Summary

This document provides an overview of lipid-soluble vitamins, including their definition, classifications, and general aspects of deficiencies and treatment.

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Vitamins Definition  Vitamins can be defined as a group of essential micronutrients that generally have the following criteria: 1. Organic compounds that are distinct from carbohydrate, proteins and lipids. 2. Natural components...

Vitamins Definition  Vitamins can be defined as a group of essential micronutrients that generally have the following criteria: 1. Organic compounds that are distinct from carbohydrate, proteins and lipids. 2. Natural components of foods that present in minute amounts. 3. Not synthesised by the body in amounts needed to meet the needs, (except for ?). 4. Essential for normal physiological function such as maintenance, growth, development and reproduction. 2 5. In their absence or insufficient supply, specific syndromes are caused. Vitamin Classes  Vitamins can be classified based on their solubilities into: 1. Fat-soluble vitamins including A, D, E and K 2. Water-soluble vitamins including ascorbic acid and vitamin B family (thiamin, riboflavin, niacin, pyridoxine, biotin, pantothenic acid, folate and cobalamin).  Fat-soluble vitamins are absorbed passively and are transported with the dietary lipids. They are found in the cellular membranes as well as the lipid droplets. They are excreted with feces.  Water-soluble vitamins are absorbed by passive and active transport. They are not stored in the body, where they are excreted with urine. Thus, their regular dietary consumption is necessary. 3 General aspects of vitamins deficiencies and treatment  Vitamin deficiency may result from either factor: 1. Inadequate intake of food enriched with the vitamin in order to meet the nutrient requirements. Or: 2. Inadequate absorption Or metabolism of the vitamin, although it is consumed in the proper amount.  Treatment of vitamin deficiency is generally based on administration of large doses of the vitamin by different routes as well as increasing dietary intake of that vitamin. 4 1. Fat soluble vitamins Vitamin A  Vitamin A (retinoids) refer to three compounds: alcohol (retinol), aldehyde (retinal) and the acid (retinoic acid).  Plants also contain a group of compounds known as carotenoids, where the β- carotene is the most important one.  In the body, stored retinol is esterified to a fatty acid (palmitate, called retinyl- palmitate). These active forms of vitamin A are only found in animal 5 products. Carotenoids are also metabolise to retinoids in the body. 1. Fat soluble vitamins Vitamin A  Functions of vitamin A: Mainly, vitamin A has an essential role in vision, where retinal is the structural component of visual pigments of the rod and cone cells (which are photoreceptor cells) of the retina, where retinal is essential to photoreception. The 11-cis- retinal constitutes the photosensitive group of various pigment proteins (rhodopsin in the rods and iodopsin in the cones). Photoreception results from light-induced isomerisation of 11-cis-retinal to the completely all-trans forms. In the rod, rhodopsin (rhodopsin consists of opsin protein moiety and reversibly covalently bound cofactor, retinal) progresses through a series of reactions leading to the dissociation of bleached rhodopsin into all-trans- retinal and opsin. Such reaction is coupled to nervous stimulation of visual centers of the brain. All-trans-retinal are converted back to the 11-cis-retinal 6 for subsequent binding to opsin. 1. Fat soluble vitamins Vitamin A The vision cycle 7 1. Fat soluble vitamins Vitamin A  Deficiency of vitamin A: 1. Blindness; due to inability to synthesise adequate amounts of the visual pigments. 2. Night blindness (nyctalopia); an impairment ability to adapt from being in bright light to being in darkness. 3. Xerophthalmia (dry eyes, the eye fails to produce tears); dryness of conjunctivae and cornea. If untreated it can lead to corneal ulceration and ultimately blindness. http://upload.wikimedia.org/wikipedia/commons/thumb/f/f1/Pink_eye.jpg/190px-Pink_eye.jpg 4. Follicular hyperkeratosis; a characteristic changes in skin texture, where the hair follicles are blocked with plugs of keratin causes the distinctive “goose flesh”. The skin becomes dry, scaly and rough. 8 1. Fat soluble vitamins Vitamin A  Toxicity of vitamin A: Large doses of vitamin A overcome the capacity of the liver to store the vitamin which produces intoxication leading to a liver disease. Hypervitaminosis A in humans is characterised by: dry lips, dryness in nasal mucosa and eyes, scaling and peeling of skin, Hair loss and nail fragility, headache, nausea and vomiting. Increase hip fracture was also reported in women. Toxicities due to carotenoids are low, and accumulation of β-carotene have no side effects apart from yellowing the skin (hypercarotenodermia). 9 1. Fat soluble vitamins Vitamin D  Vitamin D is known as the sunshine vitamin, as the modest exposure to sunlight is sufficient for most people to produce their own vitamin D using the ultraviolet light of the sun and sterol in the skin.  Two sterols can serve as precursors of vitamin D: 1. 7-Dehydrocholesterol, in animals. 2. Ergosterol, in plants. Each of the precursors undergo a reaction of photolytic ring opening when exposed to ultraviolet light: 1. 7-Dehydrocholestrol → cholecalciferol or vitamin D3 2. Ergosterol → Ergocalciferol or vitamin D2  In turn, cholecalciferol and ergocalciferol undergo metabolism to the active form, 1,25-dihydroxyvitamin D3 (calcitriol). 