All-trans-retinyl esters are the substrates for isomerization in the vertebrate visual cycle.
The identification of the critical enzyme(s) that carries out the trans to cis isomerization producing 11-cis-retinol during the operation of the visual cycle remains elusive. Confusion exists in the literature as to the exact nature of the isomerization substrate. At issue is whether it is an all-trans-retinyl ester or all-trans-retinol (vitamin A). As both putative substrates interconvert rapidly in retinal pigment epithelial membranes, the choice of substrate can be ambiguous. The two enzymes that effect interconversion of all-trans-retinol and all-trans-retinyl esters are lecithin retinol acyl transferase (LRAT) and retinyl ester hydrolase (REH). The retinyl ester or all-trans-retinol pools are radioactively labeled separately in the presence of inhibitors of LRAT and REH, effectively preventing their interconversion. Pulse-chase experiments unambiguously demonstrate that all-trans-retinyl esters, and not all-trans-retinol, are the precursors of 11-cis-retinol. When the all-trans-retinyl ester pool is radioactively labeled, the resulting 11-cis-retinol is labeled with the same specific activity as the precursor ester. The converse is true with vitamin A. These data unambiguously establish all-trans-retinyl esters as the precursors of 11-cis-retinol.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 45 Shattuck Street, Boston, Massachusetts 02115, USA.
Deviprasad R
DR
Gollapalli
Robert R
RR
Rando
D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002417:Cattle; D004951:Esterification; D066298:In Vitro Techniques; D007700:Kinetics; D010857:Pigment Epithelium of Eye / Q000378:metabolism / Q000528:radiation effects; D012168:Retinal Pigments / Q000737:chemistry* / Q000378:metabolism* / Q000528:radiation effects; D012176:Retinoids / Q000737:chemistry* / Q000378:metabolism* / Q000528:radiation effects; D013237:Stereoisomerism; D013379:Substrate Specificity; D014801:Vitamin A / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects
D012168:Retinal Pigments; D012176:Retinoids; D014801:Vitamin A; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase; D002265:Carboxylic Ester Hydrolases; C022523:retinyl esterase