* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Water Soluble Vitamins نسح انيز .د
Survey
Document related concepts
Genetic code wikipedia , lookup
Nucleic acid analogue wikipedia , lookup
Peptide synthesis wikipedia , lookup
Metalloprotein wikipedia , lookup
Fatty acid metabolism wikipedia , lookup
Nicotinamide adenine dinucleotide wikipedia , lookup
Amino acid synthesis wikipedia , lookup
Citric acid cycle wikipedia , lookup
Biosynthesis wikipedia , lookup
15-Hydroxyeicosatetraenoic acid wikipedia , lookup
Specialized pro-resolving mediators wikipedia , lookup
Fatty acid synthesis wikipedia , lookup
Butyric acid wikipedia , lookup
Transcript
Water Soluble Vitamins زينا حسن.د Objectives: by reading this topic; the student would be able to: 1. Define vitamins and illustrate vitamin classification. 2. Describe the structure, dietary sources, and metabolism of water soluble vitamins. 3. Identify the biochemical role of different water soluble vitamins. 4. Correlate deficiency in vitamin levels with clinical conditions. LECTURE 1 Vitamins are group of complex organic compounds present in very small quantities in food and absorbed into the body during digestion. The name vitamin is obtained from "vital amines“. They are not synthesized in the body except Vitamin K. Vitamins can perform their work in very small quantities. Hence, the total daily requirement is usually very small. FUNCTIONS OF VITAMINS Vitamins help to keep good Health. Vitamins are required for metabolism and they create metabolically active enzymes which are very essential for various functions of our body. Vitamins are very important the proper growth Ensuring protection against the viruses. CLASSIFICATION OF VITAMINS 1. Fat-soluble vitamins They are soluble in fat and They are absorbed by the body from the intestinal tract. They are stored in the body's fatty tissue ± Liver. The four fat-soluble vitamins are A, D, E, and K. 2. Water-soluble vitamins Water-soluble vitamins – vitamin C and vitamin B Complex. Any leftover water-soluble vitamins leave the body through urine. Vitamin B12 is the only water-soluble vitamin that can be stored in the liver for many years. Page 1 زينا حسن.د Water Soluble Vitamins VITAMIN B Group Introduction: In general B complex group have well defined Coenzyme functions in the cellular metabolism. They include: Thiamine (B1), Riboflavin (B2), Niacin, Pantothenic acid, Pyridoxine (B6), Biotin, Folic acid, and Cobalamine (B12). Sources: there are some general sources for all B complex group including: germinating seeds, wheat germ, beans, yeast, liver, egg yolk, milk, vegetables, fish, honey, and meat. These vitamins present in food and are readily absorbed in GIT, usually there is no appreciable storage, the excess is excreted in urine after metabolism. Washing before cooking and draining the water after cooking will result in loss of much of the water soluble vitamins. 1. Thiamine (B1): Structure: It is a basic substance contains a pyrimidine ring linked to a thiazole ring. It is fairly stable in acid solutions but is rapidly destroyed in alkaline medium. OH of the hydroxyethyl group in the thiazole can be esterified with 2 molecules of phosphoric acid to form Thiamine pyrophosphate (TPP) which is the active coenzyme form of the vitamin. Metabolism: Free thiamine is readily absorbed by the small intestine. It is phosphorylated mainly in the liver to form TPP. There is no storage of B1 vitamin so regular supplies are needed in the diet. Functions: TPP acts as a coenzyme in the following reactions: 1. Oxidative decarboxylation reactions, Mg++ ions are required for the activation; as in d carboxylation odf α-ketoglutaric acid. 2. Transketolation reactions; in hexose-mono-phosphate shunt pathway of glucose metabolism. 3. Oxidative decarboxylation of branched chain amino acids, like valine, leucine, and isoleucine; Flavin-Adenine-dinucleotide (FAD), niacinamide-adenine-dinucleotide (NAD), and Mg++ are also required for the reaction. Page 2 Water Soluble Vitamins زينا حسن.د RDA: 1.5 mg/day. Recommended Dietary allowance (RDA) is the level of intake of essential nutrients sufficient to meet the nutritional needs of healthy individuals in general population Clinical correlations: Deficiency: this will result in a condition called beri-beri which has two components: 1. Cardiovascular failure: enlargement of the heart and edema. 