Retinoids anhydroretinol

Figure 2.1. Major physiologically active retinoids. Relative molecular masses (Mr) retinol, 286.5 retinaldehyde, 284.4 retinoic acid, 300.4 13,14-dihydroxy-retinol, 318.5 4-oxoretinol, 301.5 retroretinol, 286.5 14-hydroxy-retroretinol, 302.5 anhydroretinol, 269.6 4-oxo-retinoic acid, 315.4 4-hydroxyretinoic acid, 316.4 dehydroretinol, 284.4 retinyl acetate, 328.5 and retinyl palmitate, 524.9. 

Anhydroretinol binds to plasma and intracellular RBPs, but not to the cellular retinoic acid binding proteins (CRABPs) or retinoid receptors. In experimental animals, it protects against the development of chemically induced tumors while showing none of the toxic effects of other retinoids. 

Hydroxyretroretinol, 4-oxoretinol, emd anhydroretinol, as well as possibly other retinoids, edso bind to and activate the RAR family of receptors at physiologiced concentrations, but do not bind to the RXR family. 4-Oxoretinol is formed from edl-trans-retinol in differentiating cells 10% to 15% of intracellular retinol may be oxidized to 4-oxoretinol during an 18-hour period, wheretis there is no formation of tJl-trans-retinoic acid or 9-c/s-retinoic acid. 

Korichneva, I. and Hammerling, U. (1999) F-actin as a functional target for retro-retinoids a potential role in anhydroretinol-triggered cell death. J. Cell Sci. 112(Pt 15), 2521-2528. 

Retinoids are readily protonated. Investigations of the mechanism of protonation of anhydroretinol (58) with anhydrous hydrogen chloride showed that very complex ionic mixtures were formed (Bulgrin and Lockhart, 1974). The retinyl carbonium ion ( = 585 nm) has been characterized in the protonation of retinol (1) (Bobrowski and Das, 1982). The color change after protonation with about 80% sulfuric acid was utilized for the quantitative determination of retinoic acid (3). The acids (51) and (52), after quenching of the red carbonium ions, were determined to be rearrangement products (Tsukida et aL, 1978a, 1980, 1981 Ito eta/., 1980). 

For practical purposes, retinol and its esters are the only naturally occurring retinoids that fluoresce appreciably under normal conditions. Anhydroretinol (A8), retinoic acid, and retinaldehyde do not fluoresce in conventional assay procedures but may do so at very low temperatures or under special conditions. The possible use of fluorescence assay for other retinoids has not been effectively explored. 

Fig. 2. HPLC analysis of neutral retinoids in tissues and plasma Samples were eluted from a reverse-phase Waters ODS column (1.2 x 10 cm) at 2 mL/min with a linear gradient of 15% water in methanol to methanol over 20 min, followed by 30 min of methanol. 1, 5,6-epoxyretinol 2, aU-trans-retinol, 3, all-/ra -retinal, 4, anhydroretinol, 5, retinyl docosahexanoate 6, retinyl palmitoleate 7, retinyl linoleate 8, retinyl palmitate and retinyl oleate, 9, retinyl stearate These specific examples illustrate the analyses of neutral-tissue retinoids equilibrated with orally fed [ HJretinol and extracted from (A) rat small-intestine mucosa (dashed line) or kidney (solid line) (B) plasma (dashed line) or liver (solid line) The concentrations of retinol and most retinyl esters in tissues and blood, however, are sufficiently large for detection by UV at 325 nm.

Retinol, retinyl esters, and retinyl ethers and the carotene phytofluene display bright yellow-green fluorescence on TLC plates or open colunms when illuminated with a long-wavelength (366-nm) mercury lamp, and anhydroretinol appears red. Other retinoids and carotenoids are not fluorescent under these conditions, and must be identified by other methods such as absorption of iodine vapor (formation of brown spots when placed in a chamber containing iodine... 

Meyer et al. analyzed plasma retinol plus endogenous aW-trans and i-cis retinoic acid isocratically by normal-phase HPLC, using hexane 2-propanol acetic acid as mobile phase (90). Extraction of the retinoic acids required acidification of the sample however, too much acid can result in dehydration of retinol to anhydroretinol, and hydrolysis of endogenous retinoyl P-glucuronide (90). A synthetic retinoid sulfonic acid was used as internal standard. By using absorbance at 350 nm, limits of detection were 1.7 nM (0.5 (ig/L) for retinoic acid isomers, 35 nM (10 Xg/L) for retinol. 13-Demethyl retinoic acid has also been used as internal standard (142). Lanvers et al. used normal-phase HPLC with gradient elution (hexane 2-propanol glacial acetic acid) to analyze 13-c/x retinoic acid, 9-cis retinoic acid, aW-trans retinoic acid, retinol, and the 4-oxo metabolites of the retinoic acid isomers (143). Plasma samples were treated with ethanol to denature proteins, and then were extracted with hexane after addition of saturated ammonium sulfate solution (pH 5). 

Interestingly a new class of intracellular messenger molecules, the retro-retinoids were recently identified [43-45]. Both the growth supportive 14-hydroxyl-retro-retinol (14-HHR) pathway and the growth suppressive anhydroretinol (AR) pathway have been described. The AR-producing enzyme ARase has been purified to homogeneity. It is not yet known whether... 

Derguini F, Nakanishi K, Buck J, Haemmerling U, Gruen F (1994) Spectroscopic studies of anhydroretinol, an endogenous mammalian and insect retro-retinoid. Angew them Int Ed Eng 33 1837-1839... 

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