Reactome | PDE6 hydrolyses cGMP to GMP

PDE6 hydrolyses cGMP to GMP

Stable Identifier

R-HSA-74059

Type

Reaction [transition]

Species

Homo sapiens

Compartment

photoreceptor disc membrane, cytosol

ReviewStatus

5/5

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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
2473195	Control of light-sensitive current in salamander rods Hodgkin, AL, Nunn, BJ	J. Physiol. (Lond.)	1988
2837463	Regulation of cyclic GMP metabolism in toad photoreceptors. Definition of the metabolic events subserving photoexcited and attenuated states Dawis, SM, Walseth, TF, Heyman, RA, Graeff, RM, Goldberg, ND	J. Biol. Chem.	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 Mohandas, T, Sparkes, RS, Tuteja, R, Inana, G, Danciger, M, Klisak, I, Tuteja, N, 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 Herz, LR, Chader, GJ, 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 Ledbetter, D, Davis, RL, Champagne, MS, vanTuinen, P, Wasmuth, JJ, McConnell, DG, Baehr, W, Pittler, SJ	Genomics	1990
4359491	Regulation of cyclic nucleotide concentrations in photoreceptors: an ATP-dependent stimulation of cyclic nucleotide phosphodiesterase by light Bitensky, MW, Miki, N, Marcus, FR, Keirns, JJ, Freeman, J	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 Lin, BY, Riess, O, Weber, B, Hutchinson, G, Kowbel, D, Schappert, K, Andrew, S, Collins, C, Hayden, MR	Nucleic Acids Res.	1991