Lecture 10 - Vitamins 1 PDF

Vitamins PHB231 Fat Soluble Vitamins Lecture 10 By the end of this lecture, you should be able to: Identify the difference between macro and micronutrients. Define vitamins. Illustrate the classification of vitamins. State the functions of fat-soluble vitamins. State the associated d...

Vitamins PHB231 Fat Soluble Vitamins Lecture 10 By the end of this lecture, you should be able to: Identify the difference between macro and micronutrients. Define vitamins. Illustrate the classification of vitamins. State the functions of fat-soluble vitamins. State the associated disorders of fat-soluble vitamins.  Nutrients A nutrient is defined as a substance that provides nourishment, essential for growth, development and the maintenance of life. Humans perform various functions, so well- structured system requires the nutrients (foods) in the right proportion so that normal metabolic functions would be established.  Vitamins Vitamins are chemically unrelated organic compounds that cannot be synthesized in adequate quantities by humans and, therefore, must be supplied by the diet. They differ from macronutrients at: Structure: They are individual units; they are not linked together. Function: Do not yield usable energy when broken down; they assist the enzymes that release energy from carbohydrates, fats, and proteins. Amount ingested: measured in micrograms (μg) or milligrams (mg), rather than grams (g). Classification Fat soluble vitamins  Fat soluble vitamins Vitamin A (Retinol) It is a fat-soluble vitamin that comes primarily from animal sources as retinol (preformed vitamin A), a retinoid. RDA is 900 retinol activity equivalents (RAE) for males and 700 RAE for females. In comparison, 1 RAE = 1 μg of retinol, 12 μg of β- carotene, or 24 μg of other carotenoids. A. Structure  A. Structure 1. Retinol: an alcohol, found in animal tissues as a retinyl ester with long-chain FA. It is the storage form of vitamin A. 2. Retinal: This is the aldehyde derived from the oxidation of retinol. Retinal and retinol can readily be interconverted. 3. Retinoic acid: This is the acid derived from the oxidation of retinal and can not give Retinol or Retinal. 4. β-Carotene: Plant foods contain β-carotene (provitamin A), which can be oxidatively and symmetrically cleaved in the intestine to yield two molecules of retinal.  B. Absorption and transport to and from liver 1. Retinyl esters from the diet are hydrolyzed in the intestinal mucosa. 2. Retinol (derived from esters and from the reduction of retinal from β- carotene cleavage) is re-esterified to long-chain FA within the enterocytes and secreted as a component of chylomicrons into the lymphatic system. 3. Retinyl esters contained in chylomicron remnants are taken up by, and stored in the liver. 4. When needed, retinol is released from the liver and transported through the blood to extrahepatic tissues by retinol-binding protein complexed with transthyretin.  C. Function Visual Cycle Rhodopsin, the visual pigment of the rod cells in the retina Epithelial cell maintenance Essential for normal differentiation of epithelial tissues and mucus secretion and, thus supports the body’s barrier-based defense against pathogens. Reproduction Support spermatogenesis in the male and prevent fetal resorption in the female.  D. Clinical indications 1. Deficiency: Mild: Nyctalopia (Night blindness) is difficulty to see in dim light. Severe deficiency: leads to xerophthalmia, a pathologic dryness of the conjunctiva and cornea, caused, in part, by increased keratin synthesis. Untreated: corneal ulceration and, ultimately, in blindness because of the formation of opaque scar tissue. 2. Skin conditions: Dermatologic problems such as acne, psoriasis and skin aging are treated with retinoic acid or its derivatives.  E. Retinoid toxicity 1. Vitamin A: excessive intake produces a toxic syndrome called hypervitaminosis A. Dry skin. Enlarged and cirrhotic liver. Rise of the intracranial pressure. Risk of teratogenicity in pregnant women. 2.  Fat soluble vitamins Vitamin D (Calcitriol): The D vitamins are a group of sterols that have a hormone-like function. The active molecule, 1,25-dihydroxycholecalciferol ([1,25-diOH-D3], or calcitriol), binds to intracellular receptor proteins. Vitamin D occurs naturally in fatty fish, liver, and egg yolk. Milk, unless it is artificially fortified, is not a good source. The RDA for individuals ages 1–70 years is 15 μg/day and 20 μg/day if over age 70 years. Breast milk is a poor source of vitamin D.  A. Distribution and metabolism 7-Dehydrocholesterol is an intermediate in cholesterol synthesis and converted to cholecalciferol in the skin. Ergocalciferol (vitamin D2), found in plants, and cholecalciferol (vitamin D3), found in animal tissues, are sources of preformed vitamin D activity. Vitamins D2 and D3 are not biologically active but are converted in vivo to calcitriol, the active form of the D vitamin, by two sequential hydroxylation reactions: 25-hydroxylation in the liver to form 25-hydroxycholecalciferol, the predominant form in the blood. 