Visual phototransduction (Homo sapiens)

From WikiPathways

Revision as of 14:09, 8 May 2014 by Anwesha (Talk | contribs)
Jump to: navigation, search
6, 25, 38, 54, 66...908, 37, 68, 84, 112...23, 118, 154, 17916, 32150142107155, 161, 1688, 128, 135, 1728213, 116, 12959, 151109, 16271, 85, 89, 100, 117...95, 115, 17930, 13255142262, 54, 15633, 80, 13320, 39, 121115, 14243, 57, 18032, 53155, 161, 16818210799, 12228, 79, 13836, 125, 128, 14150, 11573, 113, 126, 18349, 81125, 15252, 64108, 1394, 14070, 8711516, 32179, 11, 18, 22, 78...24, 106, 13686, 146, 17430, 1326946, 47, 131103, 137278, 172342639, 51, 56, 67, 97...102, 10440, 164103, 15371, 100, 13410721, 103, 15310231, 74, 114, 16312, 14397, 12123, 11817112444, 76, 110, 158, 16661, 62, 8315, 29, 60, 111, 145...3, 35, 48, 88, 9310, 917, 14, 72, 75, 94...10545, 58, 65, 128, 169...2632, 534140, 130, 16435, 48, 88ApoB-48TGPL complex OPN1MWatRAL TTR tetramer cytosolendoplasmic reticulum lumenHSCApoB-48TGPL complex N-ACYL-GNAT1 cytosolOPN1LWatRAL mature CMatREs cytosolN-ACYL-GNAT1 p-S334,S338,S343-MII PDE6 TTRRBP4atROL EnterocyteGUCA1ACa2+ FNTAFNTB TTR tetramer CR RLBP111cROL GNAT1-GTP atREs CRatREsHSPGapoE CRatREs HSRod inner segmentCALM1Ca2+CNG channel cytosolRod outer segmentTTRRBP4STRA6 RPERLBP1atROL endoplasmic reticulum lumenCone outer segmentendoplasmic reticulum lumenMETAP12Co2+ RHO11cRAL CNG channel HScytosolendoplasmic reticulum lumenMII METAP1/2 cytosolGNB1GNGT1 endoplasmic reticulum lumenN-ACYL-GNAT1 RBP1atROL PDE6 CRatREs N-ACYL-GNAT1 photoreceptor disc membraneCRatREsHSPGapoE p-S334,S338,S343-MII lipid particleGUCA1BCa2+ ApoB-48TGPL complex CALM1Ca2+ GNB1GNGT1 spherical HDL ApoB-48TGPL complex CNG channel GNAT1-GDP GNAT1-GTPPDE6 GUCA1CCa2+ TTR tetramer CNG channel HSPG atREs CR OPN1SW11cRAL spherical HDL photoreceptor disc membranephotoreceptor disc membranephagolysosomeOPN1LW11cRAL HSPGs p-RHOSAG GNAT1-GDP atREs TTRRBP4atROLSTRA6 S-farn-GRK1RCVRNCa2+ cGMPCNG channel early endosomeRLBP111cROL GUCACa2+ HSPGs p-MIISAG HSatREs RBP4atROL RBP2atRAL Lymphatic circulationCR RLBP111cRAL Muller cellRBP2atROL ApoB-48TGPL complex Gt-GDP LPLLPL spherical HDLapoC-IIapoC-IIIapoE CR RCVRNCa2+ N-ACYL-GNAT1 HSHSHS/HPIN-PGs HSatREs HSHSphotoreceptor disc membranenascent CM cytosolMETAP22Co2+ nascent CMatREs RLBP111cRAL Cone opsinsatRAL BCMO1Fe2+ RGS9-1GNB5RGS9BP ApoB-48TGPL complex RBP1atROL nascent CMatREs HS/HPIN-PGs HSp-S478-RGS9-1GNB5RGS9BP atREs PPEF1Mg2+ OPN1MW11cRAL GNB1GNGT1 RBP1atROL lipid particleHSPGLPLLPL PNLIPCLPS ApoB-48TGPL complex ApoB-48TGPL complex GNAT1-GTP Gt-GTP TTR tetramer Cone opsins11cRAL RLBP111cROL ApoB-48TGPL complex Parenchymalendoplasmic reticulum lumenCR CRatREs HSGNAT1-GTP OPN1SWatRAL PPEF1 APOC2 PL atROLp-RHOSAGHSHSAPOE NADP+GTP APOBCHEST CNGA1 HSHSCHOL CHEST APOA1Ca2+atRAL atR-LINA HSHSFNTAHSTTRRBP4atROLHSCHOL PEPL TAGs cGMP APOEatR-PALM HSRBP4HSAPOC2 11cRAL CNGA1 Ca2+ atR-LINA GNAT1-GTPCa2+ HSHSHSHSCALM1 ATPCALM1 HSNADPHGTPHSnascent CMatREsS-farn-GNGT1 N-RCVRN HSAPOA2MYS-CoAHSHSHSPDE6BCHOL ATPS-farn-GNGT1MYO7ALRATAPOA1CHEST TTRRBP4atROLSTRA6RBP3N-APOA1N-atRALAPOA2HSPG2NADPHPALMRBP1atROLRHO11cRALHSCHEST FPPCHEST FAsspherical HDLapoC-IIapoC-IIIapoEAPOBHSTAG GUCA1C atR-PALM APOA4 K+nascent CMN-HSFNTAFNTBHSHSHSCHOL Na+HSHSAPOC3 FAsHSCHOL 11cRAL CHEST SAG CHEST APOBatROL Na+APOA4 nascent CMatREsRBP2METAP1/2HSRLBP1 LRPsatRAL GUCYsLRATspherical HDLN-HSHSPiAPOE H2OHSHScGMPN-PDE6AHSH+ABCA4ADPOPN1SW RLBP1 11cROLTAGs BCMO1 CHEST HSHSNMT1/2RCVRNRDH12RBP4APOE atRALH+N-HSatROL isomeraseatR-STEA APOC3 PL HSHSPGLPLLPLHSNADP+HSTTRRBP4STRA6H+METAP2APOBCHOL APOA1N-N-PL PRKCA/QAPOC3 HSatRAL NRPEH+HSCa2+Cone apo-opsinsRGS9 isoform 3 HSHSRBP4Ca2+HSDAGAKRsHSRBP2atRALHSatR-PALM atR-OLEA atREsRCVRN PhotonRBP1PPiAPOC3 GNB1 atR-PALM PL MIIAPOBatROLatROLPL CNGB1 RBP3CHOL HSatR-STEA atRALHSRGS9BP 11cROLHSTAGs atRAL RBP1 PL APOA2APOA2HSPAGNAT1-GTPPDE6TTR HSHSNADP+HSp-S334,S338,S343-RHO TAGs LRATCHOL CALM1Ca2+CNG channelAPOE H2OHSPiHSTAGs GTP HSHSAPOA4 HSRBP1atROLCHOL CRatREsHSCHOL HSPDE6HSPDE6ALDLRHSAPOA1mature CMatREsCALM1Ca2+REHNADHHS11cRALTAGs atR-STEA atRAL RDH5HSRLBP111cRALH+HS11cRDHHSREHHSN-PLB1H+N-HSPGsHSHSN-HSatROL HSTAGs H2OADPCa2+ atR-STEA GDP CHEST APOEGNB1GNGT1CHEST TTR APOA2Cone opsins11cRALPNLIPCLPSCRRBP4GNB1 RPALMatROL HSN-HSPiSTRA6 HSAPOC2 RBP2atROLRBP1atROLHSHSRBP1 Ca2+ atROLRBP1RGS9-1GNB5RGS9BPRBP1atRALPDE6G RBP1PL RLBP1atROLN-HSHSRLBP111cROLNADPHAPOA2RLBP1 GUCA1A RCVRNCa2+HSatROL PL HSGNAT1 APOC2 PhotonHSAPOA1NREHHSS-farn-GNGT1 O2LCFAs11cROLHSRDH10/11RGS9BP HSHSAPOA1TAG OPN1SW atROLTTR tetramerRLBP111cROLN-HSATPAPOE OPN1LW Fe2+ PDE6G S-farn-GRK1RCVRNCa2+RHO APOBN-acyl-GNAT1RBP3APOA1CNGA1 atROL atRALNAD+acyl-CoARLBP1 APOBatR-LINA p-S334,S338,S343-MIIAPOA4 atR-PALM HSatR-OLEA HSHSOPN1LW APOE atROL Ca2+ SDC1 RHO A2EHSHSCRatREsHSPGapoETAGs HSHSGNB5-1 SAG GTPCLPS HSNa+atR-LINA GDPL-MetA2ERDH11APOBHSHSHSMETAP1HSHSHSH+p-S478-RGS9-1GNB5RGS9BPCRatREsHSPGapoERBP4atROLCa2+PL APOA4 RLBP1 H2OHSNa+RLBP111cRALHSPALMFACYLsSLC24A1atROLHSHSRLBP1atROL atROL ADPHSRBP2CHOL DHRS3NADPHAPOA4 APOA111cRAL HSSTRA6 CNGB1 atREsADPATPGt-GDPRLBP1 atREsHS11cRPALMRDH8S-farn-GRK1HS11cROL HSSTRA611cRAL APOA1Ca2+atR-LINA APOA2GNB5-1 H2OGNAT1HSRLBP111cROLHSGDP NADP+11cROL NADP+atR-OLEA HSPiatR-LINA PNLIP atROLH2OatR-STEA H2OHSp-S334,S338,S343-RHO HSLPL RBP3APOC3 HSMg2+ HSRPE65HSHSunknown NAT11cROL S-farn-GNGT1 p-S478-RGS9 isoform 3 APOC2 FACYLsK+cGMPCNG channelHSTTR betaCp-S334,S338,S343-RHON-A2ES-farn-GRK1 APOBH2OCNG channelAPOE RBP2p-MIISAGA2PEOPN1MW APOC3 Gt-GTPCoA-SHH2OHSHSFNTB atR-OLEA NAPEPLDGMPBCMO1Fe2+HSGNGT1HSH+NRPEGUCACa2+PPEF1Mg2+PPiHSRBP1APOC2 HSHSHSH2OGUCA1BPDE6BCone opsinsatRALRHOFACYLsHSGUCASAGRBP4N-HSatR-STEA HSTTR APOA4 atR-OLEA HSAPOA4 HSatROLHSABCA4CRN-HSAPOA4 HSAPOC2 N-FAsAPOA2CNGB1 atR-OLEA HSCo2+ H2ORBP1 atR-PALM CHEST APOA1HSRBP2TAGs PL H+NADPHN-p-S334,S338,S343-RHO HSHSN-GTP HSHSGNAT1-GDPAPOC3 HSGNB1 APOA2OPN1MW 19, 985, 1004242635, 10071717742961707763119, 9842


Description

No description

Comments

Wikipathways-description 
Visual phototransduction is the process by which photon absorption by visual pigment molecules in photoreceptor cells is converted to an electrical cellular response. The events in this process are photochemical, biochemical and electrophysiological and are highly conserved across many species. This process occurs in two types of photoreceptors in the retina, rods and cones. Each type consists of two parts, the outer segment which detects a photon signal and the inner segment which contains the necessary machinery for cell metabolism. Each type of cell functions differently. Rods are very light sensitive but their flash response is slow so they work best in twilight conditions but are not good at detecting objects moving quickly. Cones are less light-sensitive and have a fast flash response so they work best in daylight conditions and are better at detecting fast moving objects than rods.

The visual pigment consists of a chromophore (11-cis-retinal, 11cRAL, A1) covalently attached to a GPCR opsin family member. The linkage is via a Schiff base forming retinylidene protein. Upon photon absorption, 11cRAL isomerises to all-trans retinal (atRAL), changing the conformation of opsin to an activated form which can activate the regulatory G protein transducin (Gt). The alpha subunit of Gt activates phosphodiesterase which hydrolyses cGMP to 5'-GMP. As high level of cGMP keep cGMP-gated sodium channels open, the lowering of cGMP levels closes these channels which causes hyperpolarization of the cell and subsequently, closure of voltage-gated calcium channels. As calcium levels drop, the level of the neurotransmitter glutamate also drops causing depolarization of the cell. This effectively relays the light signal to postsynaptic neurons as electrical signal (Burns & Pugh 2010, Korenbrot 2012, Pugh & Lamb 1993).

11cRAL cannot be synthesised in vertebrates. Vitamin A from many dietary sources is the precursor for 11cRAL. It is taken from food in the form of esters such as retinyl acetate or palmitate or one of four caretenoids (alpha-carotene, beta-carotene, gamma-carotene and beta-cryptoxanthin). Retinoids are transported from the gut to be stored in liver, until required by target organs such as the eye (Harrison & Hussain 2001, Harrison 2005). In the eye, in the form 11cRAL, it is used in the retinoid (visual) cycle to initiate phototransduction and for visual pigment regeneration to ready the photoreceptor for the next phototransduction event (von Lintig 2012, Blomhoff & Blomhoff 2006, von Lintig et al. 2010, D'Ambrosio et al. 2011, Wang & Kefalov 2011, Kefalov 2012, Wolf 2004).

Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=2187338

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Nakano M, Kelly EJ, Rettie AE.; ''Expression and characterization of CYP4V2 as a fatty acid omega-hydroxylase.''; PubMed Europe PMC Scholia
  2. Zhong H, Molday LL, Molday RS, Yau KW.; ''The heteromeric cyclic nucleotide-gated channel adopts a 3A:1B stoichiometry.''; PubMed Europe PMC Scholia
  3. Addlagatta A, Hu X, Liu JO, Matthews BW.; ''Structural basis for the functional differences between type I and type II human methionine aminopeptidases.''; PubMed Europe PMC Scholia
  4. Turkish AR, Henneberry AL, Cromley D, Padamsee M, Oelkers P, Bazzi H, Christiano AM, Billheimer JT, Sturley SL.; ''Identification of two novel human acyl-CoA wax alcohol acyltransferases: members of the diacylglycerol acyltransferase 2 (DGAT2) gene superfamily.''; PubMed Europe PMC Scholia
  5. D'Ambrosio DN, Clugston RD, Blaner WS.; ''Vitamin A metabolism: an update.''; PubMed Europe PMC Scholia
  6. Colville CA, Molday RS.; ''Primary structure and expression of the human beta-subunit and related proteins of the rod photoreceptor cGMP-gated channel.''; PubMed Europe PMC Scholia
  7. Kamps MP, Buss JE, Sefton BM.; ''Rous sarcoma virus transforming protein lacking myristic acid phosphorylates known polypeptide substrates without inducing transformation.''; PubMed Europe PMC Scholia
  8. Yen CL, Brown CH, Monetti M, Farese RV.; ''A human skin multifunctional O-acyltransferase that catalyzes the synthesis of acylglycerols, waxes, and retinyl esters.''; PubMed Europe PMC Scholia
  9. Allikmets R, Singh N, Sun H, Shroyer NF, Hutchinson A, Chidambaram A, Gerrard B, Baird L, Stauffer D, Peiffer A, Rattner A, Smallwood P, Li Y, Anderson KL, Lewis RA, Nathans J, Leppert M, Dean M, Lupski JR.; ''A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy.''; PubMed Europe PMC Scholia
  10. Dartnall HJ.; ''The photosensitivities of visual pigments in the presence of hydroxylamine.''; PubMed Europe PMC Scholia
  11. Kawaguchi R, Yu J, Ter-Stepanian M, Zhong M, Cheng G, Yuan Q, Jin M, Travis GH, Ong D, Sun H.; ''Receptor-mediated cellular uptake mechanism that couples to intracellular storage.''; PubMed Europe PMC Scholia
  12. Miki N, Keirns JJ, Marcus FR, Freeman J, Bitensky MW.; ''Regulation of cyclic nucleotide concentrations in photoreceptors: an ATP-dependent stimulation of cyclic nucleotide phosphodiesterase by light.''; PubMed Europe PMC Scholia
  13. Cobbs WH.; ''Light and dark active phosphodiesterase regulation in salamander rods.''; PubMed Europe PMC Scholia
  14. Lowe DG, Dizhoor AM, Liu K, Gu Q, Spencer M, Laura R, Lu L, Hurley JB.; ''Cloning and expression of a second photoreceptor-specific membrane retina guanylyl cyclase (RetGC), RetGC-2.''; PubMed Europe PMC Scholia
  15. Tao L, Pandey S, Simon MI, Fong HK.; ''Structure of the bovine transducin gamma subunit gene and analysis of promoter function in transgenic mice.''; PubMed Europe PMC Scholia
  16. Huang X, Honkanen RE.; ''Molecular cloning, expression, and characterization of a novel human serine/threonine protein phosphatase, PP7, that is homologous to Drosophila retinal degeneration C gene product (rdgC).''; PubMed Europe PMC Scholia
  17. Hu G, Jang GF, Cowan CW, Wensel TG, Palczewski K.; ''Phosphorylation of RGS9-1 by an endogenous protein kinase in rod outer segments.''; PubMed Europe PMC Scholia
  18. Imanishi Y, Gerke V, Palczewski K.; ''Retinosomes: new insights into intracellular managing of hydrophobic substances in lipid bodies.''; PubMed Europe PMC Scholia
  19. Bell IM, Gallicchio SN, Abrams M, Beese LS, Beshore DC, Bhimnathwala H, Bogusky MJ, Buser CA, Culberson JC, Davide J, Ellis-Hutchings M, Fernandes C, Gibbs JB, Graham SL, Hamilton KA, Hartman GD, Heimbrook DC, Homnick CF, Huber HE, Huff JR, Kassahun K, Koblan KS, Kohl NE, Lobell RB, Lynch JJ, Robinson R, Rodrigues AD, Taylor JS, Walsh ES, Williams TM, Zartman CB.; ''3-Aminopyrrolidinone farnesyltransferase inhibitors: design of macrocyclic compounds with improved pharmacokinetics and excellent cell potency.''; PubMed Europe PMC Scholia
  20. Krispel CM, Chen D, Melling N, Chen YJ, Martemyanov KA, Quillinan N, Arshavsky VY, Wensel TG, Chen CK, Burns ME.; ''RGS expression rate-limits recovery of rod photoresponses.''; PubMed Europe PMC Scholia
  21. Han M, DeDecker BS, Smith SO.; ''Localization of the retinal protonated Schiff base counterion in rhodopsin.''; PubMed Europe PMC Scholia
  22. Hu X, Addlagatta A, Lu J, Matthews BW, Liu JO.; ''Elucidation of the function of type 1 human methionine aminopeptidase during cell cycle progression.''; PubMed Europe PMC Scholia
  23. Mata NL, Radu RA, Clemmons RC, Travis GH.; ''Isomerization and oxidation of vitamin a in cone-dominant retinas: a novel pathway for visual-pigment regeneration in daylight.''; PubMed Europe PMC Scholia
  24. Takahashi Y, Moiseyev G, Ablonczy Z, Chen Y, Crouch RK, Ma JX.; ''Identification of a novel palmitylation site essential for membrane association and isomerohydrolase activity of RPE65.''; PubMed Europe PMC Scholia
  25. deSolms SJ, Ciccarone TM, MacTough SC, Shaw AW, Buser CA, Ellis-Hutchings M, Fernandes C, Hamilton KA, Huber HE, Kohl NE, Lobell RB, Robinson RG, Tsou NN, Walsh ES, Graham SL, Beese LS, Taylor JS.; ''Dual protein farnesyltransferase-geranylgeranyltransferase-I inhibitors as potential cancer chemotherapeutic agents.''; PubMed Europe PMC Scholia
  26. Kaylor JJ, Cook JD, Makshanoff J, Bischoff N, Yong J, Travis GH.; ''Identification of the 11-cis-specific retinyl-ester synthase in retinal Müller cells as multifunctional O-acyltransferase (MFAT).''; PubMed Europe PMC Scholia
  27. Emeis D, Kühn H, Reichert J, Hofmann KP.; ''Complex formation between metarhodopsin II and GTP-binding protein in bovine photoreceptor membranes leads to a shift of the photoproduct equilibrium.''; PubMed Europe PMC Scholia
  28. Sun H, Molday RS, Nathans J.; ''Retinal stimulates ATP hydrolysis by purified and reconstituted ABCR, the photoreceptor-specific ATP-binding cassette transporter responsible for Stargardt disease.''; PubMed Europe PMC Scholia
  29. Schoenlein RW, Peteanu LA, Mathies RA, Shank CV.; ''The first step in vision: femtosecond isomerization of rhodopsin.''; PubMed Europe PMC Scholia
  30. Piriev NI, Purishko VA, Khramtsov NV, Lipkin VM.; ''[The organization of the gamma-subunit gene of human photoreceptor cyclic GMP phosphodiesterase]''; PubMed Europe PMC Scholia
  31. Zheng J, Trudeau MC, Zagotta WN.; ''Rod cyclic nucleotide-gated channels have a stoichiometry of three CNGA1 subunits and one CNGB1 subunit.''; PubMed Europe PMC Scholia
  32. Horner TJ, Osawa S, Schaller MD, Weiss ER.; ''Phosphorylation of GRK1 and GRK7 by cAMP-dependent protein kinase attenuates their enzymatic activities.''; PubMed Europe PMC Scholia
  33. Harrison EH, Hussain MM.; ''Mechanisms involved in the intestinal digestion and absorption of dietary vitamin A.''; PubMed Europe PMC Scholia
  34. Chen TY, Illing M, Molday LL, Hsu YT, Yau KW, Molday RS.; ''Subunit 2 (or beta) of retinal rod cGMP-gated cation channel is a component of the 240-kDa channel-associated protein and mediates Ca(2+)-calmodulin modulation.''; PubMed Europe PMC Scholia
  35. Wang JS, Kefalov VJ.; ''The cone-specific visual cycle.''; PubMed Europe PMC Scholia
  36. Dhallan RS, Macke JP, Eddy RL, Shows TB, Reed RR, Yau KW, Nathans J.; ''Human rod photoreceptor cGMP-gated channel: amino acid sequence, gene structure, and functional expression.''; PubMed Europe PMC Scholia
  37. Crabb JW, Goldflam S, Harris SE, Saari JC.; ''Cloning of the cDNAs encoding the cellular retinaldehyde-binding protein from bovine and human retina and comparison of the protein structures.''; PubMed Europe PMC Scholia
  38. Biswas EE, Biswas SB.; ''The C-terminal nucleotide binding domain of the human retinal ABCR protein is an adenosine triphosphatase.''; PubMed Europe PMC Scholia
  39. Subbaraya I, Ruiz CC, Helekar BS, Zhao X, Gorczyca WA, Pettenati MJ, Rao PN, Palczewski K, Baehr W.; ''Molecular characterization of human and mouse photoreceptor guanylate cyclase-activating protein (GCAP) and chromosomal localization of the human gene.''; PubMed Europe PMC Scholia
  40. Dawis SM, Graeff RM, Heyman RA, Walseth TF, Goldberg ND.; ''Regulation of cyclic GMP metabolism in toad photoreceptors. Definition of the metabolic events subserving photoexcited and attenuated states.''; PubMed Europe PMC Scholia
  41. Haeseleer F, Sokal I, Li N, Pettenati M, Rao N, Bronson D, Wechter R, Baehr W, Palczewski K.; ''Molecular characterization of a third member of the guanylyl cyclase-activating protein subfamily.''; PubMed Europe PMC Scholia
  42. Collins C, Hutchinson G, Kowbel D, Riess O, Weber B, Hayden MR.; ''The human beta-subunit of rod photoreceptor cGMP phosphodiesterase: complete retinal cDNA sequence and evidence for expression in brain.''; PubMed Europe PMC Scholia
  43. Tucker JE, Winkfein RJ, Cooper CB, Schnetkamp PP.; ''cDNA cloning of the human retinal rod Na-Ca + K exchanger: comparison with a revised bovine sequence.''; PubMed Europe PMC Scholia
  44. He X, Lobsiger J, Stocker A.; ''Bothnia dystrophy is caused by domino-like rearrangements in cellular retinaldehyde-binding protein mutant R234W.''; PubMed Europe PMC Scholia
  45. Ruiz A, Winston A, Lim YH, Gilbert BA, Rando RR, Bok D.; ''Molecular and biochemical characterization of lecithin retinol acyltransferase.''; PubMed Europe PMC Scholia
  46. Liou GI, Ma DP, Yang YW, Geng L, Zhu C, Baehr W.; ''Human interstitial retinoid-binding protein. Gene structure and primary structure.''; PubMed Europe PMC Scholia
  47. Harrison EH.; ''Mechanisms of digestion and absorption of dietary vitamin A.''; PubMed Europe PMC Scholia
  48. Khani SC, Abitbol M, Yamamoto S, Maravic-Magovcevic I, Dryja TP.; ''Characterization and chromosomal localization of the gene for human rhodopsin kinase.''; PubMed Europe PMC Scholia
  49. Hurley JB, Stryer L.; ''Purification and characterization of the gamma regulatory subunit of the cyclic GMP phosphodiesterase from retinal rod outer segments.''; PubMed Europe PMC Scholia
  50. Codina J, Stengel D, Woo SL, Birnbaumer L.; ''Beta-subunits of the human liver Gs/Gi signal-transducing proteins and those of bovine retinal rod cell transducin are identical.''; PubMed Europe PMC Scholia
  51. Baylor DA, Nunn BJ, Schnapf JL.; ''The photocurrent, noise and spectral sensitivity of rods of the monkey Macaca fascicularis.''; PubMed Europe PMC Scholia
  52. Fong SL, Fong WB, Morris TA, Kedzie KM, Bridges CD.; ''Characterization and comparative structural features of the gene for human interstitial retinol-binding protein.''; PubMed Europe PMC Scholia
  53. Balasubramanian N, Levay K, Keren-Raifman T, Faurobert E, Slepak VZ.; ''Phosphorylation of the regulator of G protein signaling RGS9-1 by protein kinase A is a potential mechanism of light- and Ca2+-mediated regulation of G protein function in photoreceptors.''; PubMed Europe PMC Scholia
  54. Ben-Shabat S, Parish CA, Vollmer HR, Itagaki Y, Fishkin N, Nakanishi K, Sparrow JR.; ''Biosynthetic studies of A2E, a major fluorophore of retinal pigment epithelial lipofuscin.''; PubMed Europe PMC Scholia
  55. Haeseleer F, Huang J, Lebioda L, Saari JC, Palczewski K.; ''Molecular characterization of a novel short-chain dehydrogenase/reductase that reduces all-trans-retinal.''; PubMed Europe PMC Scholia
  56. Yamaki K, Tsuda M, Shinohara T.; ''The sequence of human retinal S-antigen reveals similarities with alpha-transducin.''; PubMed Europe PMC Scholia
  57. von Lintig J.; ''Metabolism of carotenoids and retinoids related to vision.''; PubMed Europe PMC Scholia
  58. Magnani R, Dirk LM, Trievel RC, Houtz RL.; ''Calmodulin methyltransferase is an evolutionarily conserved enzyme that trimethylates Lys-115 in calmodulin.''; PubMed Europe PMC Scholia
  59. de Sauvage FJ, Keshav S, Kuang WJ, Gillett N, Henzel W, Goeddel DV.; ''Precursor structure, expression, and tissue distribution of human guanylin.''; PubMed Europe PMC Scholia
  60. Bustamante JJ, Ziari S, Ramirez RD, Tsin AT.; ''Retinyl ester hydrolase and the visual cycle in the chicken eye.''; PubMed Europe PMC Scholia
  61. Weber B, Riess O, Hutchinson G, Collins C, Lin BY, Kowbel D, Andrew S, Schappert K, Hayden MR.; ''Genomic organization and complete sequence of the human gene encoding the beta-subunit of the cGMP phosphodiesterase and its localisation to 4p 16.3.''; PubMed Europe PMC Scholia
  62. Goridis C, Virmaux N.; ''Light-regulated guanosine 3',5'-monophosphate phosphodiesterase of bovine retina.''; PubMed Europe PMC Scholia
  63. Gonzalez-Fernandez F, Kurz D, Bao Y, Newman S, Conway BP, Young JE, Han DP, Khani SC.; ''11-cis retinol dehydrogenase mutations as a major cause of the congenital night-blindness disorder known as fundus albipunctatus.''; PubMed Europe PMC Scholia
  64. Smith SO.; ''Structure and activation of the visual pigment rhodopsin.''; PubMed Europe PMC Scholia
  65. Clack JW, Springmeyer ML, Clark CR, Witzmann FA.; ''Transducin subunit stoichiometry and cellular distribution in rod outer segments.''; PubMed Europe PMC Scholia
  66. Oprian DD, Asenjo AB, Lee N, Pelletier SL.; ''Design, chemical synthesis, and expression of genes for the three human color vision pigments.''; PubMed Europe PMC Scholia
  67. von Lintig J, Kiser PD, Golczak M, Palczewski K.; ''The biochemical and structural basis for trans-to-cis isomerization of retinoids in the chemistry of vision.''; PubMed Europe PMC Scholia
  68. Chen CK, Burns ME, He W, Wensel TG, Baylor DA, Simon MI.; ''Slowed recovery of rod photoresponse in mice lacking the GTPase accelerating protein RGS9-1.''; PubMed Europe PMC Scholia
  69. Makino ER, Handy JW, Li T, Arshavsky VY.; ''The GTPase activating factor for transducin in rod photoreceptors is the complex between RGS9 and type 5 G protein beta subunit.''; PubMed Europe PMC Scholia
  70. Hodgkin AL, Nunn BJ.; ''Control of light-sensitive current in salamander rods.''; PubMed Europe PMC Scholia
  71. Dryja TP, Hahn LB, Reboul T, Arnaud B.; ''Missense mutation in the gene encoding the alpha subunit of rod transducin in the Nougaret form of congenital stationary night blindness.''; PubMed Europe PMC Scholia
  72. Craven KB, Zagotta WN.; ''CNG and HCN channels: two peas, one pod.''; PubMed Europe PMC Scholia
  73. Azarian SM, Megarity CF, Weng J, Horvath DH, Travis GH.; ''The human photoreceptor rim protein gene (ABCR): genomic structure and primer set information for mutation analysis.''; PubMed Europe PMC Scholia
  74. Chader GJ, Herz LR, Fletcher RT.; ''Light activation of phosphodiesterase activity in retinal rod outer segments.''; PubMed Europe PMC Scholia
  75. Nathans J, Thomas D, Hogness DS.; ''Molecular genetics of human color vision: the genes encoding blue, green, and red pigments.''; PubMed Europe PMC Scholia
  76. Palczewski K, McDowell JH, Jakes S, Ingebritsen TS, Hargrave PA.; ''Regulation of rhodopsin dephosphorylation by arrestin.''; PubMed Europe PMC Scholia
  77. Wang JS, Kefalov VJ.; ''An alternative pathway mediates the mouse and human cone visual cycle.''; PubMed Europe PMC Scholia
  78. Giang DK, Cravatt BF.; ''A second mammalian N-myristoyltransferase.''; PubMed Europe PMC Scholia
  79. Ovchinnikov IuA, Abdulaev NG, Feĭgina MIu, Artamonov ID, Bogachuk AS.; ''[Visual rhodopsin. III. Complete amino acid sequence and topography in a membrane]''; PubMed Europe PMC Scholia
  80. Kedishvili NY, Chumakova OV, Chetyrkin SV, Belyaeva OV, Lapshina EA, Lin DW, Matsumura M, Nelson PS.; ''Evidence that the human gene for prostate short-chain dehydrogenase/reductase (PSDR1) encodes a novel retinal reductase (RalR1).''; PubMed Europe PMC Scholia
  81. Nathans J, Piantanida TP, Eddy RL, Shows TB, Hogness DS.; ''Molecular genetics of inherited variation in human color vision.''; PubMed Europe PMC Scholia
  82. Khramtsov NV, Feshchenko EA, Suslova VA, Terpugov BE, Rakitina TV, Atabekova NV, Shmukler BE, Lipkin VM.; ''[Structural studies of cDNA and the gene for the beta-subunit of cGMP phosphodiesterase from human retina]''; PubMed Europe PMC Scholia
  83. Korenbrot JI.; ''Speed, sensitivity, and stability of the light response in rod and cone photoreceptors: facts and models.''; PubMed Europe PMC Scholia
  84. Palczewski K, Hargrave PA, McDowell JH, Ingebritsen TS.; ''The catalytic subunit of phosphatase 2A dephosphorylates phosphoopsin.''; PubMed Europe PMC Scholia
  85. Mata NL, Weng J, Travis GH.; ''Biosynthesis of a major lipofuscin fluorophore in mice and humans with ABCR-mediated retinal and macular degeneration.''; PubMed Europe PMC Scholia
  86. Burns ME, Pugh EN.; ''Lessons from photoreceptors: turning off g-protein signaling in living cells.''; PubMed Europe PMC Scholia
  87. Chen TY, Peng YW, Dhallan RS, Ahamed B, Reed RR, Yau KW.; ''A new subunit of the cyclic nucleotide-gated cation channel in retinal rods.''; PubMed Europe PMC Scholia
  88. Poincelot RP, Millar PG, Kimbel RL, Abrahamson EW.; ''Lipid to protein chromophore transfer in the photolysis of visual pigments.''; PubMed Europe PMC Scholia
  89. Kefalov VJ.; ''Rod and cone visual pigments and phototransduction through pharmacological, genetic, and physiological approaches.''; PubMed Europe PMC Scholia
  90. Nicoletti A, Wong DJ, Kawase K, Gibson LH, Yang-Feng TL, Richards JE, Thompson DA.; ''Molecular characterization of the human gene encoding an abundant 61 kDa protein specific to the retinal pigment epithelium.''; PubMed Europe PMC Scholia
