11-cis retinal

Conjugation is crucial not only for the colors we see in organic molecules but also for the light-sensitive molecules on which our visual system is based. The key substance for vision is dietary /3-carotene, which is converted to vitamin A by enzymes in the liver, oxidized to an aldehyde called 11-frans-retinal, and then isomerized by a change in geometry of the C11-C12 double bond to produce 11-cis-retinal. 

Shichi, H. and Somers, R. L. Possible involvement of reti-nyhdene phospholipids in photoisomerization of all-frans to 11-cis retinal. /. Biol. Chem. 249 6570-6577,1974. 

The photochemistry of vision provides us with an example of host-guest supramolecular photochemistry where the smaller 11-cis-retinal guest molecule is held within the internal cavity of the much larger protein host molecule (opsin) as a result of noncovalent bonding. 

The light-absorbing part of a rod cell contains the pigment rhodopsin, which consists of the opsin attached to the 11-cis-retinal molecule (1) (Figure 12.3). Free 11-cis-retinal absorbs in the ultraviolet, but when attached to opsin the absorption is in the visible region. 

After absorbing a photon, the 11-cis-retinal undergoes photoisomerisation into its geometric isomer all-trans-retinal (2) (Figure 12.3). 

In colour vision there are three specific types of cone cell corresponding to red, green and blue receptors. The chromophore is the same for all three colours, being 11-cis-retinal bound to a protein which is structurally similar to opsin. Colour selectivity is achieved by positioning specific amino acid side chains along the chromophore so as to perturb the absorption spectrum of the chromophore. 

The study of the mechanism of vision in vertebrates 23>24) has progressed to the point where the first consequence of photon absorption has been described as an activation of the isomerization of the 11 -cis retinal chromophore of rhodopsin to all-trans. That triggers a complex sequence of reactions leading to the mysterious inside of the brain. Brrr, I had better get back — it looks dark in there. But the brain can generate sensations of light. Maybe, one day, we will be able to see enough to understand, but we ll go back just the same to a safer subject. 

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... 

In such a way we were able to conclude that the illumination of suspensions of photoreceptor outer segments by 450 nm light at 77°K, which was known to result in the rhodopsin— prelumirhodopsin transition (corresponding to 11-cis-retinal— transretinal photoisomerization of chromophore), leads also to the appearance of some reduction centers and to the conformational change of membrane. 

Retinol can be oxidized to retinal (6.2) and further to retinoic acid (6.3). Cis-trans isomerization can also occur, e.g. the conversion of all trans-retinal to 11-cis-retinal (6.4), which is important for vision. 

Shi, W. Sports, C.D. Raman, D. Shirakawa, S. Osawa, S. Weiss, E.R. Rhodopsin arginine-135 mutants are phosphorylated by rhodopsin kinase and bind arrestin in the absence of 11-cis-retinal. Biochemistry, 37, 4869-4874 (1998)... 

Light absorption converts 11-cis-retinal to all-ira is-retinal, activating rhodopsin. 

Slowly, arrestin dissociates, rhodopsin is dephosphorylated, and all-frares-retinal is replaced with 11-cis-retinal. Rhodopsin is ready for another phototransduction cycle. 

Retinol stored as retinyl esters 1 11-cis retinal is a component of... 

Structures of retinals, retinols, and 13-carotene. The structure of 11 -cis-retinal (top) indicates the numbering system used for the carbons. In rhodopsin, 11 -a. s-retinal is bound by a protonated Schiff s base linkage to a lysine of opsin. 

The geometries of all the molecules studied were optimized using the same basis sets as in the shielding calculation. Then, the initial geometries of all-trans and 11 -cis retinals were taken from the corresponding crystal structures (19, 20). 

FIGURE 8.7 The central event in human vision is absorption of a visible photon by 11-cis-retinal, which then rearranges about one of its double bonds. The chain of alternating (conjugated) single and double bonds permits absorption in the visible. 

The concluding remarks of Birge are significant. He speculates on why another double-bond isomer of retinal would not work just as well as 11 -cis retinal (holding to the assumption that a 11 -cis to 11 -trans transformation is the critical step in the visual process). Reviewing the earlier definition of photochemistry, it is seen that such a transition is actually one among many possible alternative methods of de-exciting a previously excited species. This work proposes an entirely different method of de-excitation. 

Figure 5.5.10-3 CR Composite of in-vitro absorption spectra and psychophysical responses. The discontinuous lines are in-vitro. No continuity was claimed between these two data sets although some variants of this figure show 11 -cis-retinal connected to curve C, the M-channel chromophore. See text. From Wolken, 1966...

Zhukovsky, E. Robinson, P. Oprian, D. (1991) Transducin activation by rhodopsin without a covalent bond to the 11-cis-retinal chromophore Science, vol. 251, pp 558-559... 

When a photon of light penetrates the eye, it is absorbed by the 11-cis-retinal. The absorption of light converts the 11-cis-retinal to all-trans-retinal ... 

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