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Accession Type:
Network
cGMP_regulation
Shared_Object_
cGMP_regulation
GC
PDE
 Molecule
 Enzyme
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Enzyme List for pathway PDE (Pathway Number 178)

 Molecule Name/
Site Name
Km (uM) kcat (1/s)Ratio
(k2/k3)
Enzyme TypeSubstrate Product
1 Enzyme Activity:
cGMP.PDE_basal

Enzyme Molecule:
cGMP.PDE
0.9799922.44explicit E-S complexcGMP
5primeGMP
2 Enzyme Activity:
PDE_active

Enzyme Molecule:
cGMP_PDE*
0.5800013.874Classical Michaelis-Menten
V = Etot.S.Kcat/Km+S
cGMP
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)
3 Enzyme Activity:
PDE_basal

Enzyme Molecule:
PDE
0.9799922.44Classical Michaelis-Menten
V = Etot.S.Kcat/Km+S
cGMP
5primeGMP
4 Enzyme Activity:
PKG_act

Enzyme Molecule:
cGMP2.PKG
100.60224explicit E-S complexcGMP.PDE
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.
5 Enzyme Activity:
PP1

Enzyme Molecule:
Myo_phosphatase
101.984explicit E-S complexcGMP_PDE*
cGMP.PDE
6 Enzyme Activity:
sGCppase_act

Enzyme Molecule:
cGMP2.PKG
0.512.314explicit E-S complexsGC-ppase
sGC-ppase*


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