  91. Baumann C, Bender S.; ''Kinetics of rhodopsin bleaching in the isolated human retina.''; PubMed Europe PMC Scholia
  92. Kwok-Keung Fung B, Stryer L.; ''Photolyzed rhodopsin catalyzes the exchange of GTP for bound GDP in retinal rod outer segments.''; PubMed Europe PMC Scholia
  93. Hu G, Wensel TG.; ''R9AP, a membrane anchor for the photoreceptor GTPase accelerating protein, RGS9-1.''; PubMed Europe PMC Scholia
  94. Nakano M, Kelly EJ, Wiek C, Hanenberg H, Rettie AE.; ''CYP4V2 in Bietti's crystalline dystrophy: ocular localization, metabolism of ω-3-polyunsaturated fatty acids, and functional deficit of the p.H331P variant.''; PubMed Europe PMC Scholia
  95. Salvador GA, Giusto NM.; ''Characterization of phospholipase D activity in bovine photoreceptor membranes.''; PubMed Europe PMC Scholia
  96. Chen CK, Zhang K, Church-Kopish J, Huang W, Zhang H, Chen YJ, Frederick JM, Baehr W.; ''Characterization of human GRK7 as a potential cone opsin kinase.''; PubMed Europe PMC Scholia
  97. He W, Cowan CW, Wensel TG.; ''RGS9, a GTPase accelerator for phototransduction.''; PubMed Europe PMC Scholia
  98. Lopes VS, Gibbs D, Libby RT, Aleman TS, Welch DL, Lillo C, Jacobson SG, Radu RA, Steel KP, Williams DS.; ''The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65.''; PubMed Europe PMC Scholia
  99. Premont RT, Macrae AD, Stoffel RH, Chung N, Pitcher JA, Ambrose C, Inglese J, MacDonald ME, Lefkowitz RJ.; ''Characterization of the G protein-coupled receptor kinase GRK4. Identification of four splice variants.''; PubMed Europe PMC Scholia
  100. Ueda N, Okamoto Y, Morishita J.; ''N-acylphosphatidylethanolamine-hydrolyzing phospholipase D: a novel enzyme of the beta-lactamase fold family releasing anandamide and other N-acylethanolamines.''; PubMed Europe PMC Scholia
  101. Li A, Jiao X, Munier FL, Schorderet DF, Yao W, Iwata F, Hayakawa M, Kanai A, Shy Chen M, Alan Lewis R, Heckenlively J, Weleber RG, Traboulsi EI, Zhang Q, Xiao X, Kaiser-Kupfer M, Sergeev YV, Hejtmancik JF.; ''Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2.''; PubMed Europe PMC Scholia
  102. Kaylor JJ, Yuan Q, Cook J, Sarfare S, Makshanoff J, Miu A, Kim A, Kim P, Habib S, Roybal CN, Xu T, Nusinowitz S, Travis GH.; ''Identification of DES1 as a vitamin A isomerase in Müller glial cells of the retina.''; PubMed Europe PMC Scholia
  103. Hsu YT, Molday RS.; ''Interaction of calmodulin with the cyclic GMP-gated channel of rod photoreceptor cells. Modulation of activity, affinity purification, and localization.''; PubMed Europe PMC Scholia
  104. Fan G, Siebert F, Sheves M, Vogel R.; ''Rhodopsin with 11-cis-locked chromophore is capable of forming an active state photoproduct.''; PubMed Europe PMC Scholia
  105. Pittler SJ, Baehr W, Wasmuth JJ, McConnell DG, Champagne MS, vanTuinen P, Ledbetter D, Davis RL.; ''Molecular characterization of human and bovine rod photoreceptor cGMP phosphodiesterase alpha-subunit and chromosomal localization of the human gene.''; PubMed Europe PMC Scholia
  106. Kutuzov MA, Bennett N.; ''Calcium-activated opsin phosphatase activity in retinal rod outer segments.''; PubMed Europe PMC Scholia
  107. Murakami A, Yajima T, Inana G.; ''Isolation of human retinal genes: recoverin cDNA and gene.''; PubMed Europe PMC Scholia
  108. Simon A, Lagercrantz J, Bajalica-Lagercrantz S, Eriksson U.; ''Primary structure of human 11-cis retinol dehydrogenase and organization and chromosomal localization of the corresponding gene.''; PubMed Europe PMC Scholia
  109. Michaelides M, Li Z, Rana NA, Richardson EC, Hykin PG, Moore AT, Holder GE, Webster AR.; ''Novel mutations and electrophysiologic findings in RGS9- and R9AP-associated retinal dysfunction (Bradyopsia).''; PubMed Europe PMC Scholia
  110. Wu BX, Chen Y, Chen Y, Fan J, Rohrer B, Crouch RK, Ma JX.; ''Cloning and characterization of a novel all-trans retinol short-chain dehydrogenase/reductase from the RPE.''; PubMed Europe PMC Scholia
  111. Nasonkin I, Illing M, Koehler MR, Schmid M, Molday RS, Weber BH.; ''Mapping of the rod photoreceptor ABC transporter (ABCR) to 1p21-p22.1 and identification of novel mutations in Stargardt's disease.''; PubMed Europe PMC Scholia
  112. Fesenko EE, Kolesnikov SS, Lyubarsky AL.; ''Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment.''; PubMed Europe PMC Scholia
  113. Intres R, Goldflam S, Cook JR, Crabb JW.; ''Molecular cloning and structural analysis of the human gene encoding cellular retinaldehyde-binding protein.''; PubMed Europe PMC Scholia
  114. Rattner A, Smallwood PM, Nathans J.; ''Identification and characterization of all-trans-retinol dehydrogenase from photoreceptor outer segments, the visual cycle enzyme that reduces all-trans-retinal to all-trans-retinol.''; PubMed Europe PMC Scholia
  115. Kokame K, Fukada Y, Yoshizawa T, Takao T, Shimonishi Y.; ''Lipid modification at the N terminus of photoreceptor G-protein alpha-subunit.''; PubMed Europe PMC Scholia
  116. Fuchs S, Nakazawa M, Maw M, Tamai M, Oguchi Y, Gal A.; ''A homozygous 1-base pair deletion in the arrestin gene is a frequent cause of Oguchi disease in Japanese.''; PubMed Europe PMC Scholia
  117. Okamoto Y, Morishita J, Tsuboi K, Tonai T, Ueda N.; ''Molecular characterization of a phospholipase D generating anandamide and its congeners.''; PubMed Europe PMC Scholia
  118. Hofmann KP.; ''Effect of GTP on the rhodopsin-G-protein complex by transient formation of extra metarhodopsin II.''; PubMed Europe PMC Scholia
  119. Fong SL, Bridges CD.; ''Internal quadruplication in the structure of human interstitial retinol-binding protein deduced from its cloned cDNA.''; PubMed Europe PMC Scholia
  120. Nakatani K, Yau KW.; ''Calcium and magnesium fluxes across the plasma membrane of the toad rod outer segment.''; PubMed Europe PMC Scholia
  121. Wolf G.; ''The visual cycle of the cone photoreceptors of the retina.''; PubMed Europe PMC Scholia
  122. Beharry S, Zhong M, Molday RS.; ''N-retinylidene-phosphatidylethanolamine is the preferred retinoid substrate for the photoreceptor-specific ABC transporter ABCA4 (ABCR).''; PubMed Europe PMC Scholia
  123. Baylor DA, Nunn BJ.; ''Electrical properties of the light-sensitive conductance of rods of the salamander Ambystoma tigrinum.''; PubMed Europe PMC Scholia
  124. Fowles C, Akhtar M, Cohen P.; ''Interplay of phosphorylation and dephosphorylation in vision: protein phosphatases of bovine rod outer segments.''; PubMed Europe PMC Scholia
  125. Sparrow JR, Fishkin N, Zhou J, Cai B, Jang YP, Krane S, Itagaki Y, Nakanishi K.; ''A2E, a byproduct of the visual cycle.''; PubMed Europe PMC Scholia
  126. Nishiguchi KM, Sandberg MA, Kooijman AC, Martemyanov KA, Pott JW, Hagstrom SA, Arshavsky VY, Berson EL, Dryja TP.; ''Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation.''; PubMed Europe PMC Scholia
  127. Fung BK, Hurley JB, Stryer L.; ''Flow of information in the light-triggered cyclic nucleotide cascade of vision.''; PubMed Europe PMC Scholia
  128. Zhang K, Howes KA, He W, Bronson JD, Pettenati MJ, Chen C, Palczewski K, Wensel TG, Baehr W.; ''Structure, alternative splicing, and expression of the human RGS9 gene.''; PubMed Europe PMC Scholia
  129. Hsu YT, Molday RS.; ''Modulation of the cGMP-gated channel of rod photoreceptor cells by calmodulin.''; PubMed Europe PMC Scholia
  130. Kawaguchi R, Yu J, Honda J, Hu J, Whitelegge J, Ping P, Wiita P, Bok D, Sun H.; ''A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A.''; PubMed Europe PMC Scholia
  131. Surguchov A, Bronson JD, Banerjee P, Knowles JA, Ruiz C, Subbaraya I, Palczewski K, Baehr W.; ''The human GCAP1 and GCAP2 genes are arranged in a tail-to-tail array on the short arm of chromosome 6 (p21.1).''; PubMed Europe PMC Scholia
  132. Folli C, Calderone V, Ottonello S, Bolchi A, Zanotti G, Stoppini M, Berni R.; ''Identification, retinoid binding, and x-ray analysis of a human retinol-binding protein.''; PubMed Europe PMC Scholia
  133. Osawa S, Jo R, Weiss ER.; ''Phosphorylation of GRK7 by PKA in cone photoreceptor cells is regulated by light.''; PubMed Europe PMC Scholia
  134. Cheng JB, Russell DW.; ''Mammalian wax biosynthesis. II. Expression cloning of wax synthase cDNAs encoding a member of the acyltransferase enzyme family.''; PubMed Europe PMC Scholia
  135. Young RW.; ''The renewal of photoreceptor cell outer segments.''; PubMed Europe PMC Scholia
  136. Kiser PD, Golczak M, Palczewski K.; ''Chemistry of the retinoid (visual) cycle.''; PubMed Europe PMC Scholia
  137. Yau KW, Baylor DA.; ''Cyclic GMP-activated conductance of retinal photoreceptor cells.''; PubMed Europe PMC Scholia
  138. Sokal I, Hu G, Liang Y, Mao M, Wensel TG, Palczewski K.; ''Identification of protein kinase C isozymes responsible for the phosphorylation of photoreceptor-specific RGS9-1 at Ser475.''; PubMed Europe PMC Scholia
  139. Hargrave PA, McDowell JH, Curtis DR, Wang JK, Juszczak E, Fong SL, Rao JK, Argos P.; ''The structure of bovine rhodopsin.''; PubMed Europe PMC Scholia
  140. Riazuddin SA, Shahzadi A, Zeitz C, Ahmed ZM, Ayyagari R, Chavali VR, Ponferrada VG, Audo I, Michiels C, Lancelot ME, Nasir IA, Zafar AU, Khan SN, Husnain T, Jiao X, MacDonald IM, Riazuddin S, Sieving PA, Katsanis N, Hejtmancik JF.; ''A mutation in SLC24A1 implicated in autosomal-recessive congenital stationary night blindness.''; PubMed Europe PMC Scholia
  141. Marino JP, Fisher PW, Hofmann GA, Kirkpatrick RB, Janson CA, Johnson RK, Ma C, Mattern M, Meek TD, Ryan MD, Schulz C, Smith WW, Tew DG, Tomazek TA, Veber DF, Xiong WC, Yamamoto Y, Yamashita K, Yang G, Thompson SK.; ''Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.''; PubMed Europe PMC Scholia
  142. Van Dop C, Medynski DC, Apone LM.; ''Nucleotide sequence for a cDNA encoding the alpha subunit of retinal transducin (GNAT1) isolated from the human eye.''; PubMed Europe PMC Scholia
  143. Nathans J, Hogness DS.; ''Isolation and nucleotide sequence of the gene encoding human rhodopsin.''; PubMed Europe PMC Scholia
  144. Fong SL.; ''Characterization of the human rod transducin alpha-subunit gene.''; PubMed Europe PMC Scholia
  145. Arne JM, Widjaja-Adhi MA, Hughes T, Huynh KW, Silvaroli JA, Chelstowska S, Moiseenkova-Bell VY, Golczak M.; ''Allosteric modulation of the substrate specificity of acyl-CoA wax alcohol acyltransferase 2.''; PubMed Europe PMC Scholia
  146. Tsybovsky Y, Molday RS, Palczewski K.; ''The ATP-binding cassette transporter ABCA4: structural and functional properties and role in retinal disease.''; PubMed Europe PMC Scholia
  147. Wang J, Okamoto Y, Morishita J, Tsuboi K, Miyatake A, Ueda N.; ''Functional analysis of the purified anandamide-generating phospholipase D as a member of the metallo-beta-lactamase family.''; PubMed Europe PMC Scholia
  148. Weitz D, Ficek N, Kremmer E, Bauer PJ, Kaupp UB.; ''Subunit stoichiometry of the CNG channel of rod photoreceptors.''; PubMed Europe PMC Scholia
  149. Young RW, Bok D.; ''Participation of the retinal pigment epithelium in the rod outer segment renewal process.''; PubMed Europe PMC Scholia
  150. Pugh EN, Lamb TD.; ''Amplification and kinetics of the activation steps in phototransduction.''; PubMed Europe PMC Scholia
  151. Shyjan AW, de Sauvage FJ, Gillett NA, Goeddel DV, Lowe DG.; ''Molecular cloning of a retina-specific membrane guanylyl cyclase.''; PubMed Europe PMC Scholia
  152. Wensel TG, Stryer L.; ''Reciprocal control of retinal rod cyclic GMP phosphodiesterase by its gamma subunit and transducin.''; PubMed Europe PMC Scholia
  153. Ramulu P, Kennedy M, Xiong WH, Williams J, Cowan M, Blesh D, Yau KW, Hurley JB, Nathans J.; ''Normal light response, photoreceptor integrity, and rhodopsin dephosphorylation in mice lacking both protein phosphatases with EF hands (PPEF-1 and PPEF-2).''; PubMed Europe PMC Scholia
  154. Crabb JW, Carlson A, Chen Y, Goldflam S, Intres R, West KA, Hulmes JD, Kapron JT, Luck LA, Horwitz J, Bok D.; ''Structural and functional characterization of recombinant human cellular retinaldehyde-binding protein.''; PubMed Europe PMC Scholia
  155. Katz ML, Drea CM, Eldred GE, Hess HH, Robison WG.; ''Influence of early photoreceptor degeneration on lipofuscin in the retinal pigment epithelium.''; PubMed Europe PMC Scholia
  156. Berry DC, O'Byrne SM, Vreeland AC, Blaner WS, Noy N.; ''Cross talk between signaling and vitamin A transport by the retinol-binding protein receptor STRA6.''; PubMed Europe PMC Scholia
  157. Long SB, Hancock PJ, Kral AM, Hellinga HW, Beese LS.; ''The crystal structure of human protein farnesyltransferase reveals the basis for inhibition by CaaX tetrapeptides and their mimetics.''; PubMed Europe PMC Scholia
  158. Glover CJ, Hartman KD, Felsted RL.; ''Human N-myristoyltransferase amino-terminal domain involved in targeting the enzyme to the ribosomal subcellular fraction.''; PubMed Europe PMC Scholia
  159. Parish CA, Hashimoto M, Nakanishi K, Dillon J, Sparrow J.; ''Isolation and one-step preparation of A2E and iso-A2E, fluorophores from human retinal pigment epithelium.''; PubMed Europe PMC Scholia
  160. Jones PG, Lombardi SJ, Cockett MI.; ''Cloning and tissue distribution of the human G protein beta 5 cDNA.''; PubMed Europe PMC Scholia
  161. Blomhoff R, Blomhoff HK.; ''Overview of retinoid metabolism and function.''; PubMed Europe PMC Scholia
  162. Belyaeva OV, Korkina OV, Stetsenko AV, Kim T, Nelson PS, Kedishvili NY.; ''Biochemical properties of purified human retinol dehydrogenase 12 (RDH12): catalytic efficiency toward retinoids and C9 aldehydes and effects of cellular retinol-binding protein type I (CRBPI) and cellular retinaldehyde-binding protein (CRALBP) on the oxidation and reduction of retinoids.''; PubMed Europe PMC Scholia
  163. Omer CA, Kral AM, Diehl RE, Prendergast GC, Powers S, Allen CM, Gibbs JB, Kohl NE.; ''Characterization of recombinant human farnesyl-protein transferase: cloning, expression, farnesyl diphosphate binding, and functional homology with yeast prenyl-protein transferases.''; PubMed Europe PMC Scholia
  164. Mata NL, Ruiz A, Radu RA, Bui TV, Travis GH.; ''Chicken retinas contain a retinoid isomerase activity that catalyzes the direct conversion of all-trans-retinol to 11-cis-retinol.''; PubMed Europe PMC Scholia
  165. Arfin SM, Kendall RL, Hall L, Weaver LH, Stewart AE, Matthews BW, Bradshaw RA.; ''Eukaryotic methionyl aminopeptidases: two classes of cobalt-dependent enzymes.''; PubMed Europe PMC Scholia
  166. Polans AS, Buczyłko J, Crabb J, Palczewski K.; ''A photoreceptor calcium binding protein is recognized by autoantibodies obtained from patients with cancer-associated retinopathy.''; PubMed Europe PMC Scholia
  167. Blakeley LR, Chen C, Chen CK, Chen J, Crouch RK, Travis GH, Koutalos Y.; ''Rod outer segment retinol formation is independent of Abca4, arrestin, rhodopsin kinase, and rhodopsin palmitylation.''; PubMed Europe PMC Scholia
  168. Rieke F, Baylor DA.; ''Molecular origin of continuous dark noise in rod photoreceptors.''; PubMed Europe PMC Scholia
  169. Tuteja N, Danciger M, Klisak I, Tuteja R, Inana G, Mohandas T, Sparkes RS, Farber DB.; ''Isolation and characterization of cDNA encoding the gamma-subunit of cGMP phosphodiesterase in human retina.''; PubMed Europe PMC Scholia
  170. Chassaing N, Golzio C, Odent S, Lequeux L, Vigouroux A, Martinovic-Bouriel J, Tiziano FD, Masini L, Piro F, Maragliano G, Delezoide AL, Attié-Bitach T, Manouvrier-Hanu S, Etchevers HC, Calvas P.; ''Phenotypic spectrum of STRA6 mutations: from Matthew-Wood syndrome to non-lethal anophthalmia.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
114665view16:13, 25 January 2021ReactomeTeamReactome version 75
113113view11:17, 2 November 2020ReactomeTeamReactome version 74
112347view15:27, 9 October 2020ReactomeTeamReactome version 73
101247view11:14, 1 November 2018ReactomeTeamreactome version 66
100786view20:41, 31 October 2018ReactomeTeamreactome version 65
100328view19:18, 31 October 2018ReactomeTeamreactome version 64
99874view16:01, 31 October 2018ReactomeTeamreactome version 63
99431view14:36, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99109view12:39, 31 October 2018ReactomeTeamreactome version 62
94030view13:52, 16 August 2017ReactomeTeamreactome version 61
93652view11:29, 9 August 2017ReactomeTeamreactome version 61
88350view16:18, 1 August 2016FehrhartOntology Term : 'photosignal transduction pathway' added !
86770view09:25, 11 July 2016ReactomeTeamreactome version 56
83212view10:24, 18 November 2015ReactomeTeamVersion54
81599view13:08, 21 August 2015ReactomeTeamVersion53
77056view08:35, 17 July 2014ReactomeTeamFixed remaining interactions
76761view12:12, 16 July 2014ReactomeTeamFixed remaining interactions
75146view14:09, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74793view08:53, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
11cRAL MetaboliteCHEBI:16066 (ChEBI)
11cRALMetaboliteCHEBI:16066 (ChEBI)
11cRDHREACT_160753 (Reactome)
11cROL MetaboliteCHEBI:16302 (ChEBI)
11cROLMetaboliteCHEBI:16302 (ChEBI)
11cRPALMMetaboliteCHEBI:16254 (ChEBI)
A2EMetaboliteCHEBI:71980 (ChEBI)
A2PEMetaboliteCHEBI:52592 (ChEBI)
ABCA4ProteinP78363 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
AKRsProteinREACT_161169 (Reactome)
APOA1ProteinP02647 (Uniprot-TrEMBL)
APOA2ProteinP02652 (Uniprot-TrEMBL)
APOA4 ProteinP06727 (Uniprot-TrEMBL)
APOBProteinP04114 (Uniprot-TrEMBL)
APOC2 ProteinP02655 (Uniprot-TrEMBL)
APOC3 ProteinP02656 (Uniprot-TrEMBL)
APOE ProteinP02649 (Uniprot-TrEMBL)
APOEProteinP02649 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
BCMO1 Fe2+ComplexREACT_26746 (Reactome)
BCMO1 ProteinQ9HAY6 (Uniprot-TrEMBL)
CALM1

