Tryptophan is an essential amino acid that must be obtained through diet. It plays several important roles in the body, serving as a precursor for serotonin, melatonin, niacin, and other biologically active compounds. It is also used in protein synthesis. The document outlines tryptophan's biosynthesis, functions, metabolic pathways including kynurenine and serotonin synthesis, sources in food, and importance as a nutrient for regulating feed intake and growth.

1. Tryptophan
Supervisor: Prof. Farhoomand
Presenter: M. Behroozlak
Urmia University
Departement of Animal Science
Jun 2014

2. Intoduction
• Tryptophan amino acid is the essential amino acid. This
means it must be provided through food to the body. It is
one of the amino acid which in its molecule contains an
indole ring.
• Tryptophan is glucogenic as well as ketogenic amino
acid. It has codon UGG. It has two stereoisomers,
namely L-tryptophan and D-tryptophan.
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3. Intoduction
• L-tryptophan can only be utilized in the structure or
enzymes proteins while D–tryptophan is normally
present in naturally occurring peptides. Tryptophan has
aromatic side chain and is relatively polar.
• The N of the indole ring present in tryptophan gives
polarity to this amino acid.
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4. Intoduction
• Tryptophan is an essential constituent of the diet. It
plays an important role in protein synthesis, and is also
the precursor of a variety of biologically active
compounds including serotonin, melatonin,
tryptamine, quinolinic acid and kynurenic acid.
• In addition, tryptophan is a precursor to the
coenzymes NAD and NADP, and can replace niacin as
an essential nutrient.
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5. Isolation
• While other amino acids were isolated from acid digests
of proteins, the isolation of tryptophan was first reported
by Frederick Hopkins in 1901 through hydrolysis of
casein.
• From 600 grams of crude casein one obtains 4-8 grams
of tryptophan.
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6. Biosynthesis and industrial
production
• Plants and microorganisms commonly synthesize
tryptophan from shikimic acid or anthranilate. The
latter condenses with phosphoribosylpyrophosphate
(PRPP), generating pyrophosphate as a by-product.
• After ring opening of the ribose moiety and following
reductive decarboxylation, indole-3-glycerinephosphate
is produced, which in turn is transformed into indole.
• In the last step, tryptophan synthase catalyzes the
formation of tryptophan from indole and the amino acid
serine.
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7. Biosynthesis and industrial
production
• The industrial production of tryptophan is also
biosynthetic and is based on the fermentation of serine
and indole using either wild type or genetically
modified bacteria such as B. amyloliquefaciens, B.
subtilis or E. coli.
• The conversion is catalyzed by the enzyme tryptophan
synthase.
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8. Biosynthesis and industrial
production
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9. Functions & metabolic processes of
tryptophan
• In humans, tryptophan has relatively low tissue storage
and the overall tryptophan concentration in the body is
the lowest among all amino acids, although only small
amounts are necessary for general healthy nutrition.
• While typical intake for many individuals is
approximately 900 to 1000 mg daily, the recommended
daily allowance for adults is estimated to be between
250 mg/day and 425 mg/day.
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10. Protein synthesis
• The principal role of tryptophan in the human body is as
a constituent of protein synthesis. Because tryptophan is
found in the lowest concentrations among the amino
acids, it is relatively less available and is thought to play
a rate-limiting role during protein synthesis.
• Tryptophan is also the precursor of two important
metabolic pathways, kynurenine synthesis and serotonin
synthesis.
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12. Kynurenine synthesis
• After protein synthesis, the second most prevalent
metabolic pathway of tryptophan is for the synthesis of
kynurenine, which accounts for approximately 90% of
tryptophan catabolism.
• Kynurenine is a key component in the synthesis of a
number of metabolites, but most importantly, it is the
precursor of kynurenic and quinolinic acids.
• kynurenine is known to be involved in acting as an ultra
violet (UV) filter which protects the retina of the eye
from UV damage. The effectiveness of this protection
deteriorates with age. 12

13. Kynurenine synthesis
• N-formylkynurenine and kynurenine are the first
metabolites of a complex metabolic pathway ending in
quinolinic acid, niacin, kynurenic and xanthurenic acid.
• Two enzymes are able to catalyze the conversion of
tryptophan into N-formylkynurenine: tryptophan 2,3-
dioxygenase (TDO) and indoleamine 2,3-dioxygenase
(IDO).
• These two enzymes differ in their tissue localization,
structure, substrate specificity, cofactor requirement and
function. Whereas IDO is widespread in numerous
tissues, TDO is mainly located in the liver. 13

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15. Serotonin synthesis
• It is estimated that 95% of mammalian serotonin is found
within the gastrointestinal tract, and only 3% of dietary
tryptophan is used for serotonin synthesis throughout the
body.
• It is estimated that only 1% of dietary tryptophan is used
for serotonin synthesis in the brain, but despite the
relatively low concentration of brain serotonin compared
to that in the rest of the body, it has a broad impact as a
neurotransmitter and neuromodulator and has been
implicated in numerous psychiatric conditions and
psychological processes. 15

