Figure 10.1 Structure, metabolism and function of vitamin A . Conversion of retinaldehyde to retinoic acid is irreversible. (See also Chapter 39.) |
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| 'Vitamin A' is a generic term for three compounds, retinol, retinal and retinoic acid, all of which are found in animals. Vitamin A is found in animals as retinol, retinal, and retinoic acid; its provitamin, β-carotene, is found in plant food. The term 'retinoids' has been used to define these three substances as well as other synthetic compounds associated with vitamin A-like activity. Vitamin A provitamin, β-carotene, is converted to all-trans retinal by the action of β-carotene dioxygenase in the small bowel. Further metabolism in the enterocytes produces retinol and retinoic acid (Fig. 10.1)
which are then transported to the liver where vitamin A is stored as retinol palmitate. The stores of vitamin A in the liver comprise approximately 1 year's supply. Liver, egg yolk, butter, and milk are good sources of pre-formed vitamin A. Dark-green and yellow vegetables are good sources of β-carotene. Conversion of carotenoids to vitamin A is rarely 100% efficient and the potency of foods is described in retinol equivalents (RE; 1 RE equals 1 mg of retinol or 6 mg β-carotene, or 12 mg of other carotenes).
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| Is vitamin A protective against cancer and cardiovascular disease?
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| Recently β-carotene has received attention in its role as an antioxidant. Since normal epithelial cell growth and differentiation depends on retinoids, and many human tumors (carcinomas) arise from epithelial cells, it has been proposed that vitamin A may be protective against these diseases. Indeed, some epidemiologic studies have demonstrated an inverse relationship between the vitamin A content of the diet and the risk of cancer. However, no practical conclusions regarding clinical use of vitamin A can be drawn at this time (see below).
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| Vitamin A is stored in the liver and needs to be transported to its sites of action
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| Owing to the fat-soluble nature of the vitamin, specific transport mechanisms are involved, both in the blood and at tissue sites of action. It is transported by specific proteins - serum retinal-binding protein (SRBP) and cytosolic retinal binding proteins (CRBP). In addition, retinoic acid is thought to be transported to cells either bound to albumin or to a specific retinoic acid binding protein (RABP). Other tissue proteins are also involved in the molecular trafficking of retinol to the nucleus of the cell.
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| Vitamin A deficiency presents as 'night blindness'
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| The visual pigment, rhodopsin, is found in the rod cells of the retina and is formed by the binding of 11-cis-retinal to the apoprotein opsin. When rhodopsin is exposed to light, it is bleached, retinal dissociates and is isomerized and reduced to all-trans-retinol (see Fig. 10.1). This reaction is accompanied by a conformational change and elicits a nerve impulse perceived by the brain as light (see also Chapter 39). Rod cells are responsible for vision in poor light.
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| Vitamin A deficiency often presents as defective night vision or 'night blindness'. Vitamin A also affects growth and differentiation of epithelial cells; thus its deficiency produces defective epithelialization and keratomalacia - corneal softening and opacity. Severe vitamin A deficiency leads to progressive keratinization of the cornea and to permanent blindness. In fact, vitamin A deficiency is the commonest cause of blindness in the world.
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| Subclinical vitamin A deficiency may lead to increased susceptibility to infection. Severe vitamin A deficiency occurs in the developing world. However, it is also fairly common in patients with severe liver disease or fat malabsorption.
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| Vitamin A is toxic in excess
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| Excess vitamin A administration is toxic, with symptoms including bone pain, hair loss, dermatitis, hepatosplenomegaly, nausea, vomiting, double vision, headaches and diarrhea. It is virtually impossible to develop vitamin A toxicity by ingesting normal foods; however, toxicity may result from the use of pure vitamin A supplements. Increased intake of vitamin A is also associated with teratogenicity and should be avoided during pregnancy.
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