Retinoid retinol

The successful synthesis of (all- )-retinoic acid (3) was reported by Arens and van Dorp (van Dorp and Arens, 1946) in 1946, but almost 10 years passed before Robeson et aL (1955a) were able to prepare 13-cw-retinoic acid (17). Between 1946 and 1956, a large number of papers were published on successful syntheses of the natural C20 retinoids retinol (1), retinaldehyde (2), and retinoic acid (3), and nine industrial processes for the synthesis of vitamin A were developed during this period (Isler, 1979). 

The applications surveyed in Tables 4 through 9 illustrate the general principles of vitamin E assays outlined in I.E. 1. Specifically, each matrix puts a different emphasis on the E vitamers to be determined. Thus, in serum/plasma a-tocoph-erol is clearly the main compound of interest. Accordingly, leversed-phase chromatography with UV detection is the indicated technique for this purpose. In addition, as part of the assessment of the antioxidant status of humans, tocopher-ols are determined concurrently with retinoids (retinol, retinyl palmitate) and carotenoids (particularly p-carotene). a-Tocopherol is also the principal target compound in erythrocytes and platelets but here, predictably, the quantitation of a-tocopherolquinone may also be meaningful as an indicator of oxidative stress (7). The need to assay this minor constituent in turn justifies coulometric detection. The analysis of tissues is complementary to that of plasma and red blood cells and mainly concerns the determination of a-tocopherol as well as retinoids, carotenoids, and ubiquinones (Table 6). 

Vitamin A-active compounds [1] are present in foods of animal origin as retinoids (retinol, retinyl esters, retinylaldehyde, retinoic acid) and in those of plant origin as carotenoids (only carotenoids with one unsubstituted P-ionone ring and with an 11-carbon polyene chain at least are provitamins A). Retinyl palmitate is the main form used as a food supplement [4]. 

When considering chemical peelings we are only interested in the natural retinoids - retinol, all-trans retinal and retinoic acid - the last two of which are useful in strong concentrations as peeling agents used under medical supervision. 

Because of the presence of an extended polyene chain, the chemical and physical properties of the retinoids and carotenoids are dominated by this feature. Vitamin A and related substances are yellow compounds which are unstable in the presence of oxygen and light. This decay can be accelerated by heat and trace metals. Retinol is stable to base but is subject to acid-cataly2ed dehydration in the presence of dilute acids to yield anhydrovitamin A [1224-18-8] (16). Retro-vitamin A [16729-22-9] (17) is obtained by treatment of retinol in the presence of concentrated hydrobromic acid. In the case of retinoic acid and retinal, reisomerization is possible after conversion to appropriate derivatives such as the acid chloride or the hydroquinone adduct. Table 1 Hsts the physical properties of -carotene [7235-40-7] and vitamin A. 

More specific methods involve chromatographic separation of the retinoids and carotenoids followed by an appropriate detection method. This subject has been reviewed (57). Typically, hplc techniques are used and are coupled with detection by uv. For the retinoids, fluorescent detection is possible and picogram quantities of retinol in plasma have been measured (58—62). These techniques are particularly powerful for the separation of isomers. Owing to the thermal lability of these compounds, gc methods have also been used but to a lesser extent. Recently, the utiUty of cool-on-column injection methods for these materials has been demonstrated (63). 

The specific role of vitamin A in tissue differentiation has been an active area of research. The current thinking, developed in 1979, involves initial dehvery of retinol by holo-B >V (retinol-binding protein) to the cell cytosol (66). Retinol is then ultimately oxidized to retinoic acid and binds to a specific cellular retinoid-binding protein and is transported to the nucleus. Retinoic acid is then transferred to a nuclear retinoic acid receptor (RAR), which enhances the expression of a specific region of the genome. Transcription occurs and new proteins appear during the retinoic acid-induced differentiation of cells (56). 

Retinoids Vitamin A Carotinoids Retinylesters Retinol Retinal Retinoic acid Vitamin A acid... 

Vitamin A (retinol) and its naturally occurring and synthetic derivatives, collectively referred to as retinoids (chemical structure), exert a wide variety of profound effects in apoptosis, embryogenesis, reproduction, vision, and regulation of inflammation, growth, and differentiation of normal and neoplastic cells in vertebrates. 

Retinoids are alcohols and accordingly soluble in ethanol, isopropanol, and polyethylenglycol. Major sources of natural retinoids are animal fats, fish liver oil (retinylesters) and yellow and green vegetables (carotenoids). Ingested retinylesters (RE) are hydrolyzed to retinol by enteral hydrolases in the intestine. ROL and carotenoids are absorbed by intestinal mucosa cells. 

The known beneficial effects of retinoids on malignancies are assumed to relate to retinoid receptor-mediated antipromoting and anti-initiating effects. The latter appeals to be influenced by interference of several xenobiotics with different steps of the retinoid metabolism in the target cell. Of the carotenoids, (3-carotene is the most potent retinol precursor, yet being... 

Ethanol also inhibits ADH-catalyzed retinol oxidation in vitro, and ethanol treatment of mouse embtyos has been demonstrated to reduce endogenous RA levels. The inhibition of cytosolic RolDH activity and stimulation of microsomal RolDH activity could explain ethanol-mediated vitamin A depletion, separate from ADH isoenzymes. Although the exact mechanism of inhibition of retinoid metabolism by ethanol is unclear, these observations are consistent with the finding that patients with alcoholic liver disease have depletedhepatic vitamin A reserves [review see [2]. 

Use of topical retinoids (tretinoin, tazaro-tene, retinol formulations) for 2-6 weeks prior... 

Use of topical retinoids (tretinoin, tazaro-tene, retinol formulations) for 2 to 6 weeks prior to peeling thins the stratum cornemn, reduces the content of epidermal melanin, and expedites epidermal healing. Retinoids also enhance the penetration of the peeling agent. They should be discontinued several days prior to the peeling procedure. Retinoids can be resumed post-operatively after all evidence of... 

Broad spectrmn sunscreens Retinoids Tretinoin Tazarotene Retinol... 

Kang S, Duell EA, Fisher GJ, et al (1995) Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation. J Invest Dermatol 105 549-556... 

Vitamin A (retinol) and retinoic acid are carotenoid oxidation compounds that are very important for human health. The main functions of retinoids relate to vision and cellular differentiation. With the exception of retinoids, it was only about 10 years ago that other carotenoid oxidation products were first thought to possibly exert biological effects in humans and were implicated in the prevention - or promotion of degenerative diseases. A review on this subject was recently published. ... 

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