Editing Retinal (section)

==Vision==
Retinal is a [[conjugated system#Chromophores|conjugated chromophore]]. In the [[Vertebrate eyes]], retinal begins in an 11-''cis''-retinal configuration, which — upon capturing a [[photon]] of the correct wavelength — straightens out into an all-''trans''-retinal configuration. This configuration change pushes against an opsin protein in the [[retina]], which triggers a chemical signaling cascade, which results in [[perception]] of light or images by the brain. The absorbance spectrum of the chromophore depends on its interactions with the opsin protein to which it is bound, so that different retinal-opsin complexes will absorb photons of different wavelengths (i.e., different colors of light).

===Opsins===
[[File:1415_Retinal_Isomers.jpg|thumb|An opsin protein surrounds a molecule of 11-''cis'' retinal, awaiting the arrival of a photon. Once the retinal molecule captures a photon, its configuration change causes it to push against the surrounding opsin protein which may cause the opsin to send a chemical signal to the brain indicating that light has been detected. Retinal is then converted back to its 11-''cis'' configuration by ATP phosphorylation, and the cycle begins again.]]
[[File:Rhodopsin-transducin.png|thumb|left|Animal GPCR [[rhodopsin]] (rainbow-colored) embedded in a [[lipid bilayer]] (heads red and tails blue) with [[transducin]] below it. G<sub>t</sub>α is colored red, G<sub>t</sub>β blue, and G<sub>t</sub>γ yellow. There is a bound [[guanosine diphosphate|GDP]] molecule in the G<sub>t</sub>α-subunit and a bound '''retinal''' (black) in the rhodopsin. The [[amino-terminus|N-terminus]] terminus of rhodopsin is red and the [[C-terminus]] blue. Anchoring of transducin to the membrane has been drawn in black.]]

Retinal is bound to [[opsin]]s, which are [[G protein-coupled receptor]]s (GPCRs).<ref name=Casey1988>{{cite journal |last1=Casey |first1=P J |last2=Gilman |first2=A G |title=G protein involvement in receptor-effector coupling. |journal=Journal of Biological Chemistry |date=February 1988 |volume=263 |issue=6 |pages=2577–2580 |doi=10.1016/s0021-9258(18)69103-3 |pmid=2830256|s2cid=38970721 |doi-access=free }}</ref><ref name=Attwood1994>{{cite journal |last1=Attwood |first1=T. K. |last2=Findlay |first2=J. B. C. |title=Fingerprinting G-protein-coupled receptors |journal=Protein Engineering, Design and Selection |date=1994 |volume=7 |issue=2 |pages=195–203 |doi=10.1093/protein/7.2.195|pmid=8170923 }}</ref> Opsins, like other GPCRs, have seven transmembrane [[alpha-helix|alpha-helices]] connected by six loops. They are found in the [[photoreceptor cell]]s in the [[retina]] of eye. The opsin in the vertebrate [[rod cell]]s is [[rhodopsin]]. The rods form disks, which contain the rhodopsin molecules in their membranes and which are entirely inside of the cell. The [[N-terminus]] head of the molecule extends into the interior of the disk, and the [[C-terminus]] tail extends into the cytoplasm of the cell. The opsins in the [[cone cell]]s are [[OPN1SW]], [[OPN1MW]], and [[OPN1LW]]. The cones form incomplete disks that are part of the [[plasma membrane]], so that the N-terminus head extends outside of the cell. In opsins, retinal binds covalently to a [[lysine]]<ref>{{cite journal |last1=Bownds |first1=Deric |title=Site of Attachment of Retinal in Rhodopsin |journal=Nature |date=December 1967 |volume=216 |issue=5121 |pages=1178–1181 |doi=10.1038/2161178a0 |pmid=4294735|bibcode=1967Natur.216.1178B |s2cid=1657759 }}</ref> in the seventh transmembrane helix<ref>{{cite journal |last1=Hargrave |first1=P. A. |last2=McDowell |first2=J. H. |last3=Curtis |first3=Donna R. |last4=Wang |first4=Janet K. |last5=Juszczak |first5=Elizabeth |last6=Fong |first6=Shao-Ling |last7=Mohana Rao |first7=J. K. |last8=Argos |first8=P. |title=The structure of bovine rhodopsin |journal=Biophysics of Structure and Mechanism |date=1983 |volume=9 |issue=4 |pages=235–244 |doi=10.1007/BF00535659 |pmid=6342691|s2cid=20407577 }}</ref><ref name=Palczewski2000>{{cite journal | vauthors = Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M | display-authors = 6 | title = Crystal structure of rhodopsin: A G protein-coupled receptor | journal = Science | volume = 289 | issue = 5480 | pages = 739–45 | date = August 2000 | pmid = 10926528 | doi = 10.1126/science.289.5480.739 | citeseerx = 10.1.1.1012.2275 | bibcode = 2000Sci...289..739P }}</ref><ref name=Murakami2008>{{cite journal | vauthors = Murakami M, Kouyama T | title = Crystal structure of squid rhodopsin | journal = Nature | volume = 453 | issue = 7193 | pages = 363–7 | date = May 2008 | pmid = 18480818 | doi = 10.1038/nature06925 | bibcode = 2008Natur.453..363M | s2cid = 4339970 }}</ref> through a [[Schiff base]].<ref>{{cite journal |last1=Collins |first1=F. D. |title=Rhodopsin and Indicator Yellow |journal=Nature |date=March 1953 |volume=171 |issue=4350 |pages=469–471 |doi=10.1038/171469a0 |pmid=13046517|bibcode=1953Natur.171..469C |s2cid=4152360 }}</ref><ref>{{cite journal |last1=Pitt |first1=G. A. J. |last2=Collins |first2=F. D. |last3=Morton |first3=R. A. |last4=Stok |first4=Pauline |title=Studies on rhodopsin. 8. Retinylidenemethylamine, an indicator yellow analogue |journal=Biochemical Journal |date=1 January 1955 |volume=59 |issue=1 |pages=122–128 |doi=10.1042/bj0590122 |pmid=14351151|pmc=1216098 }}</ref> Forming the Schiff base linkage involves removing the oxygen atom from retinal and two hydrogen atoms from the free amino group of lysine, giving H<sub>2</sub>O. Retinylidene is the divalent group formed by removing the oxygen atom from retinal, and so opsins have been called [[retinylidene protein]]s.

