VITAMIN A

Vitamin A is a generic term which designates any compound possessing the biological activity of retinol, the animal form of vitamin A. Retinol belongs to a family of chemical compounds known as retinoids.The term retinoids includes naturally occurring forms of vitamin A but also the many synthetic analogs of retinol, even inactive (Sporn MB et al., Fed Proc 1976, 35, 1332). The basic structure of the retinoid molecule consists of a cyclic end group, a polyene side chain with alternating double bonds and a polar end group. This structure is responsible for their color (yellow, orange, or red). Variations in side chains and end groups create the various classes of retinoids.

According to the definition given by IUPA and IUB, retinoids are a class of compounds consisting of four isoprenoid units (diterpene) joined in a head-to-tail manner. All retinoids may be formally derived from a monocyclic parent compound containing five carbon-carbon double bonds and a functional group at the end of the acyclic portion.

As shown by Moore in 1930 (Moore T, Biochem J, 1930, 24, 692) in nutritional experiments, the biosynthetic precursors of retinoids are plant carotenoids (provitamin A) of which b-carotene is most efficient. That precursor is subjected to oxidative cleavage mainly at its center (at the 15,15' carbon double bond) to yield two molecules of all-trans-retinal as it was proposed by Karrer P et al. (Helv Chim Acta 1930, 13, 1084). Later, it was also demonstrated the possibility of an eccentric cleavage reaction (at the 9',10' carbon double bond) and a stepwise process leading to only one mole of vitamin A per mole of carotene consumed (Glover J, Vitam Horm 1960, 18, 371).

The parent retinoid compound, all-trans-retinol, is a terpenoid (diterpene, a 20-carbon primary alcohol, MW: 286). The predominant forms of vitamin A in biological samples are retinol and esters of retinol having long fatty acyl chains. The synthesis of retinyl esters occurs in the intestine (Huang HS et al., J Biol Chem 1965, 240, 2839), liver (Futterman S et al., J Biol Chem 1964, 239, 4077) and in other organs (Berman ER et al., Biochim Biophys Acta 1980, 630, 36). In the majority of mammals, including man, retinyl esters can only be found in traces in blood (Krasinski SD et al., Am J Clin Nutr 1989, 49, 112). As an exception, the majority of vitamin A is transported as esters in the blood of carnivores (except Hyaenidae and Pinnipedia) : 70% in dog, 94% in silver fox, 87% in raccoon dog and 66% in mink (Schweigert FJ et al., Comp Biochem Physiol 1990, 95A, 573).
In animal tissues, retinyl palmitate is the predominant form, oleic and stearic acids being also present. This compound is hydrolyzed into retinal which undergoes reduction into retinal (reversible reaction), and then esterified to form retinyl palmitate. Activation of the retinol pathway, involves hydrolysis and reversible oxidation of retinol to retinal. Ultimately, retinal may be oxidized into retinoic acid.
11-cis-retinal is present in the retina of the eye, and retinoic acids (several forms exist) are active metabolites found in all tissues.

They are all lipid soluble, unstable in the presence of oxygen. Light catalyzes double-bond isomerization of most retinoids, photochemical reactions may lead to polymerization. They must be handle in inert atmosphere, avoiding acid medium and light. Their maximum UV absorbance is at about 325 nm with a molar coefficient of about 50,000.
One international unit (IU) of vitamin A is defined as 0.3 µg of all-trans-retinol. For nutritional works, a better term id retinol equivalent (RE), which is used to convert all sources of vitamin A and carotenoids in the diet into a single unit. 1 µg of retinol equals 1 RE and is assumed to be equivalent to 6µg of b-carotene.
In mammals, 50-80% of total retinol is present in the liver and especially in stellate cells (about 90% of the total) who regulate the vitamin A plasma concentration (about 2 µM).
Photosensitivity in animals is based on the isomerization of 11-cis-retinal to all-trans-retinal when the complex retinal-rhodopsin is exposed to light, this leads to a sequence of events generating a nerve impulse. Besides this role, retinoids regulate the growth and differentiation of normal, premalignant, and malignant cells. 
In 1987, two groups (Petkovich et al., Nature, 330, 444-450; Giguere et al., Nature, 330, 624-9) described a retinoic receptor in the cell nucleus. Since that date, several categories were discovered. The interaction of retinoic acid with its receptors leads to changes in gene expression.
The mean recommended dietary intake is considered to be about 700µg retinol for man.