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Molecule Parameter List for IP3 | 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 |
Accession and Pathway Details | |
| Accession Name | Accession No. | Accession Type | Pathway Link | Synaptic_
Network | 16 | Network |
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 |
IP3 acting as a Molecule in Synaptic_Network Network
IP3 acting as a Product of an Enzyme in Synaptic_Network Network
| | Enzyme Molecule /
Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | | 1 | PLC-Ca /
PLC-Ca | Synaptic_
Network
Accession No. : 16 | PLCbeta
Pathway No. : 73 | 19.8413 | 10 | 4 | explicit E-S complex | Substrate
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. | | 2 | PLC-Ca-Gq /
PLCb-Ca-Gq | Synaptic_
Network
Accession No. : 16 | PLCbeta
Pathway No. : 73 | 5 | 48 | 4 | explicit E-S complex | Substrate
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. | | 3 | Ca.PLC_g /
PIP2_hydrolysis | Synaptic_
Network
Accession No. : 16 | PLC_g
Pathway No. : 79 | 97.2222 | 14 | 4 | Classical 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. | | 4 | Ca.PLC_g* /
PIP2_hydrolysis | Synaptic_
Network
Accession No. : 16 | PLC_g
Pathway No. : 79 | 19.7917 | 57 | 4 | Classical 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. |
IP3 acting as a Substrate in a reaction in Synaptic_Network 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. |
| | Name | Accession Name | Pathway Name | Kf | Kb | Kd | tau | Reagents | | 1 | Degrade-IP3 | Synaptic_
Network
Accession No. : 16 | PLCbeta
Pathway No. : 73 | 2.5
(s^-1) | 0
(s^-1) | - | - | Substrate
IP3
Product
Inositol
| | | The enzyme is IP3 5-phosphomonesterase. about 45K. Actual products are Ins(1,4)P2, and cIns(1:2,4,5)P3. review in Majerus et al Science 234 1519-1526, 1986. Meyer and Stryer 1988 PNAS 85:5051-5055 est decay of IP3 at 1-3/sec | | 2 | IP3Rbind | Synaptic_
Network
Accession No. : 16 | CaRegulation
Pathway No. : 86 | 0.05
(uM^-3 s^-1) | 1
(s^-1) | Kd(af) = 2.7144(uM) | - | Substrate
IP3
IP3
IP3
IP3R
Product
IP3R*
| | | Based on Lauffenburger and Linderman 1993 Receptors page 200. The binding of IP3 in this reaction has a Hill coeff of 3. The eqns of Mahama and Linderman (cited in the book as 1993 a) are equivalent to the binding all occurring in a single step, so that is how I am doing it in this version. Their Ki1 is 0.07 uM. Lots of other data sources: Ramos-Franco et al 1998 Biophys J 75:834-839 have Ca sensitivity curves. At 250 nM free Ca, the EC50 for type 1 is 58 nM and type 2 is 194 nM. Type 3 would be about 2 uM according to Newton et al 1994 JBC 268(46):28613-28619 For the purposes of this model we use a Kd of 2.7 uM which is high but may be OK at low calcium. The details of Ca interaction with the IP3R are not included in this model. |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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