Retinol biological activity

Vitamin A (retinol, 6.1) is the parent of a range of compounds known as retinoids, which possess the biological activity of vitamin A. In general, animal foods provide preformed vitamin A as retinyl esters (e.g. 6.5, which are easily hydrolysed in the gastrointestinal tract) while plant foods provide precursors of vitamin A, i.e. carotenoids. Only carotenoids with a /3-ionone ring (e.g. /1-carotene) can serve as vitamin A precursors. /3-Carotene (6.6)... 

The leveisal of the oxidative pathway of vitamin A (retinol —r retinal —>-retinoic add) does not occur in the body, When retinoic acid is feci to animals, even in relatively large doses, there is no storage and, in fact, die molecule is rapidly metabolized and cannot be found several hours after administration. The metabolic products have not been fully identified. Several fractions from liver or intestine, isolated after administering retinoic add marked with carbon-14, have been shown to have biological activity. 

From a nutritional viewpoint, the carotenoids are classified as provitamins and inactive carotenoids. To have vitamin A activity, the carotenoid molecule must incorporate a molecule of retinol, i.e., an unsubstituted /3-ionone ring with an 11-carbon polyene chain. /3-carotene (C40H56, MW = 536.88), the most ubiquitous provitamin A carotenoid, is composed of two molecules of retinol joined tail to tail thus the compound possesses maximal (100%) vitamin A activity. The structures of all other provitamin A carotenoids incorporate one molecule of retinol and hence theoretically contribute 50% of the biological activity of /3-carotene. Among the 600 or so carotenoids that exist in nature, only about 50 possess vitamin A activity in varying degrees of potency. 

Ethers and esters derived from the alcohol also show activity in vivo. The ring structure of retinol ((i-ionone), or the more unsaturated ring in 3-dehydroretinol (dehydro-P-ionone), is essential for activity hydrogenation destroys biological activity. Of all known derivatives, all-/ran,v-retinol and its aldehyde, retinal, exhibit the greatest biological potency in vivo 3-dehydroretinol has about 40% of the potency of all-bms-retinol. 

Note One International Vitamin A Unit is the specific biologic activity of 0.3 (ig of the all-trans isomer of retinol. 

The term vitamin A can include any compound with the biological activity of the vitamin provitamin A carotenoids, retinol, and its active metabolites. 

Free retinol is chemically unstable and does not occur to any significant extent in foods or tissues. Rather, it is present as a variety of esters, mainly retinyl palmitate. Retinyl acetate is generally used as an analytical standard and in pharmaceutical preparations. Dehydroretinol (vitamin A2) is found in freshwater fishes and amphibians it has about half the biological activity of retinol. 

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). 

Anhydroretinol may arise by nonenzymic isomerization of all-trans-retinol under acidic conditions and can act as a precursor for the synthesis of other biologically active retroretinoids (McBee et al., 2000). 

A-2 Vitamin A consists of three biologically active molecules, retinol, retinal (retinaldehyde) and retinoic acid. Each of these compounds are derived from a group of molecules know as carotenoids also referred to as the provitamin A. Beta-carotene, which consists of two molecules of retinal linked at their aldehyde ends. 

Vitamin A is a fat-soluble vitamin. The RDA for vitamin A is 1-0 mg of retinol, or its equivalent. The international unit [lU) is used to compare the biological activities of various sources of vitamin A- One iU of vitamin A activity can be supplied by 0.3 pg of all-ffiflMS-relinol, 0.344 pg of all-trans-retinyl acetate, or 0,60 pg of all-frens-p-carotene. 

The biological activities of vitamin A and previtamin A are not equivalent on a per-weight basis. In humans, 6.0 mg of p-carotene is equivalent to 1.0 mg of retinol. Twelve milligrams of the other carotenoids is equivalent to 1-0 mg of retinol. The relatively low biological activity of the carotenoids is due to the inefficiency in their conversion to retinol and their ioivet availability u/beti present in foods. When -carotene is provided in pure form (dissolved in some oil and swallowed) its value is still less than that of vitamin A, Here, 2.0 mg of p-carotenc is equivalent to l.O mg of retinol. 

The term vitamin A currently is applied to compounds posse.s.sing biological activity like that of retinol. The term vilamiii Ai refers to all-/ i .v-retinol. The term retinoid is applied to retinol and its naturally occurring derivatives plus synthetic analogues, which need not have vitamin A activity. 

Vitamin A activity is expressed as USP units, international units (lU). retinol equivalents (RE), and arotene equivalents. The USP units and lU are equivalent. Each unit ex-pre.sses the activity of 0.3 /ug of all-/rans-retinol. Thus. I mg of all-/rufis-retinol has the activity of 3.333 unit.s. Other equivalents are li.sted in Table 26-3. One RE represents the biological activity of I /7g of all-rnin.t-relinol, 6 /ug of carotene. and 12 /rg of mixed dietary carotenoids. The RE i.s u.sed to convert all dietary sources of vitamin A into a single unit for easy comparison."... 

Institute of Medicine to recommend the retinol activity equivalent (RAE) as the basis of calculation of retinol intake. In this system, a ratio equivalence of 1 12 24 is recommended (i.e., 12jLlg p-carotene or 24 Ug mixed carotenoids has the same biological activity as IjLig retinol). Using this system, current RDAs for vitamin A are 900 pg RAE for men 19 years and older 700 ug RAE for women 19 years and older, with up to 770 xg RAE/day in pregnancy and up to 1300 fig RAE/day in lactation 300 to 900 fig RAE for children 1 to 18 years, dependent upon age and sex and for infants an adequate intake (AI) of 400 fig RAE at 0 to 6 months and 500 fig RAE from 7 to 12 months. ... 

Fig. 1. The structures of key retinoids and their precursors. Fish convert retinyl esters (e.g. retinyl palmitate (RP)) and carotenoids (e.g. /3-carotene) to retinol in the gut lumen prior to intestinal absorption. Retinyl esters (e.g. RP) stored in the liver are synthesized from retinol by lecithin retinol acyltransferase (LRAT) and acyl CoAiretinol acyltransferase (ARAT). The retinyl esters are mobilized through their conversion to retinol by retinyl ester hydrolase (REH), which is then transported in the circulation to various sites in the body. Retinol is further metabolized within specific tissues to retinal by alcohol dehydrogenases (ADH) or short-chain dehydrogenase/reductase. Retinal is converted to the two major biologically active forms of retinoic acid (RA) (all-trans and 9-cis RA). Retinaldehyde dehydrogenase 2 (Raldh2) synthesizes all-trans RA from all-trans precursors and 9-cis RA form 9-cis precursors.

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