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Molecule Parameter List for PIP2

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
PIP2 participated asMoleculeSum total ofEnzymeSubstrate of an enzymeProduct of an enzymeSubstrate in ReactionProduct in Reaction
No. of occurrences1004000

Accession and Pathway Details
Accession NameAccession No.Accession TypePathway Link
  • Synaptic_
    Network
  • 16Network
    Shared_Object_Synaptic_Network PKC PLA2 
    PLCbeta Gq MAPK 
    Ras EGFR Sos 
    PLC_g CaMKII CaM 
    PP1 PP2B PKA 
    AC CaRegulation 
    This model is an annotated version of the synaptic signaling network.
    The primary reference is Bhalla US and Iyengar R. Science (1999) 283(5400):381-7 but several of the model pathways have been updated.
    Bhalla US Biophys J. 2002 Aug;83(2):740-52
    Bhalla US J Comput Neurosci. 2002 Jul-Aug;13(1):49-62

    PIP2 acting as a Molecule in  
    Synaptic_Network Network
    NameAccession NamePathway NameInitial Conc.
    (uM)
    Volume
    (fL)
    Buffered
    PIP2
  • Synaptic_
    Network

    Accession No. : 16
  • Shared_Object_
    Synaptic_
    Network

    Pathway No. : 70
  • 101000Yes
    PIP2 is a bit troublesome in this model. Its level is well below what it should be based on more recent data. This value is kept in this model to correspond to the Km used in the enzymes. A scale factor of 5-10 in both terms would cancel out but improve the parameter estimate.

    PIP2 acting as a Substrate for an Enzyme in  
    Synaptic_Network Network
     Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    1PLC-Ca  /
    PLC-Ca
  • Synaptic_
    Network

    Accession No. : 16
  • PLCbeta
    Pathway No. : 73
    19.8413104explicit E-S complexSubstrate
    PIP2

    Product
    DAG
    IP3
        From Sternweis et al Phil Trans R Soc Lond 1992, also matched by Homma et al. Km of 20 is higher than for the Gq bound form, but Vmax is about 1/3 of the Gq form.
    2PLC-Ca-Gq  /
    PLCb-Ca-Gq
  • Synaptic_
    Network

    Accession No. : 16
  • PLCbeta
    Pathway No. : 73
    5484explicit E-S complexSubstrate
    PIP2

    Product
    DAG
    IP3
        From Sternweis et al, Phil Trans R Soc Lond 1992, and the values from other refs eg Homma et al JBC 263(14) pp6592 1988 match. In this model I have rather low values for PIP2. The Km values are low to match. Sternweis mentions a 5 uM Km which is what I use here, but the Homma paper suggests about 20x higher Km, which would also fit with 20x higher PIP2. So that parameter, though it is off, cancels out and the overall rate would be the same. Vmax is about 23 umol/min/mg at high Ca from Sternweis or about 60/sec. This model value is a little lower than that.
    3Ca.PLC_g  /
    PIP2_hydrolysis
  • Synaptic_
    Network

    Accession No. : 16
  • PLC_g
    Pathway No. : 79
    97.2222144Classical Michaelis-Menten
    V = Etot.S.Kcat/Km+S
    Substrate
    PIP2

    Product
    DAG
    IP3
        Wahl et al JBC 267(15) 10447-10456 1992. Homma et al JBC 263:14 1988 pp 6592. These parms are the Ca-stimulated form. This is close to Wahl's figure 7, which I am using as reference. Also see Nakanishi et al Biochem J 256 453-459 1998, Nishibe et al Science 250 :1253-1256 This model uses a rather low PIP2 of 10 uM.
    4Ca.PLC_g*  /
    PIP2_hydrolysis
  • Synaptic_
    Network

    Accession No. : 16
  • PLC_g
    Pathway No. : 79
    19.7917574Classical Michaelis-Menten
    V = Etot.S.Kcat/Km+S
    Substrate
    PIP2

    Product
    DAG
    IP3
        Mainly Homma et al JBC 263:14 1988 pp 6592. These parms are the Ca-stimulated form. Wahl et al JBC 267:15 10447-10456 1992 say that the tyrosine phosphorylated form has 7X higher affinity for substrate than control. The PIP2 levels in this model are rather low, at 10 uM.



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