Assignment for 2nd Semester Hons (FNT) 2020
Soft copy to be mailed at [email protected] by 6th April, 2020
Marks-10
Write a note on the following topics:
Vitamin D: Biochemical and Physiological Role Bioavailability Requirements Roll No. 1-15 Sources Deficiency Excess (Toxicity) Vitamin E: Biochemical and Physiological Role Bioavailability Requirements Roll No. 16-30 Sources Deficiency Excess (Toxicity) Vitamin K: Biochemical and Physiological Role Bioavailability Requirements Roll No. 31- 45 Sources Deficiency Excess (Toxicity) Water: Functions Roll No. 46-60 Daily requirements Water balance
VITAMIN D
FOR 2ND SEM (H)
BY SAJIDA KHATOON ASSISTANT PROFESSOR FNT DEPARTMENT MKC THE SUNSHINE VITAMIN
Vitamin D is a unique vitamin and its availability in the body largely depends on its synthesis in the skin when exposed to sunlight. Hence, its dietary requirement is usually very small especially in the Indian context.
VITAMIN D is widespread in nature and photosynthesized in most plants and animals exposed to sunlight Its major role in vertebrate animals and humans is to increase the absorption of calcium and phosphate for the mineralization of the skeleton. In the case of vitamin D deficiency in children, the cartilage is not calcified, causing rickets. In adults, the newly formed bone matrix (the osteoid) is not mineralized, causing osteomalacia.
Vitamin D exists in 2 forms: Vitamin D3 (cholecalciferol) of animal origin Vitamin D2 (ergocalciferol) of plant origin The precursors of vitamin D are: 7-dehydro-cholesterol in animals Ergosterol in plants
Vitamin D3, or cholecalciferol, is synthesized in the skin. Its precursor, 7-dehydrocholesterol (provitamin D3), is converted by the UV light of the sun (UVB 290–315 nm) into previtamin D3, which is slowly isomerized to vitamin D3. Vitamin D3 is photosynthesized in the skin of vertebrates by the action of solar ultraviolet (UV) B radiation on 7-dehydrocholesterol. Vitamin D2 is produced by UV irradiation of ergosterol, which occurs in molds, yeast, and higher-order plants.
Dietary vitamin D3 is absorbed from jejunum with the aid of bile salts and is incorporated within chylomicrons, which take it through the lymph and then into the blood. On release from lymph into the blood the vitamin D is removed from the chylomicrons and becomes bound to a specific vitamin D-binding protein (DBP), called alpha globulin and gets transported to the liver.
Vitamin D from the skin or diet is only short-lived in circulation (with a half-life of 1–2 days), as it is either stored in fat cells or metabolized in the liver. Vitamin D produced in the skin may last at least twice as long in the blood compared with ingested vitamin D. In circulation, vitamin D is bound to vitamin D- binding protein and transported to the liver, where it is converted to 25-hydroxyvitamin D3 (calcidiol). To be biologically activated at physiologic concentrations, 25(OH)D3 must be converted in the kidneys to 1,25-dihydroxyvitamin D3 (calcitriol) which is thought to be responsible for most, if not all, of the biologic functions of vitamin D3.
The production of calcidiol in the liver and of calcitriol in the kidney is tightly regulated. In the liver, vitamin D-25-hydroxylase is down- regulated by vitamin D and its metabolites, thereby limiting any increase in the circulating concentration of calcidiol following intakes or following production of vitamin D after exposure to sunlight. In the kidney, in response to serum calcium and phosphorus concentrations, the production of calcitriol is regulated through the action of parathyroid hormone (PTH).
Active vitamin D functions as a hormone, and its main biologic function is to maintain serum calcium and phosphorus concentrations within the normal range by enhancing the efficiency of the small intestine to absorb these minerals from the diet. When dietary calcium intake is inadequate to satisfy the body’s calcium requirement, calcitriol, along with PTH, mobilizes calcium stores from the bone. In the kidney, calcitriol together with PTH, increases calcium reabsorption by the distal renal tubules.
