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Molecule Parameter List for I1

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

I1 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	1	3	0	1

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.

I1 acting as a Molecule in  Ajay_Bhalla_2004_PKM_MKP3_Tuning Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
I1	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	PP1 Pathway No. : 341	1.8	1.5	No
I1 is a 'mixed' inhibitor, but at high enz concs it looks like a non-compet inhibitor (Foulkes et al Eur J Biochem 132 309-313 9183). We treat it as non-compet, so it just turns the enz off without interacting with the binding site. Cohen et al ann rev bioch refer to results where conc is 1.5 to 1.8 uM. In order to get complete inhib of PP1, which is at 1.8 uM, we need >= 1.8 uM.

I1 acting as a Substrate for 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
PKA-active  / PKA-phosph-I1	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	Shared_Object_ Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Pathway No. : 329	7.49996	9	4	explicit E-S complex	Substrate I1 Product I1*
#s from Bramson et al CRC crit rev Biochem 15:2 93-124. They have a huge list of peptide substrates and I have chosen high-ish rates. These consts give too much PKA activity, so lower Vmax 1/3. Now, k1 = 3e-5, k2 = 36, k3 = 9 (still pretty fast). Also lower Km 1/3 so k1 = 1e-5 Cohen et al FEBS Lett 76:182-86 1977 say rate =30% PKA act on phosphokinase beta.

I1 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	CaM(Ca)n-CaNAB  / dephosph_inhib1	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	Shared_Object_ Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Pathway No. : 329	4.97076	0.34	4	explicit E-S complex	Substrate I1* Product I1
2	PP2A  / PP2A-dephosph-I1	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	Shared_Object_ Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Pathway No. : 329	7.82828	6	4.16667	explicit E-S complex	Substrate I1* Product I1
	PP2A does most of the dephosph of I1 at basal Ca levels. See the review by Cohen in Ann Rev Biochem 1989. For now, lets halve Km. k1 was 3.3e-6, now 6.6e-6
3	CaNAB-Ca4  / dephosph_ inhib1_noCaM	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	Shared_Object_ Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Pathway No. : 329	4.97076	0.034	4	explicit E-S complex	Substrate I1* Product I1
	The rates here are so slow I do not know if we should even bother with this enz reacn. These numbers are from Liu and Storm. Other refs suggest that the Km stays the same but the Vmax goes to 10% of the CaM stim levels. Prev: k1=2.2e-9, k2 = 0.0052, k3 = 0.0013 New : k1=5.7e-8, k2=.136, k3=.034

I1 acting as a Product 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
dissoc-PP1-I1	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	PP1 Pathway No. : 341	1 (s^-1)	0 (uM^-1 s^-1)	-	-	Substrate PP1-I1 Product I1 PP1-active
Let us assume that the equil in this case is very far over to the right. This is probably safe.