Vitamin A

1. Vitamin A

2. Retinoids Precursors of vitamin A 1- Retinol It is found in animal tissues as a retinyl ester with long-chain fatty acids. 2- Retinal The aldhyde derived from the oxidation of retinol. Retinol and retinal can be interconverted. 3- Retinoicacid The acidderived from retinal. It can not be reduced in the body, and therefore, can not give rise to either retinal or retinol 4-b-carotene Plantfoods contain b-carotene, which can be cleaved in the intestine to two moleculesofretinal In humans, the conversion is insufficient, and vitamin A activity of b-carotene is only about one sixth(1/6) of that of retinol

3. Retinol (Animal Source) Retinalb-carotene (Plant Source) Retinoic Acid RETINOIDS PRECURSOR OF VITAMIN A

4. Absorption & Transport of vitamin A Transport to the Liver I- Retinol is derived from (DIET SOURCES) 1-DIET Retinyl esters (animal source) which are hydrolyzed in the intestinal mucosa, releasing retinoland free fatty acids 2- DIET b-carotenes(plant source) which is cleaved 2 retinalretinol II- Retinol is esterified with fatty acids to give retinylesters III-Retinyl esters are collected by the chylomicronsinto the lymphatic system. IV- Retinyl esters contained in the chylomicrons are taken up and stored by the liver

6. Release from the Liver • When needed, retinol is released from the liver and transported to extra hepatic tissue by plasmaretinol binding protein(RBP) • Theretinol - RBP complex attaches to specific receptors on the surface of the cells of peripheral tissues permitting retinol to enter

7. Mechanism of Action of vitamin A • Retinolis oxidized to retinoic acidinside cells. • Retinoic acidbinds with high-affinity to specific receptor proteins present in the nucleus of target tissue, such as epithelial cell. • The activated retinoic acid - receptor complexinteracts with nuclear chromatin (genes) to stimulate retinoid-specific mRNAsynthesis, resulting in the production of specific proteins that mediate several physiological functions. e.g. retinoids control the expression of keratin gene in most epithelial tissues.

10. Physiological Functions of Vitamin A • Vision • Growth • Reproduction • Epithelial cell maintenance

12. Functions of Vitamin A 1-Vision • Vitamin A is a component of the visual pigments of rodand cone cells. • Rhodopsin, the visual pigment of the rod cells in the retina, (for vision in dim light) consists of 11-cis retinal specially bound to the protein opsin. • When rhodopsin is exposed to light, a series of photochemical isomerization occurs, which results in release of all trans retinal and opsin (with bleaching of the visual pigment). • This process triggers a nerve impulse that is transmitted by the optic nerve to the brain. • Regeneration of rhodopsin requires isomerization of all trans retinal back to 11-cis retinal, which spontaneously combines with opsin to form rhodopsin.

14. 2- Growth • Vitamin A is essential for normal growth of cells (by synthesis of important proteins) • bone growth is slow in vitamin A deficiency. • Animals deprived of vitamin A suffers keratinzation of taste buds leading to losing of their appetites.

15. 3-Reproduction • Retinol & retinalare essential for normal reproduction 1- supporting spermatogenesis in males 2- preventing fetal resorption in females • Retinoic acid is inactivein maintaining reproduction & the visual cycle, BUT promotes growth. Thus, retinoic acids given only since birth to animals, leads to blindness & sterility. 4-Epithelial cells maintenance • Vitamin A is essential for normal differentiation of epithelial tissues and mucus secretion.

16. Diet Sources of Vitamin A • Sources of retinol(retinyl esters) : animal source Liver, kidney, cream, butter & egg yolk • Sources of carotenes(precursors of vitamin A) : plant source Yellow & dark green vegetables & fruits Requirement for Vitamin A • OneRE(retinol equivalents) = 1mg of retinol 12mg of b-carotene 24mg of other carotenoids • RDA for adults 900 RE for males 700RE for females

17. Clinical indications of vitamin A 1-Dietary deficiency Vitamin A, administered asretinolor retinyl esters, is used to treat patients deficient in the vitamin (not retinoic acid) Night blindness One of the earliest signs of vitamin A deficiency Difficulty in seeing in dim light. Prolonged deficiency leads to irreversible loss of visual cell. (affection of rods of retina) Xerophthalmia Severe deficiency of vitamin A Pathological dryness of the epithelium conjunctiva & cornea. It may end in corneal ulcerations and blindness.

18. 2-Acne & Psoriasis Dermatologicproblemsofacne andpsoriasis are effectively treated with retinoic acidor its derivatives. • Mild cases of acneis treated by topical application of tretinoin (All- trans retinoic acid) which is too toxic for systemic administration. • Severe recalcitrant cystic acneunresponsive to conventional therapies, isotretinoin(13-cis retinoic acid) is administered orally

19. 3-Prevention of chronic diseases • Populations consuming diets high in b-carotene show decreased incidence of heart diseases & lung & skin cancer • Consumption of foods rich in b-carotene is associated with reduced risk of cataracts and macular degeneration

20. Toxicity of Retinoids I. Vitamin A excess(hypervitaminosis A syndrome) Amounts exceeding 7.5 mg/day of retinol 1-Excessive intake of vitamin A may cause the followings: • dry skin & pruiritis are early signs • liver enlarged, cirrhotic • increased intracranial pressure (mimic symptoms of brain tumours e.g. headache etc…) 2-Pregnant females should not ingest excessive amounts of vitamin A because of its potential for causing congenital malformations in developing fetus.

21. II. Isotretinoin drug(13-cis retinoic acid) 1-Teratogenic • So, absolutely contraindicated in women with childbearing potential. • Pregnancy should be excluded before initiation of treatment & adequate contraceptive (birth control) must be used 2-Risk of coronary heart diseases Prolonged treatment with 13-cis retinoic acid leads to hyperlipidemia & increase in LDL/HDL ratio with increased risk of coronary heart diseases.