| |
Reaction
Name | Pathway Name /
Pathway No. | Kf | Kb | Kd | tau | Reagents |
| 1 | transloc_2 | Shared_Object_
CaMKII_model3
Pathway No. 263 | 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 | | 2 | transloc_1 | Shared_Object_
CaMKII_model3
Pathway No. 263 | 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 | | 3 | Stoch_Basal_
CaMKII_PSD | Shared_Object_
CaMKII_model3
Pathway No. 263 | 1
(s^-1) | 1
(s^-1) | Keq = 1(uM) | 0.5sec | Substrate:
basal_CaMKII_
PSD_control
Products:
basal_CaMKII_
PSD
|
| 4 | Release-C2 | PKA
Pathway No. 270 | 60
(s^-1) | 17.9998
(uM^-1 s^-1) | Kd(cb) = 0.3(uM) | - | Substrate:
R2C-cAMP4
Products:
PKA-active
R2-cAMP4
|
| 5 | Release-C1 | PKA
Pathway No. 270 | 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 | | 6 | PKC-stoch-input | Shared_Object_
CaMKII_model3
Pathway No. 263 | 2.5
(s^-1) | 2.5
(s^-1) | Keq = 1(uM) | 0.2sec | Substrate:
PKC-control
Products:
PKC-active
|
| 7 | inhib-PKA | PKA
Pathway No. 270 | 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 | | 8 | Inact-PP1 | PP1
Pathway No. 266 | 499.981
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.0002(uM) | - | Substrate:
I1*
PP1-active
Products:
PP1-I1*
|
| K inhib = 1nM from Cohen Ann Rev Bioch 1989, 4 nM from Foukes et al Assume 2 nM. kf /kb = 8.333e-4 | | 9 | Inact-PP1 | Shared_Object_
CaMKII_model3
Pathway No. 263 | 499.98
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.0002(uM) | - | Substrate:
I1*
PP1-active_PSD
Products:
PP1-I1*
|
| K inhib = 1nM from Cohen Ann Rev Bioch 1989, 4 nM from Foukes et al Assume 2 nM. kf /kb = 8.333e-4 | | 10 | equilib | Shared_Object_
CaMKII_model3
Pathway No. 263 | 540
(s^-1) | 60
(s^-1) | Not applicable** | - | Substrate:
CaM-Ca4-PSD
Products:
CaM-Ca4
|
| Diffusional equilibrium between PSD- and cytosolic compartment. According to D. Bary in Cell Movements 2nd ed 2001 D for proteins is 5e-7 cm^2/s giving 10 ms for a translocation of 1 um. | | 11 | dissoc-PP1-I1 | PP1
Pathway No. 266 | 1
(s^-1) | 0
(uM^-1 s^-1) | - | - | Substrate:
PP1-I1
Products:
PP1-active
I1
|
| Let us assume that the equil in this case is very far over to the right. This is probably safe. | | 12 | dissoc-PP1-I1 | PP1_PSD
Pathway No. 268 | 1
(s^-1) | 0
(uM^-1 s^-1) | - | - | Substrate:
PP1-I1
Products:
I1
PP1-active_PSD
|
| Let us assume that the equil in this case is very far over to the right. This is probably safe. | | 13 | dephosph-PDE | AC
Pathway No. 269 | 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. | | 14 | dephosph-AC2 | AC
Pathway No. 269 | 0.1
(s^-1) | 0
(s^-1) | - | - | Substrate:
AC2*
Products:
AC2
|
| Random rate. | | 15 | Ca_stoch_PSD | Shared_Object_
CaMKII_model3
Pathway No. 263 | 100
(s^-1) | 100
(s^-1) | Keq = 1(uM) | 0.005sec | Substrate:
Ca_control_PSD
Products:
Ca-PSD
|
| 16 | Ca_stoch_cyt | Shared_Object_
CaMKII_model3
Pathway No. 263 | 100
(s^-1) | 100
(s^-1) | Keq = 1(uM) | 0.005sec | Substrate:
Ca_control_cyt
Products:
Ca
|
| 17 | CaM_bind_PDE1 | AC
Pathway No. 269 | 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 | | 18 | cAMP_diffusion | AC
Pathway No. 269 | 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. | | 19 | cAMP-bind-site-B
2 | PKA
Pathway No. 270 | 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 | | 20 | cAMP-bind-site-B
1 | PKA
Pathway No. 270 | 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. |
and 
color.