10 1. Fat soluble vitamins Vitamin D 11 1. Fat soluble vitamins Vitamin D  Functions of vitamin D (calcitriol): Calcitriol involved in the maintenance of calcium and phosphorus homeostasis, which is attained by three different ways: 1. Synthesise and facilitating the function of proteins that enhance the absorption of dietary calcium and phosphorus from the gut. 2. Maintenance of normal blood levels and bone resorption of calcium and phosphorus, by the moving these minerals from the bone to the blood and vise versa. This is achieved by calcitriol together with parathyroid hormone and estrogen. 3. Maintenance of normal blood levels of calcium and phosphorus by increasing the renal 12 tubular re-absoprtion of calcium and phosphate in the kidneys. 1. Fat soluble vitamins Vitamin D  Deficiency of vitamin D: 1. Rickets; which is a result of deficiencies of calcium and phosphorus. It is characterised by structural abnormalities of the weight-bearing bones, bone pain, muscular tenderness and hypocalcemic tetany. Bones cannot withstand ordinary stress resulting in bowed legs “knock knees”, beaded ribs, pigeon breast and frontal bossing of the skull. 2. Osteomalacia; a disease involves a reduction in bone density (bone is soft and the proportion of minerals is less than organic material) and the presence of pseudofractures in specific bones and muscular weakness. 3. Osteoporosis; a disease involves diminished bone mass or weight (bone is porous and brittle and proportion of minerals to organic material such as collagene is within the reference range) with a normal histological appearance. It is associated with age and particularly in post-menopausal women, sine it is a multifactorial disease that is also 13 associated with low estrogen levels. 1. Fat soluble vitamins Vitamin D  Toxicity of vitamin D: Extensive intake of vitamin D could leads to intoxication (hypervitaminosis D) characterised by high serum levels of calcium (hypercalcemia) as well as phosphorus (hyperphosphatemia). Such condition can ultimately cause calcification of soft tissue (calcinosis) in organs including heart, lungs, kidney and ears (deafness). Patients often have headache and nausea. 14 1. Fat soluble vitamins Vitamin E  Vitamin E has a fundamental role in protecting the body against the damaging effects of free radicals that formed metabolically or are presented in the environment.  Vitamin E has two classes; tocopherols and much less biologicaly active related compound, tocotrienols.  The most important of these is α-tocopherol. 15 1. Fat soluble vitamins Vitamin E  Functions of vitamin E: Vitamin E is located in the lipid portion of the cell membranes and it functions as an antioxidant, where it protects the unsaturated phospholipids of the membrane from oxidative degradation by free radicals (such as high reactive oxygen species). Vitamin E has the ability to convert these radicals to harmless metabolites by donating hydrogens to the free radicals such as by converting ROO to ROOH (free ⚫ radical scavenging), in two steps to finally convert α-tocopherol to α-tocopherol quinone. α-tocopherol α-tocopherol quinone 16 1. Fat soluble vitamins Vitamin E  Deficiency of vitamin E: 1. Vitamin E-deficient cells exposed to an oxidative stress experience more rapid injury and necrosis. 2. In general, vitamin E deficiency targets neuromuscular, vascular and reproductive systems.  Toxicity of vitamin E: Vitamin E is one of the least toxic of the fat-soluble vitamins. This is due to the toleration of high intakes (high doses). However, very high dose of vitamin E decreases the body’s ability to use other fat-soluble vitamins, which leads to disorders related to deficiencies of these vitamins. For example, animals fed on excessive amounts of vitamin E developed impaired bone mineralization, impaired hepatic vitamin A storage and prolonged blood clotting. 17 1. Fat soluble vitamins Vitamin K  Vitamin K plays an essential role in blood clotting.  Naturally occurring vitamin K forms: 1. Phylloquinones (vitamin K1 series, synthesised by green plants) and 2. Menaquinones (vitamin K2 series, synthesised by bacteria).  Menadione (vitamin K3, a synthetic chemical compound used as a nutritional supplement), potency is twice as that of other two forms, and it is converted in liver to menaquinones (vitamin K2). 18 1. Fat soluble vitamins Vitamin K  Both of vitamin K1 series and vitamin K2 series have 2-methyl-1,4-nephthoquinone ring and alkylated side chains. Vitamin K3, on the other hand, has the ring structure, but no side chain. 19 1. Fat soluble vitamins Vitamin K  Functions of vitamin K:  Through vitamin K cycle, vitamin K plays an essential role in blood clotting. Vitamin K cycle is a process in which glutamic acid residues in clotting plasma proteins (such as thrombin) are carboxylated by vitamin K to form carboxy-glutamate which binds calcium as part of blood coagulation process.  In this process, vitamin K (in hydroquinone form) is oxidised to be converted to an epoxide, then it is restored back to its hydroquinone form by epoxide reductase followed by quinone reductase. 20 1. Fat soluble vitamins Vitamin K  In some patients, such as those who suffer from thrombosis, vitamin K cycle can be disrupted by inhibiting the re-generation of the reduced vitamin K ? (by drugs such as warfarin and dicumarol (anticoagulants). 21 1. Fat soluble vitamins Vitamin K  Deficiency of vitamin K: The predominant sign of vitamin K deficiency is hemorrhage, which is a severe cause of fatal anaemia. Such condition is characterised by prolonged blood clotting time (hypoprothrombinemia).  Toxicity of vitamin K: No any toxic effect was shown for phylloquinones or menaquinones, however menadione can be toxic, where high doses produced haemolytic anemia in rats and sever jaundice in infants. 22

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