Retinyl vitamin

Fig. 1. Vitamin A and derivatives retinol (1), retinyl acetate [127-47-9] (2), retinyl palmitate [79-81-2] (3), and retinyl propionate [7069-42-3] (4).

Spectroscopic methods such as uv and fluorescence have rehed on the polyene chromophore of vitamin A as a basis for analysis. Indirectly, the classical Carr-Price colorimetric test also exploits this feature and measures the amount of a transient blue complex at 620 nm which is formed when vitamin A is dehydrated in the presence of Lewis acids. For uv measurements of retinol, retinyl acetate, and retinyl palmitate, analysis is done at 325 nm. More sensitive measurements can be obtained by fluorescence. Excitation is done at 325 nm and emission at 470 nm. Although useful, all of these methods suffer from the fact that the method is not specific and any compound which has spectral characteristics similar to vitamin A will assay like the vitamin... 

Retinyl acetate [127-47-9] M 328.5, m 57". Separated from retinol by column chromatography, then crystd from MeOH. See Kofler and Rubin [Vitamins and Hormones (NY) 18 315 1960] for review of purification methods. Stored in the dark, under N2 or Ar, at 0°. See Vitamin A acetate p. 574 in Chapter 6. 

Retinal (Vitamin A aldehyde). Retinoic acid (Vitamin A acid), Retinyl acetate, Retinyl palmitate see entries in Chapter 4. 

Retinoids are needed for cellular differentiation and skin growth. Some retinoids even exert a prophylactic effect on preneoplastic and malignant skin lesions. Fenretlnide (54) is somewhat more selective and less toxic than retinyl acetate (vitamin A acetate) for this purpose. It is synthesized by reaction of all trans-retinoic acid (53), via its acid chloride, with g-aminophe-nol to give ester 54 (13). 

Figure 10.9 Cliromatogi ams of foitified coconut oil obtained by using (a) normal-phase HPLC and (b) GPC/noimal-phase HPLC. Peak identification is as follows 1 (a,b), DL-a-toco-pheryl acetate, 2 (b), 2,6-di-tert-butyl-4-methylphenol 2 (a) and 3 (b), retinyl acetate 3 (a) and 4 (b), tocol 4 (a) and 5 (b), ergocalciferol. Reprinted from Analytical Chemistry, 60, J. M. Brown-Thomas et al., Determination of fat-soluble vitamins in oil matrices by multidimensional liigh-peiformance liquid cliromatography , pp. 1929-1933, copyright 1988, with permission from the American Chemical Society.

Vitamin A describes a group of substances (retinol, retinyl esters, and retinal) with defined biological... 

The a-tocopherol, P-carotene (ATBC) Cancer Prevention study was a randomised-controlled trial that tested the effects of daily doses of either 50 mg (50 lU) vitamin E (all-racemic a-tocopherol acetate), or 20 mg of P-carotene, or both with that of a placebo, in a population of more than 29,000 male smokers for 5-8 years. No reduction in lung cancer or major coronary events was observed with any of the treatments. What was more startling was the unexpected increases in risk of death from lung cancer and ischemic heart disease with P-carotene supplementation (ATBC Cancer Prevention Study Group, 1994). Increases in the risk of both lung cancer and cardiovascular disease mortality were also observed in the P-carotene and Retinol Efficacy Trial (CARET), which tested the effects of combined treatment with 30 mg/d P-carotene and retinyl pahnitate (25,000 lU/d) in 18,000 men and women with a history of cigarette smoking or occupational exposure to asbestos (Hennekens et al, 1996). 

In intestinal cells, carotenoids can be incorporated into CMs as intact molecules or metabolized into mainly retinol (or vitamin A), but also in retinoic acid and apoc-arotenals (see below for carotenoid cleavage reactions). These polar metabolites are directly secreted into the blood stream via the portal vein (Figure 3.2.2). Within intestinal cells, retinol can be also esterified into retinyl esters. 

Both intact carotenoids and their apolar metabolites (retinyl esters) are secreted into the lymphatic system associated with CMs. In the blood circulation, CM particles undergo lipolysis, catalyzed by a lipoprotein lipase, resulting in the formation of CM remnants that are quickly taken up by the liver. In the liver, the remnant-associated carotenoid can be either (1) metabolized into vitamin A and other metabolites, (2) stored, (3) secreted with the bile, or (4) repackaged and released with VLDL particles. In the bloodstream, VLDLs are transformed to LDLs, and then HDLs by delipidation and the carotenoids associated with the lipoprotein particles are finally distributed to extrahepatic tissues (Figure 3.2.2). Time-course studies focusing on carotenoid appearances in different lipoprotein fractions after ingestion showed that CM carotenoid levels peak early (4 to 8 hr) whereas LDL and HDL carotenoid levels reach peaks later (16 to 24 hr). 

