PDE6 hydrolyses cGMP to GMP

Stable Identifier
R-HSA-74059
Type
Reaction [transition]
Species
Homo sapiens
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Phosphodiesterase 6 (PDE6, Pittler et al. 1990, Tuteja et al. 1990, Weber et al. 1991) undergoes brief, spontaneous activations every few minutes to sustain a low, basal rate of 3',5' cyclic GMP (cGMP) hydrolysis to 5’ GMP (Cobbs 1991, Dawis et al. 1988, Hodgkin & Nunn 1988, Rieke & Baylor 1996, Wensel & Stryer 1986). However, activated transducin (GNAT1-GTP) sustains PDE6 activation allowing it to hydrolyze cGMP at a rate limited only by diffusional access to substrate (Chader et al. 1974, Goridis & Virmaux 1974, Miki et al. 1973). This event represents another amplification step in the phototransduction cascade wherein activated PDE6 hydrolyzes thousands of cGMP molecules per second. The decline in intracellular cGMP levels results in the closure of cyclic nucleotide gated cation channels (CNG channels). Mutations in the PDE6 subunits can cause retinitis pigmentosa or congenital stationary night blindness (https://sph.uth.edu/retnet/).

Literature References
PubMed ID Title Journal Year
2837463 Regulation of cyclic GMP metabolism in toad photoreceptors. Definition of the metabolic events subserving photoexcited and attenuated states

Dawis, SM, Graeff, RM, Heyman, RA, Walseth, TF, Goldberg, ND

J. Biol. Chem. 1988
2473195 Control of light-sensitive current in salamander rods

Hodgkin, AL, Nunn, BJ

J. Physiol. (Lond.) 1988
1722240 Light and dark active phosphodiesterase regulation in salamander rods

Cobbs, WH

J. Gen. Physiol. 1991
2161380 Isolation and characterization of cDNA encoding the gamma-subunit of cGMP phosphodiesterase in human retina

Tuteja, N, Danciger, M, Klisak, I, Tuteja, R, Inana, G, Mohandas, T, Sparkes, RS, Farber, DB

Gene 1990
8913594 Molecular origin of continuous dark noise in rod photoreceptors

Rieke, F, Baylor, DA

Biophys. J. 1996
2835761 Reciprocal control of retinal rod cyclic GMP phosphodiesterase by its gamma subunit and transducin

Wensel, TG, Stryer, L

Proteins 1986
4361997 Light-regulated guanosine 3',5'-monophosphate phosphodiesterase of bovine retina

Goridis, C, Virmaux, N

Nature 1974
4366891 Light activation of phosphodiesterase activity in retinal rod outer segments

Chader, GJ, Herz, LR, Fletcher, RT

Biochim. Biophys. Acta 1974
2155175 Molecular characterization of human and bovine rod photoreceptor cGMP phosphodiesterase alpha-subunit and chromosomal localization of the human gene

Pittler, SJ, Baehr, W, Wasmuth, JJ, McConnell, DG, Champagne, MS, vanTuinen, P, Ledbetter, D, Davis, RL

Genomics 1990
4359491 Regulation of cyclic nucleotide concentrations in photoreceptors: an ATP-dependent stimulation of cyclic nucleotide phosphodiesterase by light

Miki, N, Keirns, JJ, Marcus, FR, Freeman, J, Bitensky, MW

Proc. Natl. Acad. Sci. U.S.A. 1973
1720239 Genomic organization and complete sequence of the human gene encoding the beta-subunit of the cGMP phosphodiesterase and its localisation to 4p 16.3

Weber, B, Riess, O, Hutchinson, G, Collins, C, Lin, BY, Kowbel, D, Andrew, S, Schappert, K, Hayden, MR

Nucleic Acids Res. 1991
Participants
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Catalyst Activity
Title
3',5'-cyclic-GMP phosphodiesterase activity of GNAT1-GTP:PDE6 [photoreceptor disc membrane]
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Orthologous Events
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