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Molecule Parameter List for cGMP | 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 |
Accession and Pathway Details | |
| Accession Name | Accession No. | Accession Type | Pathway Link | | cGMP_regulation | 34 | Network |
Shared_Object_cGMP_regulation, GC, PDE | Though Corbin JD. et al. Eur J Biochem. (2000) 267(9):2760-7 has been mentioned in the citation, this model has been made with inputs from different literature sources, each of which has been mentioned in the notes sections. This model features hydrolysis of cGMP by bovine PDE, phosphorylation of PDE by bovine lung PKG, and activation of bovine lung PKG by cGMP binding. These mechanisms are known to be involved in cGMP level regulation. Rates have been used from different sources and the model has been tested based on Corbin JD. et al., since their work involved measuring the PDE phosphorylation and PDE activity.
On replicating Figures 2, 3 and 4 from their paper, there is approx 30% difference in results but the qualitative shape of the curves is very similar. This might be due to the fact that the Vmax values were used from different literature sources. This might lead to the discrepancy in the numbers in this model. The values shown in this model are near estimated physiological levels.In order to replicate the Figures more closely, we have run additional simulations with concentration terms changed so as to replicate the experimental conditions exactly. |
cGMP acting as a Molecule in cGMP_regulation Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | cGMP | cGMP_regulation
Accession No. : 34 | Shared_Object_
cGMP_regulation
Pathway No. : 176 | 0 | 0.0016667 | No | | cGMP takes part in various reactions downstream. One of the interesting schemes are the binding of cGMP to the allosteric cGMP binding sites, which is supposed to be essential for the phosphorylation of PDE by PKG. So in the cGMP_PDE* enzyme complex, there is more then one cGMP molecule bound. |
cGMP acting as a Substrate for an Enzyme in cGMP_regulation Network
| | Enzyme Molecule /
Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | | 1 | PDE /
PDE_basal | cGMP_regulation
Accession No. : 34 | PDE
Pathway No. : 178 | 0.979992 | 2.4 | 4 | Classical Michaelis-Menten
V = Etot.S.Kcat/Km+S | Substrate
cGMP
Product
5primeGMP
| | 2 | cGMP.PDE /
cGMP.PDE_basal | cGMP_regulation
Accession No. : 34 | PDE
Pathway No. : 178 | 0.979992 | 2.4 | 4 | explicit E-S complex | Substrate
cGMP
Product
5primeGMP
| | 3 | cGMP_PDE* /
PDE_active | cGMP_regulation
Accession No. : 34 | PDE
Pathway No. : 178 | 0.580001 | 3.87 | 4 | Classical Michaelis-Menten
V = Etot.S.Kcat/Km+S | Substrate
cGMP
Product
5primeGMP
| | | In this cGMP_PDE* enzyme complex, there are more than one cGMP molecule bound, since initially, cGMP binding to the allosteric binding sites is essential for phosphorylation by PKG. Vmax initially from Turko et al., 1998, Biochem J, 329:505-510 and Kuroda et al., 2001, J Neurosci,21(15):5693-5702. PDE has a high catalytic rate for cGMP hydrolysis. Km values reported are ~1-2 uM in various studies, including studies with purified enzyme preparations.(Fink et al., JBC, 1999, 274(49):34613-34620 and cited refs in their paper). Value used here from Mehats et al., Trends in Endocrinology & Metabolism, 2002, 13(1):29-35. Values similar to those used by Kuroda et al.,J Neurosci, 2001, 21(15):5693-5702. Km for cGMP decreased from 0.98 to 0.58 uM and Vmax was reported to be slightly increased by phosphorylation. (Corbin et al., Eur J Biochem, 2000) |
cGMP acting as a Product of an Enzyme in cGMP_regulation Network
Enzyme Molecule /
Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | sGCtot /
sGC_act | cGMP_regulation
Accession No. : 34 | GC
Pathway No. : 177 | 30 | 22.05 | 4 | Classical Michaelis-Menten
V = Etot.S.Kcat/Km+S | Substrate
GTP
Product
cGMP
| | The range of estimates found in the literature are: Km -> 40 - 150 uM (without NO) 20 - 40 uM (with NO) Vmax -> 10 - 100 nmol/mg/min (wihtout NO) 10 - 40 umol/mg/min (with NO). ----- thru personal correspondence from T. Bellamy, Wolfson Ins. for Biomedical Sciences, UK. NO increases the Vmax of sGC by 100-200 fold, and it has been proposed that this activation occurs subsequent to the binding of NO toa heme moiety on the enzyme. (Stone and Marletta,1995, Biochemistry,34:14668-14674). |
cGMP acting as a Substrate in a reaction in cGMP_regulation 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 | PDEbind_cGMP | cGMP_regulation
Accession No. : 34 | PDE
Pathway No. : 178 | 10
(uM^-1 s^-1) | 13
(s^-1) | Kd(bf) = 1.3(uM) | - | Substrate
PDE
cGMP
Product
cGMP.PDE
| | | Kd ~1.3 uM. (Turko et al., JBC, 1996, 271(36):22240-22244, and Corbin et al., Eur J Biochem, 2000,267:2760-2767) | | 2 | cGMPbindcGK | cGMP_regulation
Accession No. : 34 | PDE
Pathway No. : 178 | 10
(uM^-1 s^-1) | 81
(s^-1) | Kd(bf) = 8.1(uM) | - | Substrate
cGK
cGMP
Product
cGMP.PKG
| | | Kinase activation in both the isoforms of cGK depends on cyclic nucleotide occupation of the two cyclic nucleotide binding sites in the regulatory domain. This event is supposed to reduce the affinity of the auto-inhibition region of the regulatory domain for the catalytic domain. Investigations revealed that cGMP binds to a slowly dissociating cyclic nucleotide binding site and induces a conformational change resulting in a partially active kinase. Subsequent occupation of the second, rapid dissociation site imparts additional conformational change until it forms the elongated shape that is reported to be associated with the fully active enzyme. (Taylor et al., 2000, JBC, 275(36):28053-28062) Dissociation rates for cGKII binding sites from Taylor et al., 2000, and other refs cited in their paper. cGMP dissociation from slow site -- 8.1/s (Smith et al., JBC,1995, 271(34):20756-20762) | | 3 | fast_site_bind | cGMP_regulation
Accession No. : 34 | PDE
Pathway No. : 178 | 10
(uM^-1 s^-1) | 37
(s^-1) | Kd(bf) = 3.7(uM) | - | Substrate
cGMP
cGMP.PKG
Product
cGMP2.PKG
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| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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