Tuesday, July 3, 2007

Vitamin B12

A type of anaemia attributed to a digestive disorder
was reported by Combe in 1822 and later recognized
as pernicious anaemia by Addison in 1849. It was not
until 1926 that Minot and Murphy started to cure patients
suffering from pernicious anaemia by feeding
them with large amounts of raw liver. The idea for this treatment originated from the discovery by Whipple
that dietary liver improved haemoglobin production
in iron-defi cient dogs. In 1929, Castle showed that the
intestinal absorption of the ‘antipernicious anaemia
principal’ required prior binding to a specifi c protein
(intrinsic factor) secreted by the stomach.
Research into isolating the active principal from
liver was hampered by the inability to induce pernicious anaemia in animals. For many years, the
only known bioassay was the haemopoietic response
of patients with the disease. Eventually, in 1948, a red
crystalline substance having the clinical activity of
liver and designated as vitamin B12 was isolated by
several independent scientifi c groups. The success of
one group, headed by Folkers (Merck and Co., USA),
was largely attributable to a microbiological assay developed
by Shorb in 1947. The complicated structure
of vitamin B12 was established by Hodgkin using X-ray
crystallography in 1955. Its complete chemical synthesis
was achieved in 1973, but because of the large
number of stages required (over 70) the procedure is
of no commercial interest.

In accordance with the literature on nutrition and
pharmacology, the term vitamin B12 is used in this
text as the generic descriptor for all cobalamins that
exhibit antipernicious anaemia activity. Individual
cobalamins will be referred to by their specifi c names
(e.g. cyanocobalamin).
The cobalamin molecule depicted in Fig. 18.1 contains
a corrin ring system and a cobalt atom, which
may assume an oxidation state of (I), (II) or (III).
There are two vitamin B12 coenzymes with known
metabolic activity in humans, namely methylcobalamin
and 5´-deoxyadenosylcobalamin (frequently
abbreviated to adenosylcobalamin and also known
as coenzyme B12). The methyl or adenosyl ligands of
the coenzymes occupy the X position in the corrin
structure. The coenzymes are bound intracellularly
to their protein apoenzymes through a covalent peptide
link, or in milk and plasma to specifi c transport
proteins. The enzyme-bound cobalamins exist as
Cyanocobalamin is the most stable of the vitamin
B12-active cobalamins and is the one mostly used in
pharmaceutical preparations and food supplementation.
Aqueous solutions of cyanocobalamin are stable
in air at room temperature if protected from light. On
exposure to light, the cyano group dissociates from
cyanocobalamin and hydroxocobalamin is formed.
In neutral and acid solution hydroxocobalamin exists
in the form of aquocobalamin (Gräsbeck & Salonen,
1976). This photolytic reaction does not cause a loss
of activity.

Naturally occurring vitamin B12 originates solely
from synthesis by bacteria and other microorganisms
growing in soil or water, in sewage, and in the
rumen and intestinal tract of animals. Any traces of
the vitamin that may be detected in plants are due to
microbial contamination from the soil or manure or,
in the case of certain legumes, to bacterial synthesis in
the root nodules.
Vitamin B12 is ubiquitous in foods of animal origin
and is derived from the animal’s ingestion of cobalamin-
containing animal tissue or microbiologically
contaminated plant material, in addition to vitamin absorbed from the animal’s own digestive tract. Liver
is the outstanding dietary source of the vitamin, followed
by kidney and heart. Muscle meats, fi sh, eggs,
cheese and milk are other important food sources.
Vitamin B12 activity has been reported in yeast, but
this has since been attributed to the presence of noncobalamin
corrinoids or vitamin B12 originating
from the enriching medium (Herbert, 1988). About
5 to 30% of the reported vitamin B12 in foods may be
microbiologically active non-cobalamin corrinoids
rather than true B12 (National Research Council,
Vitamin B12 in foods exists in several forms as reported
by Farquharson & Adams (1976). Meat and fi sh
contain mostly adenosyl- and hydroxocobalamins;
these compounds, accompanied by methylcobalamin,
also occur in dairy products, with hydroxocobalamin
predominating in milk. Sulphitocobalamin is found
in canned meats and fi sh. Cyancobalamin was only
detected in small amounts in egg white, cheeses and
boiled haddock.

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