All-fraws-retinal

Fishkin, N., Sparrow, J.R., Allikmets, R., Nakanishi, K., 2005. Isolation and characterization of a retinal pigment epithelial cell fluorophore An all-fraws-retinal dimer conjugate. Proc Natl Acad Sci USA. 102, 7091-7096. 

This photoaffinity labelling analogue of all-fraws-retinal, 95b, has been tritium labelled80 by reduction of unlabelled aldehyde 95a with [3H]-NaBH4 and subsequent oxidation of the obtained tritium-labelled retinol with activated manganese dioxide. The product 95b (specific activity 38.3 mCimmol-1) has been isolated by preparative TLC (equation 36). 

Blatz and Mohler38 have performed 2D NOE NMR experiments on the protonated f-butylamine Schiff base of all-fraws-retinal using different counterions, each carrying at least one nonexchangeable proton. The study has indicated that a proton on the counterion molecule is spatially close, in aprotic solvents, to the protons of the chromophore near the positively charged nitrogen. It has also shown that the ion-pair formation is relaxed in either the presence of excess carboxylic acid (the counterion) or when using methanol as a solvent. 

Using two-dimensional NMR spectroscopy, the spatial location of various carboxylate anions relative to the polyene chain of the protonated Schiff base of all-fraws-retinal was determined. The observed intermolecular NOE cross-peaks between a proton on the counterion and a proton near the nitrogen atom indicate the existence of ion-pair formation between the protonated retinal Schiff base and various counterions in chloroform. The results suggest that the most likely site of the carboxylate group of the counterion is in the immediate vicinity of the positively charged nitrogen atom of the retinal Schiff base. 

Figure 29-3. Chemical structures of important vitamin A species and the provitamin A carotenoid i-carotene. All-fra/w-fi-carolene (T) is the most important provitamin A carotenoid, which can be converted to all-fraws-retinal and then all-tram-retinol (If), which by definition is vitamin A. All-tram-retinol can be esterified with long-chain fatty acids to form retinyl ester (III), the storage form of vitaminA in the body.The active form of vitamin A in vision is 11-cts-retinal (TV).The transcriptionally active forms of vitaminA are all-tram-retinoic acid (V) and 9-cts-retinoic acid (VI). 13-cA-Retinoic acid (VII) has poor transcriptional regulatory activity but is used clinically as isotretinoin to treat skin diseases.

The protonated Schiff base of all-fraws-retinal in the ground state has a pKa greater than 13 [270], which provides its strong connection with the retinal by... 

Figure 23-46 The photoreaction cycle of bacteriorhodopsin. After Bullough and Henderson. 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-fraws retinal but K through N are thought to all be 13-ds. 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.

In the retinal pigment epithelium, palmitate is bound to the fatty acid binding site of the interphotoreceptor RBP, and the retinoid binding site has a high affinity for 11 -ds-retinaldehyde, which is to be transported to the photoreceptor cells. In the photoreceptor cells, the palmitate is displaced by docosahex-aenoic acid, which causes a conformational change in the protein, so that it no longer binds 11 -ds-retinaldehyde, which is delivered to the photoreceptor cells and binds all-fraws-retinol for transport back to the pigment epithelium. Here, the docosahexaenoic acid is displaced by palmitate, and the affinity of the protein for 11-ds-retinaldehyde is restored (Palczewski and Saari, 1997 Tschanz and Noy, 1997). 

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