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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
mRNA synthesis	94	Network	kinetics,  compartment_1,  compartment_2
The model consists of three major pathways: Calcium-calmodulin dependent protein kinase IV (CaMKIV), Mitogen-activated protein kinase (MAPK) and Protein Phosphatase 1 (PP1). Each of these converged on CREB activation. We also modeled further interactions with Transducer of regulated CREB activity 1 (TORC1) and the protein kinase A (PKA) pathway.

I1 acting as a Molecule in  mRNA synthesis Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
I1	mRNA synthesis Accession No. : 94	kinetics Pathway No. : 1112	1.8	1000	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  mRNA synthesis Network

Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
PKA_dash_active  / PKA_dash_ phosph_dash_I1	mRNA synthesis Accession No. : 94	kinetics Pathway No. : 1112	7.5	9	4	explicit E-S complex	Substrate I1 Product I1_star
#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  mRNA synthesis Network

	Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
1	PP2A  / PP2A_dash_ dephosph_dash_ I1	mRNA synthesis Accession No. : 94	kinetics Pathway No. : 1112	7.8283	6	4.16666666667	explicit E-S complex	Substrate I1_star 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
2	CaM(Ca)n_dash_ CaNAB  / dephosph_inhib1	mRNA synthesis Accession No. : 94	kinetics Pathway No. : 1112	4.9708	0.34	4	explicit E-S complex	Substrate I1_star Product I1
3	CaNAB_dash_Ca4  / dephosph_ inhib1_noCaM	mRNA synthesis Accession No. : 94	kinetics Pathway No. : 1112	4.9708	0.034	4	explicit E-S complex	Substrate I1_star 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  mRNA synthesis 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_dash_ PP1_dash_I1	mRNA synthesis Accession No. : 94	kinetics Pathway No. : 1112	1 (s^-1)	0 (uM^-1 s^-1)	-	-	Substrate PP1_dash_I1 Product I1 PP1_dash_ active_c
Let us assume that the equil in this case is very far over to the right. This is probably safe.