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Reaction List for pathway Gs (Pathway Number 137) | | Kd is calculated only for second order reactions, like nA+nB <->nC or nA<->nC+nD, where n is number and A,B,C,D are molecules, where as for first order reactions Keq is calculated. Kd for higher order reactions is not considered. |
| | Name | Kf | Kb | Kd | tau | Substrate | Product | | 1 |
Activate-Gs | 0.025
(s^-1) | 0
(uM^-2 s^-1) | - | - | L.R.GDP.Gabc
| Gbg
L.R
GTP.Ga
| | | This step combines several stages in GTP.Galpha release. From Berstein et al activation is at .35 - 0.7/min From Fay et al Biochem 30 5066-5075 1991 kf = .01/sec. From Brandt and Ross JBC 261(4):1656-1664 (1986) and Ransan et al Biochem J 283(2):519-524 (1992) rates around 2.5/min to 1.5/min are better. | | 2 |
GTPase | 0.0667
(s^-1) | 0
(s^-1) | - | - | GTP.Ga
| GDP.Ga
| | | From Brandt and Ross JBC 261(4):1656-1664, rate is 4/min and is agonist independent. I treat this as irreversible. | | 3 |
L-bind-R | 0.1
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 1(uM) | - | R
L
| L.R
| | | Ligand binding to receptor. From Gether et al JBC 270:28268-28275 (1995) the binding to the purified receptor is at about 1 uM, but the conformational change only happens at 30 uM. We'll take 1 uM for this, since it is already much weaker binding than to the R.Gs complex. The time-course from this paper appears remarkably slow, based on physiological data I estimate more like 10 sec. | | 4 |
L-bind-R.Gabc | 5
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.02(uM) | - | L
R.GDP.Gabc
| L.R.GDP.Gabc
| | | From Seifert et al Mol. Pharmacol 56:348-358 (1999) The EC50 for ISO is about 20 nM. | | 5 |
L.R-bind-Gabc | 10.0002
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.01(uM) | - | GDP.Gabc
L.R
| L.R.GDP.Gabc
| | | See Fay et al Biochem 30 5066-5075 1991. kf is 0.01/sec but does not account for Gs levels. kb is 0.0001/sec. The fraction of RG is about 50%, so we can estimate Kd at about the same as for Gs basal levels. This rate has to be faster since it has to feed GTP.Ga into the system faster than the GTPase. Waldhoer et al Mol Pharmacol 53:808-818 1988 say affinity for A1adenosine/Gi is 10 nM. | | 6 |
R-bind-Gabc | 0.2
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.5(uM) | - | GDP.Gabc
R
| R.GDP.Gabc
| | | Receptor binding to Gs. Scale it to the same slow rates described by Fay et al for L.R to L.R.G. From detailed balance, Kd is 50. | | 7 |
Trimerize-Gs | 6
(uM^-1 s^-1) | 0
(s^-1) | - | - | GDP.Ga
Gbg
| GDP.Gabc
| | | Negligible back-reaction. |
Pathway Details Molecule List Enzyme List Reaction List
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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