Application | Comment | Organism |
---|---|---|
pharmacology | enzyme RDH8 is a therapeutic target for controlling bis-retinoid A2E cytotoxicity | Mus musculus |
Protein Variants | Comment | Organism |
---|---|---|
additional information | generation of enzyme Rdh8-/- knockout mice. Cyclic-light-reared Rdh8-/- mice accumulates A2E and RPE lipofuscin approximately 1.5times and approximately 2times faster, respectively, than dark-reared mice. Moving Rdh8-/- mice from cyclic-light to darkness results in bis-retinoid A2E levels less than expected to have accumulated before the move. A2E levels are significantly higher in cyclic-light compared to dark-reared animals at 2, 3, and 6 months of age. In Rdh8-/- mice, the potential contribution of elevated all-trans-retinal to bis-retinoid formation can be maximized | Mus musculus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
all-trans-retinal + NADPH + H+ | Mus musculus | - |
all-trans-retinol + NADP+ | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mus musculus | D3Z6W3 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
eye | rod outer segment | Mus musculus | - |
retina | - |
Mus musculus | - |
retinal pigment epithelium | - |
Mus musculus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
all-trans-retinal + NADPH + H+ | - |
Mus musculus | all-trans-retinol + NADP+ | - |
? | |
additional information | the rod outer segment enzyme retinol dehydrogenase RDH8 uses NADPH as a cofactor. 11-cis retinal is not a substrate of RDH8. Narrow substrate specificity of RDH8 | Mus musculus | ? | - |
- |
Synonyms | Comment | Organism |
---|---|---|
RDH8 | - |
Mus musculus |
RDH8 | gen ename | Mus musculus |
retinol dehydrogenase 8 | - |
Mus musculus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NADP+ | - |
Mus musculus | |
NADPH | - |
Mus musculus |
General Information | Comment | Organism |
---|---|---|
malfunction | cyclic-light-reared Rdh8-/- knockout mice show elevated levels of all-trans retinal, contributing to RPE lipofuscin formation and accumulation. Lipofuscin accumulates in the retinal pigment epithelium (RPE) of Rdh8-/- mice | Mus musculus |
physiological function | bis-retinoids are a major component of lipofuscin that accumulates in the retinal pigment epithelium (RPE) in aging and age-related macular degeneration (AMD). Bis-retinoids are known to originate from retinaldehydes required for the light response of photoreceptor cells, relative contributions of the chromophore, 11-cis retinal, and photoisomerization product, all-trans retinal, are analyzed, overview. In photoreceptor outer segments, all-trans retinal, but not 11-cis retinal, is reduced by retinol dehydrogenase 8 (RDH8). The reductase activity of RDH8 keeps in check the generation of bis-retinoids from all-trans retinal released by photoactivated rhodopsin. There is no significant increase in lipofuscin precursor fluorescence in wild-type mouse rods following light | Mus musculus |