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Micronutrients Dr S Nayak 1 What are Macronutrients and Micronutrients? The nutrients can be divided into two major groups – “Macronutrients” and “Micronutrients”. Macronutrients are those that are needed in large quantities (tens or hundreds of grams) every day. These are: Carbohydrates, protein and fats/oils. Micronutrients are those that are needed in minute quantities (micrograms or at best milligrams). These are vitamins, minerals and trace elements. Dr S Nayak 2 Vitamins Vitamins are naturally occurring organic substances. Their coenzyme forms are active and are essential in metabolic processes. They serve nearly the same roles in all forms of life. The daily requirement of any vitamin depends on a number of factors and may increase during growth, pregnancy and lactation. They are essential nutrients of humans, and have various roles in the human body Dr S Nayak 3 Vitamins are either fat-soluble or water-soluble . • Fat soluble vitamins are vitamins A, D, E and K. • Water-soluble vitamins vitamins and vitamin C. • B-complex vitamins are vitamin B1, B2, B6, B12, niacin, folic acid, biotin and pantothenic acid. are the B-complex • Dr S Nayak 4 • Soluble vitamins, when taken in excess of body needs, are excreted in urine. • On the other hand, fat-soluble vitamins, when taken in excess, are stored in the body (particularly liver) for use at times when the intake of these vitamins is inadequate. • Most vitamins can be derived from liver, fruits, vegetables, legumes and grains. Dr S Nayak 5 Vitamin A Preformed retinoid is a collective term for retinol, retinal, and retinoic acid, all of which are biologically active. Recommended Dietary Allowance Adult: 5000 IU/day Pregnancy lactation: 4000 IU/day Infants and children: 3000 IU/day Dr S Nayak 6 Functions 1.Role of vitamin A in vision Retina of the eye contains two types of cells Rod cells (Vision in dim light) Cone cells (vision in bright light). Rod cells have a photosensitive pigment called rhodopsin, is a conjugated protein made up of opsin and 11-cis retinal Dr S Nayak 7 2. Retinoic acid form of vitamin A maintains structural and functional integrity of epithelium 3. Retinol form of vitamin A is required for growth and reproductive function. 4. Retinol is also known to require for the formation of bone and teeth. Deficiency Night blindness Keratomalacia: Dryness of the cornea, corneal epithelium becomes keratinised and opaque and may become softened and ulcerated. Follicular keratosis: Deficiency will affect hair follicles and causes scaly skin Dr S Nayak 8 Vitamin D Sources Fish liver oils, eggs, milk & butter Sunlight induces synthesis of vit. D in the body from skin cholesterol. Required Dietary Allowance Children: 400 IU/day Adults: 400 IU/day Pregnancy and lactation: 400 IU/day Vitamin D2 or D3 are not active biologically but converted to active form by hydroxylation [1,25 dihydroxyvitamin D3]. Dr S Nayak 9 Functions Helps in the mineralization of bones by enhancing absorption of calcium Deficiency The deficiency of vitamin D leads to rickets in children Signs and symptoms are bowlegs, knock knee, pigeon Chest, hypocalcemia and hypophosphatemia Dr S Nayak 10 Vitamin E Sources Vegetable oils, germinated whole-grain cereals Required Dietary Allowance Adult male : 30 IU /day Female : 25 IU/day Children : 10-20 IU/day Functions 1.Potent physiological antioxidant: Protects membranes with lipids from oxidative damage. Dr S Nayak 11 2. Vitamin E, which is present in cell membranes, prevents the destructive non-enzymatic oxidation of polyunsaturated fatty acids (PUFA) by molecular oxygen, and it maintains the membrane integrity. 3.Protects erythrocytes from hemolysis by oxidizing agents (H2O2) 4. Required for normal reproduction in animals. 