| |
Reaction
Name | Pathway Name /
Pathway No. | Kf | Kb | Kd | tau | Reagents |
| 1 | ip6_trp | MIPP
Pathway No. 158 | 0.001
(s^-1) | 1
(s^-1) | Not applicable** | - | Substrate:
IP6
Products:
IP6_ER
|
| InsP6 ER-cytosol transport. Rate based on cytosolic levels of InsP6. ER-cytosol transport for other inositol phosphates are assigned the same rate as of now, as exact transport rates are not known. | | 2 | ip5(12456)_trp | MIPP
Pathway No. 158 | 1
(s^-1) | 0.001
(s^-1) | Not applicable** | - | Substrate:
IP5(12456)_ER
Products:
IP5(12456)
|
| Ins(12456)P5 ER-cytosol transport | | 3 | ip5(13456)_trp | MIPP
Pathway No. 158 | 1
(s^-1) | 0.001
(s^-1) | Not applicable** | - | Substrate:
IP5(13456)_ER
Products:
IP5(13456)
|
| Ins(13456)P5 ER-cytosol transport | | 4 | ip4(1456)_trp | MIPP
Pathway No. 158 | 1
(s^-1) | 0.001
(s^-1) | Not applicable** | - | Substrate:
IP4(1456)_ER
Products:
IP4(1456)
|
| Ins(1456)P4 ER-cytosol transport | | 5 | ip4(1345)_trp | MIPP
Pathway No. 158 | 0.001
(s^-1) | 1
(s^-1) | Not applicable** | - | Substrate:
IP4(1345)
Products:
IP4(1345)_ER
|
| Ins(1345)P4 ER-cytosol transport | | 6 | ip3(145)_trp | MIPP
Pathway No. 158 | 1
(s^-1) | 0.001
(s^-1) | Not applicable** | - | Substrate:
IP3(145)_ER
Products:
IP3(145)
|
| Ins(145)P3 ER-cytosol transport | | 7 | CaMKII-bind-CaM | CaMKII
Pathway No. 159 | 49.9998
(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. Kd = 0.1 uM. Rate is fast (see Hanson et al Neuron 12 943-956 1994) Hanson and Schulman 1992 AnnRev Biochem 61:559-601 give tau for dissoc as 0.2 sec at low Ca, 0.4 at high. Low Ca = 100 nM = physiol. | | 8 | CaMK-thr286-bind
-CaM | CaMKII
Pathway No. 159 | 1000.2
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.0001(uM) | - | Substrate:
CaMKII-thr286
CaM-Ca4
Products:
CaMKII-thr286*-C
aM
|
| Affinity is up 1000X over the unphosphorylated CaMKII, which makes the Kd of 0.1 nM. See Hanson et al 1994 Neuron 12:943-956. Time to release is about 20 sec, so the kb is OK at 0.1/sec. as tested by a few runs. | | 9 | basal-activity | CaMKII
Pathway No. 159 | 0.003
(s^-1) | 0
(s^-1) | - | - | Substrate:
CaMKII
Products:
CaMKII-thr286
|
| This reaction represents one of the unknowns in CaMK-II biochemistry: what maintains the basal level of phosphorylation on thr 286 ? See Hanson and Schulman Ann Rev Biochem 1992 61:559-601, specially pg 580, for review. I have not been able to find any compelling mechanism in the literature, but fortunately the level of basal activity is well documented. Lisman et al propose that the levels of PP1 are very low in the postsynaptic density, and PP2A is excluded from the PSD, and this would lead to autophosphorylation at a sustained level. | | 10 | CaM-TR2-bind-Ca | CaM
Pathway No. 160 | 72
(uM^-2 s^-1) | 72
(s^-1) | Kd(af) = 1(uM) | - | Substrate:
CaM
Ca
Ca
Products:
CaM-TR2-Ca2
|
| We use the Martin et al 1985 Eur J Biochem 151(3):543-550 rates here, plus the Drabikowski and Brzeska 1982 JBC 257(19):11584-11590 binding consts. All are scaled by 3X to cell temperature. kf = 2e-10 kb = 72 Stemmer & Klee 1994 Biochem 33:6859-6866 have values of : K1=.9, K2=1.1. Assume 1.0uM for both | | 11 | CaM-TR2-Ca2-bind
-Ca | CaM
Pathway No. 160 | 3.6
(uM^-1 s^-1) | 10
(s^-1) | Kd(bf) = 2.7778(uM) | - | Substrate:
CaM-TR2-Ca2
Ca
Products:
CaM-Ca3
|
| Stemmer and Klee 1994 Biochem 33:6859-6866 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 | | 12 | CaM-Ca3-bind-Ca | CaM
Pathway No. 160 | 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. Stemmer and Klee 1994 Biochem 33:6859-6866 kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10 | | 13 | PKC-act-by-Ca | PKC
