<i>Priority Paper</i>  The metabolic pathway of visual pigment chromophore formation in <i>Drosophila melanogaster</i>

Seki, Takaharu; Isono, Kunio; Ozaki, Kaoru; Tsukahara, Yasuo; Shibata-Katsuta, Yuko; Ito, Masayoshi; Irie, Toshiaki; Katagiri, Masatoshi

doi:10.1046/j.1432-1327.1998.2570522.x

Cited by 33 publications

(22 citation statements)

References 14 publications

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“…The biochemical steps involved in this process are not understood. The involvement of a P-450 cytochrome in creation of (3R)-3-hydroxyretinal was previously demonstrated in Drosophila head extracts (42), but an isomerization reaction converting (3R)-3-hydroxyretinal to (3S)-3-hydroxyretinal has not been described. The NinaG protein could act in this process or, alternatively, within a distinct pathway responsible for (3S)-3-hydroxyretinal production.…”

Section: Resultsmentioning

confidence: 98%

The Drosophila ninaG Oxidoreductase Acts in Visual Pigment Chromophore Production

Sarfare

Ahmad

Joyce

et al. 2005

Journal of Biological Chemistry

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Section: Resultsmentioning

confidence: 98%

The Drosophila ninaG Oxidoreductase Acts in Visual Pigment Chromophore Production

Sarfare

Ahmad

Joyce

et al. 2005

Journal of Biological Chemistry

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“…As we show here, the moth NinaB can produce in a one step reaction the visual chromophore from plant-derived zeaxanthin (3,3Ј-R,R-dihydroxy-␤,␤-carotene). In higher flies, however, visual chromophore production requires further modifications of the primary cleavage product such R to S enatiomerization and/or hydroxylation reactions (30).…”

Section: Discussionmentioning

confidence: 99%

NinaB combines carotenoid oxygenase and retinoid isomerase activity in a single polypeptide

Oberhauser

Voolstra

Bangert

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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In animals, successful production of the visual chromophore (11-cis-retinal or derivatives thereof such as 11-cis-3-hydroxy-retinal) is essential for photoreceptor cell function and survival. These carotenoid-derived compounds must combine with a protein moiety (the opsin) to establish functional visual pigments. Evidence from cell culture systems has implicated that the retinal pigment epithelium protein of 65 kDa (RPE65) is the long-sought all-trans to 11-cis retinoid isomerase. RPE65 is structurally related to nonheme iron oxygenases that catalyze the conversion of carotenoids into retinoids. In vertebrate genomes, two carotenoid oxygenases and RPE65 are encoded, whereas in insect genomes only a single representative of this protein family, named NinaB (denoting neither inactivation nor afterpotential mutant B), is encoded. We here cloned and functionally characterized the ninaB gene from the great wax moth Galleria mellonella. We show that the recombinant purified enzyme combines isomerase and oxygenase (isomerooxygenase) activity in a single polypeptide. From kinetics and isomeric composition of cleavage products of asymmetrical carotenoid substrates, we propose a model for the spatial arrangement between substrate and enzyme. In Drosophila, we show that carotenoid-isomerooxygenase activity of NinaB is more generally found in insects, and we provide physiological evidence that carotenoids such as 11-cis-retinal can promote visual pigment biogenesis in the dark. Our study demonstrates that trans/cis isomerase activity can be intrinsic to this class of proteins and establishes these enzymes as key components for both invertebrate and vertebrate vision. RPE65 ͉ vision ͉ visual chromophoreA nimal visual pigments (rhodopsins) are bipartite G-proteincoupled receptors consisting of an opsin moiety and a carotenoid-derived retinylidene chromophore (1). Two fundamental issues in the pathway for visual chromophore production have resisted molecular analysis for a long time: first, the oxidative cleavage of C 40 carotenoids into C 20 retinoids; and second, the all-trans to 11-cis isomerization of retinoids.The molecular basis for the oxidative cleavage was resolved by cloning and characterization of NinaB (denoting neither inactivation nor afterpotential mutant B), which converts carotenoids into retinoids in Drosophila melanogaster (2, 3). Thereafter, several related carotenoid-15,15Ј-oxygenases (CMO1) have been identified and characterized in vertebrates including human beings (4-7). In addition, in vertebrates a second type of carotenoid-oxygenase, carotenoid-9Ј,10Ј-monooxygenase (CMO2) has been identified that cleaves carotenoids asymmetrically (8, 9), although its physiological function is not yet fully understood.The isomerization problem concerns the questions of how the visual chromophore is produced to establish functional visual pigments and, in vertebrates, how the all-trans visual photoproduct is isomerized back to the 11-cis chromophore, to maintain visual responsiveness. Recently, evidence in cell cultur...