5. Prevents liver necrosis and muscular dystrophy Deficiency Hemolysis of erythrocytes which may leads to anemia Muscular weakness, fragile RBCs. Dr S Nayak 12 Vitamin K Phylloquinone, menaquinone and menadione are the three forms of vitamin K Sources Green leafy vegetables and Tomato, It is also synthesized by microorganisms in the intestinal tract Functions Required for the maintenance of normal concentration of blood clotting factors. Deficiency Excessive bleeding Dr S Nayak 13 Vitamin C Sources Citrus fruits (Orange, lemon), Tomatoes Strawberries Green vegetables Guava fruit Required Dietary Allowance Adults: 60 mg/day Children: 40 mg/day. Dr S Nayak 14 Functions 1. Collagen synthesis. Vitamin c is involved in the hydroxylation of proline and lysine residues, which are the collagen precursors. 2. It helps in the absorption of iron. 4. Acts as an antioxidant, scavenging the free radicals and reduces the nitrosamine formation. 5. The conversion of dopa to dopamine and dopamine to nor adrenaline requires vitamin C as an activator. Deficiency Scurvy Spongy gums , loose teeth, fragile blood vessels ,aching swollen joints and delayed wound healing. Dr S Nayak 15 Thiamin [Vitamin B1] Sources Whole grains (unpolished rice, wheat), legumes (Beans, peas) Meat. Required Dietary Allowance Children: 1.2 mg/day Adults: 1.5 mg/day Pregnancy and lactation – 2.0 mg/day. Functions The coenzyme form of thiamine is Thiamin pyrophosphate (TPP) Helps to release energy from nutrients supports normal appetite and nerve function TPP is required as coenzyme for Pyruvate dehydrogenase complex, α-ketoglutarate dehydrogenase complex, Transketolase etc. Dr S Nayak 16 Deficiency Cause:alcoholism and malnutrition The overall picture of this vitamin deficiency including neurological, cardiovascular and gastrointestinal disorders is referred to as Beriberi Beriberi is of four types Dry beriberi (peripheral neuritis) Wet beriberi (cardiac manifestation) Cerebral beriberi (Wernicke-Korsakoff’s syndrome) Infantile beriberi Dr S Nayak 17 Riboflavin[B2] Sources Animal liver, yeast, green leafy vegetables, milk & eggs Required Dietary Allowance Adults: 2.0 mg/day Children: 1.2 mg/day Pregnancy and lactation: 2.0 mg/day The riboflavin has two coenzyme forms they are flavin mononucleotide (FMN). Flavin adenine dinucleotide (FAD) Some enzymes have FMN and FAD as their integral part. Such enzymes are called flavoproteins Dr S Nayak 18 Functions Helps release energy from nutrients; supports health FMN is required for: 1. L-amino acid oxidase 2. Cytochrome C reductase. FAD is required as coenzyme for: 1. Succinate dehydrogenase, 2. Pyruvate dehydrogenase complex, 3. α -ketoglutarate dehydrogenase complex, 4. Xanthine oxidase. Dr S Nayak 19 Deficiency seen in: Malabsorption, malnutrition, and chronic alcoholism Ariboflavinosis It is the medical condition caused by deficiency of riboflavin. It is often associated with protein energy malnutrition and alcoholism. Characterized by: Glossitis (Magenta colored tongue) Cheilosis (Fissuring of the lips) Fissuring at the corners of mouth, Seborrheic dermatitis, corneal vascularization are the symptoms of riboflavin deficiency. Dr S Nayak 20 Niacin [B3] Sources Lean meats (liver) Legumes, peanuts (ground nuts) Green vegetables Whole grains. Amino acid tryptophan can be converted to the coenzyme NAD. About 60 mg of tryptophan yields 1 mg of niacin. Required Dietary Allowance Adults: 16-20 mg/day. Children: 9-16 mg/day Infants: 5-8 mg/day Dr S Nayak 21 The coenzyme forms of niacin are Nicotinamide Adenine Dinucleotide (NAD) Nicotinamide Adenine Dinucleotide Phosphate (NADP). Functions Helps release energy from nutrients; supports