fat soluble vitamins
DESCRIPTION
Fat Soluble Vitamins. Vitamin A Vitamin D Vitamin E Vitamin K. Vitamin A and Carotenoids. -carotene - the major provitamin A carotenoid. Retinol (Vitamin A). -Carotene is split in the middle by β -carotene oxygenase into two molecules of retinol . Beta carotene and two examples - PowerPoint PPT PresentationTRANSCRIPT
Fat Soluble VitaminsFat Soluble VitaminsVitamin AVitamin DVitamin EVitamin K
-Carotene is split in the middle by β-carotene oxygenase into two molecules of retinol.
-carotene - the major provitamin A carotenoid
Retinol (Vitamin A)
Vitamin A and Vitamin A and CarotenoidsCarotenoids
β-Carotene
-Carotene
-Carotene
Beta carotene and two examples Beta carotene and two examples of other provitamin A carotenoids of other provitamin A carotenoids
Carotenes =Carotenes =Hydrocarbon CarotenoidsHydrocarbon Carotenoids
β-Carotene
Lycopene
-Carotene
Oxycarotenoids = XanthophyllsOxycarotenoids = Xanthophyllsβ-Cryptoxanthin
Zeaxanthin
Lutein
OH
Vitamin A Sources in DietVitamin A Sources in Diet
• Preformed vitamin A (primarily as retinyl esters) comes from animal products.
• Plant sources of vitamin A actually supply provitamin A carotenoids.
• In US, carotenoids provide only 25% Vitamin A in diet .
Foods Rich in CarotenoidsFoods Rich in Carotenoids
-caroteneβ-carotene
lycopene
luteinβ-carotene
luteinβ-carotene
-caroteneβ-carotene
β-carotene
Foods Rich in CarotenoidsFoods Rich in Carotenoids
β-carotenein cantaloupe,lycopenein watermelon
β-cryptoxanthinlycopene
β-carotene
β-cryptoxanthin
Retinyl palmitate
11-cis-retinal
Retinal, retinaldehydeall-trans-retinal
Retinoic acid
Retinoids: Biologically ImportantVitamin A compounds
Note: Meat (i. e., muscle) is low in Vitamin A
Foods Rich in Vitamin AFoods Rich in Vitamin A
Foods Rich in Vitamin AFoods Rich in Vitamin A
β-carotene-carotene
retinyl esters
retinyl estersβ-carotene
Retinol Activity Equivalent (RAE): 1μg RAE = 1 μg retinol = 2 mg -carotene in oil = 12 μg dietary β-carotene
= 24 μg other pro-A carotenoids
Previously vitamin A activity of dietary pro-A carotenoids was overestimated by a factor of 2. Retinol Equivalent: 1μg RE = 6 μg dietary -carotene or 12 μg other pro-A carotenoids (National Research Council, 1989).
1μg retinol = 3.33 IU retinol = 20 IU -caroteneIU (International Unit) = 0.3 μg retinol =0.6 μg β-carotene
Vitamin A activity of Vitamin A activity of carotenoids carotenoids
Adequate Intake 0- 6mo 400 μg RAE 7-12 mo 500 μg RAERecommended 1- 3 y 300 μg RAE Dietary 4- 8y 400 μg RAEAllowance (RDA) 9-13y 600 μg RAE >14y males 900 μg RAE >14y females 700 μg RAE Pregnancy RDA 770 μg RAELactation RDA 1300 μg RAE
Tolerable Upper Intake Level (UL) 3000 μg RAE
2001 Dietary Reference Intakes 2001 Dietary Reference Intakes for Vitamin Afor Vitamin A
Dietary Vitamin A DigestionDietary Vitamin A Digestion
FoodBeta Carotene Retinyl Esters
Retinol
Pancreatic and Brush Border
Lipases
Carotene-15,15’-
oxygenase
Dietary Vitamin A AbsorptionDietary Vitamin A Absorption
Provitamin A ConversionProvitamin A Conversion
• Provitamin A carotenoids are thought to be converted by the intestine to vitamin A in inverse proportion to the amount present in the lumen (?) and with great individual variability.
• Absorbed intact provitamin A carotenoids circulate in blood and are deposited in various tissues, which also may convert them to vitamin A (liver, kidney, testis, ovary).
• Low absorption and conversion of provitamin A carotenoids make it impossible to produce vitamin A toxicity from plant sources.
