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Vitamin B12 and Folic Acid

Vitamin B12 and Folic Acid. Objectives. Chemistry of vitamin B12 Metabolism of Vit. B12 Functions Sources and daily requirement Deficiency. VITAMIN B 12. SYNONYMS: Anti – pernicious anemia factor Extrinsic factor of Castle Animal protein factor. CHEMISTRY.

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Vitamin B12 and Folic Acid

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  1. Vitamin B12 and Folic Acid

  2. Objectives Chemistry of vitamin B12 Metabolism of Vit. B12 Functions Sources and daily requirement Deficiency

  3. VITAMIN B 12 SYNONYMS: • Anti – pernicious anemia factor • Extrinsic factor of Castle • Animal protein factor

  4. CHEMISTRY • Vitamin B12 is water soluble, heat stable and red in color. • It contains 4.35 % cobalt by weight. • It contains 63 carbon, 14 nitrogen and one cobalt atoms. • Four pyrrole rings co-ordinated with cobalt atom is called a corrin ring.

  5. CHEMISTRY • The 5th valency of the cobalt is covalently linked to a substituted benzamidazole ring. • This is then called cobalamin. • The sixth valency of the cobalt is satisfied by any of the following groups: cyanide, hydroxyl, adenosyl or methyl.

  6. CYNO COBLAMIN • When cyanide is added at the R position, the molecule is called cynocobalamine

  7. HYDROXY COBLAMIN • When hydroxyl group is attached at the R position, it is called hydroxy coblamin. • When taken up by the cells, these groups are removed and deoxyadenosyl coblamin is formed.

  8. METHYL COBLAMIN • When the methyl group replaces adenosyl group, it is known as methyl coblamin. • This is the major form seen in blood circulation as well as cytoplasm.

  9. RDA • Normal daily requirement is 1 – 2 μg / day. • During pregnancy and lactation, this is increased to 2 μg / day.

  10. DIETARY SOURCES • Vitamin B12 is not present in vegetables. • Liver is the richest source. • Meat, fish and egg are good sources. • Curd is also good source, because lactobacillus can synthesize B12.

  11. ABSORPTION OF VITAMIN B12 • Vitamin B12 combines with the intrinsic factor (IF) of castle. • Hence the B12 is otherwise is known as extrinsic factor (EF), that is the factor derived from external sources. • Intrinsic factor is secreted by the gastric parietal cells.

  12. It is a glycoprotein with a molecular weight of 50,000. • One molecule of IF can combine with two molecule of vitamin B12. • This IF-B12 complex is attached with specific receptor on mucosal cells. • The IF-B12 complex is internalized. • It may be noted that, vitamin B12 is absorbed from ileum, while folic acid is from jejunum.

  13. TRANSPORT & STORAGE • The IF is digested inside the mucosal and B12 is transported to the circulation. • In the blood methyl B12 form is predominant. • Transcobalamin II, a glycoprotein, is the specific carrier. • It is stored in the liver cells, as ado-B12 form, in combination with Transcobalamin I.

  14. Generally, B complex vitamins are not stored in the body, B12 is an exception. • Whole liver contain about 2 mg of B12 • Which is the sufficient for the requirement for 2 – 3 years. • So, B12 deficiency is seen only years after gastrectomy.

  15. BIOCHEMICAL FUNCTIONS • Synthesis of Methionine from homocystine: THF N5 METHYL THF Homocysteine METHIONINE Methyl Coblamin B12 FOLATE TRAP

  16. BIOCHEMICAL FUNCTIONS • Vitamin B12 deficiency leads to impairment of Methionine synthase, resulting in accumulation of Homocysteine and trapping folate as methyl tetra hydrofolate. • This known as folate trap.

  17. BIOCHEMICAL FUNCTIONS • ISOMERISATION OF METHYL MALONYL COA TO SUCCINYL COA

  18. DEFICIENCY MANIFESTATIONS • Adult pernicious anemia • Mucosal atrophy of stomach • Glossitis, hypersegmented neutrophils • Stomatitis • Pharyngitis • Achlorhydria • Folate Trap

  19. DEFICIENCY MANIFESTATIONS • Damage to nervous system, the sub acute combined degeneration. • Demyelination and neural death. • Mild deficiency may cause depression, confusion and less alertness.

