| |
Reaction
Name | Pathway Name /
Pathway No. | Kf | Kb | Kd | tau | Reagents |
| 1 | equilib | Shared_Object_
AMPAR_CaMKII_
weak_coupling
Pathway No. 281 | 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. | | 2 | Inact-PP1 | Shared_Object_
AMPAR_CaMKII_
weak_coupling
Pathway No. 281 | 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 | | 3 | CaM-Ca3-bind-Ca | Shared_Object_
AMPAR_CaMKII_
weak_coupling
Pathway No. 281 | 0.465
(uM^-1 s^-1) | 10
(s^-1) | Kd(bf) = 21.5054(uM) | - | Substrate:
CaM-Ca3
Ca
Products:
CaM-Ca4
|
| Use K3 = 21.5 uM here from Stemmer and Klee table 3. kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10 | | 4 | endo_const | Shared_Object_
AMPAR_CaMKII_
weak_coupling
Pathway No. 281 | 0.0004
(s^-1) | 0.0014
(s^-1) | Not applicable** | - | Substrate:
GluR23_M
Products:
GluR23_I
|
| 5 | PKC-stoch-input | Shared_Object_
AMPAR_CaMKII_
weak_coupling
Pathway No. 281 | 2.5
(s^-1) | 2.5
(s^-1) | Keq = 1(uM) | 0.2sec | Substrate:
PKC-control
Products:
PKC-active
|
| 6 | Ca_stoch_cyt | Shared_Object_
AMPAR_CaMKII_
weak_coupling
Pathway No. 281 | 100
(s^-1) | 100
(s^-1) | Keq = 1(uM) | 0.005sec | Substrate:
Ca_control_cyt
Products:
Ca
|
| 7 | Ca_stoch_PSD | Shared_Object_
AMPAR_CaMKII_
weak_coupling
Pathway No. 281 | 100
(s^-1) | 100
(s^-1) | Keq = 1(uM) | 0.005sec | Substrate:
Ca_control_PSD
Products:
Ca-PSD
|
| 8 | turnover | Shared_Object_
AMPAR_CaMKII_
weak_coupling
Pathway No. 281 | 0.018
(s^-1) | 1
(s^-1) | Not applicable** | - | Substrate:
AMPAR_bulk
Products:
A_B
|
| Represents both synthesis and degradation of the receptor. The rate is set to be rather fast for now. The forward rate also includes scaling terms because the AMPAR_bulk is in the dendritic volume of 5e-18. This means that we need to lower Kf to account for the difference in volumes. Effectively Kf is 1/sec, but the scaled version becomes 9e-20/5e-18 = 0.018 | | 9 | Ca-bind-CaNAB-Ca
2 | PP2B
Pathway No. 285 | 3.6001
(uM^-2 s^-1) | 1
(s^-1) | Kd(af) = 0.527(uM) | - | Substrate:
Ca
Ca
CaNAB-Ca2
Products:
CaNAB-Ca4
|
| This process is probably much more complicated and involves CaM. However, as I can't find detailed info I am bundling this into a single step. Based on Steemer and Klee pg 6863, the Kact is 0.5 uM. kf/kb = 1/(0.5 * 6e5)^2 = 1.11e-11 | | 10 | Ca-bind-CaNAB | PP2B
Pathway No. 285 | 10008
(uM^-2 s^-1) | 1
(s^-1) | Kd(af) = 0.01(uM) | - | Substrate:
CaNAB
Ca
Ca
Products:
CaNAB-Ca2
|
| going on the experience with CaM, we put the fast (high affinity) sites first. We only know (Stemmer and Klee) that the affinity is < 70 nM. Assuming 10 nM at first, we get kf = 2.78e-8, kb = 1. Try 20 nM. kf = 7e-9, kb = 1 | | 11 | CaMCa4-bind-CaNA
B | PP2B
Pathway No. 285 | 599.994
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.0017(uM) | - | Substrate:
CaM-Ca4
CaNAB-Ca4
Products:
CaM_Ca_n-CaNAB
|
| 12 | dissoc-PP1-I1 | PP1_PSD
Pathway No. 286 | 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 | Inact-PP1 | PP1
Pathway No. 284 | 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 | | 14 | dissoc-PP1-I1 | PP1
Pathway No. 284 | 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. | | 15 | 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. | | 16 | 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 | | 17 | 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
|
| 18 | 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
|
| 19 | 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 | | 20 | 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
|
and 
color.
