| |
Reaction
Name | Pathway Name /
Pathway No. | Kf | Kb | Kd | tau | Reagents |
| 1 | 3k-CaM*-on | IP3-3K
Pathway No. 148 | 80.358
(uM^-1 s^-1) | 180
(s^-1) | Kd(bf) = 2.24(uM) | - | Substrate:
IP3(145)
IP3_3K_CaM*
Products:
3kCaM*_ip3_
cmplx
|
| Rates from Km of enzyme Communi et al, EMBO J 16(8) | | 2 | 4pase-on | 145_dephos
Pathway No. 153 | 1.035
(uM^-1 s^-1) | 157.32
(s^-1) | Kd(bf) = 152(uM) | - | Substrate:
IP1(4)
IP1_pase
Products:
ip1_4pase_cmplx
|
| Rates derived from Ins(4)P1 4-phosphatase Km: Gee et al, Biochem J 249; 1988 | | 3 | Ca-bind-to-Trans
p | CaRegulation
Pathway No. 149 | 3600
(uM^-2 s^-1) | 144
(s^-1) | Kd(af) = 0.2(uM) | - | Substrate:
Ca
Ca
CaTransp
Products:
CaTransp-2Ca
|
| Rates from Lauffenburger abd Linderman 1993 Receptors pg 200. Kd = KCa2 = 0.2 uM | | 4 | CaM-TR2-bind-Ca | CaM
Pathway No. 146 | 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 | | 5 | PKC-basal-act | PKC
Pathway No. 147 | 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. | | 6 | 1pase-on | 134_dephos
Pathway No. 152 | 0.3572
(uM^-1 s^-1) | 45.72
(s^-1) | Kd(bf) = 128.0005(uM) | - | Substrate:
IP1(1)
IP1_pase
Products:
ip1_1pase_cmplx
|
| Rates derived from Km for Ins(1)P1-1phosphatase: Gee et al, Biochem J 249; 1988. | | 7 | IP5-inhib-5pase | 145_dephos
Pathway No. 153 | 1
(uM^-1 s^-1) | 45
(s^-1) | Kd(bf) = 44.9991(uM) | - | Substrate:
IP5(13456)
IP_5pase1
Products:
IP5-5pase-cmplx
|
| from Hoer and Oberdisse, Biochem J 278; 1991: 219-224 | | 8 | 3k-CaM-on | IP3-3K
Pathway No. 148 | 18.7497
(uM^-1 s^-1) | 42.001
(s^-1) | Kd(bf) = 2.2401(uM) | - | Substrate:
IP3_3K_CaM
IP3(145)
Products:
3kCaM_ip3_cmplx
|
| rates from Km for enzyme: Erneux et al, Biochem 214; 1993 Enzyme is 2-2.5 fold more active than ip3-3k, but Km is doubled. | | 9 | IP_4pase-inact | 134_dephos
Pathway No. 152 | 1
(uM^-1 s^-1) | 19
(s^-1) | Kd(bf) = 19(uM) | - | Substrate:
IP_4pase
IP6
Products:
IP_4pase_inact
|
| from Norris et al, JBC 269; 1994 | | 10 | ip4-3k-on | IP4-system
Pathway No. 154 | 53.7501
(uM^-1 s^-1) | 17.2
(s^-1) | Kd(bf) = 0.32(uM) | - | Substrate:
IP4(1456)
IP4-3K
Products:
ip4_3k_cmplx
|
| Rates derived from Km for enzyme: Stephens et al, Biochem J 249; 1988. | | 11 | IP6-inhib-5pase | 145_dephos
Pathway No. 153 | 1
(uM^-1 s^-1) | 16
(s^-1) | Kd(bf) = 15.9997(uM) | - | Substrate:
IP6
IP_5pase1
Products:
IP6-5pase-inhib
|
| from Hoer and Oberdisse, Biochem J 278; 1991: 219-224 | | 12 | CaM-TR2-Ca2-bind
-Ca | CaM
Pathway No. 146 | 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 | | 13 | CaM-Ca3-bind-Ca | CaM
Pathway No. 146 | 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 | | 14 | RecLigandBinding | Gq
Pathway No. 150 | 16.8
(uM^-1 s^-1) | 10
(s^-1) | Kd(bf) = 0.5952(uM) | - | Substrate:
mGluR
Glu
Products:
Rec-Glu
|
| From Martin et al FEBS Lett 316:2 191-196 1993 we have Kd = 600 nM Assuming kb = 10/sec, we get kf = 10/(0.6 uM * 6e5) = 2.8e-5 1/sec/# The off time for Glu seems pretty slow: Nicoletti et al 1986 PNAS 83:1931-1935 and Schoepp and Johnson 1989 J Neurochem 53 1865-1870 indicate it is at least 30 sec. Here we are a little faster because this is only a small part of the off rate, the rest coming from the Rec-Gq complex. | | 15 | PKC-act-by-DAG | PKC
Pathway No. 147 | 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. | | 16 | Ca-inhib-1pase | 145_dephos
Pathway No. 153 | 1
(uM^-1 s^-1) | 6
(s^-1) | Kd(bf) = 5.9999(uM) | - | Substrate:
IP_1pase
Ca
Products:
Ca-1pase-cmplx
|
| Ki from Inhorn & Majerus, BiochemJ 262(33); 1987: 15946-52 | | 17 | CaMKII-bind-CaM | CaMKII
Pathway No. 145 | 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. | | 18 | PKC-Ca-to-memb | PKC
Pathway No. 147 | 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. | | 19 | PP-IP5cmplx-on | IHP-system
Pathway No. 155 | 0.0027
(uM^-2 s^-1) | 2.5
(s^-1) | - | - | Substrate:
ATP
PP-IP5
PP-IP5-K
Products:
PP-IP5-K-complex
|
| from Huang et al, Biochem 37; 1998 Kf calculated using Km for PP-InsP5 and ATP, and Vmax of forward and backward reactions. Kb = Vmax of backward reaction | | 20 | ip4-1k-on | IP4-system
Pathway No. 154 | 31.2001
(uM^-1 s^-1) | 2.496
(s^-1) | Kd(bf) = 0.08(uM) | - | Substrate:
IP4(3456)
IP3-56K_IP4-1K
Products:
ip4_1k_cmplx
|
| Rates derives from enzyme Km and Vmax values: Yang and Shears, Biochem J 2000, 351: 551-555. |
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