Calcitriol and PTH hormone together regulate the concentration of calcium in blood plasma. This is important not only for bone formation and maintenance, but also for maintaining blood calcium levels to facilitate the proper interaction between nerves and muscles.
REQUIREMENTS
Under situations of minimal exposure to sunlight, a specific recommendation of a daily supplement of 400 IU is recommended. 1 mcg of vitamin D = 40 IU of vitamin D DEFICIENCY, why it happens?
The major source of vitamin D for children and adults is exposure to natural sunlight. Thus, the major cause of VDD is inadequate exposure to sunlight. Wearing a sunscreen with a sun protection factor (SPF) of 30 reduces vitamin D synthesis in the skin by more than 95%. UVB light cannot pass through glass and clothing; exposure of the skin to sunlight through glass and clothes will not result in vitamin D synthesis. People with a dark skin tone require at least three to five times longer exposure to make the same amount of vitamin D than a person with a white skin tone. Larger amounts of the pigment melanin in the epidermal layer result in darker skin and reduce the skin's ability to produce vitamin D from sunlight.
Season of the year (the lower the sun on the horizon in the winter, the greater the time needed) The latitude (within 1 or – 35 degrees from the equator, the most vitamin D can be produced when skin is exposed to UVB rays) A person should be exposed to sunlight 2 to 3 times per week from March through October in northern climates to accumulate enough vitamin D to get through the winter with adequate vitamin D.
The time of day (more vitamin D is synthesized by the skin when the sun is directly overhead between 11:00 am and 3:00 pm.) Older adults are at high risk of developing vitamin D insufficiency because of aging. Their skin cannot synthesize vitamin D as efficiently, they are likely to spend more time indoors, and they may have inadequate intakes of the vitamin. Patients with one of the fat malabsorption syndromes and bariatric patients are often unable to absorb the fat-soluble vitamin D, and patients with nephritic syndrome lose 25(OH)D bound to the vitamin D-binding protein in the urine. Vitamin D is fat soluble, therefore it requires some dietary fat in the gut for absorption. Individuals with reduced ability to absorb dietary fat might require vitamin D supplements. Fat malabsorption is associated with a variety of medical conditions including some forms of liver disease, cystic fibrosis, and Crohn's disease. CONSEQUENCES OF DEFICIENCY
Vitamin D deficiency is characterized by inadequate mineralization or by demineralization of the skeleton. Among children, vitamin D deficiency is a common cause of bone deformities known as rickets. Vitamin D deficiency in adults leads to a mineralization defect in the skeleton, causing osteomalacia, and induces secondary hyperparathyroidism with consequent bone loss and osteoporosis. One of the most serious disorders associated with vitamin D deficiency is the convulsive state of hypocalcemic tetany, which is caused by insufficient supplies of calcium to nerves and muscles. Potential roles for vitamin D beyond bone health, such as effects on muscle strength, the risk for cancer and for type 2 diabetes, are currently being studied.
PRESENT SCENARIO
It is pertinent to note that in India, young growing children and adults, particularly in urban areas, are physically less active and are not being exposed outdoors. Outdoor physical activity is a means of achieving adequate vitamin D status. TOXICITY (EXCESS)
Excess Vitamin D causes increased calcium absorption from intestine, leading to increased plasma calcium (hypercalcemia) Hypercalcemia is associated with deposition of calcium in many soft tissues such as kidney and arteries. It leads to formation of stones (renal calculi) Some infants are sensitive to intakes of vitamin D as low as 50 g/d, resulting in an elevated plasma concentration of calcium. This can lead to contraction of blood vessels, high blood pressure, and calcinosis—the calcification of soft tissues. Hypercalcemia in adults results in loss of appetite, nausea, weight loss and failure to thrive. The early symptoms disappear if Vitamin D rich foods are withdrawn from the diet. If hypercalcemia persists for a long period, the calcification of soft tissues can eventually cause death.
Although excess dietary vitamin D is toxic, excessive exposure to sunlight does not lead to vitamin D poisoning because there is a limited capacity to form the precursor 7-dehydrocholesterol and to take up cholecalciferol from the skin.