2. Neural component: peripheral neuritis. Re-feeding syndrome: this potentially lethal condition is defined as severe electrolyte and fluid shifts associated with metabolic abnormalities in malnourished patients undergoing re-feeding whether this is oral, enteral, or parenteral. It is associated with B1 deficiency which should be corrected and given to the patient before re-feeding is started and also the calorie repletion should be slow. Factors that increase the risk of re-feeding syndrome include: marasmus, chronic alcoholism, cancer treatment, prolonged fasting, and surgery. 2. Riboflavin (B2): Structure: it is derived from isoalloxazine ring combined with ribityl alcoholic group; which can be esterified with phosphoric acid to form Flavin-Mononucleotide (FMN). It may be linked to adenine nucleotide through a pyrophosphate linkage to form Flavine-Adenine-Dinucleotide (FAD). FMN and FAD are the two Coenzyme forms of the vitamin Functions: FMN & FAD are involved in hydrogen transfer reactions as follows: 1. FMN is a coenzyme for the enzymes cytochrome C reductase and Lamino acid oxidase. 2. FAD is a coenzyme for the enzymes Xanthine oxidase, D-amino acid oxidase and succinate dehydrogenase. RDA: 1.5-2 mg/day. Clinical correlation: Deficiency: Lesions of the lips, fissures at angles of the mouth (cheilosis), dermatitis of the face, glossitis (red tongue), and vascularization of the conjunctiva and the cornea occurs. Page 3 Water Soluble Vitamins زينا حسن.د LECTURE 2 3. Niacin: (Synonyms: P-P-factor=Pellagra Preventing factor, Nicotinic acid) Structure: Niacin is pyridine-3-carboxylic acid. Its biologically active forms are: 1. Niacinamide–Adenine-Dinucleotide (NAD). 2. Niacinamide–Adenine-Dinucleotide (NADP): the phosphorylated form of NAD. Sources: In addition to general sources of B complex vitamins; niacin can be synthesized from the essential amino acid Tryptophan. Functions: NAD & NADP function as coenzymes for hydrogen transfer enzymes (dehydrogenases) as follows: 1. NAD is a coenzyme for the enzymes Alcohole dehydrogenase and Lactic acid dehydrogenase. 2. NADP is a coenzyme for the enzymes Glucose-6-phosphate dehydrogenase. 3. Both NAD & NADP are coenzymes for the enzyme Glutamic acid dehydrogenase. RDA: 20 mg/day Clinical correlation: Deficiency: causes a disease called Pellagra (pelle=skin; Agra=rough) characterized by: dermatitis, diarrhea, and dementia (3'D's) and if not treated the 4th 'D' death follows. The dermatitis involves areas exposed to sun or pressure, in addition to loss of appetite, vomiting, stomatitis, soreness of the tongue, and mental depression. Niacin has a pharmacological action on decreasing plasma lipids; therefore niacin is used in the treatment of hyperlipidemia 4. Pyridoxine (B6): Structure: it has three related compounds: Pyridoxine occur mainly in plants; Pyridoxal and pyridoxamine which are present in animal products. Its active form is Pyridoxal Phosphate which can combine to NH3 group to form Pyridoxamine Phosphate. Page 4 Water Soluble Vitamins زينا حسن.د Functions: 1. Coenzyme for Transaminases: B6 importance in amino acid metabolism depends on its ability to take up NH3 reversibly to form pyridoxamine phosphate. 2. Coenzyme for non-oxidative decarboxylases: 3,4-di ydroxyp nylalanin →Dppamin + CO2 Glutamic acid →Gamma aminobutyric acid (GABA) + CO2 yrosin → yramin + CO2 3. Conversion of tryptophan to niacin. 4. Interconversion of glycine and serine: where it works along with folic acid. 5. Trans-sulphuration reactions Homocysti n +s rin → omos rin +cyst in 6. Synthesis of sphyngosine from serine and arachidonic acid from linoleic acid. 7. Transport of amino acids. Across cell membranes. RDA: 2 mg/day Clinical correlations: Deficiency: This may result in a hypochromic microcytic anemia because the vitamine is required at one-stage-decarboxylation- in heme synthesis. Homocystinuria and cystathioninuria occur in B6 deficiency due to impaired metabolism of methionine. Pharmacological Facts of B6: 1. Treatment with isonicotinic acid hydrazide (INH) patients with tuberculosis induces a B6 deficiency manifested by neuropathy and excretion of abnormal metabolites of tryptophan in urine. Large doses of B6 will overcome this condition. 