1-hydroxylation in the kidneys to form 1,25-diOH-D3 (calcitriol). Calcitriol formation is regulated by serum phosphate and calcium ions. Calcitriol  B. Function Maintenance of adequate serum levels of Ca2+ Intestine Bones Kidney Enhance Ca2+ When blood Minimize the absorption by Ca2+ is low, it loss of Ca2+ in stimulating the stimulates urine by synthesis of bone increasing the calcium resorption. reabsorption binding protein calbindin.  C. Clinical indication Nutritional Rickets Renal osteodystrophy Hypothyroidism Due to vitamin D Chronic kidney Lack of PTH causes deficiency, disease causes hypocalcemia and demineralization of decreased ability to hyperphosphatemia. bones cause Rickets form active vitamin Treated with vitamin in children and D as well as D and calcium Osteomalacia in increased retention supplementation. adults. of PO43−, resulting in Insufficient exposure hyperphosphatemia to daylight and/or and hypocalcemia. deficiencies in Alfacalcidol should vitamin D be administered. consumption.  D. Toxicity Like all fat-soluble vitamins, vitamin D can be stored in the body and is only slowly metabolized. High doses (100,000 IU for weeks or months) can cause loss of appetite, nausea, thirst, and weakness. Enhanced Ca2+ absorption and bone resorption results in hypercalcemia, which can lead to deposition of calcium salts in soft tissue (metastatic calcification). Excess vitamin D produced in the skin is converted to inactive forms.  Fat soluble vitamins Vitamin K: Sources of vitamin K: Diet : Vitamin K1: phylloquinone: plant origin in cabbage, kale, spinach, egg yolk, and liver. RDA is 120 μg/day for males and 90 μg for females. Normal Flora: Vitamin K2: menaquinones: intestinal flora. Supplement: Menadione (vitamin K analogue): synthetic can be converted to K2. Functions: Synthesis of blood clotting proteins. Synthesis of bone proteins.  A. Role of Vitamin K in blood clotting Vitamin K is required in the hepatic synthesis of prothrombin and blood clotting factors II, VII, IX, and X. Mechanism: Coenzyme that activates carboxylation of clotting factors by carboxylase enzyme. Carboxylation happens at glutamic acid residues of clotting factors forming γ- carboxyglutamyl residue (Gla). Gla has the ability to form a complex with calcium ion. Complexes of clotting factors with calcium can bind to platelets activating the conversion of prothrombin into thrombin thus clot formation. Why EDTA is used as an anticoagulant ?  A. Role of Vitamin K in blood clotting h = hydroquinone e = epoxide VKOR = vitamin K epoxide reductase. A. Role of Vitamin K in blood clotting  B. Vitamin K deficiency and toxicity Deficiency: True deficiency of vitamin K is rare as it is normally produced by normal gut flora. Because infants has sterile gut it is recommended newborn receives one prophylactic dose of vitamin K. Toxicity: Prolonged administration of large doses of menadione can produce hemolytic anemia and jaundice in the infant. Therefore, it is no longer used to treat vitamin K deficiency.  C. Vitamin K Cycle Active form of vitamin K (reduced form) is oxidized during carboxylation reaction of clotting factors. Active form s restored by Vitamin K epoxide reductase. Anticoagulants as warfarins work like inhibitors for Vitamin K epoxide reductase keeping vitamin K in the inactive form which interferes with clotting mechanism. C. Vitamin K Cycle  Fat soluble vitamins Vitamin E: The E vitamins consist of eight naturally occurring tocopherols, of which α-tocopherol is the most active). Vitamin E functions as an antioxidant in preventing nonenzymic oxidations (for example, oxidation of LDL and peroxidation of polyunsaturated FA). Note: Vitamin C regenerates active vitamin E.  A. Sources of Vitamin E Vegetable oils are rich sources of vitamin E. Liver and eggs contain moderate amounts. The RDA for α-tocopherol is 15 mg/day for adults. The vitamin E requirement increases as the intake of PUFA increases to limit FA peroxidation.  B. Importance and clinical significance in CVD Antioxidant effect of Vitamin E which makes it a good factor decreasing oxidative stress. Some studies claims vitamin E has protective effect against CVD due to decreasing oxidative stress and activation of transduction pathway for the transport and efflux of cholesterol. This results in cholesterol efflux from macrophages and the subsequent prevention of foam cell formation While other studies denies any beneficial effect of vitamin E against CVD.  C. Vitamin E toxicity Vitamin E is the least toxic of the fat-soluble vitamins. Toxicity is not observed with normal supply from vitamin E in diet. Prolonged high doses of Vitamin E supplement may interfere with blood clotting as vitamin E quinone may inhibit carboxylation of clotting factors (effect appear specially with patient receives vitamin E with anticoagulants like Warfarins).