Vitamin A

Vitamin A
Chemical structure of retinol, one of the major forms of vitamin A

Vitamin A is a group of unsaturated nutritional organic compounds that includes retinol, retinal, retinoic acid, and several provitamin A carotenoids (most notably beta-carotene).[1] Vitamin A has multiple functions: it is important for growth and development, for the maintenance of the immune system and good vision.[2] Vitamin A is needed by the retina of the eye in the form of retinal, which combines with protein opsin to form rhodopsin, the light-absorbing molecule[3] necessary for both low-light (scotopic vision) and color vision.[4] Vitamin A also functions in a very different role as retinoic acid (an irreversibly oxidized form of retinol), which is an important hormone-like growth factor for epithelial and other cells.[2][5]

In foods of animal origin, the major form of vitamin A is an ester, primarily retinyl palmitate, which is converted to retinol (chemically an alcohol) in the small intestine. The retinol form functions as a storage form of the vitamin, and can be converted to and from its visually active aldehyde form, retinal.

All forms of vitamin A have a beta-ionone ring to which an isoprenoid chain is attached, called a retinyl group. Both structural features are essential for vitamin activity.[6] The orange pigment of carrots (beta-carotene) can be represented as two connected retinyl groups, which are used in the body to contribute to vitamin A levels. Alpha-carotene and gamma-carotene also have a single retinyl group, which give them some vitamin activity. None of the other carotenes have vitamin activity. The carotenoid beta-cryptoxanthin possesses an ionone group and has vitamin activity in humans.

Vitamin A can be found in two principal forms in foods:

    Retinol, the form of vitamin A absorbed when eating animal food sources, is a yellow, fat-soluble substance. Since the pure alcohol form is unstable, the vitamin is found in tissues in a form of retinyl ester. It is also commercially produced and administered as esters such as retinyl acetate or palmitate.[7]
    The carotenes alpha-carotene, beta-carotene, gamma-carotene; and the xanthophyll beta-cryptoxanthin (all of which contain beta-ionone rings), but no other carotenoids, function as provitamin A in herbivores and omnivore animals, which possess the enzyme beta-carotene 15,15'-dioxygenase which cleaves beta-carotene in the intestinal mucosa and converts it to retinol.[8] In general, carnivores are poor converters of ionone-containing carotenoids, and pure carnivores such as cats and ferrets lack beta-carotene 15,15'-dioxygenase and cannot convert any carotenoids to retinal (resulting in none of the carotenoids being forms of vitamin A for these species).

carrots

Vitamin A is found naturally in many foods:

    cod liver oil (30000 μg 3333%)
    liver (turkey) (8058 μg 895%)
    liver (beef, pork, fish) (6500 μg 722%)
    liver (chicken) (3296 μg 366%)
    capsicum, red (2081 μg 231%)
    sweet potato (961 μg 107%)
    carrot (835 μg 93%)
    broccoli leaf (800 μg 89%)
    butter (684 μg 76%)
    kale (681 μg 76%)
    collard greens (frozen then boiled) (575 μg 64%)
    dandelion greens (508 μg 56%)
    spinach (469 μg 52%)
    pumpkin (426 μg 43%)
    collard greens (333 μg 37%)
    cheddar cheese (265 μg 29%)
    cantaloupe melon (169 μg 19%)
    egg (140 μg 16%)
    apricot (96 μg 11%)
    papaya (55 μg 6%)
    tomatoes (42 μg 5%)
    mango (38 μg 4%)
    pea (38 μg 4%)
    broccoli florets (31 μg 3%)
    milk (28 μg 3%)
    bell pepper, green (18 μg 2%)
    spirulina (3 μg 0.3%)

Note: Data taken from USDA database.[18] Bracketed values are retinol activity equivalences (RAEs) and percentage of the adult male RDA, per 100 grams of the foodstuff (average).

