REGULATION OF ISOMEROHYDROLASE ACTIVITY IN THE VISUAL CYCLE

While the overall biosynthetic pathway leading from all-trans-retinoid s to Il-cis-retinoids in the visual cycle is understood, little is kno wn about which step(s) may be rate-limiting and how control is exerted . One possible tar et for control is the isomerohydrolase. which proce sses all-trans-retinyl esters into Il-cis-retinol. The basal rate of 1 1-cis-retinol synthesis from all-trans-retinyl esters is extremely slo w using bovine retinal pigment epithelial membranes [3.5 pmol of 11-ci s-retinol min(-1) (mg of protein)(-1)], and only small amounts of 11-c is-retinyl eater are formed. proteins stimulates II-cis-retinol format ion by a factor of approximately 13. Specific protein-protein interact ions are probably unimportant because bovine serum albumin and the phy siologically relevant cellular retinaldehyde binding protein (CRALBP) both stimulate Il-cis-retinol formation to the same extent, although C RALBP 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 visu al cycle need not be the isomerohydrolase. Also, 11-cis-retinol is sho wn to inhibit isomerohydrolase, providing a simple mechanism for regul ation of the visual cycle and the stimulating effect of binding protei ns.