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Molecule Parameter List for AA | 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 |
AA acting as a Molecule in Synaptic_Network Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | AA | Synaptic_
Network
Accession No. : 16 | Shared_Object_
Synaptic_
Network
Pathway No. : 70 | 0 | 1000 | No | | Arachidonic Acid. This messenger diffuses through membranes as well as cytosolically, has been suggested as a possible retrograde messenger at synapses. |
AA 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 | PLA2-Ca* /
kenz | Synaptic_
Network
Accession No. : 16 | PLA2
Pathway No. : 72 | 20 | 5.4 | 4 | explicit E-S complex | Substrate
APC
Product
AA
| | | Based on Leslie and Channon 1990 BBA 1045:261, in relation to the other PLA2 inputs (not including MAPK). Ca alone is rather a weak input. | | 2 | PIP2-PLA2* /
kenz | Synaptic_
Network
Accession No. : 16 | PLA2
Pathway No. : 72 | 20 | 11.04 | 4 | explicit E-S complex | Substrate
APC
Product
AA
| | | Based on Leslie and Channon 1990 BBA 1045:261. | | 3 | PIP2-Ca-PLA2* /
kenz | Synaptic_
Network
Accession No. : 16 | PLA2
Pathway No. : 72 | 20 | 36 | 4 | explicit E-S complex | Substrate
APC
Product
AA
| | | Based on AA generation by different stimuli according to Leslie and Channon 1990 BBA 1045:261 | | 4 | DAG-Ca-PLA2* /
kenz | Synaptic_
Network
Accession No. : 16 | PLA2
Pathway No. : 72 | 20 | 60 | 4 | explicit E-S complex | Substrate
APC
Product
AA
| | | Based on Leslie and Channon 1990 BBA 1045:261. | | 5 | PLA2*-Ca /
kenz | Synaptic_
Network
Accession No. : 16 | PLA2
Pathway No. : 72 | 20 | 120 | 4 | explicit E-S complex | Substrate
APC
Product
AA
| | | This form should be 3 to 6 times as fast as the Ca-only form, from Lin et al 1993 Cell 269-278 Nemenoff et al 1993 JBC 268:1960 Several forms contribute to the Ca-stimulated form, so this rate has to be a factor larger than their total contribution. I assign Vmax as the scale factor here because there is lots of APC substrate, so all the PLA2 complex enzymes are limited primarily by Vmax. |
AA 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-Ca-AA | Synaptic_
Network
Accession No. : 16 | PKC
Pathway No. : 71 | 0.0012
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 83.3333(uM) | - | Substrate
AA
PKC-Ca
Product
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 | | 2 | PKC-act-by-AA | Synaptic_
Network
Accession No. : 16 | PKC
Pathway No. : 71 | 0.0001
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 833.3333(uM) | - | Substrate
AA
PKC-cytosolic
Product
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. | | 3 | PKC-n-DAG-AA | Synaptic_
Network
Accession No. : 16 | PKC
Pathway No. : 71 | 0.018
(uM^-1 s^-1) | 2
(s^-1) | Kd(bf) = 111.1111(uM) | - | Substrate
AA
PKC-DAG
Product
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. | | 4 | Degrade-AA | Synaptic_
Network
Accession No. : 16 | PLA2
Pathway No. : 72 | 0.4
(s^-1) | 0
(s^-1) | - | - | Substrate
AA
Product
APC
| | | Degradation pathway for AA. APC is a convenient buffered pool to dump it back into, though the actual metabolism is probably far more complex. For the purposes of the full model we use a rate of degradation of 0.4/sec to give a dynamic range of AA comparable to what is seen experimentally. Wijkander and Sundler 1991 Eur J Biochem 202:873 Leslie and Channon 1990 BBA 1045:261 |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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