Ca2+

CNG channel
ComplexREACT_165396 (Reactome)
CALM1 Ca2+ComplexREACT_164501 (Reactome)
CALM1 ProteinP62158 (Uniprot-TrEMBL)
CHEST MetaboliteCHEBI:17002 (ChEBI)
CHOL MetaboliteCHEBI:16113 (ChEBI)
CLPS ProteinP04118 (Uniprot-TrEMBL)
CNG channelComplexREACT_165342 (Reactome)
CNGA1 ProteinP29973 (Uniprot-TrEMBL)
CNGB1 ProteinQ14028 (Uniprot-TrEMBL)
CR

atREs HSPG

apoE
ComplexREACT_160816 (Reactome)
CR

atREs HSPG

apoE
ComplexREACT_161371 (Reactome)
CR atREsComplexREACT_160494 (Reactome)
CRComplexREACT_161208 (Reactome)
CRComplexREACT_161439 (Reactome)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Co2+ MetaboliteCHEBI:27638 (ChEBI)
CoA-SHMetaboliteCHEBI:15346 (ChEBI)
Cone apo-opsinsProteinREACT_160347 (Reactome)
Cone opsins 11cRALComplexREACT_161031 (Reactome)
Cone opsins atRALComplexREACT_161282 (Reactome)
DAGMetaboliteCHEBI:18035 (ChEBI)
DHRS3ProteinO75911 (Uniprot-TrEMBL)
FACYLsMetaboliteREACT_160603 (Reactome)
FAsMetaboliteREACT_150811 (Reactome)
FAsMetaboliteREACT_161544 (Reactome)
FNTA FNTBComplexREACT_164027 (Reactome)
FNTAProteinP49354 (Uniprot-TrEMBL)
FNTB ProteinP49356 (Uniprot-TrEMBL)
FPPMetaboliteCHEBI:50277 (ChEBI)
Fe2+ MetaboliteCHEBI:18248 (ChEBI)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GMPMetaboliteCHEBI:17345 (ChEBI)
GNAT1 ProteinP11488 (Uniprot-TrEMBL)
GNAT1-GDPComplexREACT_165079 (Reactome)
GNAT1-GTP PDE6ComplexREACT_164412 (Reactome)
GNAT1-GTPComplexREACT_165254 (Reactome)
GNAT1ProteinP11488 (Uniprot-TrEMBL)
GNB1 GNGT1ComplexREACT_164629 (Reactome)
GNB1 ProteinP62873 (Uniprot-TrEMBL)
GNB5-1 ProteinO14775-1 (Uniprot-TrEMBL)
GNGT1ProteinP63211 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
GUCA Ca2+ComplexREACT_165513 (Reactome)
GUCA1A ProteinP43080 (Uniprot-TrEMBL)
GUCA1BProteinQ9UMX6 (Uniprot-TrEMBL)
GUCA1C ProteinO95843 (Uniprot-TrEMBL)
GUCAProteinREACT_165364 (Reactome)
GUCYsProteinREACT_165199 (Reactome)
Gt-GDPComplexREACT_165568 (Reactome)
Gt-GTPComplexREACT_164539 (Reactome)
H+MetaboliteCHEBI:15378 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HSProteinO00468 (Uniprot-TrEMBL)
HSProteinO75056 (Uniprot-TrEMBL)
HSProteinO75487 (Uniprot-TrEMBL)
HSProteinP18827 (Uniprot-TrEMBL)
HSProteinP31431 (Uniprot-TrEMBL)
HSProteinP34741 (Uniprot-TrEMBL)
HSProteinP35052 (Uniprot-TrEMBL)
HSProteinP51654 (Uniprot-TrEMBL)
HSProteinP78333 (Uniprot-TrEMBL)
HSProteinP98160 (Uniprot-TrEMBL)
HSPG

LPL

LPL
ComplexREACT_7472 (Reactome)
HSPG2ProteinP98160 (Uniprot-TrEMBL)
HSPGsProteinREACT_122831 (Reactome)
HSProteinQ8N158 (Uniprot-TrEMBL)
HSProteinQ9Y625 (Uniprot-TrEMBL)
K+MetaboliteCHEBI:29103 (ChEBI)
L-MetMetaboliteCHEBI:16643 (ChEBI)
LCFAsMetaboliteCHEBI:15904 (ChEBI)
LDLRProteinP01130 (Uniprot-TrEMBL)
LPL ProteinP06858 (Uniprot-TrEMBL)
LRATProteinO95237 (Uniprot-TrEMBL)
LRPsProteinREACT_161047 (Reactome)
METAP1/2ComplexREACT_164731 (Reactome)
METAP1ProteinP53582 (Uniprot-TrEMBL)
METAP2ProteinP50579 (Uniprot-TrEMBL)
MIIComplexREACT_161020 (Reactome)
MYO7AProteinQ13402 (Uniprot-TrEMBL)
MYS-CoAMetaboliteCHEBI:15532 (ChEBI)
Mg2+ MetaboliteCHEBI:18420 (ChEBI)
N-ProteinP11488 (Uniprot-TrEMBL)
N-acyl-GNAT1ProteinREACT_164094 (Reactome)
NAD+MetaboliteCHEBI:15846 (ChEBI)
NADHMetaboliteCHEBI:16908 (ChEBI)
NADP+MetaboliteCHEBI:18009 (ChEBI)
NADPHMetaboliteCHEBI:16474 (ChEBI)
NAPEPLDProteinQ6IQ20 (Uniprot-TrEMBL)
NMT1/2ProteinREACT_164124 (Reactome)
NREHREACT_160866 (Reactome)
NRPEMetaboliteCHEBI:71063 (ChEBI)
Na+MetaboliteCHEBI:29101 (ChEBI)
O2MetaboliteCHEBI:15379 (ChEBI)
OPN1LW ProteinP04000 (Uniprot-TrEMBL)
OPN1MW ProteinP04001 (Uniprot-TrEMBL)
OPN1SW ProteinP03999 (Uniprot-TrEMBL)
PAMetaboliteCHEBI:16337 (ChEBI)
PALMMetaboliteCHEBI:15756 (ChEBI)
PDE6AProteinP16499 (Uniprot-TrEMBL)
PDE6BProteinP35913 (Uniprot-TrEMBL)
PDE6G ProteinP18545 (Uniprot-TrEMBL)
PDE6ComplexREACT_24605 (Reactome) cGMP selective hydrolase
PEMetaboliteCHEBI:16038 (ChEBI)
PL MetaboliteCHEBI:16247 (ChEBI)
PLB1ProteinQ6P1J6 (Uniprot-TrEMBL)
PNLIP CLPSComplexREACT_9829 (Reactome)
PNLIP ProteinP16233 (Uniprot-TrEMBL)
PPEF1 Mg2+ComplexREACT_164344 (Reactome)
PPEF1 ProteinO14829 (Uniprot-TrEMBL)
PPiMetaboliteCHEBI:29888 (ChEBI)
PRKCA/QProteinREACT_165136 (Reactome)
PhotonREACT_18935 (Reactome)
PiMetaboliteCHEBI:18367 (ChEBI)
RBP1 atROLComplexREACT_160365 (Reactome)
RBP1 atROLComplexREACT_160550 (Reactome)
RBP1 atROLComplexREACT_160558 (Reactome)
RBP1 ProteinP09455 (Uniprot-TrEMBL)
RBP1ProteinP09455 (Uniprot-TrEMBL)
RBP2 atRALComplexREACT_25547 (Reactome)
RBP2 atROLComplexREACT_25941 (Reactome)
RBP2ProteinP50120 (Uniprot-TrEMBL)
RBP3ProteinP10745 (Uniprot-TrEMBL)
RBP4 atROLComplexREACT_160786 (Reactome)
RBP4ProteinP02753 (Uniprot-TrEMBL)
RCVRN Ca2+ComplexREACT_165025 (Reactome)
RCVRN ProteinP35243 (Uniprot-TrEMBL)
RCVRNProteinP35243 (Uniprot-TrEMBL)
RDH10/11ProteinREACT_160646 (Reactome)
RDH11ProteinQ8TC12 (Uniprot-TrEMBL)
RDH12ProteinQ96NR8 (Uniprot-TrEMBL)
RDH5ProteinQ92781 (Uniprot-TrEMBL)
RDH8ProteinQ9NYR8 (Uniprot-TrEMBL)
REHREACT_160374 (Reactome)
REHREACT_161495 (Reactome)
RGS9 isoform 3 ProteinO75916-3 (Uniprot-TrEMBL)
RGS9-1

GNB5

RGS9BP
ComplexREACT_164446 (Reactome)
RGS9BP ProteinQ6ZS82 (Uniprot-TrEMBL)
RHO 11cRALComplexREACT_160981 (Reactome)
RHO ProteinP08100 (Uniprot-TrEMBL)
RHOProteinP08100 (Uniprot-TrEMBL)
RLBP1 11cRALComplexREACT_161180 (Reactome)
RLBP1 11cROLComplexREACT_160715 (Reactome)
RLBP1 atROLComplexREACT_161152 (Reactome)
RLBP1 ProteinP12271 (Uniprot-TrEMBL)
RLBP1ProteinP12271 (Uniprot-TrEMBL)
RPALMMetaboliteCHEBI:17616 (ChEBI)
RPE65ProteinQ16518 (Uniprot-TrEMBL)
S-farn-GNGT1 ProteinP63211 (Uniprot-TrEMBL)
S-farn-GNGT1ProteinP63211 (Uniprot-TrEMBL)
S-farn-GRK1

