The visual cycle is a circular enzymatic pathway, which is the front-end of phototransduction. It regenerates 11-cis-retinal. For example, the visual cycle of mammalian rod cells is as follows:
#all-trans-retinyl ester + HO → 11-cis-retinol + fatty acid; RPE65 isomerohydrolases;
#11-cis-retinol + NAD → 11-cis-retinal + NADH + H; 11-cis-retinol dehydrogenases;
#11-cis-retinal + aporhodopsin → rhodopsin + HO; forms Schiff base linkage to lysine, -CH=NH-;
#rhodopsin + hν → metarhodopsin II (i.e., 11-cis photoisomerizes to all-trans):
#:(rhodopsin + hν → photorhodopsin → bathorhodopsin → lumirhodopsin → metarhodopsin I → metarhodopsin II);
#metarhodopsin II + HO → aporhodopsin + all-trans-retinal;
#all-trans-retinal + NADPH + H → all-trans-retinol + NADP; all-trans-retinol dehydrogenases;
#all-trans-retinol + fatty acid → all-trans-retinyl ester + HO; lecithin retinol acyltransferases (LRATs).
Steps 3, 4, 5, and 6 occur in rod cell outer segments; Steps 1, 2, and 7 occur in retinal pigment epithelium (RPE) cells.
RPE65 isomerohydrolases are homologous with beta-carotene monooxygenases; the homologous ninaB enzyme in Drosophila has both retinal-forming carotenoid-oxygenase activity and all-trans to 11-cis isomerase activity.