All-trans-retinyl Esters Are the Substrates for Isomerization in the Vertebrate Visual Cycle
Abstract
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.
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In both scenarios for retinyl ester mobilization from retinosomes, LRAT activity creates the substrate for RPE65.
“In both scenarios, LRAT activity creates the substrate for RPE65 [90].”
From Molecular Basis for Vitamin A Uptake and Storage in Vertebrates (2016) · cites this paper as [90]
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- Authors
- Gollapalli, D. R., & Rando, R. R.
- Affiliations
- Harvard University (US)
- Corresponding author
- Rando, Robert R.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2003-04-25
- Volume
- 42
- Issue
- 19
- Pages
- 5809-5818
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W2068179693
- Cited by
- 63
- References
- 0
- Citations by year
- 2025: 2 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 2 · 2013: 3 · 2012: 3
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Eye Institute (EY-04096)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Keywords
- visual cycle, all-trans-retinol, 11-cis-retinol, trans-cis isomerization, LRAT, retinyl ester hydrolase, retinal pigment epithelium, vitamin A, vitamin A metabolism
- MeSH terms
- Acyltransferases, Animals, Carboxylic Ester Hydrolases, Cattle, Esterification, Kinetics, Pigment Epithelium of Eye, Retinal Pigments, Retinoids, Stereoisomerism, Substrate Specificity, Vitamin A, In Vitro Techniques
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