RCVRN

Ca2+
ComplexREACT_165115 (Reactome)
S-farn-GRK1 ProteinQ15835 (Uniprot-TrEMBL)
S-farn-GRK1ProteinQ15835 (Uniprot-TrEMBL)
SAG ProteinP10523 (Uniprot-TrEMBL)
SAGProteinP10523 (Uniprot-TrEMBL)
SDC1 ProteinP18827 (Uniprot-TrEMBL)
SLC24A1ProteinO60721 (Uniprot-TrEMBL)
STRA6 ProteinQ9BX79 (Uniprot-TrEMBL)
STRA6ProteinQ9BX79 (Uniprot-TrEMBL)
TAG MetaboliteCHEBI:17855 (ChEBI)
TAGs MetaboliteCHEBI:17855 (ChEBI)
TTR

RBP4

STRA6
ComplexREACT_160434 (Reactome)
TTR

RBP4 atROL

STRA6
ComplexREACT_161016 (Reactome)
TTR

RBP4

atROL
ComplexREACT_161464 (Reactome)
TTR ProteinP02766 (Uniprot-TrEMBL)
TTR tetramerComplexREACT_160686 (Reactome)
acyl-CoAMetaboliteREACT_164186 (Reactome)
atR-LINA MetaboliteCHEBI:70762 (ChEBI)
atR-OLEA MetaboliteCHEBI:70760 (ChEBI)
atR-PALM MetaboliteCHEBI:17616 (ChEBI)
atR-STEA MetaboliteCHEBI:70761 (ChEBI)
atRAL MetaboliteCHEBI:17898 (ChEBI)
atRALMetaboliteCHEBI:17898 (ChEBI)
atREsMetaboliteREACT_150876 (Reactome)
atREsMetaboliteREACT_161167 (Reactome)
atROL MetaboliteCHEBI:17336 (ChEBI)
atROL isomeraseREACT_160708 (Reactome)
atROLMetaboliteCHEBI:17336 (ChEBI)
betaCMetaboliteCHEBI:17579 (ChEBI)
cGMP CNG channelComplexREACT_164720 (Reactome)
cGMP MetaboliteCHEBI:16356 (ChEBI)
cGMPMetaboliteCHEBI:16356 (ChEBI)
mature CM atREsComplexREACT_160469 (Reactome)
nascent CM atREsComplexREACT_161397 (Reactome)
nascent CM atREsComplexREACT_161453 (Reactome)
nascent CMComplexREACT_161528 (Reactome)
p-MII SAGComplexREACT_164622 (Reactome)
p-RHO SAGComplexREACT_165105 (Reactome)
p-S334,S338,S343-MIIComplexREACT_165535 (Reactome)
p-S334,S338,S343-RHO ProteinP08100 (Uniprot-TrEMBL)
p-S334,S338,S343-RHOProteinP08100 (Uniprot-TrEMBL)
p-S478-RGS9 isoform 3 ProteinO75916-3 (Uniprot-TrEMBL)
p-S478-RGS9-1

GNB5

RGS9BP
ComplexREACT_164327 (Reactome)
spherical HDL

apoC-II apoC-III

apoE
ComplexREACT_6983 (Reactome)
spherical HDLComplexREACT_14247 (Reactome)
unknown NATREACT_164765 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
11cRALREACT_160240 (Reactome)
11cRDHmim-catalysisREACT_160139 (Reactome)
11cROLArrowREACT_160208 (Reactome)
11cROLArrowREACT_160228 (Reactome)
11cROLREACT_160184 (Reactome)
11cRPALMREACT_160228 (Reactome)
A2EArrowREACT_160080 (Reactome)
A2PEArrowREACT_160162 (Reactome)
A2PEREACT_160080 (Reactome)
ABCA4mim-catalysisREACT_111189 (Reactome)
ABCA4mim-catalysisREACT_160211 (Reactome)
ADPArrowREACT_111189 (Reactome)
ADPArrowREACT_160211 (Reactome)
ADPArrowREACT_163640 (Reactome)
ADPArrowREACT_163992 (Reactome)
AKRsmim-catalysisREACT_160311 (Reactome)
APOEArrowREACT_160151 (Reactome)
APOEREACT_160149 (Reactome)
ATPREACT_111189 (Reactome)
ATPREACT_160211 (Reactome)
ATPREACT_163640 (Reactome)
ATPREACT_163992 (Reactome)
BCMO1 Fe2+mim-catalysisREACT_25117 (Reactome)
CALM1 Ca2+REACT_163913 (Reactome)
CNG channelArrowREACT_163894 (Reactome)
CNG channelREACT_163913 (Reactome)
CNG channelREACT_164008 (Reactome)
CR

atREs HSPG

apoE
REACT_160151 (Reactome)
CR atREsREACT_160239 (Reactome)
CRArrowREACT_160151 (Reactome)
CRArrowREACT_160186 (Reactome)
CRArrowREACT_160239 (Reactome)
CRREACT_160149 (Reactome)
Ca2+ArrowREACT_163682 (Reactome)
Ca2+ArrowREACT_163839 (Reactome)
Ca2+ArrowREACT_163982 (Reactome)
Ca2+REACT_163682 (Reactome)
Ca2+REACT_163809 (Reactome)
Ca2+REACT_163982 (Reactome)
Ca2+TBarREACT_163992 (Reactome)
CoA-SHArrowREACT_163718 (Reactome)
CoA-SHArrowREACT_163903 (Reactome)
Cone apo-opsinsArrowREACT_160146 (Reactome)
Cone opsins atRALREACT_160146 (Reactome)
DAGArrowREACT_160186 (Reactome)
DHRS3mim-catalysisREACT_160119 (Reactome)
FACYLsREACT_160247 (Reactome)
FACYLsREACT_160266 (Reactome)
FACYLsREACT_25108 (Reactome)
FAsArrowREACT_160151 (Reactome)
FAsArrowREACT_160160 (Reactome)
FAsArrowREACT_160208 (Reactome)
FAsArrowREACT_160239 (Reactome)
FNTA FNTBmim-catalysisREACT_163835 (Reactome)
FPPREACT_163835 (Reactome)
GDPArrowREACT_163833 (Reactome)
GNAT1 ArrowREACT_163720 (Reactome)
GNAT1 REACT_163718 (Reactome)
GNAT1 REACT_163903 (Reactome)
GNAT1-GDPArrowREACT_163662 (Reactome)
GNAT1-GDPREACT_163859 (Reactome)
GNAT1-GTP PDE6REACT_163662 (Reactome)
GNAT1-GTP PDE6mim-catalysisREACT_163662 (Reactome)
GNAT1-GTP PDE6mim-catalysisREACT_163760 (Reactome)
GNAT1-GTPArrowREACT_163674 (Reactome)
GNAT1-GTPREACT_163927 (Reactome)
GNB1 GNGT1ArrowREACT_163674 (Reactome)
GNB1 GNGT1REACT_163859 (Reactome)
GNGT1REACT_163835 (Reactome)
GTPREACT_163833 (Reactome)
GUCA Ca2+TBarREACT_163996 (Reactome)
GUCAArrowREACT_163996 (Reactome)
GUCAREACT_163809 (Reactome)
GUCYsmim-catalysisREACT_163996 (Reactome)
Gt-GDPREACT_163833 (Reactome)
Gt-GTPArrowREACT_163833 (Reactome)
H+ArrowREACT_160124 (Reactome)
H+ArrowREACT_160138 (Reactome)
H+ArrowREACT_160139 (Reactome)
H+ArrowREACT_160151 (Reactome)
H+ArrowREACT_160208 (Reactome)
H+ArrowREACT_160228 (Reactome)
H+ArrowREACT_160239 (Reactome)
H+REACT_160119 (Reactome)
H+REACT_160121 (Reactome)
H+REACT_160140 (Reactome)
H+REACT_160311 (Reactome)
H+REACT_25000 (Reactome)
H2OArrowREACT_160162 (Reactome)
H2OREACT_111189 (Reactome)
H2OREACT_160080 (Reactome)
H2OREACT_160146 (Reactome)
H2OREACT_160151 (Reactome)
H2OREACT_160160 (Reactome)
H2OREACT_160208 (Reactome)
H2OREACT_160211 (Reactome)
H2OREACT_160228 (Reactome)
H2OREACT_160239 (Reactome)
H2OREACT_163662 (Reactome)
H2OREACT_163760 (Reactome)
H2OREACT_163839 (Reactome)
H2OREACT_25063 (Reactome)
H2OREACT_25240 (Reactome)
HSPG