VITAMIN E
BY SAJIDA KHATOON FOR 2ND SEM (H) ASSISTANT PROFESSOR FNT DEPARTMENT MKC Vitamin E is a naturally occurring fat soluble vitamin that exists in eight different forms: . Alpha (α), beta (β), gamma (γ) and delta (δ) tocopherol . Alpha (α), beta (β), gamma (γ) and delta (δ) tocotrienol They have varying levels of biological activity.
Alpha (α) tocopherol appears to be the most active form. It is the only form that is recognised to meet human requirements. Serum concentrations of alpha- tocopherol depend on the liver, which takes up the nutrient after absorption of all the forms from the small intestine. The liver then preferentially secretes only alpha-tocopherol and metabolizes and excretes the other vitamin E forms.
As a result, blood and cellular concentrations of other forms of vitamin E are lower than those of alpha-tocopherol and thus have been less studied. FUNCTIONS
Vitamin E has powerful antioxidant activities which protect cells from the damaging effects of free radicals. Free radicals are produced endogenously when the body metabolises food to energy. Exogenous sources come from exposure to cigarette smoke, air pollution and ultraviolet radiation from the sun. Free radicals combine with oxygen and form reactive oxygen species (ROS) that damage cells.
Vitamin E is a fat soluble vitamin, therefore it is able to mix with and protect lipid molecules from oxidation.
Vitamin E acts as the first line of defense against a specific form of oxidation known as lipid peroxidation, which involves formation of peroxide derivatives of lipids.
When free radicals attack lipids of cell membranes, a highly damaging chain reaction is initiated, leading to widespread damage to the structure and function of the membranes. Vitamin E is a potent chain-breaking antioxidant that inhibits the production of ROS molecules. It reacts with the lipid peroxide radicals formed by peroxidation of polyunsaturated fatty acids before they can establish a chain reaction. Vitamin E is located primarily within the phospholipid bilayer of cell membranes. Although vitamin E is primarily located in cell and organelle membranes where it can exert its maximum protective effect, its concentration may only be one molecule for every 2000 phospholipid molecules. This suggests that after its reaction with free radicals it is rapidly regenerated, possibly by other antioxidants like vitamin C. Vitamin E may be required for the normal functioning of the immune system. It regulates the production of prostaglandins (vasodilator) and may control the aggregation of blood platelets during the formation of blood clots. It is also involved in the metabolism of nucleic acids and proteins, the functioning of mitochondria and the regulation of the production of various hormones. The antioxidant property of vitamin E helps in inhibiting the formation of lipofuscin, a pigment that accumulates within tissues during aging. Vitamin E is also involved in sparing the trace element selenium within the body and in protecting vitamin A against oxidative damage. Vitamin E protects the organism against the damage which maybe caused by nitrosamines known to be strong tumour promoters. Vitamin E reduces the levels of inflammation inducing cytokines, the proteins that cause the joint swelling, pain and tenderness, seen in rheumatoid arthritis. VITAMIN E AND SELENIUM
Selenium is a component of numerous enzymes including the enzyme glutathione peroxidase which is an enzyme that converts lipid peroxides to alcohols and water, while combining two glutathione molecules. In tissues that normally contain little glutathione peroxidase, vitamin E is essential to prevent peroxidation. In other tissues, selenium maybe essential to remove hydrogen peroxide because there is little catalase present in the tissues. Selenium alongwith vitamin E is required for maintaining liver integrity. Vitamin E is necessary to prevent muscular dystrophy and selenium is needed to prevent pancreatic fibrosis. Peroxide damage is found in tissues when either vitamin E or selenium is absent from the diet. ABSORPTION AND METABOLISM