16. Serotonin synthesis
• Tryptophan is the precursor of serotonin (5-HT or 5-
hydroxytryptamine), an important neuromediator
regulating gastrointestinal functions, mood, appetite.
• Serotonin seems to act as a trophic factor in the
developing brain and is also a neurotransmitter.
Serotonin has a modulatory role in neural information
processing. It is thought to inhibit a variety of behaviors
including aggression, impulsivity, selection of food and
arousal, sexual behavior and reaction to pain. In
addition, serotonin is involved in the control of mood.
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17. Tryptamine synthesis
• Tryptamine is another biologically active compound that
is derived from tryptophan. The immediate
decarboxylation of tryptophan results in the synthesis of
trace amounts of tryptamine, which is an important
neuromodulator of serotonin.
• Numerous animal studies have indicated that tryptamine
acts as a control for the balance between excitatory and
inhibitory functions of serotonin, and in other instances,
tryptamine acts as a neurotransmitter with specific
receptors that are independent of serotonin function.
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18. Melatonin synthesis
• Melatonin is a hormone produced in the tryptophan/
serotonin pathway, which regulates diurnal rhythms and
influences the reproductive and immune systems, as well
as digestive processes and gastrointestinal motility.
• During periods of darkness, it is actively secreted from
the pineal gland to induce neural and endocrine effects
that regulate circadian rhythms of behavior, physiology,
and sleep patterns.
• Synthesis of melatonin is inhibited by light.
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20. NAD/NADP synthesis
• Tryptophan also plays a role as a substrate for synthesis
of the coenzymes nicotinamide adenine dinucleotide
(NAD) and NAD phosphate (NADP).
• NAD and NADP are coenzymes essential for electron
transfer reactions (i.e. redox reactions) in all living
cells.
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These coenzymes can be synthesized de novo from
ingested tryptophan, or from ingestion of niacin
(i.e. vitamin B3).

21. Niacin synthesis
• Interestingly, tryptophan can act as a substrate for niacin
synthesis through the kynurenine/ quinolinic acid
pathway.
• However, this is a less efficient use of tryptophan since
approximately 60 mg of tryptophan are necessary to
generate a single milligram of niacin.
• Thus, an intake of 900mg of tryptophan should result in
the synthesis of about 15mg niacin, while a daily intake
of 11 to 13mg niacin is adequate to prevent depletion of
body stores of niacin. 21

22. Physiological metabolism of
tryptophan
• Unlike other amino acids, tryptophan circulates in blood
and plasma mainly (90%) bound to albumin. Only 10–
20% of tryptophan is present as free form in the plasma.
• Tryptophan is transported into the brain by a transporter
located in capillaries of the blood–brain barrier (BBB).
• In the bloodstream, tryptophan competes with other large
neutral amino acids (LNAA).
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23. Physiological metabolism of
tryptophan
• The LNAA comprise leucine, valine, isoleucine, the
three branched chain amino acids (BCAA), tyrosine,
phenylalanine and methionine.
• Consequently, tryptophan entry into the brain is
influenced by the ratio between tryptophan and amino
acids sharing the same transporter and, particularly,
BCAA, which are present in higher proportion than
tryptophan in plasma.
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24. Physiological metabolism of
tryptophan
• To some extent, tryptophan availability to the brain can be
enhanced by ingestion of carbohydrates and reduced by
ingestion of proteins.
• Carbohydrate ingestion does not change the levels of
circulating tryptophan, but it does decrease
concentrations of LNAA through activation of insulin,
which increases the relative availability of tryptophan for
transport into the brain.
• In contrast, protein contains relatively low concentrations
of tryptophan and ingestion of a protein meal increases
the LNAA concentration relative to tryptophan. 24

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27. Tryptophan: a key nutrient in the
regulation of feed intake
• It has been clearly demonstrated in piglets that an
adequate dietary Trp:Lys ratio, enhances feed intake.
• The effect of tryptophan on appetite regulation could be
mediated through the regulation of the central production
of serotonin which is involved in the regulation of
satiation and appetite.
• Melatonin which is produced from tryptophan in the
gastrointestinal tract, may serve as a signal for the
synchronization of the feeding and digestion processes.
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28. Tryptophan: a key nutrient in the
regulation of feed intake
• The effect of tryptophan on the regulation of appetite
could also be explained by its effect on the gene
expression and the synthesis of the ghrelin hormone.
Ghrelin is an appetite stimulating hormone produced
and secreted by the stomach and the duodenum.
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Dietary tryptophan content improving ghrelin gene
expression, it increases feed intake and weight gain.

29. Tryptophan: a key nutrient in the
regulation of feed intake
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30. Biological roles of tryptophan
• Tryptophan is usually the fourth limiting amino acid
after lysine, threonine and the sulphur amino acids
(methionine + cysteine).
• As lysine and threonine, tryptophan is an indispensable
amino acid for body protein deposition and growth.
Thus, deficiency in tryptophan affects the utilization of
dietary lysine and threonine and consequently animal
growth.
• Besides its utilization for protein synthesis, tryptophan is
involved in other biological functions such as appetite
regulation, immune response and health maintenance 30

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32. Sources of tryptophan
• Tryptophan is found in foods of animal origin as well
foods of plant origin in abundant amount. Some of the
foods in which it is present are as follow:
• Animal Origin: Chicken, turkey, fish, egg, milk,
cheese, beef etc.
• Plant origin: Nuts, peanuts, peanut butter, pumpkin
seed, soy, sunflower seed, rice, banana, potato and
wheat flower etc.
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