2. B6 is found to be of value in treatment of nausea and vomiting during pregnancy (morning sickness), 5. Pantothenic acid (B3): (Synonyms: Pantothenic in Greek =from everywhere) Structure: it is a pseudopeptide formed by combination of a butyric acid d rivativ wit β–alanine. Functions: it is a component of a very important coenzyme called Coenzyme A (HS-CoA) which has the following functions: Page 5 Water Soluble Vitamins زينا حسن.د 1. Formation of acetyl-CoA and fatty acyl-CoA. 2. Formation of acyl-carrier protein required for synthesis of fatty acids. 3. Acetyl-CoA is the starting point for citric acid cycle and fatty acid biosynthesis. 4. Adrenal cortical function since acetyl CoA is required for steroid ring synthesis. 5. Succinyl-CoA is a component of citric acid cycle. 6. Fatty acyl-CoA formation point for the oxidation of fatty acid or for their incorporation into triglycerides or phospholipids. RDA: 5-15 mg/day Clinical correlation: Deficiency: due to the widespread of this vitamin, its deficiency is very rare. 6. Biotin (Vitamin H): Structure: It is a heterocyclic compound containing sulphur. Sources: In addition to general sources of B complex vitamins; large amounts of this vitamin are synthesized by intestinal flora, but this source of supply is lost during therapy with sulphonamides and antibiotics. Avidin is a basic protein in egg white which is capable of forming an unabsorbable complex with biotin thus also depriving the availability of the vitamin. Functions: it is a coenzyme in CO2 transfer reactions (or CO2 fixation) involved in gluconeogenesis, lipogenesis, and fatty acid synthesis: 1. Acetyl-CoA to Malonyl-CoA. 2. Pyruvate to oxalacetate. 3. Propionyl-CoA to methylmalonyl-CoA. RDA: 100-300 µg/day Clinical correlation: Deficiency: this is very rare leading to alopecia, gastrointestinal and nervous symptoms. Page 6 Water Soluble Vitamins زينا حسن.د LECTURE 3 7. Folic acid: Structure: The term folic acid is derived from its widespread presence in green leafy vegetables (folium=leaf). The major parts of folic acid are: 1. Pteridine nucleus. 2. Para aminobenzoic acid (PABA). 3. Glutamic acid. All three parts form Pteroylglutamic acid (PGA). The reduced form of the vitamin (by addition of 4 hydrogens to the pteridine moiety), will make Tetrahydrofolic acid which is the active form of the vitamin. Sources: In addition to general sources of B complex vitamins; folic acid is found in green leafy vegetables. Many microorganisms can synthesize folic acid from PABA including those inhabiting the intestinal tract. Functions: Formation of the active form of Folic acid (Tetrahydrofolic acid) is brought about by a folic acid reductase enzyme which requires NADPH and Ascorbic acid as coenzymes. The tetrahydrofolaic acid can reversibly combine with a carbon unit at N5 or N10; and this is the basis of its function. The one carbon moiety can be derived from several sources and be utilized to form several compounds; as follows: 1. One carbon moiety donors: like methyl group of methionine or thymine. 2. One carbon moiety acceptors: as in homocysteine or uracil to form methionine. Folate Cycle Tetrahydrofolate takes up a one carbon moiety (-CH3) at N5 position. The methyl group is transferred to cobalamine which helps methylation of homocysteine to form methionine. The folate is returned to the folate pool to further take part in one carbon transfer reactions. Otherwise, folate remains trapped with the methyl group and its further functioning is impaired. This close correlation of folic acid and B12 is called the "Folate Cycle". Page 7 Water Soluble Vitamins زينا حسن.