Describe the key enzymatic steps in the visual cycle converting bleached all- trans-retinal back into lightsensitive 11-cis-retinal.

The visual cycle is a series of biochemical reactions that occur in the retina of the eye, which helps in maintaining the continuous supply of 11-cis-retinal, a light-sensitive molecule found in the rod and cone cells. In the presence of light, 11-cis-retinal isomerizes to all-trans-retinal, leading to a series of reactions that result in an electrical signal being sent to the brain. The visual cycle then allows the conversion of all-trans-retinal back to 11-cis-retinal, thus restoring the light sensitivity of the photoreceptor cells.

The first key step in the visual cycle is the conversion of all-trans-retinol to 11-cis-retinol, catalyzed by the enzyme RPE65 (retinal pigment epithelium-specific 65 kDa protein). RPE65 is an isomerase found in the retinal pigment epithelium (RPE) cells. The enzyme cleaves the ester bond between all-trans-retinol and fatty acids, producing all-trans-retinyl esters. Then, RPE65 converts the all-trans-retinyl esters to 11-cis-retinol.

The next step in the visual cycle is the oxidation of 11-cis-retinol to 11-cis-retinal, catalyzed by the enzyme 11-cis-retinol dehydrogenase (RDH5). This enzyme belongs to the short-chain dehydrogenase/reductase (SDR) family and is present in RPE cells. RDH5 oxidizes 11-cis-retinol to 11-cis-retinal by removing two hydrogen atoms from the molecule.

Once 11-cis-retinal is synthesized, it is transported back to the outer segment of rod and cone photoreceptor cells. This process involves the binding of 11-cis-retinal to cellular retinaldehyde-binding protein (CRALBP), which shuttles it across the interphotoreceptor matrix.

The final step in the visual cycle is the formation of visual pigments. In the rod cells, 11-cis-retinal combines with the protein opsin to form rhodopsin, a light-sensitive pigment. In the cone cells, 11-cis-retinal combines with three different photopsin proteins to form cone opsins, responsible for color vision. Once the visual pigments are formed, the photoreceptor cells regain their light sensitivity, and the visual cycle is complete. In summary, the key enzymatic steps in converting all-trans-retinal back to light-sensitive 11-cis-retinal in the visual cycle are RPE65-catalyzed isomerization, RDH5-catalyzed oxidation, and the formation of visual pigments in photoreceptor cells by combining with opsin proteins.