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FAT SOLUBLE VITAMINS

Dr Greeshma Dept of Biochemistry. FAT SOLUBLE VITAMINS. NUTRIENTS. Macronutrients Carbohydrates Lipids Proteins Micronutrients Vitamins Minerals. Vitamins. Organic compounds required in minimal amount for normal growth and maintenance of good health

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FAT SOLUBLE VITAMINS

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  1. DrGreeshma Deptof Biochemistry FAT SOLUBLE VITAMINS

  2. NUTRIENTS • Macronutrients • Carbohydrates • Lipids • Proteins • Micronutrients • Vitamins • Minerals

  3. Vitamins • Organic compounds required in minimal amount for normal growth and maintenance of good health • Micronutrients Vitamins are derived from a variety of foods.

  4. Vitamins • Vitamine vital + amine (vital for life) (contain amino groups)

  5. VITAMINS: CHARACTERISTICS • Proper utilization of macronutrients • Not synthesized in sufficient quantities Vitamins that can be synthesized in our body: • Vitamin D : skin • Vitamin K, Biotin : intestinal flora • Niacin : from tryptophan

  6. VITAMINS: CLASSIFICATION • Fat soluble vitamins • vitamin A • vitamin D • vitamin E • vitamin K Water soluble vitamins vitamin B complex vitamin C

  7. FAT SOLUBLE VITAMINS • polyisoprenoid derivatives • Absorption require bile salts facilitated / active transport • Stored in liver • Deficiency occurs when stores are depleted • Toxicity is common

  8. FAT SOLUBLE VITAMINS

  9. VITAMIN DEFICIENCIES • Vitamin A deficiency - Xerophthalmia • Vitamin D deficiency - Rickets • Vitamin K deficiency - Clotting disorders

  10. FAT SOLUBLE VITAMINS • Chemistry • Metabolism • Functions • Nutritional aspects Sources RDA • Deficiency • Toxicity

  11. FAT SOLUBLE VITAMINS VITAMIN A

  12. VITAMIN A – structure • six membered ,β-ionone( cyclohexenyl) ring and a 11 carbon polyisoprenoid chain with a functional group. R

  13. VITAMIN A - Chemistry • 3 Biologically active forms • Retinal – aldehyde form • Retinol - alcohol form • Retinoic acid – oxidation of retinal • Its heat stable and light sensitive • Provitamin form is – βcarotene( green vegetables, • fruits and carrots) • Activated to vit A in the intestine .

  14. 11 12 VITAMIN A • β carotene is cleaved to two molecules of retinal in the human intestine. • 2 geometric isoforms all trans retinal 11-cis retinal Cleavage at this point can yield two molecules of Vit A

  15. VITAMIN A • Conversion to active form β-Carotene ( provitamin form) β -Carotene dioxygenase (intestine) Retinal Retinal +

  16. VITAMIN A Reductase • Retinol ( alcohol) Retinal ( aldehyde) NAD NADH+ H⁺ Retinoic acid

  17. VITAMIN A: METABOLISMdigestion and absorption Retinyl esters β carotene FFA Retinol Retinol Chylomicrons Intestinal lumen l Intestinal mucosal cell Diet β carotene β carotene -Carotene dioxygenase Retinal Retinal reductase Retinol FFA Retinylesters

  18. VITAMIN A: STORAGE AND TRANSPORT Target tissues Retinol binding protein (RBP) Retinol Retinol Liver Intestinal cell Diet Retinol Retinyl esters Chylomicron Retinol palmitate ( Storage)

  19. VITAMIN A: UPTAKE • Retinol-RBP complex binds to specific receptors on the retina, skin, gonads and other tissues • Attaches on DNA binding sites activation of genes

  20. VITAMIN A: FUNCTIONS • Retinal – vision (Prosthetic groups – visual pigments) • Retinol – Reproduction • Retinoic acid - growth and differentiation • β – Carotene – antioxidant • Mediate immune response • Maintain epithelial cell integrity • Anti carcinogenic action

  21. VITAMIN A: VISION(WALDS VISUAL CYCLE) • Retinal is a precursor for formation of visual pigment- rhodopsin (11 cis-retinal+opsin) • Rods of retina – dim light vision – Rhodopsin • Cones of retina – color vision – Conopsin Rhodopsin (11 cisretinal+ opsin) All trans retinal + Opsin (conformational changes) Generation of nerve impulse Vision (dimlight / color) light

  22. VITAMIN A:VISION(WALDS VISUAL CYCLE) • Generation of nerve impulse • Regeneration of Rhodopsin

  23. Vitamin A: Generation Of Nerve Impulse Hyperpolarisation (Nerve impulse) Visual centre OpsinAll trans retinal Dim Light Rhodopsin Photorhodopsin Bathorhodopsin Isomerisationand dissociation Lumirhodopsin Metarhodopsin I Closure of Na+ channels Metarhodopsin II Metarhodopsin III

  24. WALDS VISUAL CYCLE

  25. VITAMIN A: DARK ADAPTATION TIME Bright light depletes the stores of rhodopsin in rods When a person shifts suddenly from bright light to a dim light area, there is difficulty in seeing After a few minutes rhodopsin is resynthesized & vision is improved. This period is called “Dark adaptation time” time required to adapt the eye to see objects in dim light time taken to resynthesize rhodopsin Vitamin A deficiency: increased dark adaptation time

  26. VITAMIN A: GROWTH Retinoic acid : regulates growth, development and tissue differentiation -assist in glycoprotein synthesis and sulfation of the mucopolysaccharidesin bone matrix - Normal differentiation and mucous secretion of epithelium Prevents keratinisation of epithelial tissues.

