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vitamin A

Monday 23 March 2009

Definition: Vitamin A is a group of related natural and synthetic chemicals that exert a hormone-like activity or function.

Vitamin A, a bi-polar molecule formed with bi-polar covalent bonds between carbon and hydrogen, is linked to a family of similarly shaped molecules, the retinoids, which complete the remainder of the vitamin sequence. Its important part is the retinyl group, which can be found in several forms.

In foods of animal origin, the major form of vitamin A is an ester, primarily retinyl palmitate, which is converted to an alcohol (retinol) in the small intestine. Vitamin A can also exist as an aldehyde (retinal), or as an acid (retinoic acid).

Precursors to the vitamin (provitamins) are present in foods of plant origin as some of the members of the carotenoid family of compounds.

All forms of vitamin A have a beta-ionone ring to which an isoprenoid chain is attached. This structure is essential for vitamin activity.

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.

The retinyl group, when attached to a specific protein, is the only primary light absorber in visual perception, and the compound name is related to the retina of the eye.

Vitamin A can be found in various forms:

- retinol is the form of vitamin A absorbed when eating animal food sources. It is a yellow, fat-soluble, vitamin with importance in vision and bone growth. Since the alcohol form is unstable, the vitamin is usually produced and administered in a form of retinyl acetate or palmitate.

- other retinoids, a class of chemical compounds that are related chemically to vitamin A, are used in medicine.

Forms

Retinol, perhaps the most important form of vitamin A, is the transport form and, as the retinol ester, also the storage form. It is oxidized in vivo to the aldehyde retinal (the form used in visual pigment) and the acid retinoic acid. Important dietary sources of vitamin A are animal derived (e.g., liver, fish, eggs, milk, butter).

Yellow and leafy green vegetables such as carrots, squash, and spinach supply large amounts of carotenoids, many of which are pro-vitamins that can be metabolized to active vitamin A in vivo; the most important of these is beta-carotene. A widely used term, retinoids, refers to both natural and synthetic chemicals that are structurally related to vitamin A but do not necessarily have vitamin A activity.

As with all fats, the digestion and absorption of carotenes and retinoids require bile, pancreatic enzymes, and some level of antioxidant activity in the food.

Retinol, whether derived from ingested esters or from beta-carotene (through an intermediate oxidation step involving retinal), is transported in chylomicrons to the liver for esterification and storage. More than 90% of the body’s vitamin A reserves are stored in the liver, predominantly in the perisinusoidal stellate (Ito) cells.

In normal persons who consume an adequate diet, these reserves are sufficient for at least 6 months’ deprivation. Retinoic acid, on the other hand, can be absorbed unchanged; it represents a small fraction of vitamin A in the blood and is active in epithelial differentiation and growth but not in the maintenance of vision.

When dietary intake of vitamin A is inadequate, the retinol esters in the liver are mobilized, and released retinol is then bound to a specific retinol-binding protein, synthesized in liver. The uptake of retinol by the various cells of the body is dependent on surface receptors specific for retinol-binding protein, rather than receptors specific for the retinol. Retinol is transported across the cell membrane, where it binds to a cellular retinol-binding protein, and the retinol-binding protein is released back into the blood.

Function.

In humans, the best-defined functions of vitamin A are as follows:
- Maintaining normal vision in reduced light
- Potentiating the differentiation of specialized epithelial cells, mainly mucus-secreting cells
- Enhancing immunity to infections, particularly in children.

In addition, the retinoids, beta-carotene, and some related carotenoids have been shown to function as photoprotective and antioxidant agents.

The visual process involves four forms of vitamin A-containing pigments: rhodopsin in the rods, the most light-sensitive pigment and therefore important in reduced light, and three iodopsins in cone cells, each responsive to specific colors in bright light.

The synthesis of rhodopsin from retinol involves :
- (1) oxidation to all-trans-retinal;
- (2) isomerization to 11-cis-retinal;
- (3) interaction with the rod protein opsin to form rhodopsin.

