11-cw retinal

Opsin itself is colorless, whereas 1 l-cis-retinal absorbs strongly at 370 nm. The combination of opsin with 11-cw-retinal produces a remarkable shift of Vax to longer wavelengths (430 nm to 620 nm, depending on the species). Similar shifts in wavelength for 11-cw-retinal in combination with simple... 

Rhodopsin Consists of 11-cw-Retinal Bound to the Protein, Opsin... 

Absorption spectra of rhodopsin and of 11-cw-retinal in hexane solution. The absorption of rhodopsin in the 280-nm region is due mainly to the opsin. 

Figure 32.23. Atomic Motion in Retinal. The Schiff-base nitrogen atom moves 5 A as a consequence of the light-induced isomerization of 11-cw-retinal to all-tra 5-retinal by rotation about the bond shown in red. 

Chen, Y., Houghton, L.A., Brenna, J.T. and Noy, N. (1996) Docosahexaenoic acid modulates the interactions of the interphotoreceptor retinoid-binding protein with 11-cw-retinal. J. Biol. Chem. 271 20507-20515. 

Recently Inoue and coworkers also reported ab initio study of shieldings for linear ir-conjugated systems. A photoreceptive protein such as rhodopsin (Rh) or bacte-riorhodopsin (bR) possesses a retinal isomer bound to a lysine residue via the protonated Schiff base linkage. Rh exists in the rod cell of the retina of vertebrate and possesses 11 -cw-retinal (Figure 2), which is isomerized into the all-trans form by the absorption of photons, finally leading to signal transduction. 

They contain two pigments, rhodopsin and retinochrome. The two pigments have the same supramolecule (protein), have common chromophore retinal, but they differ in their bound chromophore stereochemistry (Scheme 13). Cephalopod rhodopsin has 11-cw-retinal as chromophore where as retinochrome has all-trans-retinal as chromophore [161,162], and when exposed to light they get interconverted (Scheme 13). [163]. More interestingly, the cephalopod leti-nochrome has been used to achieve one-way 11-cis isomerization induced by light. Retinal all-trans, 13-cis, and 9-cis isomers were mixed with retinochrome and irradiated at 390 nm to get specifically 11-cw-retinal (Scheme 14) [164,165]. 

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-cw-retinal, which isomerizes to the lower energy aW-trans-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-tra 5-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 W-cis form. The ll-c -retinal is then sent back to the eye, ready to receive the next photon. 

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... 

A few minutes after cis-trans isomerization the 11-cw-retinal is recovered by an isomerase and recombined with a rhodopsin protein. The isomerization all-tram 11-cw is a dark reaction and occurs with activated retinol esters (Fig. 5.2.7). A nucleophilic group of an enzyme is reversibly added in a Michael reaction to Cll and the 5 kcal needed for the unfavorable isomerization comes from the cleavage of the activated ester. The resulting diene with the nucleophile added to the terminal allylic position is then hydrated and the nucleophile eliminated again. The trans-cis isomerization has thus been achieved in a controllable nucleophilic addition-elimination cycle, which is typical for biological reactions. The stereochemistry of the system is not disturbed. The other chemically plausible isomerization, namely via homolysis of the double bond and biradical formation, is not used in biological systems because it may lead to uncontrolled polymerization and side reactions with the protein (Rando, 1990). 

The conversion of a cis isomer to the trms isomer (or vice versa) is a process called cis-trans isomerization. Such conversions are crucial in the vision process. The molecules in the retina that respond to light are rhodopsin, which has two components called 11-cw-retinal and opsin. Retinal is the light-sensitive component, and opsin is a protein molecule. Upon receiving a photon in the visible region, 11-cw-retinal isomer-izes to all-trans retinal by breaking a carbon-carbon tt bond. With the TT bond broken, the atoms connected by the carbon-... 

The primary event in the vision process is the conversion of 11-cw-retinal to the aU-trans isomer of rhodopsin. The double bond at which the isomerization occurs is between carbon number 11 and carbon number 12. For simplicity, most of the H atoms are omitted. In the absence of light, this transformation takes place about once in a 1000 years ... 

FIGURE 12.15 The attachment of 11-cw-retinal to the protein is via a nitrogen atom (dark, on the far right), called a Schiff base, belonging to the side group of the peptide lysine. Short bonds are dashed (=). The bond involved in the cis-trans isomerization is marked by a star. 

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. 

The light-sensitive compound in rods is called rhodopsin. In 1952, Nobel Laureate George Wald (Harvard University) and his co-workers showed that the chromophore in rhodopsin is the conjugated polyunsaturated system of 11-cw-retinal. Rhodopsin is produced by a chemical reaction between 11 -ch-retinal and a protein called opsin. 

Fig 2 Transfer of 11-cw-retinal from IRBP to umlamdiar vesicles of DOPC Vesicles containing 2 mol% PY-PC (2 mM) were mixed with 11-cw-retmal-IRBP complex (1 iiM, ligand/protein mole ratio = 2) Transfer of the ligand from IRBP to vesicles was followed by the time-dependent decrease in the fluorescence of the probe (excitation, 330 nm emission, 400 nm) The inset shows the residuals of the fit of the trace to a single first-order reaction... 

Fig. 3 Transfer of 11 -cw-retinal from IRBP to unilamellar vesicles of DOPC in the presence of docosahexaenoic acid. Experiments were earned out as described in the Legend to Fig. 2 m the presence of 10 jiM docosahexaenoic acid Insets show the residuals corresponding to the fit of the traces to a single first-order reaction (A), or to two first order reactions (B)...

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