Retinol vitamin A and

Transthyretin (TTR) A protein complex found in blood that binds both retinol (vitamin A) and thyroxine. 

Zachman, R. D. (1989). Retinol (vitamin A) and the neonate Special problems of the human premature infant. Am. J. Clin. Nutr. 50, 413-424. 

VITAMIN A. This substance also has been referred to as retinol, axerophthol, biosterol, vitamin Ai, anti-xerophthalmic vitamin, and anti-infective vitamin. The physiological forms of the vitamin include Retinol (vitamin A ) and esters 3-dehydroretinol (vitamin A2) and esters 3-dehydroretinal (retinme-2) retinoic acid neovitamin A neo-b-vitamin Ai. The vitamin is required by numerous animal species. All vertebrates and some invertebrates convert plant dietary carotenoids in gut to vitamin Ai. which is absorbed. Most animal species store appreciable amounts... 

B Stancher, F Zonta. High-performance liquid chromatography of the unsaponifiable from samples of marine and freshwater fish fractionation and identification of retinol (vitamin A)) and dehydroretinol (vitamin A2) isomers. J Chromat 287 353-364, 1984. 

Other antioxidant species are synthesized by cells like uric acid, ubiquinol or thiols (cystein, homocystein, etc.). In addition, many compounds found in food display antioxidant properties retinol (vitamin A) and its precursor /(-carotene, and polyphenols (flavonoids, etc.). Figure 8.2 shows the apparent standard potential of some LMWA and ROS explaining the spontaneous oxido-reduction reactions at the origin of the antioxidant protection system. 

Small proteins in the mucus surrounding the sensory epithelial cells bind the odorants and bring them across the mucus to the receptor. These odorant-binding proteins (OBPs) have been cloned and identified (the binding proteins for retinol (vitamin A) and cholesterol belong to the same family). The OBPs function as carriers of small lipophilic compounds. Terrestrial animals, in contrast to aquatic animals, can only smell volatile, lipophilic odorants. 

Retinoic acid, an endogenous retinoid, is an oxidized metabolite of retinol (vitamin A), and the most potent known inducer of differentiation in vitro (17-191. It is, therefore, most likely the form of vitamin A which promotes normal cellular differentiation. Because cancer is fundamentally a loss of cellular differentiation, physiological concentrations of retinoic acid may play an important role in the etiology of cancer. 

Separation of tocopherols from other fat-soluble vitamins. a-TocopheroI can be readily resolved by TLC on silica gel or alumina from other fat-soluble vitamins (61). On silica gel, it migrates ahead of the D vitamins but more slowly than retinol (vitamin A) and phylloquinone (vitamin K]). The differentiation of the free tocopherol and its acetate and succinate esters, which are frequently used in pharmaceutical preparations, is also straightforward (61). 

Lera and coworkers successfully employed this thallium(i) hydroxide-aecelerated Suzuki reaction in the stereocontrolled polyene syntheses of retinol (vitamin A) and derivatives and polyenic alarm pheromones of cephalaspidean molluscs navenone A and haminol Despite some initial examples where thallium(i) ethoxide failed as an alternative for thallium(i) hydroxide there are an appreciable number of cases where thallium(i) ethoxide furnished great results. The first successful use of thallium(i) ethoxide was reported by Chamberlin and coworkers in the total synthesis of microcystin LA, a serine-threonine phosphatase inhibitor (Scheme 20.17). A few years after the synthesis of mieroeystin L, Roush and coworkers extended the use of thallium(i) ethoxide in Suzuki couplings for a range of boronic acids and halides. Simultaneously, Danishefslq and Chemler ... 

SW McClean, ME Ruddel, EG Gross, JJ DeGiovanna, GL Peck. Liquid-chromato-graphic assay for retinol (vitamin A) and retinol analogs in therapeutic trials. Clin Chem 28 693-696, 1982. 

Humans do not have the ability to synthesize retinol (vitamin A) and have thus evolved to derive this compound from the diet, either directly as preformed retinol from foods of animal origin or from the metabohsm of carotenoids primarily derived from plant tissues. Several hundred carotenoids have been isolated, named and their structures elucidated, but only a few have a known biochemical role in human metabolism or are present in the diet in sufficient quantities to be detected in plasma (Khachik et al. 1992). The chemical... 