LPL

LPL
mim-catalysisREACT_160186 (Reactome)
HSPGsArrowREACT_160151 (Reactome)
HSPGsREACT_160149 (Reactome)
K+ArrowREACT_163982 (Reactome)
K+REACT_163982 (Reactome)
L-MetArrowREACT_163720 (Reactome)
LCFAsArrowREACT_160186 (Reactome)
LDLRmim-catalysisREACT_160308 (Reactome)
LRATmim-catalysisREACT_160247 (Reactome)
LRATmim-catalysisREACT_160266 (Reactome)
LRATmim-catalysisREACT_25108 (Reactome)
LRPsmim-catalysisREACT_160272 (Reactome)
METAP1/2mim-catalysisREACT_163720 (Reactome)
MIIREACT_163992 (Reactome)
MIImim-catalysisREACT_163833 (Reactome)
MYO7AArrowREACT_160208 (Reactome)
MYS-CoAREACT_163718 (Reactome)
N-ArrowREACT_163718 (Reactome)
N-acyl-GNAT1ArrowREACT_163903 (Reactome)
NAD+REACT_160124 (Reactome)
NADHArrowREACT_160124 (Reactome)
NADP+ArrowREACT_160119 (Reactome)
NADP+ArrowREACT_160121 (Reactome)
NADP+ArrowREACT_160140 (Reactome)
NADP+ArrowREACT_160311 (Reactome)
NADP+ArrowREACT_25000 (Reactome)
NADP+REACT_160138 (Reactome)
NADP+REACT_160139 (Reactome)
NADPHArrowREACT_160138 (Reactome)
NADPHArrowREACT_160139 (Reactome)
NADPHREACT_160119 (Reactome)
NADPHREACT_160121 (Reactome)
NADPHREACT_160140 (Reactome)
NADPHREACT_160311 (Reactome)
NADPHREACT_25000 (Reactome)
NAPEPLDmim-catalysisREACT_160080 (Reactome)
NMT1/2mim-catalysisREACT_163718 (Reactome)
NREHmim-catalysisREACT_160151 (Reactome)
NREHmim-catalysisREACT_160239 (Reactome)
NRPEArrowREACT_160211 (Reactome)
NRPEREACT_160162 (Reactome)
NRPEREACT_160211 (Reactome)
Na+ArrowREACT_163682 (Reactome)
Na+ArrowREACT_163982 (Reactome)
Na+REACT_163682 (Reactome)
Na+REACT_163982 (Reactome)
O2REACT_25117 (Reactome)
PAArrowREACT_160080 (Reactome)
PALMArrowREACT_160228 (Reactome)
PALMArrowREACT_25063 (Reactome)
PALMArrowREACT_25240 (Reactome)
PDE6ArrowREACT_163662 (Reactome)
PDE6REACT_163927 (Reactome)
PEArrowREACT_160267 (Reactome)
PEREACT_160285 (Reactome)
PLB1mim-catalysisREACT_25063 (Reactome)
PNLIP CLPSmim-catalysisREACT_25240 (Reactome)
PPEF1 Mg2+mim-catalysisREACT_163839 (Reactome)
PPiArrowREACT_163835 (Reactome)
PPiArrowREACT_163996 (Reactome)
PRKCA/Qmim-catalysisREACT_163640 (Reactome)
Photonmim-catalysisREACT_160165 (Reactome)
Photonmim-catalysisREACT_160286 (Reactome)
PiArrowREACT_111189 (Reactome)
PiArrowREACT_160211 (Reactome)
PiArrowREACT_163662 (Reactome)
PiArrowREACT_163839 (Reactome)
RBP1 atROLREACT_160247 (Reactome)
RBP1 atROLREACT_160266 (Reactome)
RBP1ArrowREACT_160107 (Reactome)
RBP1ArrowREACT_160247 (Reactome)
RBP1ArrowREACT_160266 (Reactome)
RBP1REACT_160072 (Reactome)
RBP1REACT_160275 (Reactome)
RBP1REACT_160295 (Reactome)
RBP2 atRALREACT_160311 (Reactome)
RBP2 atRALREACT_25000 (Reactome)
RBP2 atROLArrowREACT_160311 (Reactome)
RBP2 atROLArrowREACT_25000 (Reactome)
RBP2 atROLREACT_25108 (Reactome)
RBP2ArrowREACT_25108 (Reactome)
RBP2REACT_160101 (Reactome)
RBP2REACT_25146 (Reactome)
RBP3mim-catalysisREACT_160091 (Reactome)
RBP3mim-catalysisREACT_160222 (Reactome)
RBP3mim-catalysisREACT_160292 (Reactome)
RBP3mim-catalysisREACT_160302 (Reactome)
RBP4 atROLREACT_160076 (Reactome)
RBP4REACT_160244 (Reactome)
RCVRN Ca2+REACT_163661 (Reactome)
RCVRNTBarREACT_163992 (Reactome)
RDH10/11mim-catalysisREACT_160138 (Reactome)
RDH11mim-catalysisREACT_25000 (Reactome)
RDH12mim-catalysisREACT_160140 (Reactome)
RDH5mim-catalysisREACT_160124 (Reactome)
RDH8mim-catalysisREACT_160121 (Reactome)
REACT_111189 (Reactome) Rhodopsin (RHO) is localised to both the disc membrane and the plasma membrane of rod outer segments (ROS). All-trans-retinal (atRAL) released from rhodopsin during the bleaching process, needs to translocate to the cytosol for reduction to all-trans-retinol (atROL) via all-trans-retinol dehydrogenases. Although atRAL can diffuse through membranes unaided, there exists an ABC transporter on disc membranes which may facilitate the transport of excess atRAL. Retinal-specific ATP-binding cassette transporter (ABCA4, ABCR) is the only ABC transporter which mediates the transport of retinoids (Biswas & Biswas 2000). Studies using bovine ABCA4 demonstrates atRAL transport (Sun et al. 1999). Human ABCR was found to be identical to the ABC transporter linked to Stargardt's disease type 1 (STGD1, MIM:248200), a cause of macular degeneration in childhood (Nasonkin et al. 1998).
REACT_160072 (Reactome) Once all-trans-retinol (atROL) enters the retinal pigment epithelium (RPE) and before esterification takes place, atROL binds to cellular retinol-binding protein 1 (RBP1) (Folli et al. 2001). The resultant complex (RBP1:atROL) serves as a substrate for lecithin retinol acyltransferase (LRAT), the main enzyme responsible for the esterification of atROL.
REACT_160076 (Reactome) In the bloodstream, circulating retinol binding protein 4 (RBP4, in complex with atROL), binds transthyretin (TTR, a 51 kDa protein) in a 1:1 molar complex (Naylor & Newcomer, 1999). The resultant TTR:RBP4:atROL complex is larger and therefore less susceptible to glomerular filtration, maintaining normal levels of retinoid and RBP4 in the circulation. In TTR-deficient mice, plasma levels of atROL and RBP4 were observed to be 5% of wild type levels, highlighting the importance of TTR binding to RBP4:atROL (Episkopou et al. 1993). TTR is also a transporter for thyroxine in the brain (not shown here) (Herbert et al. 1986).
REACT_160080 (Reactome) The outer segment of photoreceptor cells is shed every 10-14 days to be completely replaced. The shed material is phagocytosed and transferred to the retinal pigment epithelium (RPE). Diretinoid-pyridinium-phosphatidylethanolamine (A2PE) can be hydrolysed to diretinoid-pyridinium-ethanolamine (A2E), a prominent constituent of lipofuscin (the material deposited in retinal tissue which accumulates over time and is implicated in macular degeneration). Evidence suggests this happens before transfer to RPE cells as part of the phagocytosed outer segment. A2E has been detected in outer segments (Ben-Shabat et al. 2002) and an N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (NAPEPLD) activity detected in rat, mouse and human proteins (Okamoto et al. 2004, Ueda et al. 2005, Wang et al. 2006). This activity has been shown to hydrolyse A2PE to A2E in bovine outer segments before phagocytosis and transfer to RPE cells, suggesting A2PE is hydrolysed to A2E in photoreceptor outer segment membranes (Sparrow et al. 2003, Salvador & Giusto 1998).
REACT_160091 (Reactome) Although interphotoreceptor retinoid-binding protein (RBP3, IRBP) (Fong & Bridges 1988, Fong et al. 1990) is not required to move all-trans-retinol (atROL) from photoreceptor cells to the retinal pigment epithelium (RPE), it may function to regulate retinoid trafficking and possibly protect retinoids from biochemical damage. RBP3 is secreted by photoreceptor cells into the interphotoreceptor matrix (IPM), where, being a larger protein (135kDa) than the IPM space, becomes trapped (see mini-review Gonzalez-Fernandez & Ghosh 2008). It is through this space that retinoids move between the RPE and photoreceptor outer segments during the retinoid cycle. Once atROL enters the RPE, it binds with RBP1.
REACT_160092 (Reactome) Once photoreceptor outer segments are phagocytosed, inclusive of A2E, they are delivered to retinal pigment epithelial (RPE) cells for disposal. However, A2E has been shown to be resistant to any sort of degradative enzyme thus accumulates in the RPE. The relationship between lipofuscin accumulation and retinal degeneration is illustrated by Stargardt disease type 1 (STGD1, MIM:248200) (Allikmets et al. 1997).
REACT_160101 (Reactome) In enterocytes, all-trans-retinal (atRAL) binds to RBP2 (CRBPII) for stabilisation, metabolism and transport (Fierce et al. 2008).
REACT_160107 (Reactome) When the body is in a retinoid-sufficient state, all-trans-retinol (atROL) is transferred to hepatic stellate cells (HSCs) for storage. The transfer was established in rat experiments (Blomhoff et al. 1982, Blomhoff et al. 1984). The mechanism of transport is as yet unknown.
REACT_160117 (Reactome) The majority of all-trans-retinal (atRAL) simply diffuses across membranes into the cytosol. Experiments performed with mice rods demonstrate that atRAL diffusion is independent of assisted transport by ABCA4 (Mata et al. 2000, Blakeley et al. 2011).
REACT_160119 (Reactome) All-trans-retinal (atRAL) can diffuse across membranes to the cytosol and is reduced to all-trans-retinol (atROL) by the action of a short-chain dehydrogenase/reductase 3 using NADP+/NADPH as cofactor (Haeseleer et al. 1998).
REACT_160121 (Reactome) The reversible, NADP(H)-dependent reduction of all-trans-retinal (atRAL) to all-trans-retinol (atROL) occurs in both rod and cone photoreceptor cells where multiple retinol dehydrogenases (RHDs) are located. RHDs belong to the short-chain dehydrogenase/reductase (SDR) superfamily. RDH8 (located in photoreceptor outer segments) is partially responsible, together with other RDHs, for mediating this reaction. The activity for human RDH8 is inferred from a bovine experiment (Rattner et al. 2000).
REACT_160124 (Reactome) Another member of the short-chain dehydrogenases/reductases (SDR) family, RDH5, can (reversibly) catalyse the oxidation of 11-cis-retinol (11cROL) to 11-cis-retinal (11cRAL) in retinal pigment epithelium (RPE) cells using NAD+ as cofactor (Simon et al. 1996, Gonzalez-Fernandez et al. 1999). Cellular retinaldehyde-binding protein (RLBP1), the protein bound to 11cRAL in RPE, is not present in photoreceptor cells.
REACT_160138 (Reactome) Using NADP+ as cofactor, several members of the short-chain dehydrogenases/reductases (SDR) family can (reversibly) catalyse the oxidation of 11-cis-retinol (11cROL) to 11-cis-retinal (11cRAL) in retinal pigment epithelium (RPE) cells. Retinol dehydrogenases 10 and 11 (RDH10 and 11) are two such members utilizing the cofactor NADP+ (Wu et al. 2002, Kedishvili et al. 2002 respectively). Cellular retinaldehyde-binding protein (RLBP1), the protein bound to 11cRAL in RPE, is not present in photoreceptor cells.
REACT_160139 (Reactome) 11-cis-specific retinol dehydrogenase (11cRDH) activity found in chicken retina mediates the oxidation of 11-cis-retinol (11cROL) to 11-cis-retinal (11cRAL) using NADP+ as cofactor (Mata et al. 2002). The chicken protein that possesses this activity has not yet been identified. The actual enzyme responsible remains to be identified in human, even as evidence exists for this activity and for the alternative retinoid (visual) cycle in cones (Wang & Kefalov 2009). 11cRAL is the visual chromophore that is able to bind to opsins.
REACT_160140 (Reactome) The reversible, NADP(H)-dependent reduction of all-trans-retinal (atRAL) to all-trans-retinol (atROL) occurs in both rod and cone photoreceptor cells where multiple retinol dehydrogenases (RHDs) are located. RHDs belong to the short-chain dehydrogenase/reductase (SDR) superfamily. RDH12 (located in photoreceptor inner segments) is partially responsible, together with other RDHs, for mediating this reaction (Belyaeva et al. 2005).
REACT_160145 (Reactome) Chylomicrons (CM) are large (75–450 nm), spherical lipoprotein particles secreted by intestinal cells postprandially and transport dietary fat and fat-soluble vitamins in the lymphatic system (Nayak et al. 2001, During & Harrison 2007). All-trans-retinyl esters (atREs) are packaged into nascent chylomicrons.
REACT_160146 (Reactome) After the very fast isomerisation of 11-cis-retinal (11cRAL) to all-trans-retinal (atRAL) by light stimulation, slower events lead to exposure of atRAL to the aqueous environment, resulting in the hydrolysis of the Schiff base linkage. Although other intermediate products are formed, the ultimate result is the release of atRAL from opsins, which returns to the apo-opsin form (Baumann & Bender 1973). These series of slow decay reactions are called light bleaching of opsin and ends when atRAL, which can diffuse across membranes to the cytosol, is reduced to all-trans-retinol (atROL)
REACT_160148 (Reactome) The canonical rod retinoid (visual) cycle is too slow to account for the photosensitivity of cones in bright light conditions. Novel enzyme activities demonstrated in ground-squirrel and chicken retinas produce a novel pathway of chromophore regeneration specific for cones. The first reaction in Muller cells, the isomerization of all-trans-retinol (atROL) to 11-cis-retinol (11cROL), is mediated by an as-yet-uncharacterised atROL isomerase (Mata et al. 2002, Mata et al. 2005). This reaction is proposed to take place in all vertebrates including humans (Wang & Kefalov 2009).
REACT_160149 (Reactome) When the low-density lipoprotein receptor (LDLR) is missing, saturated or inhibited, chylomicron remnants (CRs) containing all-trans-retinyl esters (atREs) bind apolioprotein E (apoE). ApoE, secreted by hepatocytes, acts as a high-affinity ligand for the LDL-related receptor protein (LRP) family. CR:atREs:apoE then binds to cell-surface heparan sulfate proteoglycan (HSPG), abundant in the space of Disse. HSPG/apoE binding plays a critical role in the capture of CR:atREs, ready for internalization via LRPs (Futamura et al. 2005, Yamauchi et al. 2008).
REACT_160151 (Reactome) Once inside liver parenchymal cells, all-trans-retinyl esters (atREs), are hydrolysed to all-trans-retinol (atROL) and fatty acids (FAs) by a neutral, all-trans-retinyl ester hydrolase (NREH). No NREH has been characterised yet although both acidic and neutral REH activity has been shown to be associated with endosomes and plasma membrane preparations from rodent livers (Harrison & Gad 1989, Gad & Harrison 1991, Hagen et al. 1999). As the acidity increases, early endosomes change to late endosomes and further hydrolysis of atREs is mediated by acid retinyl ester hydrolase (AREH). Like NREH, AREH has not yet been characterised (see refs above). The translocation mechanism of atROL to cytosol is unknown.
REACT_160160 (Reactome) Retinyl esters (REs) are stored in lipid droplets (LDs) in hepatic stellate cells (HSCs) until there is a demand for retinoid by the body. Mobilization of atREs stores require lipases with retinyl ester hydrolase (REH) activity. At present, the identity of the REH mediating atRE mobilization is unknown (see reviews Shirakami et al. 2012, Schreiber et al. 2012). In studies performed with rat livers, Mello et al. found that the carboxylesterases ES4 and ES10 possessed REH activity and were localised to HSCs (Mello et al. 2008) but it's not confirmed that these are the actual REHs involved in retinoid mobilization. The human orthologue to these rat enzymes is presently unknown.
REACT_160162 (Reactome) A phosphatidyl-pyridinium bisretinoid compound, A2PE, is formed through condensation of N-retinylidene-PE (NRPE) and a second all-trans-retinol (atRAL) molecule (Parish et al. 1998, Mata et al. 2000). This most likely happens when atRAL is abundant.
REACT_160165 (Reactome) Upon photon absorption, 11-cis-retinal (11cRAL) is isomerised to all-trans-retinal (atRAL). The structure of cone opsins which can ultimately activate G-proteins to initiate phototransduction is denoted as R* (Fan et al. 2002). R* is still bound to atRAL at this stage. The isomerisation is a very fast photochemical process (femtoseconds) (Schoenlein et al. 1991) followed by slower events described in the following reaction.
REACT_160168 (Reactome) Nascent chylomicrons (CMs) acquire copies of apolipoproteins C-II, C-III, and E from circulating spherical (mature) high-density lipoprotein particles, becoming mature chylomicrons (Havel et al. 1973, Bisgaier & Glickman 1983). Here, this interaction is annotated to involve the transfer of a single copy of each lipoprotein, but a mature chylomicron in fact contains approximately 25 copies of apolipoprotein E and 180 copies of C apolipoproteins (Bhattacharya & Redgrave 1981).
REACT_160184 (Reactome) Cellular retinaldehyde-binding protein (RLBP1, CRALBP) (Intres et al. 1994) is abundant in retinal pigment epithelium (RPE) and Muller cells of the retina where it plays a role in sequestering 11-cis retinoids produced during the retinoid cycle. The natural ligands are 11-cis-retinol (11cROL) and 11-cis-retinal (11cRAL) (Crabb et al. 1998).
REACT_160186 (Reactome) Lipoprotein lipase dimers (LPL:LPL) are tethered to heparan sulfate proteoglycans (HSPG) at endothelial cell surfaces (Fernandez-Borja et al. 1996; Peterson et al. 1992). Both syndecan 1 (Rosenberg et al. 1997) and perlecan (Goldberg 1996) HSPG molecules are capable of tethering LPL. The LPL enzyme catalyzes the hydrolysis and release of triacylglycerols (TG) associated with circulating chylomicrons to leave a CM remnant (CR). This reaction is annotated here as causing the hydrolysis and release of 50 molecules of TG. In vivo, the number is much larger, and TG depletion probably occurs in the course of multiple encounters between a chylomicron and endothelial LPL. This reaction is strongly activated by chylomicron-associated apo C-II protein both in vivo and in vitro (Jackson et al. 1986). Chylomicron-associated apoC-II protein inhibits LPL activity in vitro (Brown and Baginsky 1972), and recent studies have indicated a positive regulatory role for apoA-5 protein, though its molecular mechanism of action remains unclear (Marcais et al. 2005; Merkel and Heeren 2005). CRs can then be taken up by liver parenchymal cells in two ways; 1) directly by the LDL receptor or 2) apoE/HSPG-directed uptake by LDL receptor-related proteins.
REACT_160187 (Reactome) Early experiments in frog and other species determined that the outer segments of photoreceptors are renewed by phagocytosis and transfer to retinal pigment eplithelial (RPE) cells for processing. A2E, formed in disc membranes of outer segments, is taken along with the phagolysosome (Young 1967, Young & Bok 1969, Katz et al. 1986). Here, for simplicity, only A2E is shown in the phagolysosome.
REACT_160208 (Reactome) All-trans-retinol esters (atREs) serve as substrates for retinoid isomerohydrolase (RPE65), located in retinal pigment epithelium (RPE) cells. RPE65 hydrolyses atREs to 11-cis-retinol (11cROL), thus performing an isomerase activity as well as hydrolysis. RPE65 is membrane-bound, this being dependent on the palmitylation of the residue Cys-112 (Takahashi et al. 2009). RPE65 normally undergoes a light-dependent translocation to become more concentrated in the central region of RPE cells. This translocation requires Unconventional myosin-VIIa (MYO7A or USH1B) (Lopes et al. 2011).
REACT_160211 (Reactome) Bovine studies (Beharry et al. 2004) have indicated NRPE to be the preferred substrate for ABCA4 (ABCR, rim protein, RmP) (Azarian et al. 1998), which acts an inward-directed retinoid flippase and facilitates the transfer of NRPE to the cytoplasmic side of the disc membrane. This transfer is essential to avoid build up of potentially toxic retinoid intermediates which are implicated in many retinal degenerative diseases (see review Tsybovsky et al. 2010). Defective ABCA4 cannot perform this function leading to impaired vision and blindness disorders such as Stargardt disease (MIM:248200).
REACT_160215 (Reactome) Nascent chylomicrons (CM) containing all-trans-retinyl esters (atREs) are secreted from intestinal cells and transported to the liver via the lymphatic system (Nayak et al. 2001, During & Harrison 2007).
REACT_160222 (Reactome) The transfer of 11-cis-retinol (11cROL) from Muller cells to cone photoreceptor cells is thought to be mediated by interphotoreceptor retinoid-binding protein RBP3 (Liou et al. 1989, Fong & Bridges 1988) but the mechanism is poorly understood (Gonzalez-Fernandez & Ghosh 2008).
REACT_160228 (Reactome) This human event has been inferred from an as-yet-uncharacterised protein which has been demonstrated to possess retinyl ester hydrolase (REH) activity in chicken retina to hydrolyse 11-cis-retinyl palmitate (11cRPALM) to 11-cis-retinol (11cROL) (Bustamante et al. 1995).
REACT_160239 (Reactome) Once inside liver parenchymal cells, all-trans-retinyl esters (atREs), are hydrolysed to all-trans-retinol (atROL) and fatty acids (FAs) by a neutral, all-trans-retinyl ester hydrolase (NREH). No NREH has been characterised yet although both acidic and neutral REH activity has been shown to be associated with endosomes and plasma membrane preparations from rodent livers (Harrison & Gad 1989, Gad & Harrison 1991, Hagen et al. 1999). As the acidity increases, early endosomes change to late endosomes and further hydrolysis of atREs is mediated by acid retinyl ester hydrolase (AREH). Like NREH, AREH has not yet been characterised (see refs above). The translocation mechanism of atROL to cytosol is unknown.
REACT_160240 (Reactome) Human opsin-2 is a G-protein coupled photoreceptor found in the disc membranes of rod outer segments (ROS) (Nathans & Hogness 1984). It is an integral membrane protein and covalently binds the chromophore 11-cis-retinal (11cRAL) to form rhodopsin (RHO). Binding occurs via a protonated Schiff base linkage at Lys-296 (Fan et al. 2002) with Glu-113 at helix 3 serving as the counterion of the protonated Schiff base (Han et al. 1993). 11cRAL is completely embedded within the RHO structure. Opsins found in cone outer segments which bind 11cRAL are described in the cone visual cycle. Unlike other GPCRs in which direct ligand binding activates the receptor, rhodopsin is in an inactive state when bound to 11cRAL (which acts as an inverse agonist).
REACT_160244 (Reactome) At the stellate cell surface, all-trans-retinol (atROL) binds to retinol binding protein 4 (RBP4, holo-RBP) (Kanai et al. 1968). atROL is insoluble in aqueous conditions and it's thought RBP4 picks up atROL from the outer leaflet of the plasma membrane. RBP4 is a 21 kDa protein secreted into the bloodstream by the liver in an atROL-dependent manner. Defects in RBP4 cause retinol-binding protein deficiency (RBP deficiency, MIM:180250), causing night vision problems and progressive atrophy of the retinal pigment epithelium (RPE) (Seeliger et al. 1999).
REACT_160247 (Reactome) All-trans-retinyl esters (atREs) are the main storage form of retinol in hepatic stellate cells (HSCs). Lecithin retinol acyltransferase (LRAT) mediates the esterification of all-trans-retinol (atROL) with a variety of fatty acyl groups (FACYLs) to form REs which are stored in lipid droplets in the cytosol. Cellular retinol-binding protein 1 (RBP1) is an effective donor of atROL for LRAT (Ruiz et al. 1999).
REACT_160266 (Reactome) Lecithin retinol acyltransferase (LRAT) mediates the esterification of all-trans-retinol (atROL) to form all-trans-retinyl esters (atREs). atREs are stored in lipid droplet form called retinosomes (Imanishi et al. 2004). Cellular retinol-binding protein 1 (RBP1) is an effective donor of atROL for LRAT (Ruiz et al. 1999). LRAT is an important enzyme required for the clearance of atROL as it drives the uptake of atROL from the bloodstream through the receptor STRA6 (Kawaguchi et al. 2011) and clearance of atROL from rod outer segments (ROS). In addition, the esterified form of atROL serves as substrate for RPE65.
REACT_160267 (Reactome) Once NRPE is "flipped" to the cytoplasmic side of disc membranes by the ABC transporter ABCA4, it can dissociate to all-trans-retinal (atRAL) and phosphatidylethanolamine (PE). atRAL is thus released to re-enter the retinoid cycle to reform the visual chromophore 11-cis-retinal (11cRAL) (Tsybovsky et al. 2010).
REACT_160272 (Reactome) When the low-density lipoprotein receptor (LDLR) is missing, saturated or inhibited, chylomicron remnants (CRs) containing all-trans-retinyl esters (atREs) can be cleared from circulation by interaction with cell-surface heparan sulfate proteoglycan (HSPG) and secreted apolipoprotein E (apoE). This complex is then presented to LDL receptor-related proteins (LRPs; reviews May et al. 2007, Li et al. 2001, Hussain 2001) for internalization (Ji et al. 1993).
REACT_160275 (Reactome) All-trans-retinol (atROL) binds to cellular retinol-binding protein 1 (RBP1) (Folli et al. 2001). RBP1 is thought to be required for intracellular transport of atROL in the liver.
REACT_160278 (Reactome) Stimulated by retinoic acid gene 6 protein homologue (STRA6) acts as a high-affinity cell-surface receptor for the TTR:RBP4:atROL complex (Berry et al. 2012). Once bound, STRA6 removes atROL and transports it into cells expressing STRA6 receptors, including eye (Kawaguchi et al. 2007). Defects in STRA6 cause microphthalmia syndromic type 9 (MCOPS9, Matthew-Wood syndrome or Spear syndrome; MIM:601186) (Chassaing et al. 2009). The uptake of atROL is driven by the conversion of atROL to retinyl ester (RE) by LRAT (Kawaguchi et al. 2011).
REACT_160285 (Reactome) In the disc membranes of photoreceptor outer segments, all-trans-retinal (atRAL) can spontaneously and reversibly react with phosphatidiylethanolamine (PE, cephalin; a phospholipid found in in membranes) to form a Schiff base product, N-retinylidene-phosphatidylethanolamine (NRPE) (Poincelot et al. 1969, Parish et al. 1998, Mata et al. 2000). Then, either NRPE is "flipped" over to the cytoplasmic side of disc membranes by ABCA4 where it can dissociate (thus releasing atRAL to re-enter the retinoid cycle) or it can condense with another atRAL to form a toxic diretinal compound. The route taken is determined by whether a functional ABCA4 protein is present or not.
REACT_160286 (Reactome) The visual pigment rhodopsin consists of a seven transmembrane helix protein, opsin (RHO), to which an 11-cis-retinal (11cRAL) chromophore is bound as a protonated Schiff base (Hargrave et al. 1983, Nathans & Hogness 1984, Ovchinnikov et al. 1983). The covalent bond between opsin and its retinal ligand, which is unique among G protein coupled receptors, helps to confer extraordinary stability in darkness (Baylor et al. 1984). 11cRAL is an inverse agonist, that quenches the weak ability of opsin to activate transducin G protein (Gt). Upon photon absorption, 11cRAL isomerizes in a few hundred femtoseconds (Schoenlein et al. 1991) and with a high quantum efficiency of 0.7 (Dartnall 1968). Then in the next few milliseconds, opsin undergoes a rearrangement in structure that renders it catalytically active (MII aka metarhodopsin II or R*) (Emeis et al. 1982). The isomerisation is a very fast photochemical process (femtoseconds) followed by slower events (Smith 2010).

