Medicinal Chemistry

(Jacob Rumans) #1

Biotin deficiency can be triggered only experimentally, using diets rich in raw egg
white. The latter contains avidin, a 70 kD protein that binds biotin in an inactive form.
The deficiency leads to dermatitis and hair loss in rats.


8.2.8.7 Vitamin B 12 (Cobalamin)


Vitamin B 12 (8.50, cobalamin) is an extremely complex molecule consisting of a corrin
ring system similar to heme. The central metal atom is cobalt, coordinated with a
ribofuranosyl-dimethylbenzimidazole. Vitamin B 12 occurs in liver, but is also produced
by many bacteria and is therefore obtained commercially by fermentation. The vitamin
is a catalyst for the rearrangement of methylmalonyl-CoA to the succinyl derivative in
the degradation of some amino acids and the oxidation of fatty acids with an odd
number of carbon atoms. It is also necessary for the methylation of homocysteine to
methionine.


Lack of B 12 leads to pernicious anemia, an uncommon but potentially fatal disease if
untreated. In 1926, Minot and Murphy discovered that raw liver could keep patients
with the disease alive. The vitamin itself was isolated only in 1948. As little as 3–6 ×
10 −^6 g is curative, and the large amounts of the vitamin taken by some fadists are therefore


ENDOGENOUS MACROMOLECULES 507
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