Absorption of vitamin E from the intestine depends on adequate pancreatic function, biliary secretion, and micelle formation. Conditions for absorption are like those for dietary lipid, that is, efficient emulsification, solubilisation within mixed bile salt micelles, uptake by enterocytes, and secretion into the circulation via the lymphatic system. Emulsification takes place initially in the stomach and then in the small intestine in the presence of pancreatic and biliary secretions. The resulting mixed micelle aggregates the vitamin E molecules, solubilises the vitamin E, and then transports it to the brush border membrane of the enterocyte probably by passive diffusion. Within the enterocyte, tocopherol is incorporated into chylomicrons and secreted into the intracellular space and lymphatic system and subsequently into the blood stream. Chylomicrons carry tocopherol from the enterocyte to the liver, where they are incorporated into parenchymal cells as chylomicron remnants. The catabolism of chylomicrons takes place in the systemic circulation through the action of cellular lipoprotein lipase. During this process tocopherol can be transferred to high-density lipoproteins (HDLs). The tocopherol in HDLs can transfer to other circulating lipoproteins, such as LDLs and very low-density lipoproteins (VLDLs) Most alpha tocopherol then enters the cells of peripheral tissues. Although most tissues store vitamin E, adipose tissue is the site of maximal vitamin E storage. REQUIREMENTS
Alpha tocopherol requirement is related to its protective antioxidant property on essential fatty acid content of the diet. The suggested intake is 0.8 mg/g of EFA. So, the RDA of alpha tocopherol is 7.5 – 10 mg 1mg = 1.5 IU d-alpha-tocopherol SOURCES
Vegetable oils and invisible fat of cereals and other foods like nuts and vegetables contribute to adequate tocopherol content in Indian diets. Almond is the nut with the highest level of tocopherols. Rice bran oil contains high amount of tocotrienols and oryzanol which have antioxidant activity.
Wheat germ oil is a rich source which contains 120mg alpha tocopherol/100g oil.
In general, plant foods are richer sources of vitamin E than animal foods. DEFICIENCY
Vitamin E deficiency is quite rare in humans. It happens almost exclusively in people with an inherited or acquired condition that impairs their ability to absorb the vitamin (for instance, cystic fibrosis, short bowel syndrome or bile duct obstruction) and in those who cannot absorb dietary fat or have rare disorders of fat metabolism. Symptoms of vitamin E deficiency include muscle weakness, vision problems, immune system changes, numbness, difficulty in walking and tremors as well as a poor sense of balance. Deficiency can also lead to neuromuscular problems such as spinocerebellar ataxia. Premature infants have difficulty in absorbing lipids so vitamin E is administered by injection or by mouth in water miscible form, which is readily absorbed. Vitamin E deficient infants when given oxygen therapy to help them through critical periods causes damage to the retina of eye leading to permanent blindness. So, vitamin E in doses upto 100mg/day is given to protect against the severity of a condition known as retrolental fibroplasia. Vitamin E deficiency can also cause anaemia due to the oxidative damage to the red blood cells, retinopathy and the impairment of the immune response. If untreated, vitamin E deficiency may result in blindness, heart disease, permanent nerve damage and impaired thinking.
Vitamin E deficiency leads to increased aggregation of platelets in the blood. The damage suffered by cells during vitamin E deficiency has been linked to the onset of several types of cancer, the early stages of atherosclerosis, premature aging and arthritis. TOXICITY
α-tocopherol does not accumulate to “toxic” levels in the liver or extrahepatic tissues. The only consistent finding of the adverse effects of excess α-tocopherol was the observation that vitamin E caused increased bleeding tendencies, likely as a result of interference with vitamin K status.
In infants there is stronger evidence linking large oral or intravenous doses of vitamin E with toxicity. High doses to premature infants may result in liver and kidney failure, ascites, decreased blood platelet number and eventually death.
Vitamin K comprises several molecular forms that have a common 2-methyl-1,4- naphthoquinone ring but differ in the structures of the side chain at the 3-position. In plants the only important molecular form is phylloquinone (old nomenclature vitamin K1) whereas bacteria synthesise a spectrum of molecular forms based on repeating unsaturated 5-carbon (prenyl) units. These are designated menaquinone-n (abbreviated MK-n) according to the number (n) of prenyl units.
The intestinal absorption of vitamin K follows a well-established pathway that applies to most dietary lipids, which includes bile salt- and pancreatic-dependent solubilization, uptake of mixed micelles into the enterocytes, the packaging of dietary lipids into chylomicrons, and their exocytosis into the lymphatic system.
