title: Stereoisomeric specificity of the retinoid cycle in the vertebrate retina.
abstract: Understanding of the stereospecificity of enzymatic reactions that regenerate the universal chromophore required to sustain vision in vertebrates, 11-cis-retinal, is needed for an accurate molecular model of retinoid transformations. In rod outer segments (ROS), the redox reaction involves all-trans-retinal and pro-S-NADPH that results in the production of pro-R-all-trans-retinol. A recently identified all-trans-retinol dehydrogenase (photoreceptor retinol dehydrogenase) displays identical stereospecificity to that of the ROS enzyme(s). This result is unusual, because photoreceptor retinol dehydrogenase is a member of a short chain alcohol dehydrogenase family, which is often pro-S-specific toward their hydrophobic alcohol substrates. The second redox reaction occurring in retinal pigment epithelium, oxidation of 11-cis-retinol, which is largely catalyzed by abundantly expressed 11-cis-retinol dehydrogenase, is pro-S-specific to both 11-cis-retinol and NADH. However, there is notable presence of pro-R-specific activities. Therefore, multiple retinol dehydrogenases are involved in regeneration of 11-cis-retinal. Finally, the cellular retinaldehyde-binding protein-induced isomerization of all-trans-retinol to 11-cis-retinol proceeds with inversion of configuration at the C(15) carbon of retinol. Together, these results provide important additions to our understanding of retinoid transformations in the eye and a prelude for in vivo studies that ultimately may result in efficient pharmacological intervention to restore and prevent deterioration of vision in several inherited eye diseases.
authors.affiliation: Departments of Ophthalmology, Chemistry, and Pharmacology, University of Washington, Seattle, Washington 98195, USA.
authors.forename: G F
authors.initials: GF
authors.lastname: Jang
authors.forename: J K
authors.initials: JK
authors.lastname: McBee
authors.forename: A M
authors.initials: AM
authors.lastname: Alekseev
authors.forename: F
authors.initials: F
authors.lastname: Haeseleer
authors.forename: K
authors.initials: K
authors.lastname: Palczewski
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002460:Cell Line; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism*; D018411:Spodoptera; D013237:Stereoisomerism; D013379:Substrate Specificity; D014162:Transfection; D014714:Vertebrates; D014801:Vitamin A / Q000378:metabolism
chemical_list: D004792:Enzyme Precursors; D011994:Recombinant Proteins; D012176:Retinoids; D009243:NAD; D014801:Vitamin A; D009249:NADP; D000429:Alcohol Oxidoreductases; C113992:trans-retinol dehydrogenase; C022520:retinol dehydrogenase