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“…support the assignment of the component eluting at 3.8 min, as alltrans-3-hydroxyretinal and the component eluting at 4.1 min contains its geometric isomer 11-cis-3-hydroxyretinal. Likely the 4.1 min peak obtained from the photoisomerized all-trans-3-hydroxyretinal contains other cis isomers, but other isomers are not a major component of biological samples (1,11). HPLC-UV-visible-MS results for the chromatographic peak with t r ϭ 3.5 min revealed a max of ϳ324 nm (Fig.…”

Section: -Hydroxyretinol Accumulates In Ninag Mutantmentioning

confidence: 82%

“…5 to account for the current information regarding (3S)-3-hydroxyretinal biosynthesis in Drosophila. Xanthophylls, such as lutein and zeaxanthin that are hydroxylated at the C-3 position of the retinoid ring and ␤-carotene, are the major dietary source of chromophore precursors (11,16). All naturally occurring xanthophylls are in the 3R,3ЈR configuration thereby ruling out the possibility of obtaining retinoid species in 3S configuration by direct cleavage of such xanthophylls by an oxygenase.…”

Section: Discussionmentioning

confidence: 99%

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The Role of Drosophila ninaG Oxidoreductase in Visual Pigment Chromophore Biogenesis

Ahmad

Joyce

Boggess

et al. 2006

Journal of Biological Chemistry

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We previously reported (Sarfare, S., Ahmad, S. T., Joyce, M. V., Boggess, B., and O'Tousa, J. E. (2005) J. Biol. Chem. 280, 11895-11901) that the Drosophila ninaG gene encodes an oxidoreductase involved in the biosynthesis of the (3S)-3-hydroxyretinal serving as chromophore for Rh1 rhodopsin and that ninaG mutant flies expressing Rh4 as the major opsin accumulate large amounts of a different retinoid. Here, we show that this unknown retinoid is 11-cis-3-hydroxyretinol. Reversed phase high performance liquid chromatography coupled with a photodiode array UV-visible absorbance detector and mass spectrometer revealed a major product eluting at a retention time, t r , of 3.5 min with a max of ϳ324 nm and with a base peak in the mass spectrum at m/z 285. These observations are identical with those of the 3-hydroxyretinol standard. The base peak in the electrospray ionization mass spectrum arises from the loss of a water molecule from the protonated molecule at m/z 303 because of fragmentation in the ion source. These results suggest that 11-cis-3-hydroxyretinol is an intermediate required for chromophore biogenesis in Drosophila. We further show that ninaG mutants fed on retinal as the sole source of vitamin A are able to synthesize 3-hydroxyretinoids. Thus, the NinaG oxidoreductase is not responsible for the initial hydroxylation of the retinal ring but rather acts in a subsequent step in chromophore production. These data are used to review chromophore biosynthesis and propose that NinaG acts in the conversion of (3R)-3-hydroxyretinol to the 3S enantiomer.Photoisomerization of a retinoid chromophore covalently linked to the apoprotein opsin underlies the light-sensing ability of rhodopsins. Animals lack the ability to synthesize retinoids de novo and, therefore, derive retinoids from carotenoids present in the diet. In insects, three kinds of vitamin A derivatives, retinal, (3R)-3-hydroxyretinal, and (3S)-3-hydroxyretinal, function as chromophores (1). The Dipteran suborder Cyclorrapha that includes Drosophila is the only suborder described so far that utilizes (3S)-3-hydroxyretinal as the Rh1 rhodopsin chromophore (2). The use of (3S)-3-hydroxyretinal occurs in visual pigments exhibiting both UV and visible light sensitivity. This led to the suggestion that UV light sensitivity is because of the unique ability of (3S)-3-hydroxyretinal to accept energy transferred from a UV-sensitizing pigment (1).The Drosophila ninaG mutant is characterized by an abnormal electroretinogram response lacking the prolonged depolarization afterpotential. The lack of prolonged depolarization afterpotential, a characteristic of a group of "nina" 2 genes, is a manifestation of low levels of the major opsin, Rh1, expressed in the R1-6 photoreceptor cells (3). Low Rh1 rhodopsin in ninaG mutants is not due to defects in Rh1 opsin transcription, but rather, the ability to synthesize the Rh1 chromophore is defective. However, the ninaG defect does not affect the expression of minor opsins Rh4 and Rh6 (4). Rh4 and Rh6 are expressed in the R7 a...

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Priority Paper The metabolic pathway of visual pigment chromophore formation in Drosophila melanogaster

Cited by 33 publications

References 14 publications

The Drosophila ninaG Oxidoreductase Acts in Visual Pigment Chromophore Production

The Drosophila ninaG Oxidoreductase Acts in Visual Pigment Chromophore Production

NinaB combines carotenoid oxygenase and retinoid isomerase activity in a single polypeptide

The Role of Drosophila ninaG Oxidoreductase in Visual Pigment Chromophore Biogenesis

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