Vitaminquick Reviews
1. 2. 3. 4.
5.
Chemistry of vitamin B12 Metabolism of Vit. B12 Functions Sources and daily requirement Deficiency
SYNONYMS:
Anti – pernicious anemia factor
Extrinsic factor of Castle
Animal protein factor
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.
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.

When cyanide is added at the R position, the molecule is called cynocobalamine

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.

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.
Normal daily requirement is 1 – 2 μg / day.
During pregnancy and lactation, this is increased to 2 μg / day.
Vitamin B12 is not present in vegetables.
Liver is the richest source.
Meat, fish and egg are good sources.
Curd
is
also
good
source,
lactobacillus can synthesize B12.
because
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.
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.
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.
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.

Synthesis of Methionine from homocystine: homocystine THF
N5 METHYL THF Homocysteine
METHIONINE Methyl Coblamin B12
FOLATE TRAP

Vitamin B12 deficiency leads to impairment of
Methionine
accumulation
synthase, of
resulting
Homocysteine
in and
trapping folate as methyl tetra hydrofolate. 
This known as folate trap.

ISOMERISATION OF METHYL MALONYL COA TO SUCCINYL COA
Adult pernicious anemia Mucosal atrophy of stomach Glossitis, hypersegmented neutrophils Stomatitis Pharyngitis Achlorhydria Folate Trap
Damage to nervous system, the sub acute combined degeneration.
Demyelination and neural death.
Mild deficiency may cause depression, confusion and less alertness.
Peripheral blood smear showing hypersegmented neutrophils, characteristic of megaloblastic anemia.
Megaloblastic anemia
NUTRITIONAL:  Vitamin B 12 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.
Decrease in absorption Elderly people Addisonian pernecious anemia Gastric atrophy Fish tapeworm Pregnancy Inherited defects
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.
Folic Acid
1. 2. 3. 4. 5. 6.
Chemistry Metabolism Functions Sources and daily requirement Deficiency Folic acid antagonist
SYNONYMS: Liver lactobacillus Caseifactor Vitamin M Streptococcus Lactis R (SLR) factor pteroyl glutamic acid (PGA).
The designation folic acid is applied to a number of compounds which contain the following group. Pteridine nucleus Para Amino Benzoic Acid Glutamic Acid
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

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.
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. intestine
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: 1. 2. 3.
Purines ( carbon 2 & 8), deoxy thymydylic acid. Glycine, serine, ethanolamine and choline. N – formylmethionine.

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.



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.

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.
Folic Acid Deficiency and Homocysteinimia
•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

Choline is trimethyl hydroxy ethanolamine.

Best and Huntsman (1934) found that, Choline deficiency in rats produced fatty liver
and
importance.
established
its
nutritional
CH3
H3C
N+
CH3
CH2
CH2
OH
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.
Inositol is hexahydroxy – cyclohexane.
It is also known as myo – Inositol or meso – inositol.

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.

For some hormones, inositol act as a second messenger at the membrane level for the release of Ca2+ ions.
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.
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.

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.

PABA is synthesized by the bacteria and is essential for their growth.

The sulfa drug sulfonilamide is a structural analogue of PABA.
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.

Bioflavonoids act as antioxidant and protect ascorbic acid from being destroyed.

It
is
suggested
property
may
that, be
this
antioxidant
responsible
maintenance of capillary permeability. permeability
for