160 Introduction to Human Nutrition
remarkably lacking in tryptophan, that problems of
defi ciency occur. Trigonelline in coffee beans is
demethylated to nicotinic acid during roasting, and
moderate coffee consumption may meet a signifi cant
proportion of niacin requirements.
Unavailable niacin in cereals
Chemical analysis reveals niacin in cereals (largely in
the bran), but this is biologically unavailable, since it
is bound as niacytin – nicotinoyl esters to a variety of
macromolecules. In wheat bran some 60% is esteri-
fi ed to polysaccharides, and the remainder to poly-
peptides and glycopeptides.
Treatment of cereals with alkali (e.g., by soaking
overnight in calcium hydroxide solution, as is the tra-
ditional method for the preparation of tortillas in
Mexico) and baking with alkaline baking powder
releases much of the nicotinic acid. This may explain
why pellagra has always been rare in Mexico, despite
the fact that maize is the dietary staple.
Up to 10% of the niacin in niacytin may be biologi-
cally available as a result of hydrolysis by gastric
acid.
Absorption and metabolism
Niacin is present in tissues, and therefore in foods,
largely as the nicotinamide nucleotides. The post-
mortem hydrolysis of NAD(P) is extremely rapid in
animal tissues, so it is likely that much of the niacin
of meat (a major dietary source of the preformed
vitamin) is free nicotinamide.
Nicotinamide nucleotides present in the intestinal
lumen are not absorbed as such, but are hydrolyzed
to free nicotinamide. Many intestinal bacteria
have high nicotinamide deamidase activity, and
a signifi cant proportion of dietary nicotinamide
may be deamidated in the intestinal lumen. Both
nicotinic acid and nicotinamide are absorbed from
the small intestine by a sodium-dependent saturable
process.
The nicotinamide nucleotide coenzymes can be
synthesized from either of the niacin vitamers and
from quinolinic acid, an intermediate in the metabo-
lism of tryptophan. In the liver, synthesis of the coen-
zymes increases with increasing intake of tryptophan,
but not preformed niacin. The liver exports nicotin-
amide, derived from turnover of coenzymes, for
uptake by other tissues.
Catabolism of NAD(P)
The catabolism of NAD+ is catalyzed by four
enzymes:
● NAD glycohydrolase, which releases nicotinamide
and ADP-ribose;
● NAD pyrophosphatase, which releases nicotin-
amide mononucleotide; this can be either hydro-
lyzed by NAD glycohydrolase to release nicotin-
amide, or reutilized to form NAD;
● ADP-ribosyltransferases;
● poly(ADP-ribose) polymerase.
The activation of ADP-ribosyltransferase and
poly(ADP-ribose) polymerase by toxins, oxidative
stress or DNA damage may result in considerable
depletion of intracellular NAD(P), and may indeed
provide a protective mechanism to ensure that cells
that have suffered very severe DNA damage die as a
result of NAD(P) depletion. The administration of
DNA-breaking carcinogens to experimental animals
results in the excretion of large amounts of nicotin-
amide metabolites and depletion of tissue NAD(P);
addition of the compounds to cells in culture has a
similar effect. Chronic exposure to such carcinogens
and mycotoxins may be a contributory factor in the
etiology of pellagra when dietary intakes of trypto-
phan and niacin are marginal.Urinary excretion of niacin and metabolites
Under normal conditions there is little or no urinary
excretion of either nicotinamide or nicotinic acid.
This is because both vitamers are actively reabsorbed
from the glomerular fi ltrate. It is only when the con-
centration is so high that the reabsorption mecha-
nism is saturated that there is any signifi cant excre-
tion of niacin.
Nicotinamide in excess of requirements for
NAD synthesis is methylated by nicotinamide N-
methyltransferase. N^1 -Methylnicotinamide is actively
secreted into the urine by the proximal renal
tubules. N^1 -Methylnicotinamide can also be meta-
bolized further, to yield methylpyridone-2- and
4-carboxamides.
Nicotinamide can also undergo oxidation to nico-
tinamide N-oxide when large amounts are ingested.
Nicotinic acid can be conjugated with glycine to form
nicotinuric acid (nicotinoyl-glycine) or may be meth-
ylated to trigonelline (N^1 -methylnicotinic acid). It is