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Literature summary for 1.1.1.300 extracted from

  • Boyer, N.P.; Thompson, D.A.; Koutalos, Y.
    Relative contributions of all-trans and 11-cis retinal to formation of lipofuscin and A2E accumulating in mouse retinal pigment epithelium (2021), Invest. Ophthalmol. Vis. Sci., 62, 1 .
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
pharmacology enzyme RDH8 is a therapeutic target for controlling bis-retinoid A2E cytotoxicity Mus musculus

Protein Variants

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/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
all-trans-retinal + NADPH + H+ Mus musculus
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all-trans-retinol + NADP+
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?

Organism

Organism UniProt Comment Textmining
Mus musculus D3Z6W3
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-

Source Tissue

Source Tissue Comment Organism Textmining
eye rod outer segment Mus musculus
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retina
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Mus musculus
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retinal pigment epithelium
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Mus musculus
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Substrates and Products (Substrate)

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 ?
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Synonyms

Synonyms Comment Organism
RDH8
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Mus musculus
RDH8 gen ename Mus musculus
retinol dehydrogenase 8
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Mus musculus

Cofactor

Cofactor Comment Organism Structure
NADP+
-
Mus musculus
NADPH
-
Mus musculus

General Information

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