Trans-Retinol vitamin

Carotene is an isoprenoid found abundantly in carrots that is an accessory photosynthetic pigment and a precursor of all-trans-retinol (Vitamin A) (Figure 19.25). 

Fig. 1. Absorption spectra of a -trans retinol (vitamin A] alcohol, trans 3,4-didehydroretinol (vitamin A2 alcohol, ) in methanol...

The parent vitamin A compound, retinol, has the empirical formula C2oH3oO and a molecular weight (MW) of 286.44. The molecule comprises a cyclohexenyl (/3-ionone) ring attached at the carbon-6 (C-6) position to a polyene side chain whose four double bonds give rise to cis-trans (geometric) isomerism. The predominant isomer, all-trans-retinol (Fig. 1), possesses maximal (100%) vitamin A activity and is frequently accompanied in natural foodstuffs by smaller amounts of 13-ds-retinol, which exhibits 75% relative activity in the rat (6). Other cis isomers of retinol also occur in nature, but they are of low potency, and their contribution to the total vita-... 

Vitamin A (trans-retinol) is called an isoprenoid alcohol because it consists, in part, of units of a single five-carbon compound called isoprene ... 

FIGURE 29.4 Chemical structure of vitamin A (all-trans retinol, (a//- )-3,7-dimethyl-9-(2,6,6-trimethyl-l-cyclohexenyl)-2,4,6,8-nonatetraen-l-ol). 

In the intestinal mucosal cells, /3-carotene is cleaved via an oxygenase (an enzyme that introduces molecular 02 into organic compounds) to frans-retinal (aldehyde form of trans-retinol, as shown in Table 6.2), which in turn is reduced to frans-retinol, vitamin Av Retinol is then esterified with a fatty acid, becomes incorporated into chylomicrons, and eventually enters the liver, where it is stored in the ester form until it is required elsewhere in the organism. The ester is then hydrolyzed, and vitamin Ax is transported to its target tissue bound to retinol-binding protein (RBP). Since RBP has a molecular weight of only 20,000 and would be easily cleared by the kidneys, it is associated in the bloodstream with another plasma protein, prealbumin. 

Figure 6.6 indicates the various reactions typical of vitamin Av Retinoic acid, oxidized trans-retinal, is apparently involved in epithelial cell physiology. Retinol phosphate, trans-retinol esterified with a phosphate residue, associates with various membrane structures through its hydrophobic isoprenoid residue, leaving its hydrophilic phosphate group in contact with the aqueous environment. It serves as an anchor for growing oligosaccharide chains in the same manner as dolichol phosphate does (see Chapter 18). 

Vitamin A is a fat-soluble vitamin involved in critical biological functions, such as embryonic development, growth and vision. It has three primary forms retinol, retinal and retinoic acid. In addition, (3-carotene can be converted to some extent in the body into retinol and is therefore called provitamin A. The bioactivity of these vitamin A compounds varies considerably, ranging from 100% for all-trans retinol, 75% for 13-eis retinol and to just 17% for (3-carotene. All-trans retinol is the major form of vitamin A in milk fat, with values ranging from 8.0 to 12.0 pg/g fat in samples of commercial butter. In contrast, 13-cA retinol is present at a very low... 

The vitamin A content of foods is often given in terms of the international unit (IU). One IU of vitamin A is defined as 0.3 tg of all-trans-retinol. The term retinol equivalent (RE) is used to convert all sources of vitamin A and carotenoids in the diet to a single unit. One RE is by definition 1 pg of all-trans retinol, 12 pg of P-carotene, or 24 pg of other (mixed) provitamin A carotenoids. The recommended dietary allowance for vitamin A ranges from 375 pg RE/day for infants to 1,000 RE/day for adults. 

Q s-retinol has 75% of the biological activity of aU-trans-retinol, and reti-naldehyde has 90%. Food composition tables give total preformed vitamin A as the sum of aU-trans-retinol -i- 0.75 x 13-c/s-retinol - - 0.9 x retinaldehyde (Holland et al., 1991). 

MYVPACK OLEOVITAMIN A OPHTHALAMIN PREPALIN RETINOL aU-trans RETINOL RETRO-VITAMIN A TESTAVOL VAFLOL VI-ALPHA VITAMIN A1 VITAMIN A1 ALCOHOL aU-trans-VITAMIN A ALCOHOL VITAVEL-A VITPEX VOGAN VOGAN-NEU... 

Vitamin A activity can be expressed either as international units lU (1 lU equaling 0.3 micrograms of aH-trans-retinol or 0.6 micrograms of all-trara-beta-carotene) or, more correctly, in retinol equivalents (RE) where 1 RE equals 1 microgram of all-trara-retinol, 6 micrograms of all-trara-beta-carotene or 12 micrograms of other provitamin A carotenoids. Table 1 gives the activities of different forms of vitamin A in RE and lU. 

