COBALAMIN

Vitamin B12
Introduction
Vitamin B12 is also known as anti pernicious
anaemia or extrinsic factor of castle
It is a unique vitamin synthesised only by
microorganisms and not by animals and plants
It was the last vitamin to be discovered
Chemistry
Vitamin B12 is a water soluble heat, stable and red in colour
It contains 4.35% cobalt by weight
Four pyrrole rings coordinated with a cobalt atom is called
as corrin ring
The corrin ring has four pyrrol units like porphyrin
Two of the pyrrol units (A and D)are directly bound to each
other, whereas the two other (B and C) are held by methene
bridges
The groups, namely methyl, acetamide and propionamide
are the substituent on the pyrrole rings
Cobalt present at the centre of the corrin Ring is
bonded to the four pyrrrole nitrogen.
Cobalt also holds benzimidazole (DMB) containing
ribose, 5- phosphate and amino isopropanol
A nitrogen atom dimethyl benzimidazole is linked to
cobalt
The amide group of aminoisopropanol binds with D
ring of corrin
The cobalt atom also possesses a sixth substituent
group located above the plane of the corrin ring
All the forms of vitamin B12 are called cobalamin
because of the presence of cobalt atom
Different forms of cobalamin include
1) cyanocabalamin- it refers to the isolated form of
vitamin B12 in which cyanide was added to promote
crystallisation of cobalamin during the isolation process
2) hydroxycobalamin-it was usually present in the
tissues and in the naturally occurring forms of vitamin
B12
3) methylcobalamin- methyl group replaces
adenosine group
Absorption
In the food vitamin B12 is present as a complex with
proteins
The free form of vitamin B 12 is released by cooking HCL
present in gastric juice and proteins by Pepsi in stomach
Mechanism
The absorbance of vitamin B12 requires intrinsic factor
Intrinsic factor is a glycoprotein secreted by vital cells of
stomach
Vitamin B 12 combines with intrinsic factor
The vitamin B12 intrinsic factor complex reaches the
ileum where it is absorbed
In cells, vitamin B 12 is released from its complex the
portal circulation
Transport
In the portal blood, it is transported in combination
with transcobalmin II
Vitamin B 12 is presented to cells where it is taken
up by the cells through receptor medicated
endocytosis
Storage
It is mainly stored in liver leucocytes and gastric
mucosa
It is as complex with transcobalmin I & II
Biochemical functions
About 10 enzymes requiring vitamin B12 have been
identified
Most of them are found bacteria ( mutase ,
ribonucleotide reductase , etc)
There are two reactions in mammals that dependent on
1) synthesis of methionine from homosysteine
Methyl cobalamin is essential for the conversion of
homocysteine to methionine and formation of FH4
and from methyl FH4
The reaction is catalyzed by homocysteine methyl
transferase
Significance of the reaction
The circulating methyl FH4 is converted to FH4
FH4 is either used for storage as folylpolyglutamate
form or it is utilised for other reactions such as
formation of methylene FH4
Methyl folate trap-
In b12 deficiency impaired conversion of methyl FH4
to FH4 results in accumulation of methyl FH4 & called
as methyl folate trap
2) isomerization of methyl CoA to succinyl CoA
The degradation of odd chain fatty acids and some
a,ion acids (valine , leucine etc) and pyrimidines
( thymine & uracil) produce propionyl CoA , and imp.
Coumpound methylmalonyl CoA
The methyl Maloney CoA mutase converts methyl
malonyl CoA to succinyl CoA in the presence of vitamin
B12 , deoxyadenosyl cobalamin
Dietary sources
Rich sources of vitamin B12 are meats , eggs , milk ,
sea foods
B12 is synthesized by microorganisms
Vitamin B12 is not present in plant sources
RDA
Adults = -1 ug/day
Pregnancy & lactation = -2ug/day
Deficiency
Causes-
Inadequate intake seen in pure vegetarians and rarely in
alcoholism
Impaired absorption
This is mainly caused by lack of intrinsic factor called pernicious
anaemia and it is caused by destruction of gastric mucosa.
impaired storage and transport
In adequate utilisation of vitamin occurs because of
liver diseases and abnormalities of transport proteins
Increased requirements are seen in hyperthyroidism
infancy and thalassaemia
Increased excretion occurs in nephrotic syndrome
Clinical features
Vitamin B12 deficiency is characterised by
Megaloblastic anaemia
Feature of megaloblastic anaemia include pallor ,
fatigue, glossitis , (briefly red tongue), and slight
yellow discolouration of the conjunctiva due to
increased unconjugated bilirubin
Progression of anaemia may result in angina &
congestive cardiac failure
gastro intestinal dysfunction
GIT epithelial cells are undergoing rapid turnover and
dependent on vitamin B12
B12 deficiency results in weight, loss and diarrhoea
Demylination of nervous tissue
Damage to nervous system is seen in B12 deficiency
There is demyelination affecting the cerebral cortex
as well as dorsal column and pyramidal tract
Alteration of tendon and deep sense and reflects loss
of position sense unsteadiness in gate, positive
Rhomberg sign and positive Bibin sign are seen
Achlorhydria
Absence of acid in gastric juice is associated with
B12 deficiency
Assessment of B12 deficiency.
Serum B12, it is quantitated by radio immuno essay
or by ELISA.
Methyl melodic acid. Is excreted in urine.
FIGLU excretion test
Peripheral smear peripheral blood and bone
marrow morphology shows megaloblastic anaemia
Homocysteinuria Excretion of homocysteine in
urine
Schilling test
Radioactive labelled (cobalt-60) vitamin B12 1ug is
given orally
In gastric atrophy cases there is no absorption hands
the entire radio activities. Excreted in faeces and
radio activities is not observed in liver.
If the cause is nutritional deficiency, there will be
increased absorption
Then radioactive is noted in liver region with very
little excretion in feces.