^ \ C O O H
F IG U R E 3 8 -1 9
Structures of nicotinic acid and nicotinamide.
serum screening for Down’s syndrome, which includes
measuring separate subunits of hCG (free cr-hCG and free
/1-hCG), unconjugated estriol, and AFP, has proven to be
more effective than triple-marker assessment. The confir-
matory test for Down’s syndrome is karyotype analysis.
Serum AFP levels are elevated in hepatocellular carci-
nomas and malignancies involving ovaries and testes. Yolk
sac tumors, which occur more frequently in the ovaries of
young women, and girls, and in the testes of boys, raise
serum levels of AFP. Serum hCG measurement is also
helpful in the diagnosis and management of germ cell tu-
mors. Thus, hCG and AFP are also used as tumor markers.
Niacin (nicotinic acid; pyridine-3-carboxylic acid) and
nicotinamide are precursors of NAD+
(Figure 38-19). Niacin occurs in meat, eggs, yeast, and
whole-grain cereals in conjunction with other members
of the vitamin B group. Little is known about absorption,
transport, and excretion of niacin and its coenzyme forms.
A limited amount of niacin can be synthesized in the body
from tryptophan, but it is not adequate to meet metabolic
was originally thought to be due to inadequate
dietary niacin and tryptophan. In some parts of the world,
it is associated with consumption of diets high in maize
(American corn), which, like other cereal grains, is rela-
tively deficient in tryptophan and niacin. In addition, about
% of the niacin in maize is protein-bound and not bi-
ologically available. Several bound forms of niacin have
been characterized. They include niacinogens (peptides of
M.W. 12,000-13,000) and niacytin, isolated from wheat
Pellagra is currently thought to be due to imbalance of
dietary amino acids and deficiency of niacin. The common
variety of maize is rich in leucine, which inhibits synthesis
of nicotinic acid mononucleotide and causes deficiency of
NAD+ and NADP+. A strain of maize known as opaque
contains less leucine and does not cause pellagra unless
excess leucine is added to the diet.
H O — CH.— C — CH
— C H — COOH
Pantoic a d d
F IG U R E 3 8 -2 0
Structure of pantothenic acid (pantoyl-jS-alanine).
Pellagra-like symptoms can occur in
Hartnup’s disease is an
inherited disorder of amino acid transport (Chapter 17)
in which niacin deficiency presumably develops because
niacin intake is inadequate to supply metabolic needs when
combined with the decreased absorption of dietary tryp-
tophan. In carcinoid syndrome, up to 60% of avail-
able dietary tryptophan is diverted to formation of
5-hydroxytryptamine (serotonin) by what is normally a
Pantothenic Acid (Pantoyl-/3-AIanine)
Pantothenic acid is ubiquitous in plant and animal tissues
and especially abundant in foods rich in other B vita-
mins. No RDA has been established, but a daily intake of
5-10 mg is thought to be adequate for adults. Deficiency
in humans is unknown.
Pantothenic acid is a precursor for the synthesis of coen-
zyme A (CoA, CoASH) and forms part of the “swing-
ing sulfhydryl arm” of the fatty acid synthase complex
(Chapter 19). Its structure is shown in Figure 38-20.
Biotin is widely distributed in foods. Beef liver, yeast,
peanuts, kidney, chocolate, and egg yolk are especially
rich sources. The intestinal flora synthesizes biotin. Fecal
excretion reflects this enteric synthesis. Total daily urinary
and fecal excretion exceeds the dietary intake.
Biotin deficiency occurs when large amounts of raw egg
white are consumed. Egg white contains
(M.W. 70,000) that binds biotin strongly and specifically,
preventing its absorption from the intestine. Because of
the tight binding and specificity of biotin, avidin-labeled
probes have been used to detect proteins and nucleic acids
to which biotin has been covalently attached (“biotiny-
lated” molecules). Avidin is a homotetramer. Each sub-
unit contains 128 amino acids and binds one molecule of
biotin. The affinity of avidin for biotin is abolished by
heat and other dénaturants. Biotin deficiency can result
from sterilization of the intestine by antibiotics and from
administration of biotin analogues.