Pathway No. 161 | 0.6
(uM^-1 s^-1) | 0.5
(s^-1) | Kd(bf) = 0.8333(uM) | - | Substrate:
PKC-cytosolic
Ca
Products:
PKC-Ca
|
| This Kd is a straightforward result from the Schaechter and Benowitz 1993 J Neurosci 13(10):4361 curves. The time-course is based on the known rapid activation of PKC and also the fact that Ca association with proteins is typically quite fast. My guess is that this tau of 2 sec is quite conservative and the actualy rate may be much faster. The parameter is quite insensitive for most stimuli. | | 14 | PKC-act-by-DAG | PKC
Pathway No. 161 | 0.008
(uM^-1 s^-1) | 8.6348
(s^-1) | Kd(bf) = 1079.377(uM) | - | Substrate:
DAG
PKC-Ca
Products:
PKC-Ca-DAG
|
| Ca.PKC interaction with DAG is modeled by this reaction. Kf based on Shinomura et al PNAS 88 5149-5153 1991 and Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and uses the constraining procedure referred to in the general notes for PKC. | | 15 | PKC-Ca-to-memb | PKC
Pathway No. 161 | 1.2705
(s^-1) | 3.5026
(s^-1) | Keq = 2.7569(uM) | 0.21sec | Substrate:
PKC-Ca
Products:
PKC-Ca-memb*
|
| Membrane translocation is a standard step in PKC activation. It also turns out to be necessary to replicate the curves from Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and Shonomura et al 1991 PNAS 88:5149-5153. These rates are constrained by matching the curves in the above papers and by fixing a rather fast (sub-second) tau for PKC activation. | | 16 | PKC-DAG-to-memb | PKC
Pathway No. 161 | 1
(s^-1) | 0.1
(s^-1) | Keq = 0.1(uM) | 0.909sec | Substrate:
PKC-Ca-DAG
Products:
PKC-DAG-memb*
|
| membrane translocation step for Ca.DAG.PKC complex. Rates constrained from Shinomura et al 1991 PNAS 88:5149-5153 and Schaechter and Benowitz 1993 J Neurosci 13(10):4361 as derived in the references cited in PKC general notes. | | 17 | PKC-act-by-Ca-AA | PKC
Pathway No. 161 | 0.0012
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 83.3333(uM) | - | Substrate:
PKC-Ca
AA
Products:
PKC-Ca-AA*
|
| Ca-dependent AA activation of PKC. Note that this step combines the AA activation and also the membrane translocation. From Schaechter and Benowitz 1993 J Neurosci 13(10):4361 | | 18 | PKC-act-by-DAG-A
A | PKC
Pathway No. 161 | 2
(s^-1) | 0.2
(s^-1) | Keq = 0.1(uM) | 0.455sec | Substrate:
PKC-DAG-AA
Products:
PKC-DAG-AA*
|
| Membrane translocation step for PKC-DAG-AA complex. Rates from matching concentration-effect data in our two main references: Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and Shinomura et al 1988 PNAS 88: 5149-5153 | | 19 | PKC-basal-act | PKC
Pathway No. 161 | 1
(s^-1) | 50
(s^-1) | Keq = 50(uM) | 0.02sec | Substrate:
PKC-cytosolic
Products:
PKC-basal*
|
| Basal activity of PKC is quite high, about 10% of max. See Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and Shinomura et al 1991 PNAS 88:5149-5153. This is partly due to basal levels of DAG, AA and Ca, but even when these are taken into account (see the derivations as per the PKC general notes) there is a small basal activity still to be accounted for. This reaction handles it by giving a 2% activity at baseline. | | 20 | PKC-act-by-AA | PKC
Pathway No. 161 | 0.0001
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 833.3333(uM) | - | Substrate:
AA
PKC-cytosolic
Products:
PKC-AA*
|
| AA stimulates PKC activity even at rather low Ca. Schaechter and Benowitz 1993 J Neurosci 13(10):4361 Note that this one reaction combines the initial interaction and also membrane translocation. |
and 
color.
indicates that ordering is done according to ascending or descending order.