Trans-Retinol

Park, S.-M. 1978. Electrochemical studies of P-carotene, all-trans-retinal and all-trans-retinol in tetrahydro-furan. J. Electrochem. Soc. 125 216-222. 

Moreover, efficient rhodopsin regeneration may precede enzymatic reduction of all-fran.v-retinal to all-trans-retinol in the aged retina (Figure 15.2c) (Schadel et al., 2003). Upon rhodopsin regeneration, all-trans-retinal is released from the exit site of the protein into the lipid membrane (Figure 15.2c) (Schadel et al., 2003). From here the removal of all-tnms-retinal to the outer leaflet of the disc membrane is dependent on activity of ATP-binding cassette trasporter A4 (ABCA4) present in the rim of photoreceptor disc, known also as ABCR protein. 

Figure 15.11 The biochemical reactions that result in the conversion of trans-retinal to ds-retinal, to continue the detection of light To continue the process, trans-retinal must be converted back to c/s-retinal. This is achieved in three reactions a dehydrogenase converts trans-retinal to trans-retinol an isomerase converts the trans-retinol to c/s-retinol and another dehydrogenase converts c/s-retinol to c/s-retinal. To ensure the process proceeds in a clockwise direction (i.e. the process does not reverse) the two dehydrogenases are separated. The trans-retinal dehydrogenase is present in the photoreceptor cell where it catalyses the conversion of trans-retinal to trans-retinol which is released into the interstitial space, from where it is taken up by an epithelial cell. Here it is isomerised to c/s-retinol and the same dehydrogenase catalyses its conversion back to c/s-retinal. This is released by the epithelial cell into the interstitial space from where it is taken up by the photoreceptor cell. This c/s-retinal then associates with the protein opsin to produce the light-sensitive rhodopsin to initiate another cycle. The division of labour between the two cells may be necessary to provide different NADH/NAD concentration ratios in the two cells. A high ratio is necessary in the photoreceptor cell to favour reduction of retinal and a low ration in the epithelial cell for the oxidation reaction (Appendix 9.7).

Rutten, A. A., Wilmer, J. W., and Beems, R. B. (1988a). Effects of all-trans retinol and cigarette smoke condensate on hamster tracheal epithelium in organ culture. I. A cell proliferation study. Virchows Arch. B Cell Pathol. Inch Mol. Pathol. 55,167-175. 

Swatschek, D., Schatton, W., Muller, W. E. G., and Kreuter, J. (2002). Microparticles derived from marine sponge collagen (SCMPs) Preparation, characterization and suitability for dermal delivery of all-trans retinol. Eur. ]. Pharm. Biopharm. 54,125-133. 

Figure 15 Hydrogenation of all-trans-retinal to all-trans-retinol.

Sauer, J.-M. Sipes, I.G. (1995) Modulation of chemical-induced lung and liver toxicity by all-trans-retinol in the male Sprague-Dawley rat. Toxicology, 105, 237-249... 

The parent vitamin A compound, retinol, has the empirical formula C2oH3oO and a molecular weight (MW) of 286.44. The molecule comprises a cyclohexenyl (/3-ionone) ring attached at the carbon-6 (C-6) position to a polyene side chain whose four double bonds give rise to cis-trans (geometric) isomerism. The predominant isomer, all-trans-retinol (Fig. 1), possesses maximal (100%) vitamin A activity and is frequently accompanied in natural foodstuffs by smaller amounts of 13-ds-retinol, which exhibits 75% relative activity in the rat (6). Other cis isomers of retinol also occur in nature, but they are of low potency, and their contribution to the total vita-... 

For many applications, fluorescence detection offers no real advantages over absorbance detection, and the linear response range is more limited. Moreover, the fluorescence response of 13-d.v-retinol is less than that of all-trans-retinol, the relative fluorescence depending upon the solvent (133,134). 

Reversed-phase chromatography using semiaqueous mobile phases can separate all-trans-retinol from 13-cis-retinol, albeit rather poorly. Further separation of the minor cis isomers is not... 

Vitamin A (trans-retinol) is called an isoprenoid alcohol because it consists, in part, of units of a single five-carbon compound called isoprene ... 

Over the years, the form shown in frame A has been loosely defined as all-trans retinol. 

