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Reaction List for 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 Act-PLC-CaPLCbeta

Pathway No. 151
3
(uM^-1 s^-1)
1
(s^-1)
Kd(bf) = 0.3333(uM)-  Substrate:
 Ca
 PLC

 Products:
 PLC-Ca
  Affinity for Ca = 1uM without AlF, 0.1 with: from Smrcka et al science 251 pp 804-807 1991 so [Ca].kf = kb so kb/kf = 1 * 6e5 = 1/1.66e-6 Assigned affinity to a Kd of 0.333 to maintain balance.
2 PLC-bind-GqPLCbeta

Pathway No. 151
2.52
(uM^-1 s^-1)
1
(s^-1)
Kd(bf) = 0.3968(uM)-  Substrate:
 PLC
 G*GTP

 Products:
 PLC-Gq
  this binding does not produce active PLC. This step was needed to implement the described (Smrcka et al) increase in affinity for Ca by PLC once Gq was bound. The tempkin are the same as the binding step for Ca-PLC to Gq. Kd is constrained by detailed balance.
3 PLC-Gq-bind-CaPLCbeta

Pathway No. 151
30
(uM^-1 s^-1)
1
(s^-1)
Kd(bf) = 0.0333(uM)-  Substrate:
 PLC-Gq
 Ca

 Products:
 PLC-Ca-Gq
  this step has a high affinity for Ca, from Smrcka et al. 0.1uM so kf /kb = 1/6e4 = 1.666e-5:1. See the Act-PLC-by-Gq reaction. Raised kf to 5e-5 based on match to conc-eff curves from Smrcka et al.
4 Inact-PLC-GqPLCbeta

Pathway No. 151
1.6667
(s^-1)
0
(uM^-1 s^-1)
--  Substrate:
 PLC-Ca-Gq

 Products:
 PLC-Ca
 G*GDP
  Rate of 100/min to account for GAP activity of PLC: Biddlecome et al, JBC, 271, 14, 7999-8007, 1996
5 Act-PLC-by-GqPLCbeta

Pathway No. 151
25.2
(uM^-1 s^-1)
1
(s^-1)
Kd(bf) = 0.0397(uM)-  Substrate:
 PLC-Ca
 G*GTP

 Products:
 PLC-Ca-Gq
  Affinity for Gq is > 20 nM (Smrcka et al Science251 804-807 1991) so [Gq].kf = kb so 40nM * 6e5 = kb/kf = 24e3 so kf = 4.2e-5, kb =1
6 Degrade-DAGPLCbeta

Pathway No. 151
0.15
(s^-1)
0
(s^-1)
--  Substrate:
 DAG

 Products:
 PC
  Rate based on basal and activated levels of DAG
7 basalPLCbeta

Pathway No. 151
0.003
(s^-1)
0
(uM^-1 s^-1)
--  Substrate:
 PIP2

 Products:
 DAG
 IP3(145)
  accounts for other PLC isoforms that contribute to basal levels of IP3
8 PKC-act-by-CaPKC

Pathway No. 147
0.6
(uM^-1 s^-1)
0.5
(s^-1)
Kd(bf) = 0.8333(uM)-  Substrate:
 PKC-cytosolic
 Ca

 Products:
 PKC-Ca
  This Kd is a straightforward result from the Schaechter and Benowitz 1993 J Neurosci 13(10):4361 curves. The time-course is based on the known rapid activation of PKC and also the fact that Ca association with proteins is typically quite fast. My guess is that this tau of 2 sec is quite conservative and the actualy rate may be much faster. The parameter is quite insensitive for most stimuli.
9 PKC-act-by-DAGPKC

Pathway No. 147
0.008
(uM^-1 s^-1)
8.6348
(s^-1)
Kd(bf) = 1079.377(uM)-  Substrate:
 DAG
 PKC-Ca

 Products:
 PKC-Ca-DAG
  Ca.PKC interaction with DAG is modeled by this reaction. Kf based on Shinomura et al PNAS 88 5149-5153 1991 and Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and uses the constraining procedure referred to in the general notes for PKC.
10 PKC-Ca-to-membPKC

Pathway No. 147
1.2705
(s^-1)
3.5026
(s^-1)
Keq = 2.7569(uM)0.21sec  Substrate:
 PKC-Ca

 Products:
 PKC-Ca-memb*
  Membrane translocation is a standard step in PKC activation. It also turns out to be necessary to replicate the curves from Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and Shonomura et al 1991 PNAS 88:5149-5153. These rates are constrained by matching the curves in the above papers and by fixing a rather fast (sub-second) tau for PKC activation.
11 PKC-DAG-to-membPKC