  27. VITAMIN A: FUNCTIONS Reproduction: Regulates gene expression Embryo development- development of CNS, CVS, limbs and eyes Supports spermatogenesis, oogenesis and placental development. Antioxidant property β – Carotene: traps peroxy radicals prevent cardiovascular disease, cancer, cataract

  28. VITAMIN A: FUNCTIONS • Immune response • Stimulates the immune system • Regulate humoral response, cell-mediated immunity, • Vitamin A deficiency: infection ( due to keratinisation of mucosal lining of respiratory and gastrointestinal tracts)

  29. VITAMIN A: FUNCTIONS • Maintenaceof normal epithelium and skin and also prevents keratinisation. Vit A increases synthesis of glycoprotein, which is one of the constituents of membrane and mucous secretion • Retinol promotes synthesis of transferrin

  30. VITAMIN A: FUNCTIONS - retinol and retinoic acid act as a hormone and affect the transcription of specific proteins

  31. VITAMIN A: SOURCES • Retinoids • Fish liver oil • Egg • Milk • Butter Carotenoids Carrot Mango Papaya Green leafy vegetables Spinach Tomatoes

  32. VITAMIN A: RDA • Children – 400-600μg/day • Men – 750-1000 μg/day • Women – 750 μg/day • Pregnancy – 1000 μg/day • Lactation - 1200 μg/day

  33. KeratinizationVitamin A deficiency symptom

  34. VITAMIN A: DEFICIENCY • Affects 1/3 of children < 5 years • Preventable blindness in children Causes • Primary deficiency: Reduced intake • Secondary deficiency: Liver cirrhosis, renal disease Protein – calorie malnutrition Nephrotic syndrome, malabsorption, chronic diarrhea, pancreatic insufficiency Alcoholism – destruction of stellatecells

  35. Causes of deficiency 1. malnutrition 2.Steatorrhea as in obstructive jaundice (defective absorption) and pancreatitis(indigestion of fat) 3. Cirrhosis of liver (reduced synthesis of retinol binding protein, RBP). 4. Chronic nephrosis (RBP is excreted through urine)

  36. VITAMIN A: DEFICIENCY MANIFESTATIONS • Ocular manifestations (earliest signs: loss of sensitivity to green light & impairment of adaptation to dim light) • Infections • Renal calculi • Growth retardation

  37. VITAMIN A: OCCULAR MANIFESTATIONS • Nyctalopia (Night blindness) - diminished visual acuity in dim light • Xerophthalmia - Dryness of cornea and conjunctiva Keratinization of epithelial tissues Reduction in mucus secretion • Keratomalacia - softening of cornea

  38. VITAMIN A: OCCULAR MANIFESTATIONS • Bitot’s spots - greyish- white plaques • increased thickness of conjunctiva • build-up of keratin debris in opaque plaques – heaping up of desquamated keratinized epithelial cells

  39. VITAMIN A: INFECTIONS • Skin infections • Respiratory tract infections • Urinary tract infections Biochemical basis • keratinizing metaplasia of epithelium • atrophy of epithelium • reduced mucus secretion • reduced immune response • Reproductive failure and growth retardation observed in experimental animals

  40. VITAMIN A: assesment of deficiency • Dark adaptation time: increased • Serum RBP is reduced (Normal RBP: 40 – 50μg/ml) • Serum vitamin A is reduced (Normal vitamin A :20 - 100μg/dl)

  41. VITAMIN A: Treatment Of Deficeincy • Supplementation of vitamin A

  42. Vitamin A: Therapeutic Applications 1. Reduces Complications Of Measles 2. Precancerous Lesions Respond To Carotenoids 3. As Topical Creams For Acne And Psoriasis

  43. VITAMIN A: TOXICITY (HYPERVITAMINOSIS A) • Long-term supplement use • Fatal dose (12 g) • Nausea • Vomiting • Headache • Blurred vision

  44. VITAMIN A: CAROTENODERMIA • Orange-yellow discoloration of the skin. • excess intake of carotenoids

  45. FAT SOLUBLE VITAMINS VITAMIN D

  46. VITAMIN D: CHEMISTRY • Antirachiticvitamin • Sunshine vitamin • Acts like steroid hormone • Role in calcium and Phosphorus metabolism

  47. VITAMIN D: CHEMISTRY • Ergosterol ( Provitamin D2) - plants, fungi, irradiated yeast • ErgosterolErgocalciferol(Vitamin D2) • 7-dehydrocholesterol Cholecalciferol(Vit D3) • Vitamin D is the only vitamin synthesized from cholesterol sunlight sunlight

  48. 7 dehydrocholesterol and ergosterol are provitamins

  49. VITAMIN D: METABOLISM Skin Cholecalciferol (Vit D3) Transport Vitamin D binding protein Liver • Vitamin D2 and vitamin D3 are biologically inactive

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