Vitamin A

An introduction to Vitamins

1. VITAMINS Dr. P. N. ANSIL

2. What are vitamins ? Essential organic compounds that are required in small amounts for normal growth, maintenance of good health and for the proper utilization of other nutrients . Nutrients that our body does not make on its own. Thus we must obtain them from the foods we eat, or via vitamin supplements.

3. Classification of Vitamins

4. Fat soluble vitamins Soluble in fat Absorbed along with other lipids Requires carrier proteins Stored in liver Deficiency manifests only when stores are depleted Toxicity - Hypervitaminosis may result Single large does may prevent deficiency E.g. A,D,E & K Soluble in water Absorption is simple No requirement of carrier protein Excreted in urine Deficiency manifests rapidly as there is no storage Unlikely , since excess is excreted Regular dietary supply is required E.g. B complex & C Difference between fat soluble and water soluble vitamins Water soluble vitamins

5. Hydrophobic Isoprene derivatives They cannot be synthesized by the body Supplied by the diet Absorption along with fat Transport: By lipoprotein & Specific binding protein Surplus amount stored – liver & adipose tissue Excess consumption leads to accumulation & toxic effects. Lipid soluble vitamins - common features

6. VITAMIN A

7. Introduction Vitamin A is an essential nutrient needed in small amounts for the normal functioning of the visual system, and maintenance of cell function for growth, epithelial integrity, red blood cell production, immunity and reproduction. Vitamin A deficiency (VAD) is a major nutritional concern in poor societies, especially in lower income countries like INDIA.

8. Where does it come from? Animal Sources Eggs Meat Cheese Milk Liver Kidney Fish liver oils Plant Sources Carrots Sweet Potatoes Apricots Broccoli Spinach Pumpkin Papaya Mango

9. Vitamin A (Preformed and Provitamin ) Retinoids : Natural & synthetic forms of Vitamin A Preformed: Three preformed compounds that are metabolically active and found in animal products Retinol – alcohol form Present in animal tissues as retinyl ester with long chain fatty acid Retinal or retinaldehyde – aldehyde form Obtained by oxidation of retinol Retinal & Retinol are interconvertible Retinoic acid – acid form Produced by oxidation of Retinal

10. Provitamin : Carotenoids ( β -carotene) can yield 2 retinols when metabolized in the body β -carotene found in plants Has 2 β -ionone rings connected by a polyprenoid chain

11. Absorption Retinoids Retinyl esters broken down to free retinol & FA in small intestine - requires bile, digestive enzymes, integration into micelles Once absorbed, retinyl esters reformed in intestinal cells 90% of retinoids can be absorbed Carotenoids Absorbed intact, absorption rate much lower Intestinal cells can convert carotenoids to retinoids

12. Approximately 80% is absorbed . It is passed along with fat through the lymphatic system into blood stream . Absorption is poor in case of diarrhea , jaundice and abdominal disorder. Absorption increases if taken with fat. Vitamin A which is not absorbed is excreted within 1 or 2 days in feces .

13. Transport Transported via chylomicrons from intestinal cells to the liver Transported from the liver to target tissue as retinol via retinol-binding protein (RBP; MW. 21,000). From intestine to Liver From liver to tissue Plasma retinol binding protein(RBP)– to cell membrane- Cellular retinoic-acid binding protein(CRBP) –retinol—cytoplasm—HRE— GENE EXPRESSION Chylomicron

14. Summary of Vitamin A absorption

15. Summary of the functions of Vitamin A compounds

16. Storage The liver has enormous capacity to store in the form of retinol palmitate . Under normal conditions a well-fed person has sufficient Vitamin A reserves to meet his need for 6 to 9months or more .

17. Excretion of Vitamin A Not readily excreted Kidney disease and aging increase risk of toxicity because excretion is impaired

18. Functions of Vitamin A Vision : Vitamin A is a component of the visual pigment rhodopsin . Retinal is bound to the protein opsin . Growth : Vitamin A deficiency causes loss of appetite. Slow bone growth. Affects CNS. Reproduction : Retinol and retinal are essential for normal reproduction Maintenance of epithelial cells : Essential for normal differentiation of epithelial tissues and mucus secretion

19. Role of Vitamin A in Vision Visual Cycle (Wald’s Visual Cycle) A process by which light impacting on the retina of the eye is converted to an electrical signal The optic nerve carries the electrical signal to the brain (nerve impulse) The brain processes the signal into an image

20. Role of Vitamin A in Vision Retina is a light-sensitive layer of cells at the back of the eye where an image is formed Retina consists of: Rod and cone cells (photosensitive cells) Rod cells process black & white image Cone cells process c o l o r image

21. Rod Cell Cone Cell

22. Role of Vitamin A in Vision Normal vision depends on the retina and on adequate vitamin A In the retina, vitamin A in the form of retinal binds to a protein called opsin to make rhodopsin [11 -cis – retinal- opsin ] in rod cells Rhodopsin is a light-sensitive pigments

