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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

AA participated as	Molecule	Sum total of	Enzyme	Substrate of an enzyme	Product of an enzyme	Substrate in Reaction	Product in Reaction
No. of occurrences	1	0	0	0	5	4	0

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
MAPK-bistability -fig1c	35	Network	Shared_Object_MAPK-bistability-fig1c, Sos, PKC, MAPK, PLA2, Ras, PDGFR
Model for figure 1c in Bhalla US et al. Science (2002) 297(5583):1018-23. The demo for this figure is available here. This synaptic signaling model is without the MKP-1 feedback, so it is bistable and remains so over long periods.

AA acting as a Molecule in MAPK-bistability-fig1c Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
AA	MAPK-bistability -fig1c Accession No. : 35	Shared_Object_ MAPK-bistability -fig1c Pathway No. : 179	6.12	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 MAPK-bistability-fig1c Network

	Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
1	PLA2-Ca* / kenz	MAPK-bistability -fig1c Accession No. : 35	PLA2 Pathway No. : 183	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	MAPK-bistability -fig1c Accession No. : 35	PLA2 Pathway No. : 183	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	MAPK-bistability -fig1c Accession No. : 35	PLA2 Pathway No. : 183	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	MAPK-bistability -fig1c Accession No. : 35	PLA2 Pathway No. : 183	20	60	4	explicit E-S complex	Substrate APC Product AA
	Based on Leslie and Channon 1990 BBA 1045:261.
5	PLA2*-Ca / kenz	MAPK-bistability -fig1c Accession No. : 35	PLA2 Pathway No. : 183	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 MAPK-bistability-fig1c 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	MAPK-bistability -fig1c Accession No. : 35	PKC Pathway No. : 181	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	MAPK-bistability -fig1c Accession No. : 35	PKC Pathway No. : 181	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	MAPK-bistability -fig1c Accession No. : 35	PKC Pathway No. : 181	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	MAPK-bistability -fig1c Accession No. : 35	PLA2 Pathway No. : 183	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

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