Mutations in RHO can give rise to autosomal dominant or recessive forms of retinitis pigmentosa or autosomal dominant congenital stationary night blindness (https://sph.uth.edu/retnet/). Retinitis pigmentosa is a progressive form of blindness marked by an initial degeneration of rods, followed by the secondary loss of cones.
REACT_160292 (Reactome) All-trans-retinol (atROL), the product of the reduction of all-trans-retinal (atRAL) released from rod and cone opsins, needs to be regenerated back to the visual chromophore 11-cis-retinal (11cRAL). For the regenerative steps, rods transports atROL back into the retinal pigment epithelium (RPE) while cones utilise Muller cells. Although interphotoreceptor retinoid-binding protein (RBP3, IRBP) (Fong & Bridges 1988, Fong et al. 1990) is not thought to be required to move all-trans-retinol (atROL) from photoreceptor cells to the retinal pigment epithelium (RPE) or Muller cells, it may function to regulate retinoid trafficking and possibly protect retinoids from biochemical damage. RBP3 is secreted by photoreceptor cells into the interphotoreceptor matrix (IPM), where, being a larger protein (135kDa) than the IPM space, becomes trapped (see mini-review Gonzalez-Fernandez & Ghosh 2008). It is through this space that retinoids move between Muller cells and cone photoreceptor outer segments during the cone retinoid cycle.
REACT_160295 (Reactome) All-trans-retinol (atROL) is stored in hepatic stellate cells (HSCs) in its esterified form. Before esterification takes place, atROL binds to cellular retinol-binding protein 1 (RBP1) (Folli et al. 2001). The resultant complex (RBP1:atROL) serves as a substrate for lecithin retinol acyltransferase (LRAT), the main enzyme responsible for the esterification of atROL. It is thought the binding of RBP1 serves to translocate atROL to the endoplasmic reticulum where LRAT is located.
REACT_160302 (Reactome) Interphotoreceptor retinoid-binding protein (RBP3) is the major soluble protein in the interphotoreceptor matrix (IPM) (Liou et al. 1989, Fong & Bridges 1988). It is thought to shuttle 11-cis-retinal (11cRAL) between retinal pigment epithelium (RPE) and photoreceptor outer segments during the visual cycle but the mechanism is poorly understood (Gonzalez-Fernandez & Ghosh 2008).
REACT_160307 (Reactome) Once hydrolysed from all-trans-retinyl esters (atREs), all-trans-retinol (atROL) can either be esterified for storage or secreted into the bloodstream for transport to target tissues/organs (Kanai et al. 1968). The mechanism of secretion/efflux is currently unknown.
REACT_160308 (Reactome) Chylomicron remnants (CRs) are "sieved" when they arrive at the liver by size, the appropriate sized remnants passing through the space of Disse. Once inside, CRs containing all-trans-retinyl esters (atREs) can be directly and rapidly taken up by liver parenchymal cells via the low-density lipoprotein receptor (LDLR) using apolipoprotein E (apoE) as a ligand. Internalization of remnants occur via endocytosis (see review D'Ambrosio et al. 2011). This reaction is inferred from uptake studies in mice (Yu et al. 2000). Defects in LDLR cause familial hypercholesterolemia (FH, MIM:143890), a common autosomal disease that affects about 1 in 500 people in most countries. Abnormal LDLR doesn't remove LDL from circulation resulting in high levels of LDL in blood, leading to early cardiovascular disease via atherosclerosis. The defect was first described by Brown and Goldstein (1974).
REACT_160311 (Reactome) RDH11 is the best-characterised enzyme that reduces all-trans-retinal (atRAL) to all-trans-retinol (atROL). In addition, several aldo-keto reductase (AKR) enzymes from subfamilies 1B and 1C also show all-trans-retinal (atRAL) reductase activity. AKR1B10 shows high reductase activity towards atRAL (Gallego et al. 2007, Ruiz et al. 2009) whereas AKR1C1, 1C3 and 1C4 all show much lower reductase activity towards arRAL (Ruiz et al. 2011).
REACT_160313 (Reactome) All-trans-retinol (atROL) circulates in the bloodstream in complex with transthyretin (TTR) and retinol- binding protein 4 (RBP4). The receptor Stimulated by retinoic acid gene 6 protein homologue (STRA6) acts as a high-affinity cell-surface receptor for the complex (Berry et al. 2012), removing atROL and transporting it into tissues expressing STRA6, including the eyes (Kawaguchi et al. 2007).
REACT_163640 (Reactome) In bovine experiments, phosphorylation of RGS9-1 (at Ser475, human site predicted to be at Ser478) by protein kinase C (PRKC, specifically the isozymes PRKCalpha and PRKCtheta) significantly decreased the affinity of RGS9-1 for its membrane anchor protein and GAP enhancer RGS9-1 anchor protein (R9S9BP). This represents a potential mechanism for feedback control of the photoresponse recovery in both rods and cones (Sokal et al. 2003, Balasubramanian et al. 2001, Hu et al. 2001).
REACT_163661 (Reactome) A substantial fraction of rhodopsin kinase (GRK1) is bound to recoverin (RCVRN) in darkness, when internal Ca2+ levels are high. RCVRN is an EF-hand protein (Murakami et al. 1992) that functions as a myristoyl switch. With Ca2+ bound, the myristoyl group is exposed to attach RCVRN to the membrane. When Ca2+ levels drop with light exposure, Ca2+ dissociates from RCVRN and GRK1 is released. Higher levels of free GRK1 accelerate the phosphorylation and shutoff of photoexcited rhodopsin (MII). However, this feedback mechanism proceeds too slowly to impact the single photon response that was responsible for causing the fall in Ca2+. Instead, it operates during light adaptation, where the light-induced fall in Ca2+ primes the rod to release GRK1 to act after subsequent photoisomerizations of rhodopsin. RCVRN also serves as a Ca2+ buffer within the rod outer segment. Although mutations in RCVRN are not known to cause retinal disease, some cancer-associated retinopathies result from an autoimmune attack on RCVRN (Polans et al. 1991).
REACT_163662 (Reactome) Active Gt alpha (GNAT-GTP) can be inactivated by a slow, intrinsic GTPase activity that hydrolyses GTP to GDP. Once GNAT1 has GDP bound, it no longer binds to the gamma subunit of PDE6 (PDE6-gamma) that then resumes inhibition of the catalytic subunit of PDE6. The hydrolysis of GTP is accelerated by a GAP (GTPase accelerating protein) complex that consists of Regulator of G protein signaling 9 (RGS9-1, RGS9 isoform 3) (He et al. 1998, Zhang et al. 1999), Guanine nucleotide binding protein subunit beta 5, long form (GNB5) (Makino et al. 1999) and RGS9 anchoring protein (RGS9BP, aka R9AP) (Hu & Wensel 1998). The affinity of GNAT GTP for the GAP complex is relatively low, but is increased significantly by the presence of PDE-gamma. Shutoff of Gt is the rate-limiting step in the recovery of the single photon response of rods (Chen et al. 2000, Krispel et al. 2006). Persons with defective GAP experience bradyopsia or "slow vision" in which there are difficulties in adjusting to changes in brightness and to tracking moving objects (Michaelides et al. 2010, Nishiguchi et al. 2004).
REACT_163674 (Reactome) Binding of transducin (Gt) to activated rhodopsin (MII) promotes the release of GDP from the Gt alpha subunit enabling a GTP (present in a higher concentration than GDP) to take its place. With GTP bound, Gt alpha (GNAT1-GTP) dissociates from the Gt beta:gamma subunits (GNB1:GNGT1) and from MII. MII is then available to bind and activate additional transducins. Transducin activation is the first amplifying step in visual transduction. Many findings came from bovine experiments (Pugh & Lamb 1993, Fung & Stryer 1980, Fung et al. 1981, Hofmann 1985).
REACT_163682 (Reactome) The cGMP-gated (CNG) channels are heterotetramers of three alpha subunits (CNGA1) and one beta subunit (CNGB1). Although the subunits bear structural similarities to voltage-gated potassium channels, the rod channel is only weakly voltage sensitive (Chen et al. 1993). Opening occurs with cGMP bound and rarely occurs in the absence of cGMP (hence the closed state is designated as CNG channel and the open status is designated as cGMP:CNG channel). In darkness, cGMP concentration is relatively high and cGMP-gated cation (CNG) channels are open to allow the influx of cations into the rod outer segment. The inward current is composed mainly of Na+ ions, with lesser contributions from Ca2+ ions and Mg2+ ions (Dhallan et al. 1992). The channel is outwardly rectifying so that over physiological membrane potentials, the inward current is proportional to the number of channels open and is nearly independent of voltage. Mutations in the CNG channel subunits can cause a recessive form of retinitis pigmentosa (https://sph.uth.edu/retnet/).
REACT_163718 (Reactome) After removal of the N-terminal methionine (Met) residue, the enzymes glycylpeptide N-tetradecanoyltransferase 1 and 2 (NMT1 and 2) mediate the transfer of the myristoyl (MYS) group from myristoyl-CoA to the now N-terminal glycine (Gly) residue of transducin's alpha subunit (GNAT1) (Glover et al. 1997, Giang & Cravatt 1998). Myristoylation is thought to aid enzyme function and localization. Evidence from chicken experiments suggest non-myristoylated proteins do not bind to membranes (Kamps et al. 1986).
REACT_163720 (Reactome) All eukaryotic proteins synthesized in the cytosol are initiated by methionine (Met). For the maturation of many proteins, the removal of N-terminal Met is essential and is mediated by methionine-aminopeptidases (METAPs). In human, there are two forms, METAP1 and 2 (Arfin et al. 1995). These enzymes utilise 2 cobalt ions (Co2+) as cofactors (Addlagatta et al. 2005, Hu et al. 2006, Marino et al. 2007).
REACT_163760 (Reactome) 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/).
REACT_163809 (Reactome) The activity of guanylyl cyclases is regulated by Ca2+-binding, guanylyl cyclase-activating proteins (GCAPs). This regulation is the most important negative feedback mechanism triggered by Ca2+ in light. There are three GCAPs in humans; GUCA1A (Subbaraya et al. 1994), GUCA1B (Surguchov et al. 1997) and GUCA1C (Haeseleer et al. 1999). In darkness, when intracellular Ca2+ is relatively high, GCAPs suppress guanylate cyclase activity. But the light-induced fall in Ca2+ prompts Ca2+ to dissociate from GCAPs and be replaced by Mg2+, allowing the GCAPs to stimulate guanylate cyclase activity by an order of magnitude. Different GCAPs have different affinities for Ca2+. Defects in GCAP1 give rise to cone dystrophy and Lebers congenital amaurosis (https://sph.uth.edu/retnet/).

