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Molecule List for pathway PDE (Pathway Number 178) | | Name | Initial Conc. (uM) | Volume (fL) | Buffered | | 1 | 5primeGMP | 0 | 0.0016667 | No | | | 5primeGMP - The hydrolysed product from cGMP, by the catalytic activity of PDE's. In this case the cGMP specific PDE, PDE5. | | 2 | cGK | 1.1 | 0.0016667 | No | | | cGMP dependent protein kinase (also cGKI and cGKII) They are both present in the brain. While cGKI is selectively present only in the Purkinje cells of the cerebellum, cGKII is widely expressed in the brain tissue and may be a neuronal target of cGMP. (El-Husseini et al., J Neurochem, 1995;64:2814; Hofmann et al., 2000, J Cell Sci, 113:1671-1676; Lohmann et al., 1997, Trends Biochem Sci, 22:307-312). PKG is a dimer, though the function of dimerization is not known, with some reports indicating that dimerization may not play a vital role in the activity of the enzyme. This is the inactive form, which on being bound by cGMP becomes active. The binding sites are described by their distinct rates of dissociation of bound cyclic nucleotide (fast and slow). - Taylor et al., 2000,JBC, 275(36):28053-28062. Intracellular concentration of PKG estimated to be present in vascular smooth muscle cells is around 0.3 - 0.5 uM. (Corbin et al., 2000, Eur J Biochem,267:2760-2767) | | 3 | cGMP.PDE | 0 | 0.0016667 | No | | | cGMP bound PDE. Binding of cGMP to the allosteric cGMP-binding sites has been reported to be required for phosphorylation by cGMP-dep protein Kinase, and the elements contributing to the dimerization of this protein are located in or near the allosteric cGMP-binding sites, though the function of dimerization is unknown. (Fink et al., JBC, 1999, 274(49):34613-34620) | | 4 | cGMP.PKG | 0 | 0.0016667 | No | | | cGK bound by cGMP to the amino terminal slow site, which is subsequently bound to the fast site in the next step by another cGMP molecule. (Taylor et al., JBC, 2000, 275(36): 28053-28062). Rates from Taylor et al., 2000. | | 5 | cGMP2.PKG | 0 | 0.0016667 | No | | | Phosphorylated cGMP-dependent protein kinase. cGMP binding to the inactive cGK activates it, making it participate in further downstream regulatory processes, mostly through phosphorylation regulation of its substrates. Here it phosphorylates PDE, which hydrolyses cGMP to 5primeGMP, thus maintaining the intracellular nucleotide levels. The activity of PDE is supposed to be enhanced following phosphorylation by PKG. | | 6 | cGMP_PDE* | 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. | | 7 | Myo_phosphatase | 0.5 | 0.0016667 | No | | | Rybalkin et al., JBC, 2002, 277(5):3310-3317. Myosin phosphatase reported to be involved in dephosphorylation of PDE5. Rates from Rybalkin et al., 2002. | | 8 | PDE | 0.28 | 0.0016667 | No | | | Phophosdiesterase. Degrades cGMP to 5primeGMP. Concentration used by Kuroda et al.,(J Neurosci, 2001,21(15): 5693-5702) and initially from Kotera et al., (1997, Eur J Biochem, 249:434-442). PDE 5 is highly specific for cGMP and is considered to be the main enzyme responsible for terminating the action of cGMP generated following the release of NO from nitrergic nerves, or from vascular endothelial cells. (Gibson,Eur J Pharmacol, 2001, 411:1-10). Occupation of the allosteric binding sites by cGMP is neessary for phosphorylation by PKG. In Corbinet al., EJBiochem, 2000, 267:2760-2767, Phosphorylation of PDE and PDE activity are measured, but as mentioned, due to the different sources of Vmax values the numbers could not be matched exactly with respect to the plots in the paper, and they were either more or less by a factor of two. To match the numbers exactly we have to replicate the experimental conditions exactly. |
Pathway Details Molecule List Enzyme List Reaction List
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