Retinaldehyde Schiff bases

The purple-membrane protein has a molecular mass of 26 kDa and consists of247 amino-acid residues. Each protein molecule contains the chromophore, retinal [see Fig. 23 (B), right], the same chomophore found in rhodopsin in photoreceptor cells of the eyes of vertebrates. In the protein the chromophore is present as a positively-charged retinaldehyde-Schiff base formed through covalent bonding between the aldehyde group of retinal and the amino group on the side chain oflysine-216 ofthe protein, as shown in Fig. 23 (C). 

The absorption spectra of 3,4-didehydroretinaldehydes are very similar to those of retinaldehydes (von Planta et al, 1962 Morton, 1972), whereas the spectra of retinaldehyde Schiff bases are very similar to those of the aldehydes from which these compounds are derived (Schaffer et al, 1974 Sandorfy,... 

The absorption of light by rhodopsin results in a change in the configuration of the retinaldehyde from the 11 -cis to the all- trans isomer, together with a conformational change in opsin. This results in both the release of retinaldehyde from the Schiff base and the initiation of a nerve impulse. The overall process is known as bleaching, because it results in the loss of the color of rhodopsin. 

The formation of the initial excited form of rhodopsin - bathorhodopsin -depends on the isomerization of 11-cis-retinaldehyde to a strained form of aU- frans-retinaldehyde. This occurs within picoseconds of illumination and is the only light-dependent step in the visual cycle. Thereafter, there is a series of conformational changes leading to the formation of metarhodopsin II. In metarhodopsin II, the Schiff base is unprotonated, and the retinaldehyde is in the unstrained all-trans configuration. 

The regeneration of rhodopsin following exposure to bright light requires the following steps. The a -trans retinaldehyde combines with phosphotidylethanolamine (PE) to form a protonated Schiff base N-retinylidene-PE. This complex is then exported out of the disk by an ATP-binding cassette (ABC) transporter exclusively located in the retinol disk membrane (ABCR). Outside the disk the a -trans retinaldehyde is reduced to aW-trans retinol hy a dehydrogenase and transported to retinal... 

Retinoyl imidazolide (616) was converted to retinaldehyde (2), using lithium aluminum hydride (Staab and Mannschreck, 1962). Retinonitrile (156) reacted with diisobutyl aluminum hydride (DIBAL) to give (2) (Kaegi etal., 1982). The nitrile (156) was obtained via the cyanoretinoic acid (155) by condensation of the C,8 ketone (136) or its Schiff base with cyanoacetic acid (Pommer, 1960 Smit, 1961). 

The Schiff base of retinaldehyde (2) with n-butylamine was reduced with sodium borohydride to give a secondary amine that is not very stable. 

To investigate the bonding of (llZ)-retinaldehyde (377) and (all- -reti-naldehyde (2) in rhodopsin, methods were worked out for reducing the reti-nallysine Schiff base (591) in rhodopsin to the N-substituted retinylamine derivative (592). 

In no case has the formation of an 1 l-c -retinoid from all-/ra/is-retinoid been confirmed in vitro in darkness. However, numerous studies have shown that 11-cis isomers of retinaldehyde, retinol, and retinaldehyde oxime are easily converted to all-trans in a variety of solvents (Hubbard, 1956, 1966 Futterman and Rollins, 1973 Futterman and Futterman, 1974 Rotmans et al., 1972), particularly under conditions favoring Schiff base formation or interaction with phospholipids such as phosphatidylethanolamine (Groenendijk et al., 1980). Various studies of this process have been carried out with the rationale that important clues concerning the mechanism of the reverse reaction would be obtained. 

Ae retinaldehyde is linked to the protein via a Schiff s base with lysine 216. When activated by light, the protein acts as a proton pump. Mutants lacking B. are still able to extrude Na, and to generate ATP in the light with the aid of another retinaldehyde-containing protein, halot tsin. [M. A.Kenity et al. Nature 307(1984)383-386]... 

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