  20. Peripheral blood smear showing hypersegmented neutrophils, characteristic of megaloblastic anemia. Megaloblastic anemia

  21. CAUSES OF B12 DEFICIENCY NUTRITIONAL: • Vitamin B12 deficiency is very common in India, especially among vegetarians of low socioeconomic group. • The only source for B12 in vegetarian diet is curd/ milk and lower income group may not able to afford it.

  22. CAUSES OF B12 DEFICIENCY • Decrease in absorption • Elderly people • Addisonian pernecious anemia • Gastric atrophy • Fish tapeworm • Pregnancy • Inherited defects

  23. FISH TAPEWORM

  24. FISH TAPEWORM

  25. FISH TAPEWORM

  26. TREATMENT • If megaloblastic anemia is treated with folic acid alone, the anemia may improve, but associated nervous lesions are aggravated. • Hence all macrocytic anemia's are generally treated with Folate and vitamin B12. • Therapeutic dose of B12 is 100 – 1000 microgram by intramuscular injection.

  27. Folic Acid

  28. Objectives Chemistry Metabolism Functions Sources and daily requirement Deficiency Folic acid antagonist

  29. FOLIC ACID SYNONYMS: • Liver lactobacillus • Caseifactor • Vitamin M • Streptococcus Lactis R (SLR) factor • pteroyl glutamic acid (PGA).

  30. FOLIC ACID CHEMISTRY The designation folic acid is applied to a number of compounds which contain the following group. • Pteridine nucleus • Para Amino Benzoic Acid • Glutamic Acid

  31. RDA • Adults : 400 – 500 μg/ day • Infants : 50 μg/ day • Children : 100 – 300 μg/ day Requirement increases in pregnancy & lactation • Pregnant women : 800 μg/ day • Lactating women : 600 μg/ day

  32. DIETARY SOURCES • Folic acid is widely distributed in nature. • Rich sources are green leafy vegetables, whole grains, cereals, liver, kidney, yeast and eggs. Milk is rather poor source of folic acid.

  33. ABSORPTION, TRANSPORT AND STORAGE • Most of the dietary folic acid found as polyglutamate with 3 – 7 glutamate residues is not absorbed in the intestine. • The enzyme folate conjugase present in duodenum and jejunum split the glutamate residues. • Only the monoglutamate of folic acid is absorbed from the intestine.

  34. BIOCHEMICAL FUNCTIONS • Tetrahydrofolate, the coenzyme of folic acid is actively involved in the one carbon metabolism. • THF is serves as an acceptor or donor of one carbon units (formyl, methyl etc.). COMPOUND SYNTHESIZE IN 1 CARBON METABOLISM: • Purines ( carbon 2 & 8), deoxythymydylic acid. • Glycine, serine, ethanolamine and choline. • N – formylmethionine.

  35. DEFICIENCY SYMPTOMS • In folic acid deficiency, decreased production of purines and dTMP is observed which impairs DNA synthesis. • Due to block in DNA synthesis, the maturation of erythrocytes is slowed down leading to macrocytic RBC.

  36. NORMAL RBC SMEAR

  37. MACROCYTIC ANEMIA

  38. SPINA BIFIDA • Folic acid deficiency during pregnancy may lead to neural tube defects in the fetus. • Folic acid prevents birth defects, fetal malformations such as spina bifida. • So, high doses of folic acid are recommended in pregnancy.

  39. SPINA BIFIDA

  40. RISK OF EXCESS OF FOLIC ACID • Irreversible nerve damage. • Solubility of folic acid is low, hence large doses of folic acid if given parenterally there is risk of crystallization in kidney tubules leading to renal damage.

  41. Folic Acid Deficiency and Homocysteinimia Homocys.– a risk factor For chd

  42. Folic Acid antagonist Aminopterin and Amethopterin (Methotrexate) Clinical Use:inhibit DNA synthesis especially in cancer cell. Trimethoprim Clinical Use: used to treat for bacterial infections along with sulfomethaxozole

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