Visual cycle

Moreover in the retina, iron is a cofactor of a number of other enzymes, including nitric oxide synthase, (i-carotene monooxygenase, and RPE65-isomerohydrolase converting all-tranx-retinol to 11 -m -retinol in the visual cycle. 

Golczak, M, Kuksa, V, Maeda, T, Moise, AR, and Palczewski, K, 2005b. Positively charged retinoids are potent and selective inhibitors of the Ira.ns cis isomerization in the retinoid (visual) cycle. Proc Natl Acad Sci USA 102, 8162-8167. 

Maiti, P, Kong, J, Kim, SR, Sparrow, JR, Allikmets, R, and Rando, RR, 2006. Small molecule RPE65 antagonists limit the visual cycle and prevent lipofuscin formation. Biochemistry 45, 852-860. 

Takahashi, Y., G. Moiseyev et al. (2005). Identification of conserved histidines and glutamic acid as key residues for isomerohydrolase activity of RPE65, an enzyme of the visual cycle in the retinal pigment epithelium. FEBSLett. 579(24) 5414-5418. 

Volume 315. Vertebrate Phototransduction and the Visual Cycle (Part A)... 

The interphotoreceptor retinoid-binding protein (Borst et al., 1989) functions in the regeneration of rhodopsin in the mammalian visual cycle. It is exclusive to vertebrates yet contains a repeated structure that has been found singly in bacterial and plant tail-specific proteases (TSPc) (Silber et al., 1992) and the archaeal tricorn protease (Tamura et al., 1996). The eukaryotic homologs of TSPc are likely to be inactive as... 

Answer B, Only phosphodiesterase participates as a signaling molecule in the visual cycle of photoreceptor cells. 

In lipid metabolism, ds-trans isomerism is particularly important. For example, double bonds in natural fatty acids (see p.48) usually have a as configuration. By contrast, unsaturated intermediates of p oxidation have a trans configuration. This makes the breakdown of unsaturated fatty acids more complicated (see p. 166). Light-induced cis-trans isomerization of retinal is of central importance in the visual cycle (see p.358). 

Since alcohol dehydrogenase is required for the conversion of retinol to retinal, excessive and prolonged ethanol ingestion can impair the physiological function of vitamin A. The decreased conversion of retinol to retinal results from competitive use of the enzyme by ethanol. Night blindness may result, since the visual cycle is a retinol-dependent physiological process. 

Reproduction Retinol and retinal are essential for normal repno duction, supporting spermatogenesis in the male and preventing fetal resorption in the female. Retinoic acid is inactive in maintain ing reproduction and in the visual cycle, but promotes growth and differentiation of epithelial cells thus, animals given vitamin A only as retinoic acid from birth are blind and sterile. 

Retinol A. can be enzymically formed from retinoic acid. B. is transported from the intestine to the liver in chylomicrons. C. is the light-absorbing portion of rhodopsin. D. is phosphorylated and dephosphorylated during the visual cycle. E. mediates most of the actions of the retinoids. Correct answer = B. Retinyf esters are incorporated into chylomicrons. Retinoic acid cannot be reduced to retinol. Retinal, the aldehyde form of retinol, is the chromophore for rhodopsin. Retinal is photoisomerized during the visual cycle. Retinoic acid, not retinol, is the most important retinoid. 

Polyprenyl groups are often transferred onto thiolate ions of cysteine side chains of certain proteins that bind to membranes (p. 559).68/69 We have previously considered the Ras family (Chapter 11). Recov-erin, an important protein in the visual cycle (Fig. 23-43), is another example of a prenylated protein. 

The retinal pigmented epithelium (RPE) is in intimate, anatomic, and functional contact with the retina. Separated from the retina by Bruch s membrane, the RPE serves to regulate nutrients to the retina, phagocytize retinal debris, remove metabolic end products, and control the visual cycle. From a mass transport perspective, the RPE represents the outer BRB. 

Rhodopsin, visual cycle, night vision Blood clotting factors II, VII, IX, and X Calcium and phosphorus homeostasis Antioxidant, glutathione oxidase... 

A number of geometric isomers of retinol exist because of the possible cis-trans configurations around the double bonds in the side chain. Fish liver oils contain mixtures of the stereoisomers synthetic retinol is the all-trans isomer. Interconversion between isomers readily takes place in the body. In the visual cycle, the reaction between retinal (vitamin A aldehyde) and opsin to form rhodopsin only occurs with the 11 -cis isomer. 

The lipase-catalysed hydrolysis of methyl 2-fluoro-2-arylpropionates was proposed to proceed via a mechanism whereby, after ester hydrolysis, the enzyme facilitates the elimination of fluoride ion with the formation of a carbocation stabilized by the adjacent C02 group.230 Determination of the crystal structure of human sialidase Neu2, an enzyme that catalyses the hydrolysis of sialic acids, reveals a tyrosine residue that is positioned in the active site to stabilize the carbocation proposed as an intermediate in the hydrolysis.231 ll-Fluoro-all-frans-retinol is found to undergo isomerization to its 11 -cis form in the presence of visual cycle enzymes, in contrast to a previous study where no isomerization was reported.232 The result of the prior study was taken as evidence for a carbonium ion pathway in the isomerization. Although the authors of the present study do not rule out such a mechanism, they suggest that the isomerization mechanism remains unknown. Data obtained in a study of the oxidation of... 

Trans-retinal eventually falls off of rhodopsin and must be reconverted to 11-cis-retinal and again bound by rhodopsin to get back to the starting point for another visual cycle. To accomplish this, trans-retinal is first chemically modified by an enzyme to trans-retinol—a form containing two more hydrogen atoms. A second enzyme then converts the molecule to 11-cis-retinol. Finally, a third enzyme removes the previously added hydrogen atoms to form 11-cis-rennal, a cycle is complete. ... 

Figure 29-5. The visual cycle of vitamin A is central to vision. In the retina, light stimulates the conversion of 1 l-c/.s-retinal, part of rhodopsin (Rho), to all-iraws-retinal and activates rhodopsin (Rho ).This initiates the first step of the signal transduction cascade that results in the transmission of the visual signal to the brain.The visual cycle involves biochemical and metabolic events in both the photoreceptors (rods) and the retinal pigment epithelium.

The formation of the initial excited form of rhodopsin - bathorhodopsin -depends on the isomerization of 11-cis-retinaldehyde to a strained form of aU- frans-retinaldehyde. This occurs within picoseconds of illumination and is the only light-dependent step in the visual cycle. Thereafter, there is a series of conformational changes leading to the formation of metarhodopsin II. In metarhodopsin II, the Schiff base is unprotonated, and the retinaldehyde is in the unstrained all-trans configuration. 

The rate-liniituig step in initiation of the visual cycle is the regeneration of 11 -c/s-retinaldehyde. In vitamin A deficiency, when there is hide 11 -c/s-retinyl ester in the pigment epithelium, hoth the time taken to adapt to darkness and the ability to see in poor light will be impaired. 

Chen P, Hao W, Rife L, Wang XP, Shen D, Chen J, Ogden T, Van Boemel GB, Wu L, Yang M, and Fong HK (2001) A photic visual cycle of rhodopsin regeneration is dependent on Rgr. Nature Genetics 28, 256-60. 

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