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Vitamins 5th lecture 2 nd class Biochemistry ------------------------------------------------------------------------------------------------ Vitamins are defined as small organic molecules present in diet which are required in small amounts. Most of the vitamins are not synthesized in the body and hence they must be supplied in the diet. However few vitamins are synthesized in the body. Though most of them are present in diet as such some are present as precursors. The precursor forms of vitamins are called as provitamins. In the body these provitamins are converted to vitamins. Types of vitamins: 1-Fat Soluble Vitamins They are vitamins A, D, E and K. They have some common properties. They are: 1. Fat soluble. 2. Require bile salts for absorption. 3. Stored in liver. 4. Stable to normal cooking conditions. 5. Excreted in feces. 2-Water Soluble Vitamins They are members of vitamin B complex and Vitamin C. Their common properties are 1. Water solubility. 2. Except Vitamin B12 others are not stored. 3. Unstable to normal cooking conditions. 4. Excreted in urine. MEDICAL AND BIOLOGICAL IMPORTANCE 1. Vitamins are essential for growth, maintenance and reproduction. However, they are not used for energy production. 2. Fat soluble vitamins are required for normal and color vision, blood clotting, bone formation and maintenance of membrane structure. 3. Most of the water soluble vitamins function as coenzymes or prosthetic groups of several enzymes involved in carbohydrate, lipid and amino acid metabolism etc. 4. Vitamins A and D act as steroid hormones. 5. Pregnant and lactating women require higher amounts of vitamins. During post operative recovery also vitamin requirement is more. 6. Lack of vitamin in the diet produce characteristic deficiency symptoms. Since intestinal flora synthesizes some vitamins prolonged use of antibiotics also produce vitamin deficiency. 7. Deficiency of fat soluble vitamins produce night blindness, skeletal deformation, haemorrhages and hemolysis. 8. Deficiency of water soluble vitamins produce beriberi, glossitis, pellagra, microcytic anaemia, megaloblastic anaemia and scurvy. FAT SOLUBLE VITAMINS VITAMIN A Chemistry The word Vitamin A refers to group of compounds which exhibit Vitamin A activity. They are retinol (Vitamin A alcohol), retinal (Vitamin A Vitamins 5th lecture 2 nd class Biochemistry -----------------------------------------------------------------------------------------------aldehyde) and retinoic acid (Vitamin A acid). They are also referred as retinoids. Retinal and retinoic acid are formed from retinol. Further retinal and retinol are inter convertible. But retinoic acid cannot be converted to either retinal or retinol. Vitamin A metabolism In the intestine pancreatic esterase hydrolyzes retinol esters present in the diet to retinol and free fatty acid in presence of bile salts. Retinol is absorbed by mucosal cells. β-carotenes are also absorbed by mucosal cells. Vitamins 5th lecture 2 nd class Biochemistry -----------------------------------------------------------------------------------------------Functions of vitamin A The three major retinoids retinal, retinol and retinoic acid have unique functions. 1. Retinal is required for normal and color vision. 2. Retinol is required for reproduction and growth. Retinol supports spermatogenesis, oogenesis and placental development. 3. Retinol is required for differentiation and function as steroid hormone. 4. Retinoic acid is required for the synthesis of glycoproteins or mucopolysaccharides. Retinoyl phosphate act as glycosyl carrier. 5. Retinoic acid also act as steroid hormone. It also promote growth and differentiation but only to some extent. 6. Retinol and retinoic acid are involved in regulation of gene expression. Fig: visual cycle Vitamins 5th lecture 2 nd class Biochemistry -----------------------------------------------------------------------------------------------Deficiency manifestations of Vitamin A 1. Night Blindness or Nyctalopia Visual acuity is diminished in dim light. The patient cannot read or drive a car in poor light. The dark adaptation time is increased. 2. Xerophthalmia The conjunctiva becomes dry, thick and wrinkled. The conjunctiva gets keratinized and loses its normal transparency. Dryness spreads to cornea. It becomes glazy and lusterless due to keratinization of corneal epithelium. 