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43. Vitamin B12 – sources, transport and resorption in GIT,

role in metabolism (examples of reactions), causes and
consequences of deficit, macrocytic anaemia.
02 March 2019 09:25

Cobalamin (vitamin B12) has a very complex structure with a tetrapyrrole corrin system and a
central cobalt ion.
It is only produced by bacteria, it is found in animal products, not in plant food.
A special glycoprotein, intrinsic factor, secreted by stomach mucosa is necessary for absorption
of ingested cobalamin in the small intestine.
Resorbed cobalamin is stored in the liver.
In cells, it is transformed to the cofactors methylcobalamin and deoxyadenosylcobalamin.
They are necessary for the degradation of some amino acids and mainly, together with folic acid,
are needed for remethylation of homocysteine to methionine (which is important to maintain the
pool of tetrahydrofolate for continuous synthesis of DNA bases).
The daily intake of B12 for adults is approximately 2.5 ug.
Rich sources of cobalamin are meat, offal, dairy products, and eggs.
Cobalamin is also formed by intestinal microflora, however, it is not absorbed and leaves the
body with stool.

A deficiency of cobalamin caused by insufficiency of intrinsic factor and malabsorption of

cobalamin from food.
Symptoms of deficiency are manifested as megaloblastic anemia and specific neurological
disorders.
It is treated by parenteral application of cobalamin.
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Insufficient cobalamin intake is typically found in long-term strict vegetarians (vegans), and the
first symptoms of deficiency begin to appear after 5-8 years.
In elderly people, inadequate nutrition may be potentiated by atrophy of gastric mucosa.

Cobalamin (vitamin B12) has an extremely complicated structure.

The cyclic tetrapyrrole system is called corrin, it makes a complex (chelate) with the cobalt ion.
Corrin has one interesting feature: there are only three bridges between the four pyrrole rings
(unlike porphyrin in heme).

Vitamin B12 originates only from microorganisms that produce hydroxocobalamin.

Vitamin B12 is found only in animal food.
A rich source is meat, dairy products and eggs.
Cobalamin is also produced by intestinal microflora, but it is not absorbed and is excreted in the
faces.
A non-naturally occurring semisynthetic derivative is cyanocobalamin.
It is produced by pharmaceutical companies as a substrate for injectable dosage forms.
As hydroxocobalamin forms a stable, nontoxic complex with cyanide ion, it is approved as
antidote for cyanide poisoning.

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In cells, cobalamin is converted to biologically active cofactors: methylcobalamin and

deoxyadenosylcobalamin.
Methylcobalamin is needed, together with tetrahydrofolate, for the methylation of homocysteine
to methionine.
However, this process is important from more general aspect as it maintains the pool of free
tetrahydrofolate, which is needed for the synthesis of DNA bases.
Transfer of methyl group occurs successively from methyltetrahydrofolate to hydroxycobalamin,
and from methylcobalamin to homocysteine.
In the absence of vitamin B12, the so-called folate trap develops, tetrahydrofolate is blocked as
methyltetrahydrofolate (CH3-H4F).
The metabolic consequences of folate traps are:
• Disturbed synthesis of purine and pyrimidine bases.
• Disturbed synthesis of DNA.
• Blocked cell division.
• Disturbed formation of nuclei in new erythrocytes - accumulation of megaloblasts in bone
marrow.

Deoxyadenosylcobalamin is essential for the isomerization of methylmalonyl-CoA (produced by

the carboxylation of propionyl-CoA) to succinyl-CoA.
This process is important for the utilization of propionyl-CoA, which originates from some amino
acids and odd-carbon fatty acids.

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