Chemistry. The commercial form cf vitamin A is all-trans retinol, usually formulated as the acetate or palmitate ester. The active forms are the two oxidation products (Fig. 8.1, (l)retinal, which is a structural component of the visual pigment rhodopsin, and (2)retinoic acid, which is required for cell differentiation. There are specific nuclear receptors for retinoic acid. Although the vitamin is marketed in the all-trans form, retinal and retinoic acid are present, in vivo in cis forms. There are also commercial forms related to the retinoic acid structure that have cis stereochemistry. 

Chemical structure of a -tmns retinol (vitamin Ai), the most active form of vitamin A. Oxidation of C15 to an aldehyde or an acid produces, respectively, retinaldehyde (retinal) and retinoic acid. The cis-trans isomerization of the double bond between Ci i and C12 occurs during functioning of retinaldehyde in vision. 

If E,E dienes like 163 are wanted, then such Wittig reactions are ideal as the mixed products can be equilibrated to the E,E diene by addition of small amounts of radical generators such as iodine or PhSH. The commercial (BASF) synthesis of Vitamin A involves all trans retinol 174 that can be made from two different allylic ylids derived from 175 and 178 with the appropriate aldehydes 176 and 177. In both cases E,Z mixtures are formed, but equilibration with iodine gives 174 with an all E side chain.46 A different synthesis of such compounds appeared in chapter 11. 

Terpenes contain multiples of five carbons since they are synthesized by linking together isoprene units. The isoprene unit is a branched C, unit. Vitamins A (trans -retinol), D, and E are terpenes. Other terpenes are intermediates in the biosynthesis of cholesterol. 

Synonyms Anti-infective vitamin Antixerophthalmic vitamin Axerophthol 3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatretraen-1-ol Oleovitamin A all-trans-Retinol Retrovitamin A Vitamin A Vitamin A alcohol all-trans-Vitamin A alcohol Classification Organic compd. 

Vitamin A alcohol. See Retinol Vitamin A alcohol acetate. See Retinyl acetate all-trans-Vitamin A alcohol. See Retinol Vitamin Be. See Folic acid Vitamin BX. See p-Aminobenzoic acid Vitamin Bs, calcium salt. See Calcium D-pantothenate... 

Vitamin A as all-trans Retinol 0.3 microgram 3333 lU 1. TheOTetical values... 

Vitamin A as all-trans Retinol palmitate 0.55 microgram 1818 lU 2. The format in lU has already been left in 1956... 

In the retinal cells of the eye, vitamin A (all-trans-retinol) is converted into the 11-ds-isomer, which is then oxidised to 11-cts-retinaldehde. In the dark the latter then combines with the protein opsin to form rhodopsin (visual purple), which is the photoreceptor for vision at low light intensities. When light falls on the retina, the czs-retinaldehyde molecule is converted back into the aW-trans form and is released from the opsin. This conversion results in the transmission of an impulse up the optic nerve. The all-frans-retinaldehyde is converted to all-trans-retinol, which re-enters the cycle, thus continually renewing the light sensitivity of the retina (Rg. 5.2). 

Vitamin A (retinol) is a fat-soluble vitamin important for the maintenance of skin, bone, and blood vessels, as well as for the promotion of vision (Theodosiou et al. 2010). It is obtained from the diet either as all-trans-retinol, retinyl esters, or P-carotene (Blomhoff and Blomhoff 2006) and is stored in the liver (Moise et al. 2007). Vitamin A is converted to retinoic acid (RA), which is formed mainly through intracellular oxidative metabolism by retinal dehydrogenases (RALDHs) (Lampen et al. 2000). RA plays important roles in embryonic development, organogenesis, tissue homeostasis, cell proliferation, differentiation, and apoptosis (Theodosiou et al. 2010). In adult mammals, RALDH is found in intestinal epithelial cells (lECs) and gut associated-dendritic cells (DCs) from Peyer s patches and mesenteric lymph nodes (Iwata 2004, Coombes et al. 2007). Gut-associated DCs and lECs can metabolize vitamin A to RA in vitro (Lampen 2000), which indicates they may be a source of RA in gut mucosa. RA binds to two families of nuclear receptors, RA receptor (RAR) isotypes (a, p, and y) and retinoic X receptor (RXR) isotypes (a, p, and y). RAR and RXR form heterodimers and interact with retinoic acid response elements (RAREs) within the promoters of retinoic acid responsive genes (Blomhoff and Blomhoff 2006). RAR is ubiquitously expressed and up-regulated by RA. RXR also... 

FIGURE 12.33 Vitamin A trans-retinol) is oxidized to /rawt-retinal and then enzymatically isomerized to cij-retinal. 

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