NCBS Home page
Accession List
Pathway List
Search
Authorized Users
Help
News archives

Enter a Search String

Special character and space not allowed in the query term. Search string should be at least 2 characters long.
Search in: Search for Match By


 
Result: 1 - 9 of 9 rows are displayed

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.
KfKbKdtauReagents
1 
  • RecLigandBinding
  • 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-GGq

    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-GGq

    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-GGq

    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-GqGq

    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-GqGq

    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-GqGq

    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-GqGq

    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 
  • Antag-bind-Rec-G
    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.

     
    Result: 1 - 9 of 9 rows are displayed



    Database compilation and code copyright (C) 2005, Upinder S. Bhalla and NCBS/TIFR
    This Copyright is applied to ensure that the contents of this database remain freely available. Please see FAQ for details.