Ll-cis-retinal

FIGURE 18.36 The incorporation of retinal into the light-sensitive protein rhodopsin involves several steps. All- ram-retinol is oxidized by retinol dehydrogenase and then iso-merized to ll-cis-retinal, which forms a Schiff base linkage with opsin to form light-sensitive rhodopsin. 

Mefarhodopsin II is then recycled back into rhodopsin by multi t st p sequence involving cleavage to all lran reiinft1 and cis-tntmi isom erlzatton back to ll-cis-retinal. 

In the retina a protein called opsin combines with 11-cts-retinal to form a modified protein, rhodopsin. The ll-cis-retinal portion of rhodopsin is a prosthetic group (a nonprotein portion of a protein that is necessary for its action). 

Physical and spectroscopic properties have been described for liposomes containing /3-carotene, /3-cryptoxanthin [/3,/8-caroten-3-ol (173)], or zeaxanthin [/8,/S-carotene-3,3 -diol (174)], for molecular layers of fatty acids containing carotene, and for a photoresponsive membrane prepared from ll-cis-retinal. 

Isomerization of ll-cw-retinal to the all-trans diastereomer is sterically favored because of the sterical repulsion between the 13-methyl and 10-H substituents in a planar polyene. In solutions of retinal or retinyl ester in which all stereoisomers are equilibrated by the reversible addition of iodine or trifluo-roacetic acid one finds only 0.1% of the W-cis diastereomer. The energy difference between all-trans- and ll-cis- retinal is 4.1 kcal/mol. The crystal structure of 11-cw-retinal shows a highly twisted polyene at C12-C13. The methyl group... 

Bleaching is reversed in the dark and the red-purple color of rhodopsin returns. This is thought to occur by the reduction of all-tronj-retinal to vitamin Ai (retinal), which diffuses from the rod into the pigment epithelium, where it is converted enzymatically to the 11-cm isomer of vitamin Ai. The enzymatic isomerization is followed by diffusion back into the rod, oxidation to ll-ci, -retinal, and combination with opsin to form rhodopsin. This process is shown schematically in Figure 12.5.< ... 

While the factors resulting here in a given distortion are intramolecular, the conclusions we can draw may be applied to cases where an isolated molecule is distorted by its environment. We would like to examine this approach as starting point for treating the effect of the 11-cw retinal-opsin interaction on the photoisomerization quantum yield of 11-cw to aW-trans retinal. This quantum yield increases from 0.2 for the free chromophore [9] to 0.66 in rhodopsin [10]. This value is close to that of the biacetyl sensitized reaction of the free chromophore, 0.75 [11], and indicates that the triplet state is involved to a large extent in the photoisomerization of ll-cis retinal and that intersystem crossing is inefficient. 

Fig. 7.4. Digramatic representation of the surface of rhodopsin, showing the position of ll-cis-retinal (A] in the red disk membrance.

The parent compound in the vitamin A group is called sdl-trans retinol (Fig. lA) [4]. Its aldehyde and acid forms are retinal (Fig. IB) and retinoic acid (Fig. 1C). The active form of vitamin A in vision is ll-cis retinal (Fig. ID), and a therapeutically useful form (accutane, isotretinoin) is l3-cis retinoic acid (Fig. IE). Retinyl palmitate (Fig. IF) is a major storage form, and retinoyl p-glucuronide is a biologically active, relatively non-toxic water-soluble metabolite (Fig. IG). A synthetic aromatic analog (etretin, acitretin), shows therapeutic usefulness (Fig. IH). Finally, p-carotene, a major provitamin A carotenoid, is shown in Figure II. 

Figure 1. Structures of retinal and retinal analogues. 1. ll-cis retinal 2. ll-cis 3,4-dehydroretinal 3. l -cis 3-hydroxyretinal 4. ll-cis 4-hydroxyretinal 5. ll-cis 9-desmethylretinal...

The RPE is the site of isomerization and oxidization of the dXVtrans retinol to ll-cis retinal [62]. The process for this non-photochemical isomerization is still not understood. Rando [63] has proposed that two steps occur the dW-trans retinol is first esterified, and then the dW-trans retinyl ester is converted into 1 -cis retinol. The hydrolysis of the ester is proposed to provide the energy necessary to drive the thermodynamically unfavorable process of the isomerization. Storage of the retinoid could occur both as the 1 -cis and/or the dX -trans isomer. A few of the steps involved in this process for which there have been recent findings are discussed below. 

The vitamin is important in animal growth, reproduction, the maintenance of function of mucous membranes and vision, but only in the latter case can its role be adequately defined at the molecular level. The enzymic oxidation product of retinol, ll-cis-retinal (Figure 5.6) complexes with a protein, opsin, in the retinal rods to form the conjugated protein, rhodopsin. The visual process consists of a series of reactions triggered by the photochemical isomerization of 11-cw-retinal to all-traw5-retinal. 

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