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Molecule Parameter List for cGMP_PDE* | 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_PDE* acting as a Molecule in cGMP_regulation Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | cGMP_PDE* | cGMP_regulation
Accession No. : 34 | PDE
Pathway No. : 178 | 0 | 0.0016667 | No | | Phosphorylated PDE. Phosphorylated by PKG, which requires cGMP to be bound to the allosteric binding sites on PDE. Hence there are more than one molecule of cGMP bound to the active enzyme complex, since initially, cGMP binding to the allosteric binding sites is necessary for phosphorylation of PDE by PKG. |
cGMP_PDE* acting as an Enzyme in cGMP_regulation Network
Enzyme Molecule /
Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | 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_PDE* 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 | Myo_phosphatase /
PP1 | cGMP_regulation
Accession No. : 34 | PDE
Pathway No. : 178 | 10 | 1.98 | 4 | explicit E-S complex | Substrate
cGMP_PDE*
Product
cGMP.PDE
|
cGMP_PDE* 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 | cGMP2.PKG /
PKG_act | cGMP_regulation
Accession No. : 34 | PDE
Pathway No. : 178 | 10 | 0.6022 | 4 | explicit E-S complex | Substrate
cGMP.PDE
Product
cGMP_PDE*
| | Phosphorylation of PDE actually increases the enzyme activity. And occupation of the allosteric binding sites by cGMP is necessary for phosphorylation by PKG. Phosphorylation following the occupation of the allosteric sites by cGMP. (Gibson, Eur J Pharmacol,2001,411:1-10, Corbin et al., 2000, Eur J Biochem, 267:2760-2767). Phosphorylation resulted in increases in phosphate content up to 0.6 mol per PDE5 subunit. (Corbin et al., 2000), and since PKG is known to catalyze autophosphorylation, it was found to incorporate 2 mol per PDE5 subunit in 60 mins. |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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