Opsins are prototypical [[G protein-coupled receptor]]s (GPCRs).<ref>{{cite journal |last=Lamb |first=T D |year=1996 |title=Gain and kinetics of activation in the G-protein cascade of phototransduction |journal=Proceedings of the National Academy of Sciences |volume=93 |issue=2 |pages=566–570 |pmid=8570596 |doi=10.1073/pnas.93.2.566 |pmc=40092 |bibcode=1996PNAS...93..566L|doi-access=free }}</ref> Cattle rhodopsin, the opsin of the rod cells, was the first GPCR to have its [[Protein primary structure|amino acid sequence]]<ref name=Ovchinnikov1982>{{cite journal |last1=Ovchinnikov |first1=Yu.A. |title=Rhodopsin and bacteriorhodopsin: structure-function relationships |journal=FEBS Letters |date=8 November 1982 |volume=148 |issue=2 |pages=179–191 |doi=10.1016/0014-5793(82)80805-3 |pmid=6759163|s2cid=85819100 |doi-access=free |bibcode=1982FEBSL.148..179O }}</ref> and [[Protein tertiary structure|3D-structure]] (via [[X-ray crystallography]]) determined.<ref name="Palczewski2000" />  [[Cattle]] rhodopsin contains 348 [[amino acid]] residues. Retinal binds as chromophore at Lys<sup>296</sup>.<ref name="Palczewski2000" /><ref name=Ovchinnikov1982 /> This lysine is conserved in almost all opsins, only a few opsins have lost it during [[evolution]].<ref name=Guehmann2022>{{cite journal | vauthors = Gühmann M, Porter ML, Bok MJ | title = The Gluopsins: Opsins without the Retinal Binding Lysine | journal = Cells | volume = 11 | issue = 15 | pages = 2441 | date = August 2022 | pmid = 35954284 | doi = 10.3390/cells11152441 | pmc = 9368030 | doi-access = free }}</ref> Opsins without the retinal binding lysine are not light sensitive.<ref name=Katana2019>{{cite journal |last1=Katana |first1=Radoslaw |last2=Guan |first2=Chonglin |last3=Zanini |first3=Damiano |last4=Larsen |first4=Matthew E. |last5=Giraldo |first5=Diego |last6=Geurten |first6=Bart R.H. |last7=Schmidt |first7=Christoph F. |last8=Britt |first8=Steven G. |last9=Göpfert |first9=Martin C. |title=Chromophore-Independent Roles of Opsin Apoproteins in Drosophila Mechanoreceptors |journal=Current Biology |date=September 2019 |volume=29 |issue=17 |pages=2961–2969.e4 |doi=10.1016/j.cub.2019.07.036 |pmid=31447373|s2cid=201420079 |doi-access=free |bibcode=2019CBio...29E2961K }}</ref><ref name=Leung2020>{{cite journal |last1=Leung |first1=Nicole Y. |last2=Thakur |first2=Dhananjay P. |last3=Gurav |first3=Adishthi S. |last4=Kim |first4=Sang Hoon |last5=Di Pizio |first5=Antonella |last6=Niv |first6=Masha Y. |last7=Montell |first7=Craig |title=Functions of Opsins in Drosophila Taste |journal=Current Biology |date=April 2020 |volume=30 |issue=8 |pages=1367–1379.e6 |doi=10.1016/j.cub.2020.01.068 |pmid=32243853|pmc=7252503 |bibcode=2020CBio...30E1367L }}</ref><ref>{{cite journal | vauthors = Kumbalasiri T, Rollag MD, Isoldi MC, Castrucci AM, Provencio I | title = Melanopsin triggers the release of internal calcium stores in response to light | journal = Photochemistry and Photobiology | volume = 83 | issue = 2 | pages = 273–279 | date = March 2007 | pmid = 16961436 | doi = 10.1562/2006-07-11-RA-964 | s2cid = 23060331 }}</ref> Such opsins may have other functions.<ref name=Leung2020 /><ref name=Guehmann2022 />

