title: Molecular logic of 11-cis-retinoid biosynthesis in a cone-dominated species.
abstract: The biochemical pathway to visual chromophore biosynthesis in rod-dominated animals involves minimally a two component system in which all-trans-retinyl esters, generated by the action of lecithin retinol acyltransferase (LRAT) on vitamin A, are processed into 11-cis-retinol by isomerohydrolase. Possible differences in retinoid metabolism in cone-dominated animals have been noted in the literature, so it was of interest to explore whether these differences are tangential or fundamental. Central to this issue is whether cone-dominated animals use an isomerohydrolase (IMH)-based mechanism in the predominant pathway to 11-cis-retinoids. Here, it is shown that all-trans-retinyl esters (tREs) are the direct precursors of 11-cis-retinol formation in chicken retinyl pigment epithelium/retina preparations. This conclusion is based on at least three avenues of evidence. First, reagents that block tRE synthesis from vitamin A also block 11-cis-retinol synthesis. Second, pulse-chase experiments also establish that tREs are the precursors to 11-cis-retinol. Finally, 11-cis-retinyl-bromoacetate, a known affinity-labeling agent of isomerohydrolase, also blocks chromophore biosynthesis in the cone system.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 45 Shattuck Street, Boston, Massachusetts 02115, USA.
authors.forename: Deviprasad R
authors.initials: DR
authors.lastname: Gollapalli
authors.forename: Robert R
authors.initials: RR
authors.lastname: Rando
mesh_terms: D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002458:Cell Fractionation; D002645:Chickens; D004224:Diterpenes / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000737:chemistry; D004952:Esters; D010857:Pigment Epithelium of Eye / Q000201:enzymology / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017949:Retinal Cone Photoreceptor Cells / Q000201:enzymology / Q000378:metabolism*; D051142:Retinol O-Fatty-Acyltransferase; D000084562:Retinyl Esters; D013379:Substrate Specificity; D014801:Vitamin A / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019745:cis-trans-Isomerases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000099178:Retinoid Isomerohydrolase
chemical_list: D000217:Acyltransferases; D004224:Diterpenes; D004791:Enzyme Inhibitors; D004952:Esters; D051142:Retinol O-Fatty-Acyltransferase; D000084562:Retinyl Esters; D014801:Vitamin A; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C034831:retinyl bromoacetate; C056942:lecithin-retinol acyltransferase