Conversion of carotene to retinol varies from person to person and bioavailability of carotene in food varies.[19][20]
Metabolic functionsEdit

Vitamin A plays a role in a variety of functions throughout the body, such as:

    Vision
    Gene transcription
    Immune function
    Embryonic development and reproduction
    Bone metabolism
    Hematopoiesis
    Skin and cellular health
    Antioxidant activity

Vision

The role of vitamin A in the visual cycle is specifically related to the retinal form. Within the eye, 11-cis-retinal is bound to the protein "opsin" to form rhodopsin in rods[3] and iodopsin (cones) at conserved lysine residues. As light enters the eye, the 11-cis-retinal is isomerized to the all-"trans" form. The all-"trans" retinal dissociates from the opsin in a series of steps called photo-bleaching. This isomerization induces a nervous signal along the optic nerve to the visual center of the brain. After separating from opsin, the all-"trans"-retinal is recycled and converted back to the 11-"cis"-retinal form by a series of enzymatic reactions. In addition, some of the all-"trans" retinal may be converted to all-"trans" retinol form and then transported with an interphotoreceptor retinol-binding protein (IRBP) to the pigment epithelial cells. Further esterification into all-"trans" retinyl esters allow for storage of all-trans-retinol within the pigment epithelial cells to be reused when needed.[21] The final stage is conversion of 11-cis-retinal will rebind to opsin to reform rhodopsin (visual purple) in the retina. Rhodopsin is needed to see in low light (contrast) as well as for night vision. Kühne showed that rhodopsin in the retina is only regenerated when the retina is attached to retinal pigmented epithelium,[3] which provides retinal. It is for this reason that a deficiency in vitamin A will inhibit the reformation of rhodopsin and lead to one of the first symptoms, night blindness.[22]
Gene transcriptionEdit
Main article: Gene transcription

Vitamin A, in the retinoic acid form, plays an important role in gene transcription. Once retinol has been taken up by a cell, it can be oxidized to retinal (retinaldehyde) by retinol dehydrogenases and then retinaldehyde can be oxidized to retinoic acid by retinaldehyde dehydrogenases.[23] The conversion of retinaldehyde to retinoic acid is an irreversible step, meaning that the production of retinoic acid is tightly regulated, due to its activity as a ligand for nuclear receptors.[21] The physiological form of retinoic acid (all-trans-retinoic acid) regulates gene transcription by binding to nuclear receptors known as retinoic acid receptors (RARs) which are bound to DNA as heterodimers with retinoid "X" receptors (RXRs). RAR and RXR must dimerize before they can bind to the DNA. RAR will form a heterodimer with RXR (RAR-RXR), but it does not readily form a homodimer (RAR-RAR). RXR, on the other hand, may form a homodimer (RXR-RXR) and will form heterodimers with many other nuclear receptors as well, including the thyroid hormone receptor (RXR-TR), the Vitamin D3 receptor (RXR-VDR), the peroxisome proliferator-activated receptor (RXR-PPAR) and the liver "X" receptor (RXR-LXR).[24] The RAR-RXR heterodimer recognizes retinoic acid response elements (RAREs) on the DNA whereas the RXR-RXR homodimer recognizes retinoid "X" response elements (RXREs) on the DNA; although several RAREs near target genes have been shown to control physiological processes,[23] this has not been demonstrated for RXREs. The heterodimers of RXR with nuclear receptors other than RAR (i.e. TR, VDR, PPAR, LXR) bind to various distinct response elements on the DNA to control processes not regulated by vitamin A.[21] Upon binding of retinoic acid to the RAR component of the RAR-RXR heterodimer, the receptors undergo a conformational change that causes co-repressors to dissociate from the receptors. Coactivators can then bind to the receptor complex, which may help to loosen the chromatin structure from the histones or may interact with the transcriptional machinery.[24] This response can upregulate (or downregulate) the expression of target genes, including Hox genes as well as the genes that encode for the receptors themselves (i.e. RAR-beta in mammals).