Vitamin Opsin

Bleaching is reversed in the dark and the red-purple color of rhodopsin returns. This is thought to occur by the reduction of all-Pms-retinal to vitamin Ai (retinal), which diffuses from the rod into the pigment epithelium, where it is converted enzymatically to the 1 l-c isomer of vitamin At. The enzymatic isomerization is followed by diffusion back into the rod, oxidation to 11 -rfr-retinal, and combination with opsin to form rhodopsin. This process is shown schematically in Figure 12.5.[Pg.289]

The visual pigment present in rods has been termed rhodopsin and consists of 11-m-retinal, a derivative of vitamin A1( and a lipoprotein called opsin. Recent evidence(43) suggests that in native rhodopsin the retinal chromo-phore is covalently bonded to a phosphatidylethanolamine residue of the lipid portion of opsin. The structure of 1 l-cis-retinal is as follows ... 

A deficiency of vitamin A leads to vision defects, including a visual impairment at low light levels, termed night blindness. For the processes of vision, retinol needs to be converted first by oxidation into the aldehyde retinal, and then by enzymic isomerization to cw-retinal. c -Retinal is then bound to the protein opsin in the retina via an imine linkage (see Section 7.7.1) to give the red visual pigment rhodopsin. 

Vitamin A is essential for proper functioning of the retina, for the integrity of epithelial tissue, for growth and bone development and for reproduction. For vision the active vitamin appears to be retinal as the chromophore of both rods and cones is 11-cis-retinal which, in combination with the protein opsin, forms the photoreceptor rhodopsin. Retinoic acid is the active form associated with growth, differentiation, and transformation. Both all-trans and 9-cis retinoic acid act as a steroid hormone to affect cellular differentiation, especially for morphogenesis, reproduction and for immune responses. At... 

H hstract. Until recently, all ocular photoreception was attributed to the rods and cones of the retina. However, studies on mice lacking rod and cone photoreceptors (rdjrdcl), has shown that these mice can still use their eyes to detect light to regulate their circadian rhythms, suppress pineal melatonin, modify locomotor activity and modulate pupil size. In addition, action spectra for some of these responses have characterized a novel opsin/vitamin A-based photopigment with a 480nm. Electrophysiological... 

The evidence to-date shows that vertebrate photoreception is mediated by a closely related group of proteins termed opsins. These are G protein-coupled receptors characterized by their ability to bind a vitamin A based chromophore ( -cis-retinal) via a Schiff base linkage using a lysine residue in the 7th transmembrane a helix (Fig. 1). The primary events of image detection by the rods and cones occurs with the absorption of a photon of light by ll-r/r-retinal and its photoisomerization to the AUtrans state (Bums Baylor 2001, Menon et al 2001). Although photoreception is best understood in retinal rods and cones, photoreception is not confined to these structures. In non-mammalian... 

The rd rd cl mouse has provided a powerful model to characterize the ocular non-rod, non-cone photoreceptors of mammals using action spectrum techniques. The first completed action spectrum was for the pupillary light reflex PLR (Lucas et al 2001). The results demonstrated that the PLR in rd rdcl mice is driven by a single opsin/vitamin A-based photopigment with a 479 nm. The... 

FIG. 3. Action spectra for (a) rdjrdi /and (b) +/+ mice derived from irradiance response curves at seven wavelengths from 420-580 nm. The rdirdclspectrum corresponds to an opstn/vitamin A photopigment (R = 0.976) with a at 481 nm. The +/+ action spectrum also describes an opsin photopigment (R = 0.896), but with a of 500nm. (c, d) Representative... 

It is theoretically possible that cryptochromes do not function as photopigments, but are required either for the production of another photopigment, or for the signal transduction pathway of another photopigment. Such a pigment would need to be fully resistant to severe vitamin A depletion (since photic immediate-early gene induction in the SCN is fully preserved in RBP I mice but lost in mice) and so is unlikely to be opsin-... 

Van Gelder This brings us back to the vitamin A question, where we have shown in the Kbp l Crj1Crj2 knockouts that they have essentially no suprachiasmatic nucleus (SCN) photoresponses that we can detect. We are thus able to fully deplete a Cry mutant to eliminate all photoresponses. We therefore presume that there is no hidden photopigment in those animals. We thus have to just explain the difference between the Rd-Cry mutant and Rhp-Cry mutant, and the only difference is that there is 10% photosensitivity left, which I presume is due to a novel opsin. 

A stack of about 1 000 disks in each rod cell contains the lightsensing protein rhodopsin,10 in which the chromophore 11-o i-retinal (from vitamin A) is attached to the protein opsin. When light is absorbed by rhodopsin, a series of rapid transformations releases all-frans-retinal. At this stage, the pigment is bleached (loses all color) and cannot respond to more light until retinal isomerizes back to the 11 -cis form and recombines with the protein. 

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. 

When rhodopsin absorbs light in the vision process, the cis double bond between carbons 11 and 12 isomerizes to a trans double bond. This isomerization triggers a nerve impulse telling the brain that light has been absorbed by the eye. The imine of the isomerized product is unstable and is hydrolyzed to opsin and the all-trans form of retinal (also known as vitamin A aldehyde). All-trans retinal is converted back to 11 -c/s-retinal by enzymes so that it can be used again in rhodopsin formation. 

The main physiologically active forms of vitamin A are retinaldehyde and retinoic acid, both of which are derived from retinol. Retinaldehyde functions in the visual system as the prosthetic group of the opsins, which act as the signal transducers between reception of light in the retina and initiation of the nervous impulse. 

Introduction of a cis double bond at C-11 bends the side chain of vitamin A (or of the retinal), producing a structure probably necessary for the formation of rhodopsine, a pigment generated by union of the protein, opsine, to the retinal having suitable stereochemistry. The all trans isomer does not yield the pigment. ... 

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