Regulation of isomerohydrolase activity in the visual cycle.
While the overall biosynthetic pathway leading from all-trans-retinoids to 11-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 target for control is the isomerohydrolase, which processes all-trans-retinyl esters into 11-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. However, the addition of retinol binding proteins stimulates 11-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 11-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 rate-limiting enzyme 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.
Winston
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Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Rando
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D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation / Q000502:physiology; D010857:Pigment Epithelium of Eye / Q000201:enzymology*; D012172:Retinaldehyde / Q000096:biosynthesis / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D012995:Solubility; D013997:Time Factors; D014785:Vision, Ocular / Q000502:physiology*; D019745:cis-trans-Isomerases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000099178:Retinoid Isomerohydrolase
D002352:Carrier Proteins; D012172:Retinaldehyde; D012710:Serum Albumin, Bovine; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C020932:11-cis-retinal-binding protein