Tanumihardjo, S. A., H. C. Furr, O. Amedee-Manesme, and J. A. Olson. 1990. Retinyl ester (vitamin A ester) and carotenoid composition in human liver. Int. J. Vitam. Nutr. Res. 60 307-313. 

Vitamin A deficiency affects more than 100 million children around the world (Miller and others 2002) and thus remains an important public health problem in many countries. Vitamin A is essential for vision, reproduction, growth, immune function, and general health of humans (van Lieshout and others 2001). The major sources of vitamin A in the human diet are retinyl esters (preformed vitamin A) found in foods of animal origin and provitamin A carotenoids from fruits and vegetables. Unfortunately, foods containing preformed vitamin A (meat, milk, eggs, etc.) are frequently too expensive for some economically deprived developing countries, and therefore dietary carotenoids are the main source of vitamin A in these countries. 

This method is also used to measure ex vivo low-density lipoprotein (LDL) oxidation. LDL is isolated fresh from blood samples, oxidation is initiated by Cu(II) or AAPH, and peroxidation of the lipid components is followed at 234 nm for conjugated dienes (Prior and others 2005). In this specific case the procedure can be used to assess the interaction of certain antioxidant compounds, such as vitamin E, carotenoids, and retinyl stearate, exerting a protective effect on LDL (Esterbauer and others 1989). Hence, Viana and others (1996) studied the in vitro antioxidative effects of an extract rich in flavonoids. Similarly, Pearson and others (1999) assessed the ability of compounds in apple juices and extracts from fresh apple to protect LDL. Wang and Goodman (1999) examined the antioxidant properties of 26 common dietary phenolic agents in an ex vivo LDL oxidation model. Salleh and others (2002) screened 12 edible plant extracts rich in polyphenols for their potential to inhibit oxidation of LDL in vitro. Gongalves and others (2004) observed that phenolic extracts from cherry inhibited LDL oxidation in vitro in a dose-dependent manner. Yildirin and others (2007) demonstrated that grapes inhibited oxidation of human LDL at a level comparable to wine. Coinu and others (2007) studied the antioxidant properties of extracts obtained from artichoke leaves and outer bracts measured on human oxidized LDL. Milde and others (2007) showed that many phenolics, as well as carotenoids, enhance resistance to LDL oxidation. 

Mercier, M., G. Pascal, and V. Azais-Braesco. 1990. Retinyl ester hydrolase and Vitamin A status in rats treated with 3,3, 4,4 -tetrachlorobiphenyl. Biochim. Biophys. Acta 1047 70-76. 

The overall metabolism of vitamin A in the body is regulated by esterases. Dietary retinyl esters are hydrolyzed enzymatically in the intestinal lumen, and free retinol enters the enterocyte, where it is re-esterified. The resulting esters are then packed into chylomicrons delivered via the lymphatic system to the liver, where they are again hydrolyzed and re-esterified for storage. Prior to mobilization from the liver, the retinyl esters are hydrolyzed, and free retinol is complexed with the retinol-binding protein for secretion from the liver [101]. Different esterases are involved in this sequence. Hydrolysis of dietary retinyl esters in the lumen is catalyzed by pancreatic sterol esterase (steryl-ester acylhydrolase, cholesterol esterase, EC 3.1.1.13) [102], A bile salt independent retinyl-palmitate esterase (EC 3.1.1.21) located in the liver cell plasma hydrolyzes retinyl esters delivered to the liver by chylomicrons. Another neutral retinyl ester hydrolase has been found in the nuclear and cytosolic fractions of liver homogenates. This enzyme is stimulated by bile salts and has properties nearly identical to those observed for... 

J. Boehnlein, A. Sakr, J. L. Lichtin, R. L. Bronaugh, Characterization of Esterase and Alcohol Dehydrogenase Activity in Skin. Metabolism of Retinyl Palmitate to Retinol (Vitamin A) During Percutaneous Absorption , Pharm. Res. 1994, 11, 1155-1159. 

Ye, L. Landen, W. O. Eitenmiller, R. R. Liquid Chromatographic Analysis of All-trans-Retinyf Pafmitate, P-Carotene, and Vitamin E in Fortified Foods and the Extraction of Encapsulated and Nonencapsulated Retinyl Pafmitate. J. Agric. Food Chem. 2000, 48, 4003-4008. 

