All-trans retinaldehyde

Under conditions of low light intensity, the all-trans-retinaldehyde released from rhodopsin is reduced to aU-fra s-retinol, which is then transported to the retinal pigment epithelium bound to the interphotoreceptor RBP. This protein also binds fatty acids, including palmitate and docosa-hexaenoic acid (C22 6 co3), which is known to be essential for vision and which comprises some 50% of the phospholipid of photoreceptor cells. 

The formation of the iiutial excited form of rhodopsin - bathorhodopsin -depends on the isomerization of ll-ds-retinaldehyde to a strained form of all -trans-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 11. In metai hodopsin II, the Schiff base is unprotonated, emd the retinaldehyde is in the unstrained all-trans configuration. 

C8 all-trans-Retinaldehyde acetylhydrazone [69460-76-0 61630-48-6] Acetic acid (all- )-[3,7-dimethyl-9-(2,6,6-trimethyl-1 -cyclohexen-1 -yl)-2,4,6,8-nonatetraenylidene] hydrazide... 

Saari has made the bold statement that Three derivatives of 11-cis-retinaldehyde serve as the chromophores of all known visual pigments. They are complexed with a protein component (an opsin), and the resulting protein-retinoid interactions determine the spectral sensitivity of the visual pigment. 85 No reference is given for this statement nor is any explanation of how these complexes exhibit an absorption spectrum in the visual region. However, except for the substitution of all-trans for 11 -cis in the above quotation and a slight modification to the retinoid involved, this work agrees completely with the statement and provides an explanation for how it is applied. 

A microsomal retinol dehydrogenase catalyzes the oxidation of CRBP-hound all-trans-retinol to retinaldehyde it also acts as a 3a-hydroxysteroid dehydrogenase. A similar enzyme catalyzes the oxidation of 9-cis- and 11-ds-retinol, but not all-trans-retinol again, it has 3a-hydroxysteroid dehydrogenase activity. In the eye, the major product of this enzyme is 11-cts-retinaldehyde, whereas in other tissues it is 9-cts-retinaldehyde, which is then oxidized to 9-cis-retinoic acid (Section 2.3.2.1 Chen et al., 2000 Duester, 2000, 2001 Gamble et al., 2000 NapoU, 2001). Although there is known to be an isomerase in the eye for the formation of 11-cts-retinaldehyde as a... 

RBP is relatively rich in aromatic amino acids, which create a deep hydrophobic pocket that is specific for the 8-ionone ring, polyene side chain, and polar end group. In addition to all- trans-retinol, RBP binds retinaldehyde, retinoic acid, and 13-c/s-retinol, but not retinyl esters or carotene. RBP shows considerable structural homology with 8-lactoglobulin from milk and other... 

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. 

Cis-retinol has 75% of the biological activity of all-tra/rs-retinol, and reti-naldehyde has 90%. Food composition tables give total preformed vitamin A as the sum of all-trans-retinol + 0.75 x 13-cis-retinol -I- 0.9 x retinaldehyde (Holland et al., 1991). 

Tretinoin is a synthetic (all trans) retinoic acid. Retinol and retinaldehyde are also converted into retinoic acid in the target cell where it participates in metabolic activity. The retinoic acid penetrates the cell s nucleus, where it binds with a retinoic acid receptor (RAR). The complex formed by the retinoic acid and the RAR (RA-RAR) interferes with certain areas of DNA by modulating the expression of some genes. It appears that retinoic acid alters the regulation of the cell cycle. ... 

U.v. spectra have been reported for the 9-cis- and aM-trans-C and -Q7, and the all-trans-C22 and -C24 homologues of retinol.187 Several retinaldehyde isomers in iso-octane solution with [Eu(fod)3] gave a new characteristic absorption band.188... 

Fig. 1. The structures of key retinoids and their precursors. Fish convert retinyl esters (e.g. retinyl palmitate (RP)) and carotenoids (e.g. /3-carotene) to retinol in the gut lumen prior to intestinal absorption. Retinyl esters (e.g. RP) stored in the liver are synthesized from retinol by lecithin retinol acyltransferase (LRAT) and acyl CoAiretinol acyltransferase (ARAT). The retinyl esters are mobilized through their conversion to retinol by retinyl ester hydrolase (REH), which is then transported in the circulation to various sites in the body. Retinol is further metabolized within specific tissues to retinal by alcohol dehydrogenases (ADH) or short-chain dehydrogenase/reductase. Retinal is converted to the two major biologically active forms of retinoic acid (RA) (all-trans and 9-cis RA). Retinaldehyde dehydrogenase 2 (Raldh2) synthesizes all-trans RA from all-trans precursors and 9-cis RA form 9-cis precursors.

Figure 1 Retinol and natural analogs. (A) All-trans retinol, (B) all-tra/7s retinaldehyde, (C) ai -trans retinoic acid, (D) retinylphos-phate. Dotted lines in (A) separate the four isoprenoid units composing the molecule.

In the retinal cells of the eye, vitamin A (all-trans-retinol) is converted into the 11-ds-isomer, which is then oxidised to 11-cts-retinaldehde. In the dark the latter then combines with the protein opsin to form rhodopsin (visual purple), which is the photoreceptor for vision at low light intensities. When light falls on the retina, the czs-retinaldehyde molecule is converted back into the aW-trans form and is released from the opsin. This conversion results in the transmission of an impulse up the optic nerve. The all-frans-retinaldehyde is converted to all-trans-retinol, which re-enters the cycle, thus continually renewing the light sensitivity of the retina (Rg. 5.2). 

For rhodopsin studies, retinaldehyde derivatives that possess an 11-cis configuration and cannot undergo isomerization to the all-trans form were synthesized. These compounds were obtained by incorporating the double bond in a... 

Condensation of this mixture with dimedone and acetylacetone produced reti-nylidene-ll- H dimedone (LIX) and retinylidene-ll- H acetylacetone (LVIII), respectively, as only the all-trans isomer because the 13-c/5-retinaldehyde is isomerized to the all-trans isomer under the reaction conditions used (Fig. 15) (Acton and Brossi, 1980). 

In general, recrystallization (when feasible) is the best method of purifying radiolabeled retinoids. Perry et aL (1982) found that when all-tran -retinoic acid was tritiated at very high specific activity, it had to be extensively purified by repeated recrystallization before it could be stored for any period of time. On the other hand, tritiated all-rran -retinaldehyde could not be obtained isomerically pure by recrystallization alone (Kaegi et aL, 1982a). 

A variety of isomers of retinaldehyde have been examined in relation to the rhodopsin system these include 9-cis, 9,11-di-cis, 9,13-di-cis, 7-cis, 7,9-di-cis, 7,13-di-cis, 7,9,13-tri-cis, 7,11-di-cis, all-trans, and 13-cis. Only the latter two isomers fail to combine. It has been suggested that a distance of 9.6-10.0 A from the center of the ring to C-15 may be the critical factor (Matsumoto et al., 1980). 

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