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Molecule Parameter List for cAMP

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

*cAMP* 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	4	5	4	0

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
Ajay_Bhalla_ 2004_Feedback_ Tuning	78	Network	Shared_Object_Ajay_Bhalla_2004_Feedback_Tuning, PKC, PLA2, PLCbeta, Gq, MAPK, Ras, EGFR, Sos, PLC_g, CaMKII, CaM, PP1, PP2B, PKA, AC
This model is taken from Ajay SM, Bhalla US. Eur J Neurosci. 2004 Nov;20(10):2671-80. This is the feedback model from Figure 8a.

cAMP acting as a Molecule in Ajay_Bhalla_2004_Feedback_Tuning Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
cAMP	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	Shared_Object_ Ajay_Bhalla_ 2004_Feedback_ Tuning Pathway No. : 347	0	1.5	No
The conc of this has been a problem. Schaecter and Benowitz use 50 uM, but Shinomura et al have < 5. So I have altered the cAMP-dependent rates in the PKA model to reflect this.

cAMP acting as a Substrate for an Enzyme in Ajay_Bhalla_2004_Feedback_Tuning Network

	Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
1	cAMP-PDE / PDE	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	AC Pathway No. : 362	19.8413	10	4	explicit E-S complex	Substrate cAMP Product AMP
	Best rates are from Conti et al Biochem 34 7979-7987 1995. Though these are for the Sertoli cell form, it looks like they carry nicely into alternatively spliced brain form. See Sette et al JBC 269:28 18271-18274 Km ~2 uM, Vmax est ~ 10 umol/min/mg for pure form. Brain protein is 93 kD but this was 67. So k3 ~10, k2 ~40, k1 ~4.2e-6
2	cAMP-PDE* / PDE*	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	AC Pathway No. : 362	19.8413	20	4	explicit E-S complex	Substrate cAMP Product AMP
	This form has about twice the activity of the unphosphorylated form. See Sette et al JBC 269:28 18271-18274 1994. We'll ignore cGMP effects for now.
3	PDE1 / PDE1	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	AC Pathway No. : 362	39.7006	1.667	4.0012	explicit E-S complex	Substrate cAMP Product AMP
	Rate is 1/6 of the CaM stim form. We'll just reduce all lf k1, k2, k3 so that the Vmax goes down 1/6.
4	CaM.PDE1 / CaM.PDE1	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	AC Pathway No. : 362	39.6825	10	4	explicit E-S complex	Substrate cAMP Product AMP
	Max activity ~10umol/min/mg in presence of lots of CaM. Affinity is low, 40 uM. k3 = 10, k2 = 40, k1 = (50/40) / 6e5.

cAMP acting as a Product of an Enzyme in Ajay_Bhalla_2004_Feedback_Tuning Network

	Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
1	AC1-CaM / kenz	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	AC Pathway No. : 362	20	18	4	explicit E-S complex	Substrate ATP Product cAMP

2	AC2* / kenz	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	AC Pathway No. : 362	20.1153	7	4	explicit E-S complex	Substrate ATP Product cAMP
	Reduced Km to match expt data for basal activation of AC2 by PKC. Now k1 = 2.9e-6, k2 = 72, k3 = 18
3	AC2-Gs / kenz	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	AC Pathway No. : 362	20	18	4	explicit E-S complex	Substrate ATP Product cAMP

4	AC1-Gs / kenz	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	AC Pathway No. : 362	20	18	4	explicit E-S complex	Substrate ATP Product cAMP

5	AC2*-Gs / kenz	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	AC Pathway No. : 362	60	54	4	explicit E-S complex	Substrate ATP Product cAMP

cAMP acting as a Substrate in a reaction in Ajay_Bhalla_2004_Feedback_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	cAMP-bind-site-B 1	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	PKA Pathway No. : 361	54 (uM^-1 s^-1)	33 (s^-1)	Kd(bf) = 0.6111(uM)	-	Substrate R2C2 cAMP Product R2C2-cAMP
	Hasler et al FASEB J 6:2734-2741 1992 say Kd =1e-7M for type II, 5.6e-8 M for type I. Take mean which comes to 2e-13 #/cell Smith et al PNAS USA 78:3 1591-1595 1981 have better data. First kf/kb=2.1e7/M = 3.5e-5 (#/cell). Ogreid and Doskeland Febs Lett 129:2 287-292 1981 have figs suggesting time course of complete assoc is < 1 min.
2	cAMP-bind-site-B 2	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	PKA Pathway No. : 361	54 (uM^-1 s^-1)	33 (s^-1)	Kd(bf) = 0.6111(uM)	-	Substrate R2C2-cAMP cAMP Product R2C2-cAMP2
	For now let us set this to the same Km (1e-7M) as site B. This gives kf/kb = .7e-7M * 1e6 / (6e5^2) : 1/(6e5^2) = 2e-13:2.77e-12 Smith et al have better values. They say that this is cooperative, so the consts are now kf/kb =8.3e-4
3	cAMP-bind-site-A 1	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	PKA Pathway No. : 361	74.9997 (uM^-1 s^-1)	110 (s^-1)	Kd(bf) = 1.4667(uM)	-	Substrate R2C2-cAMP2 cAMP Product R2C2-cAMP3
4	cAMP-bind-site-A 2	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	PKA Pathway No. : 361	74.9997 (uM^-1 s^-1)	32.5 (s^-1)	Kd(bf) = 0.4333(uM)	-	Substrate R2C2-cAMP3 cAMP Product R2C2-cAMP4

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