د RDA: 100 mg/day Clinical correlation: Deficiency: Since the vitamin is very much involved in the synthesis of purine ring which is a component of nucleic acids, and methylation of the pyrimidine ring to form thymine, a constituent of DNA, the most affected function will be cell multiplication. The hemopoietic system will be the earliest to be involved because it shows the maximum of cell division and multiplication normally. Macrocytic anemia, leucopenia and neurological symptoms are produced. In pregnancy there is increased requirement for folic acid by both; the mother (to prevent anemia) and the fetus (to prevent neural tube defect); therefore it is given prophylacticly to all pregnant women. Pharmacological facts of Folic acid: Sulfonamide drugs and antibiotics inhibit bacterial growth by blocking the incorporation of PABA in the folic acid synthesis (competitive inhibition). Trimethoprim inhibits the enzymatic conversion of dihydrofolate to tetrahydrofolate by bacteria thus inhibiting its growth. Methotrexate antagonizes folic acid thus inhibits cell division and multiplication as in treating leukemia and malignancy. 8. Vitamin B12 (Cobalamin): Structure: B12 molecule is composed of: 1. Corrin ring system with four pyrrole rings. 2. Trivalent cobalt atom. 3. Cyanide and azole ring of a nucleotide. Metabolism: The vitamin is absorbed from the intestine only in the presence of Intrinsic factor. Which a protein secreted from cells of the gastric mucosa. The active forms of B12 are methylcobalamin and deoxyadenosylcobalamin. Page 8 زينا حسن.د Water Soluble Vitamins Facts of B12: Intrinsic factor from gastric juice is necessary for absorption of vitamin B12. B12 is transported in plasma bound to specific carrier proteins called Transcorrin I and Transcorrin II. Functions: The vitamin functions as coenzyme after combining with an adinosyl moiety which replaces the –CN group. The pentose of the adenosine moiety is deoxyribose, and the coenzyme is called (Cobamide Coenzyme); which is involved in the following reactions: 1- Methyl-Malonyl-CoA to Succinyl CoA. 2- Methylation of homocysteine to methionine and the methylation of pyrimidine ring to form thymine. 3- Metabolism of diols; ex. Ethylene glycol. 4- Ribonucleotides to deoxyribonucleotides. RDA: 5 µg/day Clinical correlation: Deficiency: Like folic acid, B12 is also intimately connected to hemopoiesis; thus its deficiency leads to Macrocytic anemia. Sub-acute combined degeneration: Lesions in CNS along with anemia. Pernicious anemia: caused by deficiency of the Intrinsic factor associated with absence of HCL (Achlorhydria) and enzymes (Achylia) in gastric juice. VITAMIN C Group Structure: It is a white crystalline substance with a very acidic taste. It is a strong reducing substance. It is stable in the solid form and in acidic solutions, but is rapidly destroyed in alkaline solutions. Sources: Fresh green leafy vegetables and salad vegetables like cabbage, lettuce, spinach, and cucumber contain this vitamin. In addition to citrus fruits (lemons & oranges) and melons. Page 9 Water Soluble Vitamins زينا حسن.د Functions: The vitamin is intimately concerned with the metabolism of mesenchymal tissues, osteoid, dentine, and collagen. 1- Maintenance of redox potential in the cell: vitamin C plays a role of a coenzyme in hydrogen transfer reactions involving NADP and glutathione. 2- Collagen synthesis: hydroxyproline is an important amino acid in collagen; vitamin C is required for its synthesis from proline in connective tissue. 3- Tyrosine metabolism: its conversion catecholamines by dopamine-βhydrolase. 4- Absorption of iron from GIT: by converting inorganic ferric iron to the ferrous form. RDA: 70 mg/day Clinical correlation: Deficiency (Scurvy) It is failure to deposit intercellular cement substance. The capillaries become fragile and there is a tendency to hemorrhage. Wound healing is delayed due to deficiency in the formation of collagen. There is poor dentine formation in children leading to poor teeth formation. Gums are spongy swollen and bleed on slightest pressure. Osteoid of the bone is poorly laid and mineralization is inadequate. References: Lippincott's Illustrated Review in Biochemistry by Richard Harvey and Denise Ferrier; 5 th edition 2010. Unit 5, Chapters 28. Textbook of Biochemistry by Dr A V S S Rama Rao; 11th edition 2010. Chapter 11. Clinical chemistry & Metabolic medicine by Martin A. Crook; 7th edition 2008. Chapter 15. Clinical Chemistry by Michael L. Bishop and colleagues; 4th edition 2005. Part IV, chapter 31. Clinical Chemistry by William J Marshall & Stephen K Bangert; 6th edition 2008. Chapter 20. Page 10