vitamin B12

Question 1

Structure of Cobalamin

Answer 1

Vitamin B12 bears a complex corrin ring (containing pyrrols similar to porphyrin), linked to a cobalt atom held in the center of the corrin ring, by four coordination bonds with the nitrogen of the pyrrole groups. The remaining coordination bonds of the cobalt are linked with the nitrogen of dimethylbenzimidazole nucleotide and sixth bond is linked to either methyl or 5’-deoxyadenosyl or hydroxy group to form methylcobalamin, adenosylcobalamin or hydroxycobalamin.
Thus, cobalamin exists in three forms that differ in the nature of the chemical group attached to cobalt. Cynocobalamin is the commercial available form of vitamin B12.

Question 2

Active form of Vitamin B12

Answer 2

The active coenzyme forms of vitamin B12 are:
* Methylcobalamin
* Deoxyadenosylcobalamin

Question 3

Sources of cobalamin

Answer 3

• Dietary sources of vitamin B12 are of animal origin
  and include meat, eggs, milk, dairy products, fish,
  poultry, etc.
• Vitamin B12 is absent in plant foods.
• Humans obtain small amounts of vitamin B12 from
  their intestinal flora.

Question 4

Absorption, Transport and Storage of cobalamin

Answer 4

• The intestinal absorption of vitamin B12 requires an
  intrinsic factor (IF), a glycoprotein secreted by
  parietal cells of the stomach.
• In stomach IF binds the dietary vitamin B12 to form
  vitamin B12-IF complex. This complex binds to
  specific receptors on the surface of the mucosal cells
  of the ileum.
• After binding to the receptor, the bound vitamin B12
  is released from the complex and enters the illeal
  mucosal cells through a Ca2+ dependent process.
• The vitamin in mucosal cell is converted into its main
  plasma transport form to methylcobalamin. It is
  then transported by a vitamin B12 binding protein
  known as transcobalamin (TC-I and TC-II).
• Methylcobalamin which is in excess is taken up by
  the liver, stored in deoxyadenosyl B12 form.
• Liver can store about 4-5 mg of vitamin B12 in adults,
  an amount sufficient to meet the body requirements
  of vitamin B12 for 3–6 years.
• Vitamin B12 is the only water soluble vitamin that is
  stored in significant amounts in the liver.

Question 5

Functions of cobalamin

Answer 5

There are only two human enzyme systems that are
known to require vitamin B12 coenzyme.
1. Isomerization of methylmalonyl-CoA to succinyl-CoA
* Propionyl-CoA-is produced as catabolic end
product of some aliphatic amino acids and in
β-oxidation of odd chain fatty acids. The
propionyl-CoA is then converted to succinyl-CoA.
* During conversion of propionyl-CoA to succinylCoA vitamin B12 coenzyme, deoxyadenosyl cobalamine is required for the isomerization of L-methylmalonyl- CoA to succinyl-CoA.
* In vitamin B12 deficiency methylmalonyl CoA
accumulates and is excreted in urine as methylmalonic acid (Figure 7.15).
2. Conversion of homocysteine to methionine
* Methylcobalamin is a coenzyme in the conversion of homocysteine to methionine, which joins the metabolic roles of vitamin B12 and those of folic acid (for explanation see functions of folic acid). This is the only mammalian reaction known to require both vitamins.

Question 6

Nutritional Requirements of cobalamin

Answer 6

RDA for adult is 3 μg with higher allowances for
pregnancy and lactating women.

Question 7

Deficiency Manifestations of cobalamin

Answer 7

Deficiency may arise due to decreased absorption or
decreased dietary intake. Dietary deficiency is seen in
strict vegetarians, since the vitamin found only in foods
of animal origin or in microorganisms. Deficiency of
vitamin B12 leads to:
* Pernicious anemia
* Megaloblastic anemia
* Methylmalonic aciduria
* Neuropathy.
1. Pernicious anemia: It is caused by a deficiency of
intrinsic factor in the stomach, which leads to
impaired absorption of vitamin B12.It is characterized
by megaloblastic anemia and low hemoglobin level
with neurological disorders.
2. Megaloblastic anemia: It occurs due to functional
folate deficiency. The functional folate deficiency
is seen in vitamin B12 deficiency due to folate trap.
3. Methylmalonic aciduria: Because vitamin B12 is
necessary for the conversion of methylmalonic acid
to succinic acid, individuals deficient in vitamin B12
excrete excess amounts of methylmalonic acid in the
urine.
4. Neuropathy: In vitamin B12 deficiency, many
neurological symptoms appear due to progressive
degeneration of myelinated nerves. Degeneration
of myelinated nerves is due to accumulation of
L-methylmalonyl-CoA, which impaires the myelin
sheath formation. The neurological symptoms
include numbness and tingling of fingers and toes,
mental confusion, poor muscular coordination and
dementia.