Bioavailability of a nutrient is defined as the rate and extent to which the nutrient is absorbed and becomes available to the site of activity. In most diets, green leafy vegetables are the major source of phylloquinone, followed by certain phylloquinone- rich plant oils or fats that are widespread in many food products.
In the post prandial state, phylloquinone is transported mainly by TRL (triglyceride rich lipoproteins) and long chain MK-n mainly by LDL (low density lipoproteins).
Bone matrix contains several Gla proteins [e.g., osteocalcin, matrix Gla protein (MGP), Gla- rich protein] that require vitamin K for their function.
The RDA of vitamin K is 55µg as recommended by ICMR, 2010.
Toxicity may lead to excessive blood clotting, damage to cell membrane, kidney tubular degeneration, jaundice in newborn, haemolytic anaemia in infants.
VITAMIN K IS REQUIRED FOR SYNTHESIS OF BLOOD-CLOTTING PROTEINS Vitamin K was discovered as a result of investigations into the cause of a bleeding disorder— hemorrhagic (sweet clover) disease—of cattle, and of chickens fed on a fat-free diet. The missing factor in the diet of the chickens was vitamin K, while the cattle feed contained dicumarol, an antagonist of the vitamin. Antagonists of vitamin K are used to reduce blood coagulation in patients at risk of thrombosis—the most widely used agent is warfarin. Three compounds have the biologic activity of vitamin K: phylloquinone, the normal dietary source, found in green vegetables; menaquinones, synthesized by intestinal bacteria, with differing lengths of side-chain; menadione, menadiol, and menadiol diacetate, synthetic compounds that can be metabolized to phylloquinone. Menaquinones are absorbed to some extent but it is not clear to what extent they are biologically active as it is possible to induce signs of vitamin K deficiency simply by feeding a phylloquinone deficient diet, without inhibiting intestinal bacterial action.
Vitamin K Is the Coenzyme for Carboxylation of Glutamate in the Postsynthetic Modification of Calcium-Binding Proteins Vitamin K is the cofactor for the carboxylation of glutamate residues in the post-synthetic modification of proteins to form the unusual amino acid γ-carboxyglutamate (Gla), which chelates the calcium ion. Initially, vitamin K hydroquinone is oxidized to the epoxide, which activates a glutamate residue in the protein substrate to a carbanion, that reacts nonenzymically with carbon dioxide to form γ-carboxyglutamate. Vitamin K epoxide is reduced to the quinone by a warfarin-sensitive reductase, and the quinone is reduced to the active hydroquinone by either the same warfarin-sensitive reductase or a warfarin-insensitive quinone reductase. In the presence of warfarin, vitamin K epoxide cannot be reduced but accumulates, and is excreted. If enough vitamin K (a quinone) is provided in the diet, it can be reduced to the active hydroquinone by the warfarin-insensitive enzyme, and carboxylation can continue, with stoichiometric utilization of vitamin K and excretion of the epoxide. A high dose of vitamin K is the antidote to an overdose of warfarin. Prothrombin and several other proteins of the blood clotting system (Factors VII, IX and X, and proteins C and S) each contain between four and six γ-carboxyglutamate residues which chelate calcium ions and so permit the binding of the blood clotting proteins to membranes. In vitamin K deficiency or in the presence of warfarin, an abnormal precursor of prothrombin (preprothrombin) containing little or no γ-carboxyglutamate, and incapable of chelating calcium, is released into the circulation.
Vitamin K Is Also Important in the Synthesis of Bone Calcium-Binding Proteins Treatment of pregnant women with warfarin can lead to fetal bone abnormalities (fetal warfarin syndrome). Two proteins are present in bone that contain γ-carboxyglutamate, osteocalcin and bone matrix Gla protein. Osteocalcin also contains hydroxyproline, so its synthesis is dependent on both vitamins K and C; in addition, its synthesis is induced by vitamin D. The release into the circulation of osteocalcin provides an index of vitamin D status.