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Molecule Parameter List for DAG | 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 |
DAG acting as a Molecule in Synaptic_Network Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | DAG | Synaptic_
Network
Accession No. : 16 | Shared_Object_
Synaptic_
Network
Pathway No. : 70 | 0 | 1000 | No | | Baseline in model is 11.661 uM. DAG is pretty nasty to estimate. In this model we just hold it fixed at this baseline level. Data sources are many and varied and sometimes difficult to reconcile. Welsh and Cabot 1987 JCB 35:231-245: DAG degradation Bocckino et al JBC 260(26):14201-14207: hepatocytes stim with vasopressin: 190 uM. Bocckino et al 1987 JBC 262(31):15309-15315: DAG rises from 70 to 200 ng/mg wet weight, approx 150 to 450 uM. Prescott and Majerus 1983 JBC 258:764-769: Platelets: 6 uM. Also see Rittenhouse-Simmons 1979 J Clin Invest 63. Sano et al JBC 258(3):2010-2013: Report a nearly 10 fold rise. Habenicht et al 1981 JBC 256(23)12329-12335: 3T3 cells with PDGF stim: 27 uM Cornell and Vance 1987 BBA 919:23-36: 10x rise from 10 to 100 uM. Summary: I see much lower rises in my PLC models, but the baseline could be anywhere from 5 to 100 uM. I have chosen about 11 uM based on the stimulus -response characteristics from the Schaechter and Benowitz paper and the Shinomura et al papers. |
DAG 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. |
DAG 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 | PKC-act-by-DAG | Synaptic_
Network
Accession No. : 16 | PKC
Pathway No. : 71 | 0.008
(uM^-1 s^-1) | 8.6348
(s^-1) | Kd(bf) = 1079.377(uM) | - | Substrate
DAG
PKC-Ca
Product
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. | | 2 | PKC-n-DAG | Synaptic_
Network
Accession No. : 16 | PKC
Pathway No. : 71 | 0.0006
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 166.6667(uM) | - | Substrate
DAG
PKC-cytosolic
Product
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. | | 3 | DAG-Ca-PLA2-act | Synaptic_
Network
Accession No. : 16 | PLA2
Pathway No. : 72 | 0.003
(uM^-1 s^-1) | 4
(s^-1) | Kd(bf) = 1333.3333(uM) | - | Substrate
DAG
PLA2-Ca*
Product
DAG-Ca-PLA2*
| | | Synergistic activation of PLA2 by Ca and DAG. Based on Leslie and Channon 1990 BBA 1045:261 The Kd is rather large and may reflect the complications in measuring DAG. For this model it is not critical since DAG is held fixed. | | 4 | Degrade-DAG | Synaptic_
Network
Accession No. : 16 | PLCbeta
Pathway No. : 73 | 0.15
(s^-1) | 0
(s^-1) | Not applicable** | - | Substrate
DAG
Product
PC
| | | Rates based on basal and activation levels of DAG. |
** 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
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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