On the mechanism of isomerization of all-trans-retinol esters to 11-cis-retinol in retinal pigment epithelial cells: 11-fluoro-all-trans-retinol as substrate/inhibitor in the visual cycle.
The synthesis of 11-fluoro-all-trans-retinol (11-F-tROL), which is shown to be an excellent substrate for processing by visual cycle enzymes, is described. It is isomerized to its 11-cis congener subsequent to its esterification by lecithin retinol acyl transferase (LRAT) approximately as well as is vitamin A itself. The enzymatic turnover of 11-F-tROL is unaccompanied by enzyme inhibition. The previously reported lack of isomerization of this substrate had been suggested as evidence for a carbonium mechanism in the critical enzymatic isomerization pathway in vision. The mechanism of this process remains unknown.
Fishkin
Nathan
N
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 45 Shattuck Street, Boston, MA 02115, USA.
Yefidoff
Revital
R
Gollipalli
Deviprasad R
DR
Rando
Robert R
RR
D004952:Esters; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D014785:Vision, Ocular; D014801:Vitamin A / Q000737:chemistry* / Q000378:metabolism*
D004952:Esters; D014801:Vitamin A