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.

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

8. 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.

9. 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.

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

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

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

17. 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.

18. BIOCHEMICAL FUNCTIONS
ISOMERISATION OF METHYL MALONYL COA TO SUCCINYL COA

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

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

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

22. 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.

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

24. FISH TAPEWORM

25. FISH TAPEWORM

26. FISH TAPEWORM

27. 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.

28. Folic Acid

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

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

31. 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

33. 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

34. 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.

35. 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.

36. 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), deoxy thymydylic acid.
Glycine, serine, ethanolamine and choline.
N – formylmethionine.

37. 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.

38. NORMAL RBC SMEAR

39. MACROCYTIC ANEMIA

40. 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.

41. SPINA BIFIDA

42. 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.

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

44. 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

61. VITAMIN LIKE COMPOUNDS

62. CHOLINE Choline is trimethyl hydroxy ethanolamine.
Best and Huntsman (1934) found that, Choline deficiency in rats produced fatty liver and established its nutritional importance.

63. STRUCTURE OF CHOLINE
CH3
H3C N+
CH2
CH2 OH
CH3

64. BIOCHEMICAL FUNCTIONS
Choline, as a component of phospholipids is involved in membrane structure and lipid transport.
Due to the presence three methyl groups, choline is actively involved in one carbon metabolism.
Choline is a precursor for the synthesis of acetylcholine which is required for transmission of nerve impulse.

66. INOSITOL Inositol is hexahydroxy – cyclohexane.
It is also known as myo – Inositol or meso – inositol.

67. STRUCTURE OF INOSITOL

68. BIOCHEMICAL FUNCTIONS
Inositol is required for the synthesis of phosphatidyl Inositol which is a constituent of cell membrane.
It act as a lipotropic factor ( along with choline) and prevents the accumulation of fat in liver.

69. BIOCHEMICAL FUNCTIONS
For some hormones, inositol act as a second messenger at the membrane level for the release of Ca2+ ions.

71. LIPOIC ACID Lipoic acid is a sulphur containing fatty acids.
It exists in an oxidized and reduced form.
Lipoic acid is fat as well as water soluble.

72. STRUCTURE OF LIPOIC ACID

73. BIOCHEMICAL FUNCTIONS
Lipoic acid is involved in the decarboxylation reactions along with other vitamins.
The conversion of pyruvate to acetyl CoA and α – ketogluterate to succinyl CoA require LIPOIC ACID.

75. PARA AMINO BENZOIC ACID
Para amino benzoic acid (PABA) is a structural constituent of folic acid.
The deficiency of PABA was first found to be associated with failure of lactation graying of black hair in rats.

76. PARA AMINO BENZOIC ACID

77. PARA AMINO BENZOIC ACID
PABA is synthesized by the bacteria and is essential for their growth.
The sulfa drug sulfonilamide is a structural analogue of PABA.

79. BIOFLAVONOIDS
Szent – Gyorgi and his associates (1936) observed that, flavonoids, isolated from lemon peel were responsible for maintenance of normal capillary permeability.
The term vitamin P was used to this group of substance.
However, they are commonly known as BIOFLAVONOIDS.

80. BIOFLAVONOIDS

81. BIOFLAVONOIDS

82. BIOCHEMICAL FUNCTIONS
Bioflavonoids act as antioxidant and protect ascorbic acid from being destroyed.
It is suggested that, this antioxidant property may be responsible for maintenance of capillary permeability.