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Reaction Name | Pathway Name / Pathway No. | Kf | Kb | Kd | tau | Reagents |
1 | RecLigandBinding | Gq
Pathway No. 334 | 16.8003 (uM^-1 s^-1) | 10 (s^-1) | Kd(bf) = 0.5952(uM) | - | Substrate: mGluR Glu
Products: Rec-Glu
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| 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/# | 2 | Basal-Act-G | Gq
Pathway No. 334 | 0.0001 (s^-1) | 0 (uM^-1 s^-1) | - | - | Substrate: G-GDP
Products: G*GTP BetaGamma
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| kf = kg1 = 0.01/sec, kb = 0. This is the basal exchange of GTP for GDP. | 3 | Trimerize-G | Gq
Pathway No. 334 | 6 (uM^-1 s^-1) | 0 (s^-1) | - | - | Substrate: G*GDP BetaGamma
Products: G-GDP
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| kf == kg3 = 1e-5 /cell/sec. As usual, there is no back-reaction kb = 0 | 4 | Inact-G | Gq
Pathway No. 334 | 0.0133 (s^-1) | 0 (s^-1) | - | - | Substrate: G*GTP
Products: G*GDP
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| 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. 334 | 0.006 (uM^-1 s^-1) | 0.0001 (s^-1) | Kd(bf) = 0.0167(uM) | - | Substrate: G-GDP Rec-Glu
Products: Rec-Glu-Gq
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| 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. | 6 | Glu-bind-Rec-Gq | Gq
Pathway No. 334 | 16.8003 (uM^-1 s^-1) | 0.1 (s^-1) | Kd(bf) = 0.006(uM) | - | Substrate: Glu Rec-Gq
Products: Rec-Glu-Gq
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| 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. 334 | 0.01 (s^-1) | 0 (uM^-2 s^-1) | - | - | Substrate: Rec-Glu-Gq
Products: G*GTP BetaGamma Rec-Glu
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| 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. 334 | 0.6 (uM^-1 s^-1) | 1 (s^-1) | Kd(bf) = 1.6667(uM) | - | Substrate: G-GDP mGluR
Products: Rec-Gq
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| 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. | 9 | Antag-bind-Rec-G q | Gq
Pathway No. 334 | 60.0003 (uM^-1 s^-1) | 0.01 (s^-1) | Kd(bf) = 0.0002(uM) | - | Substrate: Rec-Gq mGluRAntag
Products: Blocked-rec-Gq
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| The rate consts give a total binding affinity of only |