Niacin: Nicotinic Acid and Nicotinamide

The human disease of pellagra was first described in
Spain by Casal in 1735 after the introduction of maize
into Europe from the Americas. In the 1920s, Goldberger
in the USA reported that pellagra and black
tongue in dogs responded to treatment with animal
protein and also to boiled protein-free extracts of
yeast. In 1937, Elvehjem found that the active component
in liver extracts used to successfully treat canine
black tongue was nicotinamide, and reports that nicotinic
acid cured pellagra soon followed.
Nicotinic acid and nicotinamide had been isolated
from the coenzymes now known as NAD and NADP
by 1934–1935; hence knowledge of their biochemical
roles in electron-transfer reactions preceded the discovery
of their nutritional signifi cance. By 1946, the
metabolism of dietary tryptophan to an active form
of the vitamin had been demonstrated.

In living tissues nicotinamide is the reactive moiety
of the coenzymes NAD and NADP. The structure of
NAD can be envisaged as the adenosine diphosphateribosyl
moiety, hereafter abbreviated as ADP-ribose,
attached covalently to nicotinamide through a β-Nglycosidic
linkage (Fig. 13.1). This linkage constitutes
a high-energy bond, the energy of which supplies the
driving force for various ADP-ribosylation reactions
(see Section 13.5.2). NAD glycohydrolases hydrolyse
the N-glycosidic linkage of NAD, yielding free ADPribose,
nicotinamide and a proton. Most cellular NAD
and NADP is stored in the cytoplasm, bound to protein
(Weiner & van Eys, 1983).