2 | AC
Pathway No. 289 | 0.1
(s^-1) | 0
(s^-1) | - | - | Substrate:
AC2*
Products:
AC2
|
| Random rate. | | 11 | dephosph-PDE | AC
Pathway No. 289 | 0.01
(s^-1) | 0
(s^-1) | - | - | Substrate:
cAMP-PDE*
Products:
cAMP-PDE
|
| 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. | | 12 | CaM_bind_PDE1 | AC
Pathway No. 289 | 719.982
(uM^-1 s^-1) | 5
(s^-1) | Kd(bf) = 0.0069(uM) | - | Substrate:
PDE1
CaM-Ca4
Products:
CaM.PDE1
|
| For olf epi PDE1, affinity is 7 nM. Assume same for brain. Reaction should be pretty fast. Assume kb = 5/sec. Then kf = 5 / (0.007 * 6e5) = 1.2e-3 | | 13 | cAMP_diffusion | AC
Pathway No. 289 | 300
(s^-1) | 5.4
(s^-1) | Not applicable** | - | Substrate:
cAMP
Products:
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. | | 14 | cAMP-bind-site-B
1 | PKA
Pathway No. 288 | 54
(uM^-1 s^-1) | 33
(s^-1) | Kd(bf) = 0.6111(uM) | - | Substrate:
R2C2
cAMP
Products:
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. | | 15 | cAMP-bind-site-B
2 | PKA
Pathway No. 288 | 54
(uM^-1 s^-1) | 33
(s^-1) | Kd(bf) = 0.6111(uM) | - | Substrate:
R2C2-cAMP
cAMP
Products:
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 | | 16 | cAMP-bind-site-A
1 | PKA
Pathway No. 288 | 75.0006
(uM^-1 s^-1) | 110
(s^-1) | Kd(bf) = 1.4667(uM) | - | Substrate:
R2C2-cAMP2
cAMP
Products:
R2C2-cAMP3
|
| 17 | cAMP-bind-site-A
2 | PKA
Pathway No. 288 | 75.0006
(uM^-1 s^-1) | 32.5
(s^-1) | Kd(bf) = 0.4333(uM) | - | Substrate:
cAMP
R2C2-cAMP3
Products:
R2C2-cAMP4
|
| 18 | Release-C1 | PKA
Pathway No. 288 | 60
(s^-1) | 17.9998
(uM^-1 s^-1) | Kd(cb) = 0.3(uM) | - | Substrate:
R2C2-cAMP4
Products:
PKA-active
R2C-cAMP4
|
| This has to be fast, as the activation of PKA by cAMP is also fast. kf was 10 | | 19 | Release-C2 | PKA
Pathway No. 288 | 60
(s^-1) | 17.9998
(uM^-1 s^-1) | Kd(cb) = 0.3(uM) | - | Substrate:
R2C-cAMP4
Products:
PKA-active
R2-cAMP4
|
| 20 | inhib-PKA | PKA
Pathway No. 288 | 59.9994
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.0167(uM) | - | Substrate:
PKA-active
PKA-inhibitor
Products:
inhibited-PKA
|
| This has to be set to zero for matching the expts in vitro. In vivo we need to consider the inhibition though. kf = 1e-5 kb = 1 |
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