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Reaction List for pathway Gq (Pathway Number 150) in Accession NonOsc_Ca_IP3metabolism (Accession Number 31) |
Entries are grouped according to Pathway Number and they are alternately color coded using  and  color.
Further ordering can be done to the table header.   indicates that ordering is done according to ascending or descending order.Keq is calculated only for first order reactions. Kd is calculated only for second order reactions. [nA+nB <->nC or nA<->nC+nD, where n is number and A,B,C,D are molecules] |
| Reaction Name | Pathway Name / Pathway No. | Kf | Kb | Kd | tau | Reagents | |
| 1 | | 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. |
| 2 | Basal-Act-G | Gq Pathway No. 150 | 0.0001 (s^-1) | 0 (uM^-1 s^-1) | - | - | Substrate: G-GDP Products: G*GTP BetaGamma | This is the basal exchange of GTP for GDP. So slow as to be nearly negligible. |
| 3 | Trimerize-G | Gq Pathway No. 150 | 6 (uM^-1 s^-1) | 0 (s^-1) | - | - | Substrate: G*GDP BetaGamma Products: G-GDP | kf == kg3 = 1e-5 /cell/sec. As usual, there is no back-reaction kb = 0 |
| 4 | Inact-G | Gq Pathway No. 150 | 0.0133 (s^-1) | 0 (s^-1) | - | - | Substrate: G*GTP Products: G*GDP | From Berstein et al JBC 267:12 8081-8088 1992, kcat for GTPase activity of Gq is only 0.8/min. |
| 5 | Rec-Glu-bind-Gq | Gq Pathway No. 150 | 0.006 (uM^-1 s^-1) | 0.0001 (s^-1) | Kd(bf) = 0.0167(uM) | - | Substrate: G-GDP Rec-Glu Products: 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. Closer reading of Fay et al suggests that kb <= 0.0001, so kf = 1e-8 by detailed balance. This reaction appears to be neglible. |
| 6 | Glu-bind-Rec-Gq | Gq Pathway No. 150 | 16.8 (uM^-1 s^-1) | 0.1 (s^-1) | Kd(bf) = 0.006(uM) | - | Substrate: Glu Rec-Gq Products: 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 |
| 7 | Activate-Gq | Gq Pathway No. 150 | 0.01 (s^-1) | 0 (uM^-2 s^-1) | - | - | Substrate: Rec-Glu-Gq Products: G*GTP BetaGamma Rec-Glu | This reaction is the critical one for activation of Gq. It probably encapsulates multiple steps. In this approximation the receptor-ligand- Gprotein complex splits up into GTP.Galpha, rec.ligand complex, and Gbetagamma. There is a hidden step of exchange of GDP for GTP. The reaction does not take these into account since it is assumed that both GTP and GDP levels are tightly regulated by metabolic control. 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. |
| 8 | Rec-bind-Gq | Gq Pathway No. 150 | 0.6 (uM^-1 s^-1) | 1 (s^-1) | Kd(bf) = 1.6667(uM) | - | Substrate: G-GDP mGluR Products: Rec-Gq | From Berstein et al 1992 JBC 267(12):8081-8088 we know that 15-40% of Gq binds, GTP_gamma_S. Also about 20-30% of Gq is bound to GTP. To get to these values the receptor-Gq amount should be similar. These rates are designed to give that steady state with a fast tau of 1 sec. |
| 9 | q | Gq Pathway No. 150 | 60 (uM^-1 s^-1) | 0.01 (s^-1) | Kd(bf) = 0.0002(uM) | - | Substrate: Rec-Gq mGluRAntag Products: Blocked-rec-Gq | The rate consts give a total binding affinity of under 0.2 nM, good for a strong antagonist. |