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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
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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
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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
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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
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| 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 | CaMKII-bind-CaM | CaMKII
Pathway No. 282 | 49.9997 (uM^-1 s^-1) | 5 (s^-1) | Kd(bf) = 0.1(uM) | - | Substrate: CaM-Ca4 CaMKII
Products: CaMKII-CaM
|
| This is tricky. There is some cooperativity here arising from interactions between the subunits of the CAMKII holoenzyme. However, the stoichiometry is 1. Kb/Kf = 6e4 #/cell. Rate is fast (see Hanson et al Neuron 12 943-956 1994) so lets say kb = 10. This gives kf = 1.6667e-4 H&S AnnRev Biochem 92 give tau for dissoc as 0.2 sec at low Ca, 0.4 at high. Low Ca = 100 nM = physiol. | 10 | CaMK-thr286-bind -CaM | CaMKII
Pathway No. 282 | 1000.19 (uM^-1 s^-1) | 0.1 (s^-1) | Kd(bf) = 0.0001(uM) | - | Substrate: CaMKII-thr286 CaM-Ca4
Products: CaMKII-thr286*-C aM
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| Affinity is up 1000X. Time to release is about 20 sec, so the kb is OK at 0.1 This makes Kf around 1.6666e-3 | 11 | CaM-TR2-bind-Ca | CaM
Pathway No. 283 | 71.999 (uM^-2 s^-1) | 72 (s^-1) | Kd(af) = 1(uM) | - | Substrate: CaM Ca Ca
Products: CaM-TR2-Ca2
|
| Lets use the fast rate consts here. Since the rates are so different, I am not sure whether the order is relevant. These correspond to the TR2C fragment. We use the Martin et al rates here, plus the Drabicowski binding consts. All are scaled by 3X to cell temp. kf = 2e-10 kb = 72 Stemmer & Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11. If kb=72, kf = 2e-10 (Exactly the same !).... | 12 | CaM-TR2-Ca2-bind -Ca | CaM
Pathway No. 283 | 3.6 (uM^-1 s^-1) | 10 (s^-1) | Kd(bf) = 2.7778(uM) | - | Substrate: CaM-TR2-Ca2 Ca
Products: CaM-Ca3
|
| K3 = 21.5, K4 = 2.8. Assuming that the K4 step happens first, we get kb/kf = 2.8 uM = 1.68e6 so kf =6e-6 assuming kb = 10 | 13 | neurogranin-bind -CaM | CaM
Pathway No. 283 | 0.3 (uM^-1 s^-1) | 1 (s^-1) | Kd(bf) = 3.3333(uM) | - | Substrate: neurogranin CaM
Products: neurogranin-CaM
|
| Surprisingly, no direct info on rates from neurogranin at this time. These rates are based on GAP-43 binding studies. As GAP-43 and neurogranin share near identity in the CaM/PKC binding regions, and also similarity in phosph and dephosph rates, I am borrowing GAP-43 kinetic info. See Alexander et al JBC 262:13 6108-6113 1987 | 14 | dephosph-neurogr anin | CaM
Pathway No. 283 | 0.005 (s^-1) | 0 (s^-1) | - | - | Substrate: neurogranin*
Products: neurogranin
|
| This is put in to keep the basal levels of neurogranin* experimentally reasonable. From various papers, specially Ramakers et al JBC 270:23 1995 13892-13898, it looks like the basal level of phosph is between 20 and 40%. I est around 25 % The kf of 0.005 gives around this level at basal PKC activity levels of 0.1 uM active PKC. | 15 | CaM-TR2-bind-Ca- PSD | CaM
Pathway No. 283 | 72 (uM^-2 s^-1) | 72 (s^-1) | Kd(af) = 1(uM) | - | Substrate: CaM-PSD Ca-PSD Ca-PSD
Products: CaM-TR2-Ca2-PSD
|
| Lets use the fast rate consts here. Since the rates are so different, I am not sure whether the order is relevant. These correspond to the TR2C fragment. We use the Martin et al rates here, plus the Drabicowski binding consts. All are scaled by 3X to cell temp. kf = 2e-10 kb = 72 Stemmer & Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11. If kb=72, kf = 2e-10 (Exactly the same !).... | 16 | CaM-TR2-Ca2-bind -Ca-PSD | CaM
Pathway No. 283 | 3.6 (uM^-1 s^-1) | 10 (s^-1) | Kd(bf) = 2.7778(uM) | - | Substrate: CaM-TR2-Ca2-PSD Ca-PSD
Products: CaM-Ca3-PSD
|
| K3 = 21.5, K4 = 2.8. Assuming that the K4 step happens first, we get kb/kf = 2.8 uM = 1.68e6 so kf =6e-6 assuming kb = 10 | 17 | CaM-Ca3-bind-Ca- PSD | CaM
Pathway No. 283 | 0.465 (uM^-1 s^-1) | 10 (s^-1) | Kd(bf) = 21.5048(uM) | - | Substrate: CaM-Ca3-PSD Ca-PSD
Products: CaM-Ca4-PSD
|
| Use K3 = 21.5 uM here from Stemmer and Klee table 3. kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10 | 18 | neurogranin-bind -CaM_ PSD | CaM
Pathway No. 283 | 0.3 (uM^-1 s^-1) | 1 (s^-1) | Kd(bf) = 3.3333(uM) | - | Substrate: neurogranin_PSD CaM-PSD
Products: neurogranin-CaM_ PSD
|
| Surprisingly, no direct info on rates from neurogranin at this time. These rates are based on GAP-43 binding studies. As GAP-43 and neurogranin share near identity in the CaM/PKC binding regions, and also similarity in phosph and dephosph rates, I am borrowing GAP-43 kinetic info. See Alexander et al JBC 262:13 6108-6113 1987 | 19 | dephosph-neurogr anin_ PSD | CaM
Pathway No. 283 | 0.005 (s^-1) | 0 (s^-1) | - | - | Substrate: neurogranin*_ PSD
Products: neurogranin_PSD
|
| This is put in to keep the basal levels of neurogranin* experimentally reasonable. From various papers, specially Ramakers et al JBC 270:23 1995 13892-13898, it looks like the basal level of phosph is between 20 and 40%. I est around 25 % The kf of 0.005 gives around this level at basal PKC activity levels of 0.1 uM active PKC. | 20 | 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 |