Disease relevance of Anhydro-retinol

• Further chemical studies revealed that retinol was locally deficient in the hepatomas but not in adjacent normal livers: In particular, anhydroretinol was newly detected in the tumors of spontaneous hepatoma-bearing mice, suggesting increased conversion of retinol into the inactive metabolite [1].
• Thus, anhydroretinol, at non-toxic levels, was effective as a preventive agent in this experimental model of breast cancer [2].

High impact information on Anhydro-retinol

• What further distinguishes the AR-induced form of apoptosis from classical ones is a lack of requirements of messenger RNA and protein synthesis, suggesting that the events leading to cell death are primarily initiated and play themselves out in the cytoplasm [3].
• We now provide evidence that when AR is given to T cells unmitigated by 14-HRR, rapid cell death can occur [3].
• The retro-retinoid, anhydroretinol (AR), has long been known to act as a growth inhibitor in lymphocytes, whereas 14-hydroxy-4,14-retro-retinol (14-HRR) is required for normal lymphocyte proliferation [3].
• Site-directed mutations demonstrate that this inserted lid is necessary for anhydroretinol production but not for sulfonation; thus, insertion of a helical lid can convert a sulfotransferase into a dehydratase [4].
• Anhydroretinol induces oxidative stress and cell death [5].

Biological context of Anhydro-retinol

• Hydrolysis with mild alkali yields anhydroretinol, as it does for synthetic retinyl phosphate, with absorption maxima at 388, 368, and 346 nm [6].
• Anhydroretinol (AR), a known antagonist, which works by displacing retinol from the common binding sites on serine/threonine kinases, also caused mitochondrial membrane depolarization [7].
• Teratogenicity, tissue distribution, and metabolism of the retro-retinoids, 14-hydroxy-4,14-retro-retinol and anhydroretinol, in the C57BL/6J mouse [8].
• Photochemical oxidation of retinal palmitate generates anhydroretinol, an intracellular signaling retinoid in the signal transduction cascade from the plasma membrane that causes apoptosis by generating reactive oxygen intermediates [9].

Anatomical context of Anhydro-retinol

• Anhydroretinol: a naturally occurring inhibitor of lymphocyte physiology [10].
• The circumstances are closely related to nonclassical forms of apoptosis: within 2 h of AR administration the T cells undergo widespread morphological changes, notably surface blebbing and ballooning and, inevitably, bursting [3].
• Formalin-fixed fibroblasts or cultured intestinal mucosal cells did not convert retinol into anhydroretinol [11].
• Subsequent incubation of Ret-P-Man-loaded membranes at 37 degrees C results in a non-enzymic breakdown of Ret-P-Man to beta-mannopyranosyl phosphate and anhydroretinol [12].
• Moreover incubation of metabolite-310 with the 3T12 microsomes yielded anhydroretinol (40% conversion in 30 minutes), suggesting that metabolite-310 is an intermediate in the synthesis of anhydroretinol by these cells [11].

Associations of Anhydro-retinol with other chemical compounds

• Spodoptera frugiperda retinol dehydratase catalyzes the conversion of retinol to the retro-retinoid anhydroretinol [13].
• Rapid preparation of anhydroretinol and its use as an internal standard in determination of liver total vitamin A by high-performance liquid chromatography [14].

Gene context of Anhydro-retinol

• Retinoids modulated these oxidation events directly: retinol enhanced, whereas AR suppressed, zinc release, precisely mirroring the retinoid effects on c-Raf kinase activation [15].
• These results demonstrate that Ret-P-Man synthesized in vitro is subject to non-enzymic breakdown to beta-mannopyranosyl phosphate and anhydroretinol and that the GDP-mannose:retinyl phosphate mannosyltransferase reaction is reversible [12].
• Favorable conditions for the GC/MS assay of anhydroretinol in the EI mode were defined [16].
• As determined by in vitro tests, anhydroretinol, a metabolic product of retinol, was bound specifically by serum retinol-binding protein and by cellular retinol-binding protein but not by cellular retinoic acid-binding protein or the nuclear receptors, RARs and RXRs [2].

References