FIGURE 29.4 Chemical structure of vitamin A (all-trans retinol, (a//- )-3,7-dimethyl-9-(2,6,6-trimethyl-l-cyclohexenyl)-2,4,6,8-nonatetraen-l-ol). 

Trans-retinal eventually falls off of rhodopsin and must be reconverted to 11-cis-retinal and again bound by rhodopsin to get back to the starting point for another visual cycle. To accomplish this, trans-retinal is first chemically modified by an enzyme to trans-retinol—a form containing two more hydrogen atoms. A second enzyme then converts the molecule to 11-cis-retinol. Finally, a third enzyme removes the previously added hydrogen atoms to form 11-cis-rennal, a cycle is complete. ... 

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. 

Figure 6.6 indicates the various reactions typical of vitamin Av Retinoic acid, oxidized trans-retinal, is apparently involved in epithelial cell physiology. Retinol phosphate, trans-retinol esterified with a phosphate residue, associates with various membrane structures through its hydrophobic isoprenoid residue, leaving its hydrophilic phosphate group in contact with the aqueous environment. It serves as an anchor for growing oligosaccharide chains in the same manner as dolichol phosphate does (see Chapter 18). 

Vitamin A is a fat-soluble vitamin involved in critical biological functions, such as embryonic development, growth and vision. It has three primary forms retinol, retinal and retinoic acid. In addition, (3-carotene can be converted to some extent in the body into retinol and is therefore called provitamin A. The bioactivity of these vitamin A compounds varies considerably, ranging from 100% for all-trans retinol, 75% for 13-eis retinol and to just 17% for (3-carotene. All-trans retinol is the major form of vitamin A in milk fat, with values ranging from 8.0 to 12.0 pg/g fat in samples of commercial butter. In contrast, 13-cA retinol is present at a very low... 

The vitamin A content of foods is often given in terms of the international unit (IU). One IU of vitamin A is defined as 0.3 tg of all-trans-retinol. The term retinol equivalent (RE) is used to convert all sources of vitamin A and carotenoids in the diet to a single unit. One RE is by definition 1 pg of all-trans retinol, 12 pg of P-carotene, or 24 pg of other (mixed) provitamin A carotenoids. The recommended dietary allowance for vitamin A ranges from 375 pg RE/day for infants to 1,000 RE/day for adults. 

Electronic Absorption Spectroscopy. The absorption spectra of some polyenes in the crystalline state have been studied. On adsorption of certain gases on the crystallite surfaces, a new band appears on the low-energy side of the long-wavelength band in the spectra of these polyenes, e.g. at 536, 537, and 375 nm for all- trans-ft-carotene, 15-cis-/3-carotene, and retinyl compounds, respectively.92 The surface pressure vs. area isotherms and absorption spectra of all-trans-, 9-cis-, and 13-cis-retinal, all-trans-retinol, and all- trans-retinyl acetate have been studied at air-water and air-solid interfaces, respectively. The spectra of monolayers of the isomeric retinals showed a red shift of 15 lnm compared with the solution spectra, whereas... 

Retinol. The extensively investigated retinol molecule offers a relatively simple photophysical system due to the absence of a low-lying (n, tt ) state. Two main patterns characterize the fluorescence of all-trans retinol at 295°K (1) the break-... 

T, y-T, a-T, p-cryptoxanthin, lycopene, a-carotene, p-carotene, all trans retinol, 5-T3, y-T3, a-T3, lutein, zeaxanthin (27 min)... 

Q s-retinol has 75% of the biological activity of aU-trans-retinol, and reti-naldehyde has 90%. Food composition tables give total preformed vitamin A as the sum of aU-trans-retinol -i- 0.75 x 13-c/s-retinol - - 0.9 x retinaldehyde (Holland et al., 1991). 

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... 

Anhydroretinol may arise by nonenzymic isomerization of all-trans-retinol under acidic conditions and can act as a precursor for the synthesis of other biologically active retroretinoids (McBee et al., 2000). 

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... 

Vogel S, Mendelsohn CL, Mertz JR, Piantedosi R, Waldburger C, Gottesman ME, and BlanerWS (2001) Characterization ofa new member of the fatty acid-binding protein family that binds all-trans-retinol. Journal of Biological Chemistry 276, 1353-60. 

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