section 17.3
Metabolism of Some individual Amino Acids
361
T
.
u
,
C
—
CH,— C H
—coo
- C H — C H — C O O -
T ryptophan p yrrolase
^
2
i
1
~
S
,
'
NH,
UL
NHt
NHCHO
N -Form ylkynurenine
^-H*0
F o rm am id ase
F o rm a te — 'O n e -c a rb o n pool
OH
3-H ydroxyanthranilate
FIGURE 17-24
Pathway for the synthesis of NAD from tryptophan.
X anthurenate
(excreted in urine)
types of carcinoma (from the effect of solar radiation on
DNA). When the eyes are involved, photophobia, sub-
normal visual acuity, strabismus, and nystagmus may be
present.
Tryptophan
Tryptophan
is an essential amino acid involved in
synthesis of several important compounds. Nicotinic
acid (amide), a vitamin required in the synthesis of
NAD+ and NADP+, can be synthesized from tryptophan
(Figure 17-24). About 60 mg of tryptophan can give rise to
1 mg of nicotinamide. The synthesis begins with conver-
sion of tryptophan to N-formylkynurenine by tryptophan
pyrrolase, an inducible iron-porphyrin enzyme of liver.
N-Formylkynurenine is converted to kynurenine by re-
moval of formate, which enters the one-carbon pool.
Kynurenine is hydroxylated to 3-hydroxykynurenine,
which is converted to 3-hydroxyanthranilate, catalyzed
by kynureninase, a pyridoxal phosphate-dependent en-
zyme. 3-Hydroxyanthranilate is then converted by a
series of reactions to nicotinamide ribotide, the immedi-
ate precursor of NAD. In deficiency of pyridoxal phos-
phate, 3-hydroxykynurenine accumulates and is converted
to xanthurenate, which is excreted in urine. Thus, vitamin
B6 deficiency can be diagnosed by measurement of uri-
nary xanthurenate after administration of a standard dose
of tryptophan (tryptophan load test).
5-FIydroxytryptamine (serotonin) is found in ente-
rochromaffin cells, brain, and platelets. In the former two,
it is produced from tryptophan, whereas in platelets, sero-
tonin is taken up from plasma. Synthesis involves hydrox-
ylation of tryptophan by tryptophan 5-hydroxylase and
decarboxylation by aromatic L-amino acid decarboxylase
(Figure 17-25). Hydroxylation is the rate-limiting reac-
tion, is analogous to that of phenylalanine, and requires
molecular oxygen and tetrahydrobiopterin. Serotonin is a
powerful vasoconstrictor and stimulator of smooth mus-
cle contraction. In the brain it is a neurotransmitter, and
in the pineal gland it serves as a precursor of melatonin.
Synthesis of melatonin requires N-acetylation of sero-
tonin, followed by méthylation (Figure 17-26). The role
of melatonin in humans is not understood; in frogs, it
lightens the color of skin melanocytes and blocks the
action of melanocyte-stimulating hormone (MSH) and
