Cis-trans isomerism of retinal

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). 

The primary photochemical process of vision is therefore the cis-trans isomerization of retinal in rhodopsin. The free protein opsin then leads to the production of the nerve impulse through a secondary biochemical process... 

There are also many interesting photochemical rearrangements of organic molecules. One example is the cis-trans isomerization of retinal induced by visible light, a basic... 

Figure 2.19 Schematic illustrating the photoinduced cis-trans isomerization of retinal...

Retinoids. Biosynthesis is included in a general review on vitamin A. The cis-trans isomerization of retinals by crude tissue extracts has been achieved/ After oral administration of the synthetic retinoid (187) to human subjects some eighteen metabolites were isolated from the urine and faeces, almost all having a shortened polyene chain/ °... 

The reaction heat (at O K) is assumed to be zero (Q = 0),since it follows from an analysis by ROSENPELD et al./195/, which shows that during the reaction a barrierless cis-trans isomerization of retinal in the excited singlet state (S ) of rhodopsin takes place. This conclusion is in agreement with the theoretical calculations of SALEM and BRUCKMANN /196/ and WARSHEL /194/. 

Experiments were performed at 5°C in order to arrest the cis-trans isomerization of the protonated Schiff base. Spectra with one equivalent of acid and different mixing times showed one NOE cross-peak between H15 of the retinal molecule and the proton on the counterion, as shown for a mixing time of 0.4 s in Figure 10. The strong chemical shift dependence of the H15 resonance on the concentration of the acid dictated the use of less than one equivalent of the protonating formic acid, and therefore an incomplete protonation (>80%) of the retinal, in order to avoid an overlap between the formate and the H15 peaks in the spectrum. This should not affect the observed result since an average chemical shift, between those of HI 5 of the retinal in its nonprotonated and protonated... 

The sequence of events involved in the vision process are listed in Fig. 3. The overall process triggered by the 11 -cis retinyl chromophore is very specific to the protein medium. Through cis-trans isomerization of the chromophore, light energy is transduced into chemical free energy, which in turn is utilized to cause conformational changes in the protein and ultimately activate the retinal G-protein. The important role of the protein... 

On examination of the data it now appears that the primary event in vision is a cis-trans isomerization of the retinal moiety proton(s) could be translocated on the protein, concomitant with or subsequent to the isomerization process, but not before. The isomerization of the 1 1-cw-retinal would lead to a batho product having a distorted transoid chromophore and a ground-state energy of ca. 35 kcal above rhodopsin. 

In the case of the retinal Schiff base (6) the efficiency of cis-trans isomerization of the double bond between C-II and C-12 is considerably enhanced by polar solvents on the one hand and by protonation of the Schiff base on the other hand (Becker and Freedman, 1985). This is rather important because 6 is the chromophore of rhodopsin and this isomerization represents one of the primary steps in vision. 

Chemical structure of a -tmns retinol (vitamin Ai), the most active form of vitamin A. Oxidation of C15 to an aldehyde or an acid produces, respectively, retinaldehyde (retinal) and retinoic acid. The cis-trans isomerization of the double bond between Ci i and C12 occurs during functioning of retinaldehyde in vision. 

Chemical structure (Figure 1). Molecules formally composed of four isoprene units they naturally occur as an alcohol (retinol), an aldehyde (retinal), or as an acid (retinoic acid). From each of the three basic forms two variants exist vitamin A, with a jS-ionone ring and vitamin A2 with a dehydrated S-ionone ring. Native retinoids show cis-trans isomerism of the double bonds. Carotenoids are proforms of vitamin A (Figure 2). 

Seltzer, S., MNDO barrier height for catalyzed bicycle-pedal hula-twist and ordinary cis-trans isomerizations of protonated retinal Schiff base, /. Am. Chem. Soc., 109,1627,1987. 

The initial event of rhodopsin after absorption of a photon is now confirmed to be a cis-trans isomerization of the retinal chromophore. Originally, the cis-trans isomerization hypothesis was based on the experimental facts that irradiation of rhodopsin at Hquid nitrogen temperature yields a photo-steady-state mixture containing rhodopsin, bathorhodopsin, and isorhodopsin (Figure 125.4). Because rhodopsin and isorhodopsin contain ll-c s- and 9-cis-retinals, respectively, as their chro-mophores, bathorhodopsin should have an intermediate configuration, that is, a twisted aU-tra s-retinal,... 

Figure 9.20 The photo-activated process that accounts for vision the 11-cis — 11-trans photo-isomerism of retinal...

The active compound within the bacillary layer is retinal. To simplify the photo-physics within the rods and cones hugely, absorption of a photon initiates a series of conformational changes that lead ultimately to photo-isomerization of retinal from the 11-cis isomer to the 11-trans isomer see Figure 9.20. The uncoiling of the molecule following photo-excitation triggers a neural impulse, which is detected and deconvoluted by the brain. The photochemical reaction is breakage and, after rotation, re-formation of the C=C bond. 

When light strikes the rod cells, isomerization of the C-ll/C-12 double bond takes place, and tra 5 -rhodopsin (metarhodopsin II) is formed. This cis-trans isomerization is accompanied by an alteration in molecular geometry, which generates a nerve impulse to be sent to the brain, resulting in the perception of vision. Metarhodopsin II is recycled back to rhodopsin by a multi-step sequence that involves the cleavage to all-trani-retinal and cis-trans isomerization back to 11-cA-retinal. 

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. 

Photochemical cis-trans isomerization in a conjugated polyene system is thought to be the crucial primary process in vision. The visual pigment (rhodopsin) is derived from 11 -crs-retinal by reaction of the aldehyde group with an amino substituent in a protein (opsin). There is considerable distortion in the geometry of this chromophoric group anyway, because of the spatial requirements of the protein... 

Cis-trans isomerization is an important step in the chemistry of vision, for example, the light-initiated, enzyme-catalyzed isomerization of cis to frans-retinal. 

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