Anhydroretinols

Do we know all of the special chemistry of vitamin A that is involved in its functions Retinal could form Schiff bases with protein groups as it does in the visual pigments. Redox reactions could occur. Conjugative elimination of water from retinol to form anhydroretinol is catalyzed nonenzymatically by HC1. Anhydroretinol occurs in nature and... 

Weakly adsorbed Anhydroretinol retinyl esters /3-carotene phylloquinone... 

The initial stages of the reaction between anhydroretinol (112) and anhydrous HC1 in 1,2-dichloroethane have been studied by stopped-flow spectrophotometry, and a five-step mechanism has been proposed, involving two carbonium ions, with the anhydroretinylic cation (113) forming much more rapidly than the more stable retinylic cation (114) of which it may be a precursor.51... 

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. 

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). 

Some of the retroretinoids also have cell signaling functions at a cell surface or a cytoplasmic receptor. 14-Hydroxyretroretinol is required for lymphocyte proliferation, whereas anhydroretinol is a growth inhibitor the two compounds act antagonistically. Treatment of T lymphocytes with anhydroretinol in the absence of 14-hydroxyretroretinol leads to rapid cell death. 

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. 

It is only in the last few years that researchers have tackled this difficult problem and the rapidity of these interactions have imposed the use of stt -flow tedmiques. The system hydrogen chloride-anhydroretinol-l,2-dichloroethane at roan temperature was examined spectroscopically by Bulgrin and Lookhart with a fairly fast... 

Stop-flow apparatus. The acid concentrations were around 10 M and those of anhydroretinol about ten times smaller. In the first second or so, after the mixing of the reactants the following processes gave rise to the carbocation precursors ... 

Unlike many retinol dehydrogenases, the enzyme that catalyzes the conversion of retinol to anhydroretinol, retinol dehydratase, does not use CRBP-retinol as a substrate rather, it uses free retinol (49-51). However, the enzyme responsible for biosynthesis of 14-hydroxy-4,14-retro-retinol has not yet been isolated. 

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. 

The kinetics of the reaction of retinol or retinyl acetate with HCl in acetone, to produce re/ro-anhydroretinol (176), have been studied. ... 

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. 

Retinaldehyde, retinoic acid, and anhydroretinol (A8) are much more stable under conventional conditions of mass spectrometry. In all cases, the molecular... 

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