Aromatic Lipophilic Spin Traps Effectively Inhibit RPE65 Isomerohydrolase Activity
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We previously showed that RPE65 does not specifically produce 11-cis-retinol only but also 13-cis-retinol, supporting a carbocation or radical cation mechanism of isomerization. The intrinsic properties of conjugated polyene chains result in facile formation of radical cations in oxidative conditions. We hypothesized that such radical intermediates, if involved in the mechanism of RPE65, could be stabilized by spin traps. We tested a variety of hydrophilic and lipophilic spin traps for their ability to inhibit RPE65 isomerohydrolase activity. We found that the aromatic lipophilic spin traps such as N-tert-butyl-α-phenylnitrone (PBN), 2,2-dimethyl-4-phenyl-2H-imidazole-1-oxide (DMPIO), and nitrosobenzene (NB) strongly inhibit RPE65 isomerohydrolase activity in vitro.
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Certain radical spin-trap compounds, such as PBN, inhibit RPE65-mediated isomerization in an uncompetitive manner.
“certain radical spin-trap compounds, for example N-tert-butyl-α-phenylnitrone (PBN) can inhibit RPE65-mediated isomerization in an uncompetitive manner.481,482”
From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [481]
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Self-citation
- Authors
- Poliakov, E., Parikh, T., Ayele, M., Kuo, S., Chander, P., Gentleman, S., & Redmond, T. M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Redmond, T. Michael
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2011-07-13
- Volume
- 50
- Issue
- 32
- Pages
- 6739-6741
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- PMC
- PMC3169428
- OpenAlex
- W2025323356
- Cited by
- 18
- References
- 23
- Citations by year
- 2024: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2018: 1 · 2016: 3 · 2015: 3 · 2014: 1 · 2013: 3 · 2012: 2
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Eye Institute (ZIAEY000260)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Electron Spin Resonance Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- RPE65, 11-cis-retinol, radical cations, carbocation mechanism, spin traps, N-tert-butyl-alpha-phenylnitrone, nitrosobenzene, vitamin A metabolism
- MeSH terms
- Retinoid Isomerohydrolase, Carrier Proteins, Cell Line, Electron Spin Resonance Spectroscopy, Eye Proteins, Humans, Models, Molecular, Spin Labels, cis-trans-Isomerases
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