Chyloremnants
retinylesters
Vitamin A storedin stellate cellsas retinyl esters
RBP =RetinolBindingProtein
Transthyretin =T4-bindingprotein
Hepatic Metabolism and Storage of Vitamin AHepatic Metabolism and Storage of Vitamin A
(TTR = Transthyretin)
Vitamin A FunctionsVitamin A Functions• Normal vision• Gene expression control• Reproduction (spermatogenesis)• Fetal development• Normal growth• Epithelial cell differentiation• Immune function
Carotenoid Actions and Carotenoid Actions and AssociationsAssociations
• Protection of skin and eyes from light• Antioxidant capacity (quenching free
radicals, protecting cells from oxidative damage)
• Decreasing risk of cancer (inhibition of neoplastic transformations)
• Enhancement of cell communication (expression of gap junction protein)
11-cisretinal
All-transretinal
Retinol
Retinylesters
Rhodopsin
Opsin
Bleachedrhodopsin
LIGHTphoton
Signal tooptic nerve
Vitamin A in Visual Cycle Vitamin A in Visual Cycle
Retinoic acidRetinoic acid
• a vertebrate morphogen• a therapeutic agent• a known human teratogen
Retinal Oxidase(irreversible)
Retinal
Retinoic acid
NAD or FAD
NADH or FADH2
Synthesis of Retinoic AcidSynthesis of Retinoic Acid
Gene Expression Control by Retinoic AcidGene Expression Control by Retinoic Acidvia DNA-binding nuclear receptorsvia DNA-binding nuclear receptors
Immune Functions of Immune Functions of Vitamin AVitamin A
• Maintaining level of circulating killer cells (anti-viral, anti-tumor)
• Increasing phagocytosis of macrophages
• Increasing production of lymphocytes
• Maintaining epithelial integrity
Retinoic acid and analogues are used topically Retinoic acid and analogues are used topically and systemically for treatment of psoriasis and and systemically for treatment of psoriasis and acne.acne.Severe acne before & after sytemic treatment Severe acne before & after sytemic treatment with 13-with 13-ciscis retinoic acid (isotretinoin, retinoic acid (isotretinoin, Accutane™)Accutane™)
Before After
Retinoic acid and related compounds are teratogenic when used in pharmaceutical doses. This is directly related to their role as morphogens in embryonic development.
The use of retinoic acid or synthetic analogues by pregnant women carries a high risk of birth defects in their infants. The most critical period is the first trimester of pregnancy.
For this reason, the use of retinoic acid, isotretinoin(13-cis-retinoic acid, Accutane) is contraindicated for pregnant women or women who may become pregnant.
Birth defects in child of woman taking Birth defects in child of woman taking systemic retinoic acid for psoriasissystemic retinoic acid for psoriasis
Vitamin A ToxicityVitamin A Toxicity
Acute intoxication (150 mg dose): nausea, vomiting, headache, vertigo, blurred vision, bulging fontanel in infants due to increased cerebrospinal fluid pressure
Chronic intoxication (30 mg/day): fatigue, irritability or lethargy, desquamation, alopecia, brittle nails, liver abnormalities (hepatomegaly, fibrosis, cirrhosis), bone loss and bone pain
Skeletal bone loss – osteoporosis (3 mg/day = UL) in older subjects
Hypercarotenosis = Carotenemia
Vitamin A Deficiency -Vitamin A Deficiency -XerophthalmiaXerophthalmia
• The impaired dark adaptation found in vitamin A deficiency is followed by conjunctival xerosis and keratinization.
• The latter gives rise to plaques comprised of layers of keratinized epithelial cells known as Bitot’s spots
• As deficiency progresses, keratomalacia develops, i.e., cornea becomes soft and milky in appearance and finally disentegrates, leading to blindness
Early conjunctival xerosis Early conjunctival xerosis (xerophthalmia)(xerophthalmia)
Reduction in Goblet Cell Mucin
leads to dry eyes
Later Stages of Vitamin A deficiency Later Stages of Vitamin A deficiency – Bitot’s Spots– Bitot’s Spots
Bitot’s Spot
Severe Vitamin A Deficiency - Severe Vitamin A Deficiency - KeratomalaciaKeratomalacia• Keratomalacia, involving cornea, results in blindness.• Vit A deficiency is the leading cause of preventable blindness in the world.
Other Symptoms of Vitamin A DeficiencyOther Symptoms of Vitamin A Deficiency• Failure of growth in children• Faulty bone modeling• Nerve lesions• Increased cerebrospinal fluid pressure• Follicular hyperkeratosis• Increased morbidity and mortality from
measles and diarrhea vitamin A is used for treatment of
measles
Vitamin AVitamin Adeficiencydeficiency
Follicularhyperkeratosis