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Molecule Parameter List for L.R

The statistics table lists the distribution of a molecule acting either as a substrate, product, enzyme or as a molecule within the network.
The text color of a molecule is highlighted by color.
Statistics
L.R participated asMoleculeSum total ofEnzymeSubstrate of an enzymeProduct of an enzymeSubstrate in ReactionProduct in Reaction
No. of occurrences1000012

Accession and Pathway Details
Accession NameAccession No.Accession TypePathway Link
cAMP_pathway25Network
Shared_Object_cAMP_pathway PKA AC 
Gs 
This is a model of the canonical cAMP signaling pathway:
Ligand->Receptor->G-protein->Cyclase->cAMP->PKA.
It also includes phosphodiesterases to balance out cAMP formation.Bhalla US Methods Enzymol. 2002;345:3-23

L.R acting as a Molecule in  
cAMP_pathway Network
NameAccession NamePathway NameInitial Conc.
(uM)
Volume
(fL)
Buffered
L.RcAMP_pathway
Accession No. : 25
Gs
Pathway No. : 137
01000No
Ligand.Receptor complex

L.R acting as a Substrate in a reaction in  
cAMP_pathway Network
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 reaction are not consider.
NameAccession NamePathway NameKfKbKdtauReagents
L.R-bind-GabccAMP_pathway
Accession No. : 25
Gs
Pathway No. : 137
10.0002
(uM^-1 s^-1)
0.1
(s^-1)
Kd(bf) = 0.01(uM)-Substrate
GDP.Gabc
L.R

Product
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.

L.R acting as a Product in a reaction in  
cAMP_pathway Network
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 reaction are not consider.
 NameAccession NamePathway NameKfKbKdtauReagents
1L-bind-RcAMP_pathway
Accession No. : 25
Gs
Pathway No. : 137
0.1
(uM^-1 s^-1)
0.1
(s^-1)
Kd(bf) = 1(uM)-Substrate
L
R

Product
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.
2Activate-GscAMP_pathway
Accession No. : 25
Gs
Pathway No. : 137
0.025
(s^-1)
0
(uM^-2 s^-1)
--Substrate
L.R.GDP.Gabc

Product
GTP.Ga
Gbg
L.R
  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.



Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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