Frans-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. 

Rhodopsin is a seven ot-helix trans-membrane protein and visual pigment of the vertebrate rod photoreceptor cells that mediate dim light vision. In this photoreceptor, retinal is the chromophore bound by opsin protein, covalently linked to Lys296 by a Schiff base linkage. Kpega et al.64 have studied NMR spectra of Schiff bases being derivatives of all-frans retinal and amino-p-cyclodextrins as a model of rhodopsin, where p-cyclodextrin plays a role of a binding pocket. On the basis of analysis of the chemical shift differences for the model compound in the presence and in the absence of adamantane carboxylate, it has been shown that the derivative of 3-amino-p-cyclodextrin forms dimer in water and retinoid is inserted into p-cyclodextrin cavity [31]. 

The values of the 15N CP MAS chemical shift of Lys296 nitrogen bonded to retinal via the —C=N bond ( Schiff base) was equal to 155.4 ppm for rhodopsin and 282.8 ppm for metarhodopsin (relative to 5.6 M aqueous NH4C1).70 The results proved the imine bond polarisation, which facilitates Schiff base hydrolysis. The comparison between chemical shifts for metarhodopsin and model compounds suggested that Schiff base linkage of the all-frans retinal chromophore in Metall is in a polar environment. 

C2g isoprenoids Phytol All frans-retinal Photoautotrophs Proteobacteria... 

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. 

Figure 23-46 The photoreaction cycle of bacteriorhodopsin. After Bullough and Henderson.585 The subscript numbers indicate the wavelengths of maximum absorption of each intermediate and the approximate lifetimes are given by the arrows. Resting bacteriorhodopsin as well as intermediates J and O have all-frans retinal but K through N are thought to all be 13-cz s. A proton is transferred from L to aspartate 85 and then to the exterior surface of the membrane. A proton is taken up from the exterior surface via aspartate 96 to form N.

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. 

Figure S2.4 shows the structures of 11 -c/.v-retinal and its more stable isomer all-frans-retinal. The reti-nals are related to the alcohol retinol, or vitamin A,. Mammals cannot synthesize these compounds de novo but can form them from dietary carotenoids such as /3-carotene. A deficiency of vitamin A causes night blindness, along with serious deterioration of the eyes and other tissues.

In the intestinal mucosal cells, /3-carotene is cleaved via an oxygenase (an enzyme that introduces molecular 02 into organic compounds) to frans-retinal (aldehyde form of trans-retinol, as shown in Table 6.2), which in turn is reduced to frans-retinol, vitamin Av Retinol is then esterified with a fatty acid, becomes incorporated into chylomicrons, and eventually enters the liver, where it is stored in the ester form until it is required elsewhere in the organism. The ester is then hydrolyzed, and vitamin Ax is transported to its target tissue bound to retinol-binding protein (RBP). Since RBP has a molecular weight of only 20,000 and would be easily cleared by the kidneys, it is associated in the bloodstream with another plasma protein, prealbumin. 

Metarhodopsin II is then recycled back into rhodopsin by a multi-step sequence involving cleavage to all-frans-retinal and cis-trans isomerization back to ll-cts-retinal. 

The eyes of arthropods, mollusks, and vertebrates use the cis-trans isomerization reaction to detect light. When light enters the eye, it is absorbed by an imine of 11-cA-retinal, which isomerizes to the lower energy n -lrans-retinal imine. The isomerization is detected by various enzymes that initiate an electrical impulse that enters the brain via the optic nerve. Meanwhile, the all-frans-retinal is transported to the liver ( ), where the enzyme retinal iso-merase uses acid catalysis and ATP to convert it back to the higher energy 11 -cis form. The 11 -r/.v-retinal is then sent back to the eye, ready to receive the next photon. 

In 1958 the American biochemist George Wald and his co-workers discovered that visible light isomerizes 11-cm retinal to ail-trans retinal by breaking a carbon-carbon pi bond. With the pi bond broken, the remaining carbon-carbon sigma bond is free to rotate and does so. Within 200 femtoseconds after it has absorbed a photon, the 11-cm retinal is transformed into all-fran retinal. 

The all-fran retinal does not fit into the 11-cm retinal binding site on opsin therefore, npon isomerization the trans isomer separates from the protein. At this point an electrical impulse is generated and transmitted to the brain. In the absence of light, enzymes mediate the isomerization of all-fran retinal back to 11-cm retinal, and rhodopsin is regenerated by the binding of the cis isomer to opsin, as described above. With the completion of this step, the vision cycle can begin again. 

Other recent examples of CIDNP studies on olefin isomerizations via reverse electron transfer populating the triplet, which all fall into class Ila, concerned all-frans retinal with stilbene as donor or a quinone as an acceptor, and a, P unsaturated ketones with triphenylamine or triphenylphosphine as donors °... 

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