When a photon of light impinges on the dark-adapted retina, rhodopsin undergoes a sequence of configurational changes to ultimately yield all-trans-retinal and opsin. In the process, a nerve impulse is generated (by changes in membrane potential) that is transmitted by neurons from the retina to the brain. During dark adaptation, some of the all-trans-retinal is reconverted to 11-cis-retinal, but most is reduced to retinol and lost to the retina, dictating the need for continuous input of retinol.

Vitamin A plays an important role in the orderly differentiation of mucus-secreting epithelium; when a deficiency state exists, the epithelium undergoes squamous metaplasia and differentiation to a keratinizing epithelium. The mechanism is not precisely understood; but in cell culture systems, retinoic acid (retinol is much less potent) regulates the expression of genes encoding a number of cell receptors and secreted proteins, including receptors for growth factors.

Vitamin A plays a role in host resistance to infections.70 This beneficial effect of vitamin A seems to derive in part from its ability to stimulate the immune system, possibly through the formation of a metabolite called 14-hydroxyretinol. In addition, it appears that during infections, the bioavailability of vitamin A is reduced.

The acute-phase response that accompanies many infections reduces the formation of retinol-binding protein in the liver, resulting in depression of circulating retinol levels, which in turn leads to reduced tissue availability of vitamin A. In keeping with this, supplements of the vitamin during the course of infections such as measles dramatically improve the clinical outcome.

Pathology

- Vitamin A deficiency

Vitamin A deficiency occurs worldwide either on the basis of general undernutrition or as a conditioned deficiency among individuals having some cause for malabsorption of fats. It is rarely seen in the United States and other industrialized countries, but it is not uncommon in the underprivileged populations of the world. One of the earliest manifestations of vitamin A deficiency is impaired vision, particularly in reduced light (night blindness).

Because vitamin A and retinoids are involved in maintaining the differentiation of epithelial cells, persistent deficiency gives rise to a series of changes, the most devastating of which occur in the eyes.

Collectively, the ocular changes are referred to as xerophthalmia (dry eye). First, there is dryness of the conjunctivae (xerosis) as the normal lacrimal and mucus-secreting epithelium is replaced by keratinized epithelium. This is followed by the build-up of keratin debris in small opaque plaques (Bitot spots) and, eventually, erosion of the roughened corneal surface with softening and destruction of the cornea (keratomalacia) and total blindness.

In addition to the ocular epithelium, the epithelium lining the upper respiratory passages and urinary tract is replaced by keratinizing squamous cells (squamous metaplasia).

Loss of the mucociliary epithelium of the airways predisposes to secondary pulmonary infections, and desquamation of keratin debris in the urinary tract predisposes to renal and urinary bladder stones. Hyperplasia and hyperkeratinization of the epidermis with plugging of the ducts of the adnexal glands may produce follicular or papular dermatosis.

Another serious consequence of avitaminosis A is immune deficiency. This impairment of immunity leads to higher mortality rates from common infections such as measles, pneumonia, and infectious diarrhea.

In parts of the world where vitamin A deficiency is endemic, dietary supplements reduce mortality by 20% to 30%.

- Vitamin A Toxicity

Both short- and long-term excess of vitamin A may produce toxic manifestations, a point of some concern because of the megadoses being popularized by certain health food stores.

The clinical consequences of acute hypervitaminosis A include headache, vomiting, stupor, and papilledema, symptoms also suggestive of brain tumor.

Chronic toxicity is associated with weight loss, nausea, and vomiting; dryness of the mucosa of the lips; bone and joint pain; hyperostosis; and hepatomegaly with parenchymal damage and fibrosis.

Although synthetic retinoids used for the treatment of acne are not associated with the complications listed, their use in pregnancy should be avoided owing to a well-established increase in the incidence of congenital malformations.

Recent studies indicate other untoward effects of chronic hypervitaminosis A.

Vitamin A stimulates osteoclast formation, thus leading to increased bone resorption and osteoporosis and predisposition to fractures. This is particularly true in older individuals, who are prone to osteoporosis.

See also

- vitamins