Vitamins (see Section 8.6), often added to cosmetic formulations, act as antioxidant preservatives due to their general antioxidant properties towards free radicals. Examples are retinol (vitamin A) and its precursor j5-carotene, tocopherol (vitamin E) and ascorbic acid (vitamin C). Moreover, vitamin derivatives, such as retinyl acetate, retinyl palmitate, ascorbyl palmitate, magnesium ascorbyl phosphate and tocopheryl acetate among others, are also employed as antioxidant agents. 

A variety of lipid molecules take part in diverse aspects of metabolism and its control. Polyunsaturated fatty acids and their metabolites have been discussed above. Others are the fat-soluble vitamins, retinol (vitamin A) and tocopherol (vitamin E) (Chapters 5 and 8). Sterols, such as cholesterol, regulate membrane function and act as precursors for a range of molecules with diverse metabolic activities cholecalciferol (vitamin D), which is metabolized further to hydroxylated derivatives that regulate calcium metabolism and other aspects of cellular function (Chapters 5 and 7) bile acids, which are involved in lipid absorption (Chapters 4 and 7) and steroid hormones (Chapter 7). 

The stmcture of vitamin A [11103-57-4] and some of the important derivatives are shown in Figure 1. The parent stmcture is aH-Zra/ j -retinol [68-26-8] and its lUPAC name is (all-E)-3,7-dimethyl-9-(2,6,6-trimethyl-l-cyclohexen-l-yl)-2,4,6,8-nonatetraen-l-ol (1). The numbering system for vitamin A derivatives parallels the system used for the carotenoids. In older Hterature, vitamin A compounds are named as derivatives of trimethyl cyclohexene and the side chain is named as a substituent. For retinoic acid derivatives, the carboxyl group is denoted as C-1 and the trimethyl cyclohexane ring as a substituent on C-9. The stmctures of vitamin A and -carotene were elucidated by Karrer in 1930 and several derivatives of the vitamin were prepared by this group (5,6). In 1935, Wald isolated a substance found in the visual pigments of the eye and was able to show that this material was identical with Karrer s retinaldehyde [116-31-4] (5) (7). 

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).

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. 

Biological, spectroscopic, and chromatographic methods have been used to assay vitamin A and the carotenoids. Biological methods have traditionally been based on the growth response of vitamin A—deficient rats. The utiUty and shortcomings of this test have been reviewed (52,53). This test has found apphcabiUty for analogues of retinol (54,55). Carotenoids that function as provitamin A precursors can also be assayed by this test (56). 

It is assumed that in order to have vitamin A activity a molecule must have essentially one-half of its structure similar to that of (i-carotene with an added molecule of water at the end of the lateral polyene chain. Thus, P-carotene is a potent provitamin A to which 100% activity is assigned. An unsubstituted p ring with a Cii polyene chain is the minimum requirement for vitamin A activity. y-Car-otene, a-carotene, P-cryptoxanthin, a-cryptoxanthin, and P-carotene-5,6-epoxide aU have single unsubstimted rings. Recently it has been shown that astaxanthin can be converted to zeaxanthin in trout if the fish has sufficient vitamin A. Vitiated astaxanthin was converted to retinol in strips of duodenum or inverted sacks of trout intestines. Astaxanthin, canthaxanthin, and zeaxanthin can be converted to vitamin A and A2 in guppies. ... 

Honkanen, R.D., Kontinnen, Y.T. and Mussalo-Rauhamaa, H. (1989). Vitamins A and E, retinol binding protein and zinc in rheumatoid arthritis. Clin. Exp. Rheum. 7, 465-469. 

Carotene (all-trans), (3-cryptoxanthin (all-trans and -cis), zeaxanthin (all-trans), luteoxanthin isomers, violaxanthin (all-trans and -cis), and neoxanthin (all-trans and -cis) were identified in several mango cultivars (Mercadante and others 1997 Ornelas-Paz and others 2007, 2008). Mango retinol was found to be highly bioavail-able by estimating vitamin A and carotene reserves in the liver and plasma of rats. Information on the tocopherol content in mango is very scarce, but it seems to be low (Burns and others 2003 Ornelas-Paz and others 2007). 