These results show that retinyl esters in respiratory epithelium and in alveolar cells form a pool of vitamin A, which can be used physiologically by the tissue. The formation of retinol and at least RA from retinyl esters is strictly controlled. So far an unphysiological formation of RA and a subsequent toxicity seems not possible. Retinyl esters, however, are biochemically inert with respect to gene expression or vitamin A activity as long as they are not hydrolyzed. Consequently, the inhalative application, especially in cases of insufficient lung development, could represent a true alternative. The oral contribution is hardly successful because of the poor RBP s)mthesis of the liver and the lack of availability of a parenteral solution is currently not available. 

The obtained results confirm earlier findings where vitamin A-deficient rats were used to prove the uptake of retinyl esters into lung, liver, kidney, and plasma after inhalation thereof (Biesalski, 1996). However, long-term topical administration of high vitamin A concentrations is a well-established therapy in atrophic rhinitis, rhinitis sicca, and metaplastic changes in the nasal or ocular epithelium (Deshpande et ah, 1997 Simm, 1980). The application leads to the normalization of mucous membranes and reappearance of a normal function with no side effects. 

Biesalski, H. K., and Weiser, FI. (1990). Microdetermination of retinyl esters in Guinea pig tissues under different vitamin A-status conditions. Micronutr. Anal. 7, 97-116. 

Biesalski, H. K., Reifen, R., Ftirst, P., and Edris, M. (1999). Retinyl palmitate supplementation by inhalation of an aerosol improves vitamin A status of preschool children in Gondar (Ethiopia). Br.. Nutr. 82,179-182. 

Gerlach, T., Biesalski, H. K., Weiser, H., Haeussermann, B., and Baessler, K. H. (1989). Vitamin A in parenteral nutrition Uptake and distribution of retinyl esters after intravenous application. Am. ]. Clin. Nutr. 50,1029-1038. 

Sobeck, U., Fischer, A., and Biesalski, H. K. (2003). Uptake of vitamin A in buccal mucosal cells after topical application of retinyl palmitate A randomised, placebo-controlled and double-blind trial. Br. J. Nutr. 90, 69-74. 

This class includes both vitamin A and the provitamin A carotenoids. All the compounds related to all-trani-retinol (Figure 19.11) are known as vitamin A. These compounds, together with their metabolites and synthetic derivatives, exhibiting the same properties are called retinoids. Vitamin A is found in animal products as retinyl esters (mainly palmitate). 

In the body retinol can also be made from the vitamin precursor carotene. Vegetables like carrots, broccoli, spinach and sweet potatoes are rich sources of carotene. Conversion to retinol can take place in the intestine after which retinyl esters are formed by esterifying retinol to long chain fats. These are then absorbed into chylomicrons. Some of the absorbed vitamin A is transported by chylomicrons to extra-hepatic tissues but most goes to the liver where the vitamin is stored as retinyl palmitate in stellate cells. Vitamin A is released from the liver coupled to the retinol-binding protein in plasma. 

Vitamin A absorption from the small intestine requires dietary fat and pancreatic lipase to break down retinyl esters and bile salts to promote the uptake of retinol and carotene. Drugs, such as mineral oil, neomycin and cholestyramine, that can modify lipid absorption from the gastrointestinal tract can impair vitamin A absorption. The use of oral contraceptives can signihcantly increase plasma vitamin A levels. 

Some conversion into the anhydrovitamin (112) occurs during silica gel t.l.c. of retinyl palmitate in non-polar solvents. Some new colour reactions of vitamin A are reported to be better than the Carr-Price reaction. The kinetics and mechanism of acid-catalysed isomerization of retinyl acetate into the trans-retro-derivative (113) have been studied. Oppenauer oxidation of kitol (39) results in specific cyclopentanol-cyclopentanone oxidation. ... 

Retinol (vitamin A) is found in foods of mammalian origin in the form of retinyl ester, or in fruits and vegetables as carotenoids with provitamin A activity, especially P-carotene (provitamin A). In enterocytes, retinol binds to cellular retinol-binding protein type II (CRBPII), which directs the esterification by the enzyme lecithin retinol acyltransferase (LRAT). 

They also developed a second process via other dihalo-compounds [36]. Treatment of the 1,2-bromo-hydroxy chain with TiCl4 in DME, gave mainly the l-bromo-4-chloro unit. Condensation with the Ci0 sulfone in DMF, in the presence of /BuOK gave the retinyl-sulfoneacetate. Elimination of the tolylsulfmate with KOH in DMF produced vitamin A acetate in 87% yield, Fig. (14). 

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