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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

DAG 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	4	4	0

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning	77	Network	Shared_Object_Ajay_Bhalla_2004_PKM_MKP3_Tuning,  PKC,  PLA2,   PLCbeta,  Ras,  Gq,   MAPK,  EGFR,  Sos,   PLC_g,  CaMKII,  CaM,   PP1,  PP2B,  PKA,   AC,  MKP3,  PKM
This model is based on Ajay SM, Bhalla US. Eur J Neurosci. 2004 Nov;20(10):2671-80. This is the feedforward model with MPK3 from figure 8a.

DAG acting as a Molecule in  Ajay_Bhalla_2004_PKM_MKP3_Tuning Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
DAG	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	Shared_Object_ Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Pathway No. : 329	0	1.5	No

DAG acting as a Product of an Enzyme in  Ajay_Bhalla_2004_PKM_MKP3_Tuning Network

	Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
1	PLC-Ca  / PLC-Ca	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	PLCbeta Pathway No. : 332	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. k1 = 1.5e-5, now 4.2e-6 k2 = 70/sec; now 40/sec k3 = 17.5/sec; now 10/sec Note that the wording in Sternweis et al is ambiguous re the Km.
2	PLC-Ca-Gq  / PLCb-Ca-Gq	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	PLCbeta Pathway No. : 332	5.00003	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. k1 = 5e-5/sec k2 = 240/sec; now 120/sec k3 = 60/sec; now 30/sec Note that the wording in Sternweis et al is ambiguous wr. to the Km for Gq vs non-Gq states of PLC. K1 is still a bit too low. Raise to 7e-5 9 Jun 1996: k1 was 0.0002, changed to 5e-5
3	Ca.PLC_g  / PIP2_hydrolysis	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	PLC_g Pathway No. : 338	97.2222	14	4	explicit E-S complex	Substrate PIP2 Product DAG IP3
	Mainly Homma et al JBC 263:14 1988 pp 6592, but these parms are the Ca-stimulated form. It is not clear whether the enzyme is activated by tyrosine phosphorylation at this point or not. Wahl et al JBC 267:15 10447-10456 1992 say that the Ca_stim and phosph form has 7X higher affinity for substrate than control. This is close to Wahl's figure 7, which I am using as reference.
4	Ca.PLC_g*  / PIP2_hydrolysis	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	PLC_g Pathway No. : 338	19.7917	57	4	explicit E-S complex	Substrate PIP2 Product DAG IP3
	Mainly Homma et al JBC 263:14 1988 pp 6592, but these parms are the Ca-stimulated form. It is not clear whether the enzyme is activated by tyrosine phosphorylation at this point or not. Wahl et al JBC 267:15 10447-10456 1992 say that this has 7X higher affinity for substrate than control.

DAG acting as a Substrate in a reaction in  Ajay_Bhalla_2004_PKM_MKP3_Tuning 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	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	PKC Pathway No. : 330	0.008 (uM^-1 s^-1)	8.6348 (s^-1)	Kd(bf) = 1079.3729(uM)	-	Substrate DAG PKC-Ca Product PKC-Ca-DAG
	Need est of rate. Assume it is fast Obtained from param search kf raised 10 X : see Shinomura et al PNAS 88 5149-5153 1991. kf changed from 3.865e-7 to 2.0e-7 in line with closer analysis of Shinomura data. 26 June 1996: Corrected DAG data: reduce kf 15x from 2e-7 to 1.333e-8
2	PKC-n-DAG	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	PKC Pathway No. : 330	0.0006 (uM^-1 s^-1)	0.1 (s^-1)	Kd(bf) = 166.6658(uM)	-	Substrate DAG PKC-cytosolic Product PKC-DAG
	kf raised 10 X based on Shinomura et al PNAS 88 5149-5153 1991 closer analysis of Shinomura et al: kf now 1e-8 (was 1.66e-8). Further tweak. To get sufficient AA synergy, increase kf to 1.5e-8 26 June 1996: Corrected DAG levels: reduce kf by 15x from 1.5e-8 to 1e-9
3	DAG-Ca-PLA2-act	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	PLA2 Pathway No. : 331	0.003 (uM^-1 s^-1)	4 (s^-1)	Kd(bf) = 1333.3467(uM)	-	Substrate DAG PLA2-Ca* Product DAG-Ca-PLA2*
	27 June 1996 Scaled kf down by 0.015 from 3.33e-7 to 5e-9 to fit with revised DAG estimates and use of mole-fraction to calculate eff on PLA2.
4	Degrade-DAG	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	PLCbeta Pathway No. : 332	0.15 (s^-1)	0 (s^-1)	Not applicable**	-	Substrate DAG Product PC
	These rates are the same as for degrading IP3, but I am sure that they could be improved. Lets double kf to 0.2, since the amount of DAG in the cell should be <= 1uM. Need to double it again, for the same reason. kf now 0.5 27 June 1996 kf is now 0.02 to get 50 sec time course 30 Aug 1997: Raised kf to 0.11 to accomodate PLC_gamma 27 Mar 1998: kf now 0.15 for PLC_gamma

** 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