While the human body can remove an excess of any water-soluble vitamin, excesses of fat-soluble vitamins are more serious. Early arctic explorers discovered that the Inuit regarded seal liver and polar bear liver as taboo and must not be eaten. Those explorers who ignored this advice risked retinol poisoning as the livers of both these species are rich in retinol (vitamin A) that can not be excreted. The effects of retinol poisoning are extremely unpleasant. It is for this reason that fortification with fat-soluble vitamins is not likely to be undertaken. 

T.W. Knight and A.F. Death, Effects of oral and injected vitamin A (retinol) supplements on liver vitamin A and plasma carotenoid and cholesterol concentrations in cattle. Animal Sci. 69 (1999) 607-612. 

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. 

Recently we published data that even in countries with excellent food sources and availability, insufficient vitamin A supply will occur (Schulz et ah, 2007). The aim of this trial was to analyze vitamin A and p-carotene status and investigate the contribution of nutrition to vitamin A and p-carotene supply in mother-infant pairs of multiparous births or births within short birth rates. Twenty-nine volimteers aged between 21 and 36 years were evaluated for 48 hours after delivery. In order to establish overall supply, retinol and p-carotene were determined in maternal plasma, cord blood, and colostrum via HPLC analysis. A food frequency protocol was obtained from all participants. Regardless of the high-to-moderate socioeconomic background, 27.6% of participants showed plasma retinol levels below 1.4 pmol/liter, which can be taken as borderline deficiency. In addition, 46.4% showed retinol intake <66% of RDA and 50.0% did not consume liver at all, although liver contributes as a main source for preformed retinol. Despite a high total carotenoid intake of 6.9 3.9mg/day, 20.7% of mothers showed plasma levels <0.5 pmol/liter p-carotene. 

Retinol and p-carotene levels were highly significant correlated between maternal plasma versus cord blood and colostrum. In addition, significantly lower levels were found in cord blood [31.2 13% (retinol), 4.1 1.4% (p-carotene)] compared with maternal plasma. Despite the fact that vitamin A- and p-carotene-rich food is generally available, in contrast to developing countries, risk groups for low vitamin A supply indeed exist in the western world. 

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). 

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). 

Chabardes developed a process for the preparation of vitamin A and its intermediates, from cyclogeranylsulfone and Cio aldehyde-acetals [30]. For example, chlorocitral reacted with ethylene glycol, HC(OMe)3 and pyridinium tosylate to provide the chloroacetal (40%), as a mixture of two isomers. Reaction of this allylchloride with A-methylmorpholine oxide (NMO) and Nal furnished the aldehyde, as a mixture of four isomers. These compounds underwent condensation with P-cyclogeranylsulfone. Further chlorination of the sulfone-alkoxide salts, led to a mixture of sulfone-chloride acetals and their products of hydrolysis in 45-50% yield. Double elimination of the chloride and the sulfone, followed by hydrolysis with pyridinium tosylate (PPTS) gave retinal, as a mixture of all E and 13Z isomers (78/22). The overall yield from the chloroacetal was 18%. In another one-pot example, retinal was obtained in 52% yield from the aldehyde, and was then isomerised and reduced to retinol (all E 95.5, 13Z 4, 9Z 0.5) Fig. (8). 

The concentration of vitamin A and carotenoids in milk is strongly influenced by the carotenoid content of the feed. Milk from animals fed on pasture contains higher levels of carotenes than that from animals fed on concentrate feeds. There is also a large seasonal variation in vitamin A concentration summer milk contains an average of 62 fig retinol and 31 fig carotene per 100 g while the values for winter milk are 41 and 11 fig per... 

The stability of some vitamins is influenced by aw. In general, the stability of retinol (vitamin A), thiamin (vitamin Bj) and riboflavin (vitamin B2) decreases with increasing aw. At low av (below 0.40), metal ions do not have a catalytic effect on the destruction of ascorbic acid. The rate of loss of ascorbic acid increases exponentially as aw increases. The photodegradation of riboflavin (Chapter 6) is also accelerated by increasing aw. 

The retinoids, a family of molecules that are related to retinol (vitamin A), are essential for vision, reproduction, growth, and maintenance of epithelial tissues. Retinoic acid, derived from oxidation of dietary retinol, mediates most of the actions of the retinoids, except for vision, which depends on retinal, the aldehyde derivative of retinol. 

Absorption, transport, and storage of vitamin A and its derivatives. RBP = retinol-binding protein. 

---