The retinoid cycle reactions were reviewed recently (). In the ROS, light causes the isomerization (reaction a) of the rhodopsin chromophore, 11-cis-retinylidene (), to all-trans-retinylidene. All-trans-retinal () is hydrolyzed and then reduced (reaction b) in the reaction catalyzed by all-trans-retinal-specific RDH(s). All-trans-retinol () diffuses to RPE where it is esterified by LRAT (reaction c) to all-trans-retinyl esters (). All-trans-retinyl esters can be hydrolyzed by a yet unidentified retinyl hydrolase (reaction d) generating all-trans-retinol. Next, the pathway branches and all-trans-retinol, or its derivative, is isomerized to 11-cis-retinol () in a reaction that involves an abundant RPE protein, termed RPE65 (poorly defined reaction d). 11-cis-retinol is then oxidized by 11-cis-RDH (RDH5, RDH11) and other dehydrogenases () to 11-cis-retinal () (reaction e) to complete the cycle. In the dark, under conditions of low 11-cis-retinal utilization, 11-cis-retinol can also be esterified by LRAT to form 11-cis-retinyl esters () (reaction g). With chromophore depletion, hydrolysis of 11-cis-retinyl esters by retinyl ester hydrolase (REH) occurs (reaction h) (). 11-cis-retinal diffuses across the extracellular space (reaction f), is taken up by the outer segment, and recombines with aporhodopsin to regenerate rhodopsin.