23. Wald’s Visual Cycle

24. The Visual Cycle

25. Role of Vitamin A in Vision When stimulated by light, vitamin A isomerizes from its bent ‘ cis ’ form to a straighter ‘ trans ’ form and detaches from opsin The opsin molecule changes shape, which sends a signal to the brain via optic nerve and an image is formed Most retinal released in this process is quickly converted to trans-retinol and then to cis -retinal , to begin another cycle

26. Role of Vitamin A in Vision Dark Adaptation time Bright light depletes rhodopsin ( photobleaching ) Sudden shift from bright light to darkness causes difficulty in seeing Rhodopsin is synthesized in a few minutes and vision is improved in the dark

27. Role of Vitamin A in Vision The time required to synthesize rhodopsin in the dark is called dark adaptation time It is increased in vitamin A deficiency

28. Bleaching of Rhodopsin Bleaching - When exposed to light, the colour of rhodopsin changes from red to yellow Occurs in a few milliseconds Unstable intermediates are formed Rhodopsin Prelumirhodopsin Lumirhodopsin Metarhodopsin I Metarhodopsin II All- trans -retinal + Opsin

29. Light strikes the retina – biochemical changes – membrane hyperpolarization – generate nerve impulse. Hyperpolarization of the membrane is brought about by a visual cascade involving cGMP Visual cascade and cGMP

30. Visual cascade involving cGMP Decrease in cGMP closes the Na + channels in the membranes of the rod cells Result in hyperpolariztion – an excitatory response transmitted through the neuron network to the visual cortex of the brain

31. Colo ur vis ion Cones are specialized in bright and colour vision Governed by colour sensitive pigmens iodopsin – green cyanopsin – blue porphyropsin – red These pigments are complexes of protein & Vitamin A Bright light strikes retina – depending on the particular colour of the light – one or more pigments are bleached – passes nerve impulse to brain as specific colour

32. Functions of Vitamin A: Growth and Differentiation of Cells Retinoic acid is necessary for cellular differentiation Important for embryo development, gene expression Retinoic acid influences production, structure, and function of epithelial cells that line the outside (skin) and external passages (mucus forming cells) within the body

33. Epithelial cell ‘integrity’ Many epithelial cell require Vitamin A for proper differentiation and maintenance Lack of Vitamin A leads to dysfunction of epithelia The skin becomes keratinized and scaly, and mucus secretion is suppressed

34. Functions of Vitamin A: Immunity Deficiency leads to decreased resistance to infections Supplementation may decrease severity of infections in deficient person

35. Role in Prevention of cardiovascular disease Antioxidant capabilities Role in Cancer prevention Antioxidant capabilities Lung, oral, and prostate cancers Studies indicate that vitamin A-containing foods are more protective than supplements

36. What does RDA mean? Recommended Dietary Allowances These are suggested levels of essential nutrients considered adequate to meet nutritional needs of healthy individuals. Infants and children - 400-600µg/day Men - 750-1000µg/day Women - 750µg/day Pregnancy - 1000µg/day Lactation -1200µg/day

37. Vitamin A Deficiency and Diseases Nyctalopia (night blindness) Xerophthalmia Bitot ’ s spots Keratomalacia Complete blindness (in severe deficiency)

38. 1. Night Blindness Visual acuity is diminished in dim light Occurs as a result of inadequate pigment in the retina. The dark adaptation time is increased Found in pregnant women in some instances , especially during the last trimester of pregnancy when the vitamin A needs are increased .

39. It is the most specific VAD, and is the leading preventable cause of blindness Conjunctiva becomes dry, thick and wrinkled Conjunctiva gets keratinized and loses its normal transparency Cornea becomes glazy & lusterless 2. Xerophthalmia

40. 3. Bitot’s Spot Tissue spots that develop around the eye ball, causing severe dryness in the eyes . Seen as grayish-white triangular plaques firmly adherent to the conjunctiva.

41. 4.Keratomalacia One of the major cause for blindness in India . Cornea becomes soft and may burst Prolonged xerophthalmia leads to keratomalacia (softening of the cornea) If the eye collapses vision is lost.

42. Other Symptoms of VAD Alteration of skin and mucous membrane Hepatic dysfunction Headache Drowsiness Peeling of skin

43. Dark adaptation test Serum RBP Serum vitamin A 25 – 50 µg/dl ASSESSMENT OF DEFICIENCY

44. Eating of polar bear liver Excess supplementation of Vitamin A When? TOXICITY One ounce of polar bear liver contains enough vitamin A (retinol) to kill a person!

45. Hepatomegaly Increased cerebrospinal fluid pressure Disturbance in calcium homeostasis – skletal decalcificaion – tendrness of long bones Skin - Excessive dryness, desquamation TOXICITY

46. Dietary Deficiency Retinoic acid Psoriasis Pro- myelocytic leukemia c. Acne THERAPEUTIC USES

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