skin, nervous and digestive systems NAD is required as a coenzyme for PDH complex, α-ketoglutarate dehydrogenase complex to mediate the reactions. NADP is required for glucose-6-phosphate dehydrogenase and 6-phosphate gluconate dehydrogenase mediated reactions. Deficiency Pellagra which Involves skin, gastrointestinal tract and 22 central nervous system.Dr S Nayak Pyridoxine [B6] Sources Whole grains, Poultry fish Potatoes Organ meats, Eggs Legumes. Required Dietary Allowance Adults: 2.2 mg/day Children: 1.2 mg/day Infants: 3.0 mg/day Dr S Nayak 23 Functions Helps to make red blood cells Helps in amino acid and fatty acid metabolism Coenzyme form of pyridoxine is pyridoxal phosphate (PLP) PLP is required as coenzyme for the enzymes like Transaminases, Decarboxylases, Kynureninase, Cystathionine α-synthase, Cystathionine gamma-lyase and ALA synthase. Deficiency Hypochromic microcytic anemia Glossitis Pigmented scaly dermatitis similar to pellagra Dr S Nayak 24 Biotin [B7] Sources Egg yolk Organ meats (liver, kidney) Milk Legumes Nuts Required Dietary Allowance Adults: 0.3 mg/day. The intestinal bacteria also synthesize biotin to some extent. Dr S Nayak 25 Functions Biotin itself functions as coenzyme in the reactions involving fixation of CO2. Helps release energy from carbohydrates; aids in fat synthesis Pyruvate carboxylase Propionyl CoA carboxylase Acetyl CoA carboxylase Dr S Nayak 26 Pantothenic acid [B5] Sources Eggs, Animal liver,Meat , Milk, Vegetables and Grains. Required Dietary Allowance Adults: 5-10 mg/day Children: 4-5 mg/day Infants: 1-2 mg/day Conzyme form: Coenzyme A (CoASH): Required for Pyruvate dehydrogenase complex α-ketoglutarate DH complex Thiokinase Thiolase Dr S Nayak 27 Folic acid Sources Fresh green, Vegetables, Liver, Whole grains, Meat Legumes. Required Dietary Allowance Children - 300 µg/day Adults - 400 µg/day Pregnancy and lactation - 800 µg/day The coenzyme form of folic acid is tetrahydro folic acid [THF] (FH4) is the active form. The THF is a carrier of single carbon and it is involved in single carbon transfer reactions Dr S Nayak 28 Helps in the formation of DNA and new blood cells including red blood cells Deficiency • Megaloblastic anemia The deficiency of folate leads to impairment of the methionine synthase reaction due to which purine ring synthesis is impaired. The impaired synthesis of DNA prevents cell division and formation of the nucleus of new red blood cells. • Growth failure. Dr S Nayak 29 Vitamin B12 or cobalamin Sources Liver,Meat, Fish, Eggs and Milk. Human beings get small amount of vitamin B12 from their intestinal flora. Required Dietary Allowance Children: 2 µg/day Adults: 3 µ g/day Pregnancy and lactation: 4 µg/day. Active form of Vitamin B12 Methylcobalamin and Deoxyadenosylcobalamin a Dr S Nayak 30 Functions Vitamin B12 along with folic acid is required for the development of red blood cells beyond megaloblastic stage. It acts as coenzyme for the mutase enzyme which converts methyl malonyl CoA into succinyl CoA. Methylcobalamin is required in the conversion of homocysteine to methionine It is involved in the conversion of ribonucleotides to deoxyribonucleotide. Dr S Nayak 31 Deficiency Cause: malabsorption. Pernicious anemia is caused by a deficiency of intrinsic factor, which leads to impaired absorption of cobalamin. Megaloblastic anemia, Glossitis and inflammation of mouth, Methyl malonic aciduria. Dr S Nayak 32 Minerals Minerals are vital to physical and mental development. They also help protect the body against infections. Meat, fish, milk, cheese, green leafy vegetables and legumes provide most of the minerals needed by the body. Dr S Nayak 33 Minerals Minerals are inorganic chemical elements present throughout the body in varying