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Molecule Parameter List for PLC-Ca-Gq

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

PLC-Ca-Gq 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	1	0	0	1	2

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
Ajay_Bhalla_ 2004_PKM_Tuning	76	Network	PKC,  Shared_Object_Ajay_Bhalla_2004_PKM_tuning,  PLA2,   PLCbeta,  Gq,  MAPK,   Ras,  EGFR,  Sos,   PLC_g,  CaMKII,  CaM,   PP1,  PP2B,  PKA,   AC,  PKM
This model is taken from the Ajay SM, Bhalla US. Eur J Neurosci. 2004 Nov;20(10):2671-80. This is the reference feedforward model from Figure 8a.

PLC-Ca-Gq acting as a Molecule in  Ajay_Bhalla_2004_PKM_Tuning Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
PLC-Ca-Gq	Ajay_Bhalla_ 2004_PKM_Tuning Accession No. : 76	PLCbeta Pathway No. : 315	0	1.5	No
This should really be labelled PLC-G*GTP-Ca. This is the activated form of the enzyme. Mahama and Linderman assume that the IP3 precursors are not rate-limiting, but I will include those for completeness as they may be needed later.

PLC-Ca-Gq acting as an Enzyme in  Ajay_Bhalla_2004_PKM_Tuning Network

Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
PLC-Ca-Gq / PLCb-Ca-Gq	Ajay_Bhalla_ 2004_PKM_Tuning Accession No. : 76	PLCbeta Pathway No. : 315	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

PLC-Ca-Gq acting as a Substrate in a reaction in  Ajay_Bhalla_2004_PKM_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
Inact-PLC-Gq	Ajay_Bhalla_ 2004_PKM_Tuning Accession No. : 76	PLCbeta Pathway No. : 315	0.0133 (s^-1)	0 (uM^-1 s^-1)	-	-	Substrate PLC-Ca-Gq Product G*GDP PLC-Ca
This process is assumed to be directly caused by the inactivation of the G*GTP to G*GDP. Hence, kf = .013 /sec = 0.8/min, same as the rate for Inact-G. kb = 0 since this is irreversible. We may be interested in studying the role of PLC as a GAP. If so, the kf would be faster here than in Inact-G

PLC-Ca-Gq acting as a Product in a reaction in  Ajay_Bhalla_2004_PKM_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	Act-PLC-by-Gq	Ajay_Bhalla_ 2004_PKM_Tuning Accession No. : 76	PLCbeta Pathway No. : 315	25.2 (uM^-1 s^-1)	1 (s^-1)	Kd(bf) = 0.0397(uM)	-	Substrate G*GTP PLC-Ca Product PLC-Ca-Gq
	Affinity for Gq is > 20 nM (Smrcka et al Science251 804-807 1991) so [Gq].kf = kb so 40nM * 6e5 = kb/kf = 24e3 so kf = 4.2e-5, kb =1
2	PLC-Gq-bind-Ca	Ajay_Bhalla_ 2004_PKM_Tuning Accession No. : 76	PLCbeta Pathway No. : 315	29.9997 (uM^-1 s^-1)	1 (s^-1)	Kd(bf) = 0.0333(uM)	-	Substrate Ca PLC-Gq Product PLC-Ca-Gq
	this step has a high affinity for Ca, from Smrcka et al. 0.1uM so kf /kb = 1/6e4 = 1.666e-5:1. See the Act-PLC-by-Gq reac. 11 Jun 1996: Raised kf to 5e-5 based on match to conc-eff curves from Smrcka et al.