3. Bitot's Spots These are seen as greyish-white triangular plaques firmly adherent to the conjunctiva. Vitamin D The term vitamin D refers to group of two compounds that exhibit vitamin D activity. They are vitamin D2 also called as ergo calciferol and vitamin D3 also called as cholecalciferol. These active forms of vitamin D2 and vitamin D3 are formed from provitamins which are sterols. The provitamin of vitamin D2 is ergosterol which is found in ergot and yeast. It is a derivative of cholesterol. The provitamin of vitamin D3 is 7dehydrocholesterol which is found in animals. It is also a derivative of cholesterol. Synthesis of cholecalciferol or vitamin D3 Absorption, transport and storage Dietary vitamin D2 and vitamin D3 are absorbed in the small intestine in presence of bile salts. In the intestinal mucosal cells absorbed Vit D is incorporated into chylomicrons and enters circulation via lymph. In the circulation vitamin D dissociates from chylomicrons andbinds to specific vitamin D binding protein (DBP) which has higher affinity for vitamin Vitamins 5th lecture 2 nd class Biochemistry -----------------------------------------------------------------------------------------------D3. So a binary complex containing vitamin D and DBP is found in plasma. Further, vitamin D3 formed in the skin also combines with vitamin D binding protein and forms a binary complex. Different tissues take up vitamin D from DBP and vitamin D complex. Vitamin D is stored in liver and adipose tissue. Vitamin D binding protein can combine with different forms of Vitamin D. A. Vitamin D and Absorption of Calcium Calcitriol promotes the absorption of calcium and phosphorus from the intestine. In the brush-border surface, calcium is absorbed passively. From the intestinal cell to blood, absorption of calcium needs energy. It is either by the sodium-calcium exchange mechanism or by pumping out the calcium-calbindin complex. Calcitriol acts like a steroid hormone. It enters the target cell and binds to a cytoplasmic receptor. The hormonereceptor complex interacts with DNA and causes derepression and consequent transcription of specific genes that code for Calbindin (Fig.). Due to the increased availability of calcium binding protein, the absorption of calcium is increased. B. Effect of Vitamin D in Bone Mineralization of the bone is increased by increasing the activity of osteoblasts. Calcitriol coordinates the remodelling action of osteoclasts and osteoblasts. Calcitriol stimulates osteoblasts which secrete alkaline phosphatase. Due to this enzyme, the local concentration of phosphate is increased. The ionic product of calcium and phosphorus increases, leading to mineralization. Vitamins 5th lecture 2 nd class Biochemistry -----------------------------------------------------------------------------------------------C. Effect of Vitamin D in Renal Tubules Calcitriol increases the reabsorption of calcium and phosphorus by renal tubules, therefore both minerals are conserved (PTH conserves only calcium). Note: Calcitriol is the physiological active form of vitamin D. It increases the blood calcium level. Calcitonin is the peptide hormone released from thyroid gland. It decreases the blood calcium. Deficiency of Vitamin D The deficiency diseases are rickets in children and osteomalacia in adults. Hence vitamin D is known as antirachitic vitamin. WATER SOLUBLE VITAMINS VITAMIN B COMPLEX Members of vitamin B complex are (1) Thiamin (Vitamin B1) (2) Riboflavin (Vitamin B2) (3) Niacin (4) Pyridoxine (Vitamin B6) (5) Biotin (6) Folic acid (7) Cyanocobalamin (Vitamin B12) and (8) Pantothenic acid. Vitamins 5th lecture 2 nd class Biochemistry ------------------------------------------------------------------------------------------------ VITAMIN B12 Chemistry Vitamin B12 is water soluble, heat stable and red in color. It contains 4.35% cobalt by weight. It contains one cobalt atom. Four pyrrole rings co-ordinated with a cobalt atom is called a Corrin ring. a. Cyanocobalamin When cyanide is added at the R position, the molecule is called cyanocobalamin. During the isolation procedure, cyanide is added to get stable crystals. The CN group has no physiological function. b. Hydroxy cobalamin When hydroxyl group is attached at the R position, it is called hydroxy cobalamin or vitamin B12a. Injectable preparations are in this form. c. Adenosyl cobalamin (Ado-B12) When taken up by the cells, these groups are removed and deoxy adenosyl cobalamin or Ado-B12 is formed (Fig.). This is the major storage form, seen in liver. d. Methyl cobalamin When the methyl group replaces adenosyl group, it is known as methyl cobalamin. This is the major form seen in blood circulation as well as in cytoplasm of cells. The Ado-B12 and methyl B12 are the functional coenzymes in the body. Fig: structure of vit. B12 Vitamins 5th lecture 2 nd class Biochemistry ------------------------------------------------------------------------------------------------ Fig: Storage form of vit. B12 Deficiency Manifestations i. Folate trap: Vitamin B12 deficiency causes simultaneous folate deficiency due to the folate trap. Therefore all the manifestations of folate deficiency are also seen (for details see under folic acid). ii. Megaloblastic anemia: In the peripheral blood, megaloblasts and immature RBCs are observed. iii. Abnormal homocysteine level: In vitamin B12 deficiency, so that homocysteine is accumulated, leading to homocystinuria. Homocysteine level in blood has a positive correlation with myocardial infarction. So, B12 and folic acid are protective against ischemic heart disease.