Although mammals use retinal exclusively as the opsin chromophore, other groups of animals additionally use four chromophores closely related to retinal: 3,4-didehydroretinal (vitamin A<sub>2</sub>), (3''R'')-3-hydroxyretinal, (3''S'')-3-hydroxyretinal (both vitamin A<sub>3</sub>), and (4''R'')-4-hydroxyretinal (vitamin A<sub>4</sub>). Many fish and amphibians use 3,4-didehydroretinal, also called [[dehydroretinal]]. With the exception of the [[diptera]]n suborder [[Cyclorrhapha]] (the so-called higher flies), all [[insect]]s examined use the (''R'')-[[enantiomer]] of 3-hydroxyretinal. The (''R'')-enantiomer is to be expected if 3-hydroxyretinal is produced directly from [[xanthophyll]] carotenoids. Cyclorrhaphans, including ''[[Drosophila]]'', use (3''S'')-3-hydroxyretinal.<ref>{{cite journal |last1=Seki |first1=Takaharu |last2=Isono |first2=Kunio |last3=Ito |first3=Masayoshi |last4=Katsuta |first4=Yuko |year=1994 |title=Flies in the Group Cyclorrhapha Use (3S)-3-Hydroxyretinal as a Unique Visual Pigment Chromophore |journal=European Journal of Biochemistry |volume=226 |issue=2 |pages=691–696 |doi=10.1111/j.1432-1033.1994.tb20097.x |pmid=8001586 |doi-access=}}</ref><ref>{{cite journal |last1=Seki |first1=Takaharu |last2=Isono |first2=Kunio |last3=Ozaki |first3=Kaoru |last4=Tsukahara |first4=Yasuo |last5=Shibata-Katsuta |first5=Yuko |last6=Ito |first6=Masayoshi |last7=Irie |first7=Toshiaki |last8=Katagiri |first8=Masanao |year=1998 |title=The metabolic pathway of visual pigment chromophore formation in Drosophila melanogaster: All-trans (3S)-3-hydroxyretinal is formed from all-trans retinal via (3R)-3-hydroxyretinal in the dark |journal=European Journal of Biochemistry |volume=257 |issue=2 |pages=522–527 |doi=10.1046/j.1432-1327.1998.2570522.x |pmid=9826202 |doi-access=free}}</ref> [[Firefly squid]] have been found to use (4''R'')-4-hydroxyretinal.
{{Clear}}

