Regulation of isomerohydrolase activity in the visual cycle

While the overall biosynthetic pathway leading from all-trans-retinoids to Il-cis-retinoids in the visual cycle is understood, little is known about which step(s) may be rate-limiting and how control is exerted. One possible tar et for control is the isomerohydrolase. which processes all-trans-retinyl esters into Il-cis-retinol. The basal rate of 11-cis-retinol synthesis from all-trans-retinyl esters is extremely slow using bovine retinal pigment epithelial membranes [3.5 pmol of 11-cis-retinol min(-1) (mg of protein)(-1)], and only small amounts of 11-cis-retinyl ester are formed. proteins stimulates II-cis-retinol formation by a factor of approximately 13. Specific protein-protein interactions are probably unimportant because bovine serum albumin and the physiologically relevant cellular retinaldehyde binding protein (CRALBP) both stimulate Il-cis-retinol formation to the same extent, although CRALBP does so at much lower concentrations, The relatively rapid rate of isomerization in the presence of binding proteins [44.3 pmol of 11-cis-retinol min(-1) (mg of protein)(-1)] suggests that the in the visual cycle need not be the isomerohydrolase. Also, 11-cis-retinol is shown to inhibit isomerohydrolase, providing a simple mechanism for regulation of the visual cycle and the stimulating effect of binding proteins.