| | Name | Kf | Kb | Kd | tau | Substrate | Product |
| 1 |
Activate-Gq | 0.01
(s^-1) | 0
(uM^-2 s^-1) | - | - | Rec-Glu-Gq
| G*GTP
BetaGamma
Rec-Glu
|
| | This is the kcat==k3 stage of the Rec-Glu ezymatic activation of Gq. From Berstein et al actiation is at .35 - 0.7/min From Fay et al Biochem 30 5066-5075 1991 kf = .01/sec From Nakamura et al J physiol Lond 474:1 35-41 1994 see time courses. Also (Berstein) 15-40% of gprot is in GTP-bound form on stim. |
| 2 |
Antag-bind-Rec-G
q | 60
(uM^-1 s^-1) | 0.01
(s^-1) | Kd(bf) = 0.0002(uM) | - | Rec-Gq
mGluRAntag
| Blocked-rec-Gq
|
| | The rate consts give a total binding affinity of only |
| 3 |
Basal-Act-G | 0.0001
(s^-1) | 0
(uM^-1 s^-1) | - | - | G-GDP
| G*GTP
BetaGamma
|
| | kf = kg1 = 0.01/sec, kb = 0. This is the basal exchange of GTP for GDP. |
| 4 |
Glu-bind-Rec-Gq | 16.8
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.006(uM) | - | Glu
Rec-Gq
| Rec-Glu-Gq
|
| | From Fay et al kb3 = kb = 1.06e-3 which is rather slow. k+1 = kf = 2.8e7 /M/sec= 4.67e-5/sec use 5e-5. However, the Kd from Martin et al may be more appropriate, as this is Glu not the system from Fay. kf = 2.8e-5, kb = 10 Let us compromise. since we have the Fay model, keep kf = k+1 = 2.8e-5. But kb (k-3) is .01 * k-1 from Fay. Scaling by .01, kb = .01 * 10 = 0.1 |
| 5 |
Inact-G | 0.0133
(s^-1) | 0
(s^-1) | - | - | G*GTP
| G*GDP
|
| | From Berstein et al JBC 267:12 8081-8088 1992, kcat for GTPase activity of Gq is only 0.8/min |
| 6 |
Rec-bind-Gq | 0.6
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 1.6667(uM) | - | G-GDP
mGluR
| Rec-Gq
|
| | Lets try out the same kinetics as the Rec-Glu-bind-Gq This is much too forward. We know that the steady-state amount of Rec-Gq should be 40% of the total amount of receptor. This is for a different receptor, still we can try to match the value. kf = 1e-6 and kb = 1 give 0.333:0.8 which is pretty close. |
| 7 |
Rec-Glu-bind-Gq | 0.006
(uM^-1 s^-1) | 0.0001
(s^-1) | Kd(bf) = 0.0167(uM) | - | G-GDP
Rec-Glu
| Rec-Glu-Gq
|
| | This is the k1-k2 equivalent for enzyme complex formation in the binding of Rec-Glu to Gq. See Fay et al Biochem 30 5066-5075 1991. kf = 5e-5 which is nearly the same as calculated by Fay et al. (4.67e-5) kb = .04 June 1996: Closer reading of Fay et al suggests that kb <= 0.0001, so kf = 1e-8 by detailed balance. This reaction appears to be neglible. |
| 8 |
RecLigandBinding | 16.8
(uM^-1 s^-1) | 10
(s^-1) | Kd(bf) = 0.5952(uM) | - | mGluR
Glu
| Rec-Glu
|
| | kf = kf from text = 1e7 / M / sec = 10 /uM/sec = 10 / 6e5 / # / sec = 1.67e-5 kb = kr from text = 60 / sec Note that we continue to use uM here since [phenylephrine] is also in uM. 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/# |
| 9 |
Trimerize-G | 6
(uM^-1 s^-1) | 0
(s^-1) | - | - | G*GDP
BetaGamma
| G-GDP
|
| | kf == kg3 = 1e-5 /cell/sec. As usual, there is no back-reaction kb = 0 |