===Visual cycle===
{{main|Visual cycle}}
[[File:Visual cycle.svg|thumb|right|350x350px|Visual cycle]]
The visual cycle is a circular [[enzymatic pathway]], which is the front-end of phototransduction. It regenerates 11-''cis''-retinal. For example, the visual cycle of mammalian rod cells is as follows:
#[[all-trans-retinyl ester|all-''trans''-retinyl ester]] + H<sub>2</sub>O → 11-''cis''-retinol + [[fatty acid]]; [[RPE65]] isomerohydrolases;<ref>{{cite journal |last1=Moiseyev |first1=Gennadiy |last2=Chen |first2=Ying |last3=Takahashi |first3=Yusuke |last4=Wu |first4=Bill X. |last5=Ma |first5=Jian-xing |year=2005 |title=RPE65 is the isomerohydrolase in the retinoid visual cycle |journal=Proceedings of the National Academy of Sciences |volume=102 |issue=35 |pages=12413–12418 |doi=10.1073/pnas.0503460102 |pmid=16116091 |pmc=1194921 |bibcode=2005PNAS..10212413M|doi-access=free }}</ref>
#[[11-cis-retinol|11-''cis''-retinol]] + NAD<sup>+</sup> → 11-''cis''-retinal + NADH + H<sup>+</sup>; 11-''cis''-retinol dehydrogenases;
#[[11-cis retinal|11-''cis''-retinal]] + [[aporhodopsin]] → [[rhodopsin]] + H<sub>2</sub>O; forms [[Schiff base]] linkage to [[lysine]], -CH=N<sup>+</sup>H-;
#rhodopsin + [[photon|hν]] → [[metarhodopsin]] II (i.e., 11-''cis'' [[photoisomerization|photoisomerizes]] to all-''trans''):
#:(rhodopsin + hν → photorhodopsin → bathorhodopsin → lumirhodopsin → metarhodopsin I → metarhodopsin II);
#[[metarhodopsin]] II + H<sub>2</sub>O → aporhodopsin + all-''trans''-retinal;
#[[all-trans-retinal|all-''trans''-retinal]] + NADPH + H<sup>+</sup> → all-''trans''-retinol + NADP<sup>+</sup>; all-''trans''-retinol [[dehydrogenase]]s;
#all-''trans''-retinol + fatty acid → all-''trans''-retinyl ester + H<sub>2</sub>O; [[lecithin retinol acyltransferase]]s (LRATs).<ref>{{cite journal |last1=Jin |first1=Minghao |last2=Yuan |first2=Quan |last3=Li |first3=Songhua |last4=Travis |first4=Gabriel H. |year=2007 |title=Role of LRAT on the Retinoid Isomerase Activity and Membrane Association of Rpe65 |journal=Journal of Biological Chemistry |volume=282 |issue=29 |pages=20915–20924 |doi=10.1074/jbc.M701432200 |pmid=17504753 |pmc=2747659|doi-access=free }}</ref>

Steps 3, 4, 5, and 6 occur in [[rod cell|rod cell outer segments]]; Steps 1, 2, and 7 occur in [[retinal pigment epithelium]] (RPE) cells.

RPE65 isomerohydrolases are [[homology (biology)|homologous]] with beta-carotene monooxygenases;<ref name="von Lintig"/> the homologous ninaB enzyme in ''Drosophila'' has both retinal-forming carotenoid-oxygenase activity and all-''trans'' to 11-''cis'' isomerase activity.<ref name="Oberhauser08">{{cite journal |last1=Oberhauser |first1=Vitus |last2=Voolstra |first2=Olaf |last3=Bangert |first3=Annette |last4=von Lintig |first4=Johannes |last5=Vogt |first5=Klaus |year=2008 |title=NinaB combines carotenoid oxygenase and retinoid isomerase activity in a single polypeptide |journal=Proceedings of the National Academy of Sciences |volume=105 |issue=48 |pages=19000–5 |doi=10.1073/pnas.0807805105 |pmid=19020100 |pmc=2596218 |bibcode=2008PNAS..10519000O|doi-access=free }}</ref>