amounts. Like the vitamins, they cannot be synthesized in the body and must be taken with food. Minerals act as co-factors of enzymes for metabolism. Minerals form part of the structure of body tissues, such as bones, teeth and nails, blood, nerves and muscles. Dr S Nayak 34 Calcium Functions Mineralization of bones and teeth Regulator of many of the body’s biochemical processes Involved in blood clotting Involved in muscle contraction and relaxation Nerve function blood pressure and immune defenses Activates pancreatic lipase in the digestion of fats Serves as a second messenger in the action of hormones like adrenaline. Serum ionic calcium level is maintained by vitamin D and hormones like parathyroid hormone (PTH) and calcitonin. Dr S Nayak 35 Action of Vitamin D a. Increases the absorption of calcium (and phosphate) from the small intestine b. Causes bone resorption. Action of PTH on Kidney and Bone 1. PTH increases the activity of 1 α-hydroxylase in kidney, which increases the synthesis of 1-25-dihydroxy vitamin D3 and this in turn enhance the absorption of calcium from intestine. 2. It increases the reabsorption of calcium from glomerular filtrate in kidneys. 3. It causes the resorption of calcium from bone. The above process helps maintain normal calcium level Dr S Nayak 36 Hypocalcemia This provokes a characteristic hyper excitable state of the nerves and muscles called tetany. Symptoms are: • Numbness of extremities • Emotional irritability • Tightness and spasm of muscles. – Hypocalcaemia also occurs in hypoparathyroidism, rickets, osteomalacia, pancreatitis, etc. Hypercalcemia Occurs in hyperparathyroidism and hypervitaminosis D. Dr S Nayak 37 Phosphorous Functions Mineralization of bones and teeth Part of every cell Used in energy transfer and maintenance of acid-base Balance Helps in the formation of compounds like nucleic acids,nucleotides like ATP, GTP, ADP It is also required in energy metabolism, synthesis of phospholipids Dr S Nayak 38 Hypophosphatemia • Rickets • Hyperparathyroidism Clinical symptoms are muscle pain and weakness with respiratory failure and decreased myocardial output Hyperphosphatemia • Seen in hypoparathyroidism • Hypervitaminosis D • Renal failure. Elevated phosphate may cause a decrease in serum concentration. Therefore it may lead to tetany and seizures Dr S Nayak 39 Sodium Sodium (Na+) is the major cation of the extracellular fluid Functions Maintains normal fluid and electrolyte balance Assists nerve impulse initiation and muscle contraction Helps in the active transport of glucose, galactose and amino acids across intestinal mucosa and for Na+/K+ ATPase. Hyponatremia Causes • Kidney failure and defect in adrenal cortex • Vomiting and diarrhea Dr S Nayak 40 Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) Hypernatremia Causes: Hyperactivity of adrenal cortex When water loss exceeds sodium loss, as occurs with Dehydration. Clinical symptoms: high blood pressure, fluid retention and swelling Dr S Nayak 41 Potassium Most important cation of intracellular fluid Functions Intracellular K+ is essential for a number of enzymemediated reactions such as pyruvate kinase, glycogen synthesis and protein synthesis The extracellular potassium is important for its influence cardiac muscle Hypokalemia and Hyperkalemia Renal causes Dr S Nayak 42 Chloride Functions Maintains normal fluid and electrolyte balance It is involved in maintaining osmotic pressure Hypochloremia: Metabolic alkalosis Vomiting diarrhea, diuretics and gastric suction Hyperchloremia :Metabolic acidosis Dehydration, decreased renal blood flow, medications ammonium chloride and Hyperparathyroidism Dr S Nayak 43 Magnesium Magnesium (Mg2+) is the major intracellular cation Functions • It