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Vit A 3 pp - VITAMIN A 2011 Vitamin A Discovery Discovered...

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VITAMIN A 2011 Vitamin A Discovery Discovered in early 1900s by McCollum (Univ Wisconsin) and Osborne and & Mendel (Yale) Both groups studied effects of diets with purified protein and carbohydrate on growth and survival of young rats Growth ceased and rats died unless supplemented with butter, fish oils etc Unknown substance called “fat-soluble A” • Steenbock: –Factor in yellow vegetables with Vitamin A Discovery similar functions as fat-soluble factor A
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Vitamin A: Chemical Forms • Retinol • Retinol retinal • Retinal retinoic acid • Retinol can be oxidized reversibly to retinal Retinol can be oxidized reversibly to retinal same biological properties Retinal can be irreversibly oxidized to retinoic acid active in growth but not vision or reproduction Vitamin A: Structure • Chemical Forms –Retinol usually in all-trans fi i configuration –Usually present in tissues in esterified form (usually with palmitate)
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–Carotenoids •plant origin Vitamin A: Structure - carotene •essentially 2 molecules of retinal attached tail to tail
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Vitamin A: Food/ Supplement Sources • Preformed retinol-animal products – Liver – Egg yolk – Margarine (fortified) Margarine (fortified) – Milk-most fortified – Fish (tuna, sardines, herring) – Cod liver oil – Supplements- usually esters •Dietary vitamin A as retinyl ester - retinyl palmitate •Emulsification of fat-micelles taken up Digestion and Absorption Vitamin A •Retinyl esters hydrolyzed in lumen or brush border of cell Intracellular Retinoid-Binding Proteins Four cellular retinol-binding proteins (CRBP-I-IV) and 2 cellular retinoic acid binding proteins (CRABP-I & II) – expressed in different cells and tissues solubilize retinoids – protect from degradation – protect membranes which unbound A can damage – escort retinoids to enzymes that metabolize them
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• In small intestine CRBP-II is abundant –escorts retinol to lecithin:retinol Cellular Retinoid Binding Proteins escorts retinol to lecithin:retinol acyltransferase (LRAT) • esterifies retinol Provitamin A Carotenoids to Retinoids • Humans can absorb carotenoids intact • Cleaved within the mucosal cell or can be transported unmetabolized • Can also be cleaved in liver • Cleavage enzyme is 15,15’-dioxygenase – Forms 2 molecules of retinal
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Some beta-carotene can be absorbed intact Vitamin A Absorption • Retinol must be esterified to leave mucosa • Newly formed retinyl esters incorporated into chylomicrons – Chylomicrons enter lymphatic circulation Vitamin A Transport to Liver • Some retinyl esters removed from chylomicrons by tissues –chylomicron remnants remain chylomicron remnants remain • Chylomicron remnants deliver retinyl esters to liver
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• Retinyl esters taken up by liver parenchymal cells –Esters are hydrolyzed within the Vitamin A Liver Uptake & Metabolism Esters are hydrolyzed within the hepatic cells and retinol stored in stellate cells as retinyl esters
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