REACT_163833 (Reactome) In darkness, the G protein transducin (Gt) is attached to the disk membrane surface with a GDP bound to it and it is inactive. Gt is a heterotrimer of alpha1 (GNAT1) (van Dop et al. 1989, Fong 1992), beta1 (GNB1) (Codina et al. 1986) and gamma1 (GNGT1) (Tao et al. 1993) subunits. Photoactivated rhodopsin (MII or R*) catalyzes the exchange of GTP for GDP bound to Gt. Upon GTP/GDP exchange, Gt is released from MII and the Gt alpha with GTP bound (GNAT1 GTP) dissociates from Gt beta gamma subunits (GNB1:GNGT1). This mechanism was deciphered from bovine experiments (Pugh & Lamb 1993). MII proceeds to activate additional Gt molecules, making this reaction the first amplification step in the phototransduction cascade. A single activated rhodopsin molecule activates tens of Gt molecules. Defects in GNAT1 cause the Nougaret type of autosomal dominant, congenital stationary night blindness (Dryja et al. 1996, CSNBAD3; MIM:610444) . Congenital stationary night blindness is a non progressive retinal disorder characterized by impaired night vision.
REACT_163835 (Reactome) Prenylation is the process of post-translational addition of hydrophobic groups to proteins and is thought to help anchor proteins to cellular membranes. Farnesylation is a type of prenylation, where a farnesyl group (donated from farnesyl diphosphate, FPP) is added to a cysteine residue on a protein. The enzyme mediating this transfer is farnesyltransferase (FNT). FNT is a heterodimer comprising an alpha subunit (common to another prenylating enzyme called geranylgeranyltransferase, GGT) and a unique beta subunit (Long et al. 2001, Bell et al. 2002, deSolms et al. 2003). This complex recognises the CAAX box (C is the cysteine, A is any aliphatic amino acid, and X determines which enzyme acts on the protein) at the C-terminus of the target protein, in this case, the gamma subunit of transducin (GNG1) (Omer at al. 1993).
REACT_163839 (Reactome) Protein phosphatase 2A removes the phosphates from phosphorylated rhodopsin (p MII) and phosphorylated opsin (p-RHO) (Fowles et al. 1989, Palczewski et al. 1989a,b). A Ca2+ dependent opsin phosphatase is also present (Kutuzov & Bennett 1996). Serine/threonine protein phosphatases with EF hands (PPEF-1 and -2) that share homology with Drosophila retinal degeneration C (rdgC) are expressed in retina and may be responsible (Huang & Honkanen 1998), there is no evidence for a physiological role in dephosphorylating rhodopsin. Once dephosphorylated, RHO can once again bind the chromophore 11 cis retinal (11cRAL), in readiness for the next photon response.


REACT_163859 (Reactome) Once transducin alpha subunit (GNAT1) is deactivated by hydrolysis of bound GTP to GDP, it reassociates with transducin beta:gamma subunits (GNB1:GNGT1) to form inactive transducin (Gt-GDP). A stoichiometric overabundance of GNB1:GNGT1 facilitates the reassociation event. The details for this event were revealed in bovine experiments (Clark et al. 2006, Fung et al. 1981).
REACT_163871 (Reactome) Although phosphorylation of activated rhodopsin (MII) reduces transducin activation, complete deactivation occurs only after arrestin (S-antigen or SAG, Yamaki et al. 1988) binds to and sterically caps MII. SAG is capable of binding unphosphorylated MII, but with very low probability. Binding affinity increases greatly upon phosphorylation. Binding of SAG generally occurs after MII has been phosphorylated ~3 times, and binding prevents further phosphorylation. Interestingly, rods express a small amount of a splice variant of SAG, P44, but its function is not yet known. Defects in SAG cause Oguchi type 1 disease (CSNBO1; MIM:258100), a recessive form of congenital stationary night blindness characterized by impaired scotopic vision (Fuchs et al. 1995).
REACT_163890 (Reactome) Eventually the Schiff base linkage between all-trans-retinal (atRAL) and opsin is hydrolyzed. The atRAL repositions to an "exit" site within opsin and is reduced to all-trans-retinol (atROL) by retinol dehydrogenases RDH8 and RDH12 using NADPH as cofactor (see section on rod retinoid cycle), whereupon it exits the rod (Baumann & Bender 1973).
REACT_163894 (Reactome) As cGMP is hydrolysed during the activation phase of phototransduction, its intracellular concentration decreases leading to the closure of CNG channel (the closed status is designated as CNG channel) (Dhallan et al. 1992, Chen et al. 1993). Channel closure reduces the inward flux of sodium and calcium (also known as the 'dark current') resulting in cell hyperpolarisation. Cooperative binding of cGMP to the CNG channel confers additional amplification to the phototransduction cascade (Pugh & Lamb 1993, Yau & Baylor 1989).
REACT_163903 (Reactome) After removal of the N-terminal methionine (Met) residue, an unknown N-acyltransferase, similar to the enzymes glycylpeptide N-tetradecanoyltransferase 1 and 2 (NMT1 and 2), mediates the transfer of acyl groups from acyl-CoA to the now N-terminal glycine (Gly) residue of transducin's alpha subunit (GNAT1). The fatty acyl groups transferred are lauroyl (C12:0) and unsaturated myristoyl groups (C14:2 and C14:1). Myristoylation is thought to aid enzyme function and localization. This human event is inferred from bovine experiments demonstrating this activity (Kokame et al 1992).
REACT_163913 (Reactome) As the channels reopen, rising Ca2+ levels result in binding of Ca2+ to calmodulin (CALM1). By targeting the beta subunit of the channel, CALM1:Ca2+ reduces the apparent affinity of the channel for cGMP (Chen et al. 1994, Hsu & Molday 1993, Hsu & Molday 1994).
REACT_163927 (Reactome) The membrane associated cGMP phosphodiesterase 6 (PDE6) is a tetramer of two catalytic chains, alpha (PDE6A or PDEA) (Pittler et al. 1990) and beta (PDE6B or PDEB) (Weber et al. 1991), and two inhibitory gamma chains (PDE6G or PDEG) (Tuteja et al. 1990). Binding of an activated transducin alpha subunit (GNAT1-GTP) to PDE-gamma relaxes the inhibitory effect of the gamma subunit thereby activating the associated alpha or beta catalytic subunit. Because the binding of GNAT1-GTP to PDE-gamma is one to one, there is no amplification associated with this step. Some forms of autosomal recessive retinitis pigmentosa and congenital stationary night blindness are caused by mutations in PDE6 (https://sph.uth.edu/retnet/).

REACT_163954 (Reactome) Loss of all-trans-retinal (atRAL) is followed by dissociation of arrestin (SAG) from p-RHO. RHO is then available for covalent binding to 11-cis-retinal (11cRAL), supplied by the retinal pigment epithelium, to regenerate rhodopsin. SAG is capable of binding weakly to rhodopsin, so the dissociation in some rhodopsins may occur after regeneration (Baumann & Bender 1973).
REACT_163982 (Reactome) Intracellular Ca2+ is extruded from the outer segment by a Na+/Ca2+, K+ exchanger (NCKX1 encoded by SLC24A1) (Tucker et al. 1998). Operation of the exchanger is electrogenic; 4 Na+ enter and 1 K+ exits for every Ca2+ removed for a net movement of 1 positive charge inward per duty cycle. In bright light, when all of the CNG channels are closed, the exchanger continues to remove Ca2+, reducing intracellular Ca2+ by an order of magnitude. Mutations in SLC24A1 can give rise to recessive congenital stationary night blindness (Riazuddin et al. 2010).
REACT_163992 (Reactome) Activated rhodopsin (MII aka R*) must be deactivated to terminate the single photon response. Deactivation begins during the rising phase of the single photon response after MII binds rhodopsin kinase (GRK1), a serine/threonine protein kinase (Khani et al. 1996). GRK1 is activated by MII whereupon it phosphorylates MII at multiple serine and threonine sites on its C terminus. There are six serine and threonine residues that can be phosphorylated. Increasing phosphorylation progressively reduces the rate at which MII can activate transducin but full quenching requires the binding of arrestin (Burns & Pugh 2010, Korenbrot 2012). Certain mutations in GRK1 cause Oguchi type 2 disease, a rare, recessive form of congenital stationary night blindness (https://sph.uth.edu/retnet/).
REACT_163996 (Reactome) The basal, "dark" levels of cGMP are restored as part of the recovery of light response by membrane guanylyl cyclases (GUCYs). Two variants, GUCY2D (Shyjan et al. 1992) and GUCY2F (Lowe et al. 1995), mediate the synthesis of cGMP from GTP. Unlike other membrane guanylyl cyclases, the rod types are not receptors for extracellular substances. Instead, GUCYs are regulated intracellularly by guanylyl cyclase activating proteins (GCAPs), this regulation being the most important negative feedback mechanism triggered by Ca2+ in light. There are three GCAPs in humans; GUCA1A, GUCA1B and GUCA1C (Subbaraya et al. 1994, Surguchov et al. 1997, Haeseleer et al. 1999). GCAPs are Ca2+ binding proteins. When Ca2+ concentration is high (in the "dark" condition), GCAPs bind Ca2+ and inhibit GUCYs. Conversely, when Ca2+ concentration is low (as in a light response), GCAPs release Ca2+ and bind Mg2+ in its place. With Mg2+ bound, GCAPs stimulate GUCY activity by an order of magnitude. This negative feedback operates rapidly to limit the amplitude and duration of the single photon response and to dampen the effects of spontaneous PDE activations. Mutations in GUCYD can give rise to Leber's congenital amaurosis or to cone-rod dystrophy (https://sph.uth.edu/retnet/).
REACT_164008 (Reactome) Once cGMP concentration is restored to "dark" levels, it binds cooperatively to the cGMP-gated cation channel (CNG channel), inducing opening through a conformational change in the channel (open status designated as cGMP:CNG channel here) (Chen et al 1993, Dhallan et al. 1992).
REACT_25000 (Reactome) Although the enzyme catalysing retinal reduction in human enterocytes is not identified, the best candidate is retinol dehydrogenase 11 (RDH11, RalR1). It is expressed in the intestine, has a basic pH optimum, and localises to the ER membrane where LRAT catalyses the next step in the pathway. However, RDH11 catalyses retinal reduction to retinol in vitro and uses NADPH as cofactor (Fierce et al. 2008).
REACT_25063 (Reactome) Part of retinol ester hydrolase activity in the small intestine is associated with the brush border membrane but the protein having it is not identified. It is thought to be phospholipase B (Rigtrup et al. 1994).
REACT_25108 (Reactome) Transfer of fatty acyl residues (FACYLs) from lecithin is the main way to esterify all-trans-retinol (atROL). Lecithin is a generic name for the yellowy-brown fatty substances in animals and tissues. It can be composed of phosphatidylcholines, phosphatidylethanolamines, and phosphatidylinositols. Fatty acyl transfer is catalyzed by Lecithin retinol acyltransferase (LRAT) and takes place near the endoplasmic reticulum membrane. The main fatty acyl moieties that are substrates for LRAT are palmitoyl, oleoyl, stearoyl and linoleoyl groups present in the A1 position of membrane phosphatidylcholine molecules. LRAT esterifies atROL with these acyl groups to form all-trans-retinyl esters (atREs). The aim is not storage but transport via chylomicrons (Ruiz et al. 1999).
REACT_25117 (Reactome) As long as vitamin A is needed, beta-carotene-monooxygenase (BCMO1) catalyses the cleavage of carotenes, resulting mainly in retinal (Fierce et al. 2008).
REACT_25146 (Reactome) In enterocytes, the dominant retinol-binding protein is RBP2 (CRBPII) which is abundant and binds retinol faster than the cell membrane. So, even though lipophilic retinol can easily enter the cell membrane of bowel enterocytes, it is collected by the abundancy of RBP2 into the enterocyte cytosol where it is further processed (Inagami & Ong 1997).
REACT_25240 (Reactome) Part of nutritional vitamin A is in the form of retinyl esters (REs). The main fatty acids which can form esters with retinol are palmitate, oleate, stearate and linoleate. REs are digested together with other lipids, and by the same enzymes. Pancreatic lipase catalyses the hydrolysis of RE to all-trans-retinol (atROL) and fatty acid which are then both taken up by enterocytic cell membranes (Bennekum et al. 2000).
REHmim-catalysisREACT_160160 (Reactome)
REHmim-catalysisREACT_160228 (Reactome)
RGS9-1

GNB5

RGS9BP
ArrowREACT_163662 (Reactome)
RGS9-1

GNB5

RGS9BP
REACT_163640 (Reactome)
RHOArrowREACT_163839 (Reactome)
RHOREACT_160240 (Reactome)
RLBP1 11cRALArrowREACT_160124 (Reactome)
RLBP1 11cRALArrowREACT_160138 (Reactome)
RLBP1 11cRALArrowREACT_160139 (Reactome)
RLBP1 11cROLREACT_160124 (Reactome)
RLBP1 11cROLREACT_160138 (Reactome)
RLBP1 11cROLREACT_160139 (Reactome)
RLBP1REACT_160184 (Reactome)
RPALMREACT_25063 (Reactome)
RPALMREACT_25240 (Reactome)
RPE65mim-catalysisREACT_160208 (Reactome)
S-farn-GNGT1ArrowREACT_163835 (Reactome)
S-farn-GRK1REACT_163661 (Reactome)
S-farn-GRK1mim-catalysisREACT_163992 (Reactome)
SAGArrowREACT_163954 (Reactome)
SAGREACT_163871 (Reactome)
SLC24A1mim-catalysisREACT_163982 (Reactome)
STRA6REACT_160313 (Reactome)
TTR

RBP4

STRA6
ArrowREACT_160278 (Reactome)
TTR

RBP4

atROL
REACT_160313 (Reactome)
TTR tetramerREACT_160076 (Reactome)
acyl-CoAREACT_163903 (Reactome)
atRALArrowREACT_111189 (Reactome)
atRALArrowREACT_160146 (Reactome)
atRALArrowREACT_160267 (Reactome)
atRALArrowREACT_163890 (Reactome)
atRALREACT_111189 (Reactome)
atRALREACT_160101 (Reactome)
atRALREACT_160119 (Reactome)
atRALREACT_160121 (Reactome)
atRALREACT_160140 (Reactome)
atRALREACT_160162 (Reactome)
atRALREACT_160285 (Reactome)
atREsArrowREACT_160247 (Reactome)
atREsArrowREACT_160266 (Reactome)
atREsArrowREACT_25108 (Reactome)
atREsREACT_160145 (Reactome)
atREsREACT_160160 (Reactome)
atREsREACT_160208 (Reactome)
atROL isomerasemim-catalysisREACT_160148 (Reactome)
atROLArrowREACT_160107 (Reactome)
atROLArrowREACT_160119 (Reactome)
atROLArrowREACT_160121 (Reactome)
atROLArrowREACT_160140 (Reactome)
atROLArrowREACT_160151 (Reactome)
atROLArrowREACT_160160 (Reactome)
atROLArrowREACT_160239 (Reactome)
atROLArrowREACT_160278 (Reactome)
atROLArrowREACT_25063 (Reactome)
atROLArrowREACT_25240 (Reactome)
atROLREACT_160072 (Reactome)
atROLREACT_160244 (Reactome)
atROLREACT_160275 (Reactome)
atROLREACT_160295 (Reactome)
atROLREACT_25146 (Reactome)
betaCREACT_25117 (Reactome)
cGMP CNG channelmim-catalysisREACT_163682 (Reactome)
cGMPArrowREACT_163894 (Reactome)
cGMPArrowREACT_163996 (Reactome)
cGMPREACT_163760 (Reactome)
cGMPREACT_164008 (Reactome)
mature CM atREsArrowREACT_160168 (Reactome)
nascent CM atREsREACT_160168 (Reactome)
nascent CMREACT_160145 (Reactome)
p-RHO SAGArrowREACT_163890 (Reactome)
p-S334,S338,S343-MIIArrowREACT_163992 (Reactome)
p-S334,S338,S343-MIIREACT_163871 (Reactome)
p-S334,S338,S343-RHOArrowREACT_163954 (Reactome)
p-S334,S338,S343-RHOREACT_163839 (Reactome)
p-S478-RGS9-1

GNB5

RGS9BP
ArrowREACT_163640 (Reactome)
spherical HDL

apoC-II apoC-III

apoE
REACT_160168 (Reactome)
spherical HDLArrowREACT_160168 (Reactome)
unknown NATmim-catalysisREACT_163903 (Reactome)
Personal tools