is an essential activator of many enzymes especially those involving transfer of phosphate groups from ATP. • Examples are hexokinase and phosphofructokinase. • It also activates a number of enzymes like – Enolase, – Glucose-6-P dehydrogenase, – Pyruvate carboxylase, – Thiokinase, – Glucose 6 Phospho gluconate dehydrogenase. Dr S Nayak 44 Iron Functions Iron is necessary for the synthesis of certain proteins Iron containing proteins in the body are of two types: Heme proteins (Hemoglobin, myoglobin, catalase and cytochrome) and non-heme proteins (ferritin, transferrin, aconitase and sucinate dehydrogenase). Essential in the formation of blood Involved in the transport and storage of oxygen in the blood It is a cofactor bound to several non-heme enzymes Required for the proper functioning of cells Dr S Nayak 45 Ferritin is the storage form of iron and transferrin is the transport form Deficiency Hypochromic microcytic anemia (microcytic RBC of reduced size). Causes: haemorrhage, malabsorption Iron overload Haemosiderosis and haemochromatosis Dr S Nayak 46 Copper Functions A need for copper is linked to its functional role in several copper containing enzymes. 1. Ceruloplasmin 2. Cytochrome oxidase 3. Dopamine-oxidase of catecholamine synthetic pathway. 4. Monoamine oxidase and diamine oxidase. 5. Cytoplasmic superoxide dismutase 6. Lysyl oxidase involved in cross-linking process in the conversion of tropocollagen to collagen. 7. Tyrosinase of melanin synthetic pathway is a Cu dependent enzyme. Dr S Nayak 47 Deficiency Hypochromic microcytic anemia Wilson’s disease or Hepatolenticular degeneration It is a fatal inherited disease. Blood copper level decreases. There is an excessive storage of copper in the liver, kidney, brain and cornea Menkes syndrome or Kinky-hair disease It is a rare X-linked recessive disorder Both serum copper and ceruloplasmin and liver copper content are reduced. Depigmentation of the skin and hair Dr S Nayak 48 Zinc Essential for normal growth, development and reproduction It is required as an activator ion for: • Carbonic anhydrase • Alkaline phosphatase • Liver alcohol dehydrogenase • Carboxyl peptidase A • DNA polymerase • Cytosolic superoxide dismutase Deficiency Dwarfism Acrodermatitis enteropathica: autosomal recessive disorder Dr S Nayak 49 Manganese Manganese acts as a cofactor or an activator for several enzymes Acetyl CoA carboxylase Mitochondrial superoxide dismutase Arginase 6 Phosphate-gluconate dehydrogenase Squalene synthetase Isocitrate dehydrogenase Glutamine synthetase Kinases Dr S Nayak 50 Selenium It acts as an antioxidant: It is an integral component of glutathione peroxidase. This enzyme scavenging the free radicals and protect the cells and membranes against oxidative damage. So, this mineral complements the action of vitamin E. Dr S Nayak 51 Iodine Involved in the synthesis of thyroid hormones, triiodothyronine (T3) and tetraiodothyronine (t4), which influence a large number of metabolic functions. Deficiency Cretinism in children: Severe iodine deficiency in mothers leads to intrauterine or neonatal hypothyroidism results in Cretinism in their children, a condition characterized by mental retardation,dwarfism, slow growth Endemic goitre in adults: It is an enlarged thyroid with decreased thyroid hormone production. Dr S Nayak 52 Fluoride Involved in the formation of dental enamel and prevents dental caries Involved in the formation of teeth and skeleton Inhibits osteoporosis in old age Deficiency: Dental caries and osteoporosis. Excess fluoride causes fluorosis. In this condition there is mottling of enamel. The mottled enamel is discolored, corroded and pitted. Dr S Nayak 53 Ref: Essentials of Biochemistry by Dr Nayak Thank you Dr S Nayak 54