Pathway No. 147
1
(s^-1)
0.1
(s^-1)
Keq = 0.1(uM)0.909sec  Substrate:
 PKC-Ca-DAG

 Products:
 PKC-DAG-memb*
  membrane translocation step for Ca.DAG.PKC complex. Rates constrained from Shinomura et al 1991 PNAS 88:5149-5153 and Schaechter and Benowitz 1993 J Neurosci 13(10):4361 as derived in the references cited in PKC general notes.
12 
  • PKC-act-by-Ca-AA
  • PKC

    Pathway No. 147
    0.0012
    (uM^-1 s^-1)
    0.1
    (s^-1)
    Kd(bf) = 83.3333(uM)-  Substrate:
     PKC-Ca
     AA

     Products:
     PKC-Ca-AA*
      Ca-dependent AA activation of PKC. Note that this step combines the AA activation and also the membrane translocation. From Schaechter and Benowitz 1993 J Neurosci 13(10):4361
    13 
  • PKC-act-by-DAG-A
    A
  • PKC

    Pathway No. 147
    2
    (s^-1)
    0.2
    (s^-1)
    Keq = 0.1(uM)0.455sec  Substrate:
     PKC-DAG-AA

     Products:
     PKC-DAG-AA*
      Membrane translocation step for PKC-DAG-AA complex. Rates from matching concentration-effect data in our two main references: Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and Shinomura et al 1988 PNAS 88: 5149-5153
    14 PKC-basal-actPKC

    Pathway No. 147
    1
    (s^-1)
    50
    (s^-1)
    Keq = 50(uM)0.02sec  Substrate:
     PKC-cytosolic

     Products:
     PKC-basal*
      Basal activity of PKC is quite high, about 10% of max. See Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and Shinomura et al 1991 PNAS 88:5149-5153. This is partly due to basal levels of DAG, AA and Ca, but even when these are taken into account (see the derivations as per the PKC general notes) there is a small basal activity still to be accounted for. This reaction handles it by giving a 2% activity at baseline.
    15 PKC-act-by-AAPKC

    Pathway No. 147
    0.0001
    (uM^-1 s^-1)
    0.1
    (s^-1)
    Kd(bf) = 833.3333(uM)-  Substrate:
     AA
     PKC-cytosolic

     Products:
     PKC-AA*
      AA stimulates PKC activity even at rather low Ca. Schaechter and Benowitz 1993 J Neurosci 13(10):4361 Note that this one reaction combines the initial interaction and also membrane translocation.
    16 PKC-n-DAGPKC

    Pathway No. 147
    0.0006
    (uM^-1 s^-1)
    0.1
    (s^-1)
    Kd(bf) = 166.6667(uM)-  Substrate:
     PKC-cytosolic
     DAG

     Products:
     PKC-DAG
      Binding of PKC to DAG, non-Ca dependent. Kf based on Shinomura et al PNAS 88 5149-5153 1991 Tau estimated as fast and here it is about the same time-course as the formation of DAG so it will not be rate-limiting.
    17 PKC-n-DAG-AAPKC

    Pathway No. 147
    0.018
    (uM^-1 s^-1)
    2
    (s^-1)
    Kd(bf) = 111.1111(uM)-  Substrate:
     PKC-DAG
     AA

     Products:
     PKC-DAG-AA
      This is one of the more interesting steps. Mechanistically it does not seem necessary at first glance. Turns out that one needs this step to quantitatively match the curves in Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and Shinomura et al 1991 PNAS 88:5149-5153. There is a synergy between DAG and AA activation even at low Ca levels, which is most simply represented by this reaction. Tau is assumed to be fast. Kd comes from matching the experimental curves.
    18 ip6_trpMIPP

    Pathway No. 144
    0.001
    (s^-1)
    1
    (s^-1)
    Not applicable**-  Substrate:
     IP6

     Products:
     IP6_ER
      InsP6 ER-cytosol transport. Rate based on cytosolic levels of InsP6. ER-cytosol transport for other inositol phosphates are assigned the same rate as of now, as exact transport rates are not known.
    19 ip5(12456)_trpMIPP

    Pathway No. 144
    1
    (s^-1)
    0.001
    (s^-1)
    Not applicable**-  Substrate:
     IP5(12456)_ER

     Products:
     IP5(12456)
      Ins(12456)P5 ER-cytosol transport
    20 ip5(13456)_trpMIPP

    Pathway No. 144
    1
    (s^-1)
    0.001
    (s^-1)
    Not applicable**-  Substrate:
     IP5(13456)_ER

     Products:
     IP5(13456)
      Ins(13456)P5 ER-cytosol transport
    ** This is a trasport reation between compartments of different volumes. Therefore Kd is not applicable. Please Note Kf, Kb units are in number of molecules instead of concentration

     
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