Tryptophan | Wikipedia audio article


Tryptophan (symbol Trp or W) is an α-amino
acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an
α-carboxylic acid group, and a side chain indole, making it a non-polar aromatic amino
acid. It is essential in humans, meaning the body
cannot synthesize it; it must be obtained from the diet. Tryptophan is also a precursor to the neurotransmitter
serotonin, the hormone melatonin and vitamin B3. It is encoded by the codon UGG. Like other amino acids, tryptophan is a zwitterion
at physiological pH where the amino group is protonated (–NH3+; pKa=9.39) and the
carboxylic acid is deprotonated ( –COO−; pKa=2.38).==Function==Amino acids, including tryptophan, are used
as building blocks in protein biosynthesis, and proteins are required to sustain life. Many animals (including humans) cannot synthesize
tryptophan: they need to obtain it through their diet, making it an essential amino acid. Tryptophan is among the less common amino
acids found in proteins, but it plays important structural or functional roles whenever it
occurs. For instance, tryptophan and tyrosine residues
play special roles in “anchoring” membrane proteins within the cell membrane. In addition, tryptophan functions as a biochemical
precursor for the following compounds: Serotonin (a neurotransmitter), synthesized
by tryptophan hydroxylase. Melatonin (a neurohormone) is in turn synthesized
from serotonin, via N-acetyltransferase and 5-hydroxyindole-O-methyltransferase enzymes. Niacin, also known as vitamin B3, is synthesized
from tryptophan via kynurenine and quinolinic acids. Auxins (a class of phytohormones) are synthesized
from tryptophan.The disorder fructose malabsorption causes improper absorption of tryptophan in
the intestine, reduced levels of tryptophan in the blood, and depression.In bacteria that
synthesize tryptophan, high cellular levels of this amino acid activate a repressor protein,
which binds to the trp operon. Binding of this repressor to the tryptophan
operon prevents transcription of downstream DNA that codes for the enzymes involved in
the biosynthesis of tryptophan. So high levels of tryptophan prevent tryptophan
synthesis through a negative feedback loop, and when the cell’s tryptophan levels go down
again, transcription from the trp operon resumes. This permits tightly regulated and rapid responses
to changes in the cell’s internal and external tryptophan levels.==Recommended dietary allowance==
In 2002, the U.S. Institute of Medicine set a Recommended Dietary Allowance (RDA) of 5
mg/kg body weight/day of Tryptophan for adults 19 years and over.===Dietary sources===
Tryptophan is present in most protein-based foods or dietary proteins. It is particularly plentiful in chocolate,
oats, dried dates, milk, yogurt, cottage cheese, red meat, eggs, fish, poultry, sesame, chickpeas,
almonds, sunflower seeds, pumpkin seeds, buckwheat, spirulina, and peanuts. Contrary to the popular belief that cooked
turkey contains an abundance of tryptophan (with this being used as an explanation for
sleepiness following consumption of the meat), the tryptophan content in turkey is typical
of poultry.==Use as a dietary supplement==
Because tryptophan is converted into 5-hydroxytryptophan (5-HTP) which is then converted into the neurotransmitter
serotonin, it has been proposed that consumption of tryptophan or 5-HTP may improve depression
symptoms by increasing the level of serotonin in the brain. Tryptophan is sold over the counter in the
United States (after being banned to varying extents between 1989 and 2005) and the United
Kingdom as a dietary supplement for use as an antidepressant, anxiolytic, and sleep aid. It is also marketed as a prescription drug
in some European countries for the treatment of major depression. There is evidence that blood tryptophan levels
are unlikely to be altered by changing the diet, but consuming purified tryptophan increases
the serotonin level in the brain, whereas eating foods containing tryptophan does not. This is because the transport system that
brings tryptophan across the blood–brain barrier also transports other amino acids
which are contained in protein food sources. High blood plasma levels of other large neutral
amino acids prevent the plasma concentration of tryptophan from increasing brain concentration
levels.In 2001 a Cochrane review of the effect of 5-HTP and tryptophan on depression was
published. The authors included only studies of a high
rigor and included both 5-HTP and tryptophan in their review because of the limited data
on either. Of 108 studies of 5-HTP and tryptophan on
depression published between 1966 and 2000, only two met the authors’ quality standards
for inclusion, totaling 64 study participants. The substances were more effective than placebo
in the two studies included but the authors state that “the evidence was of insufficient
quality to be conclusive” and note that “because alternative antidepressants exist which have
been proven to be effective and safe, the clinical usefulness of 5-HTP and tryptophan
is limited at present”. The use of tryptophan as an adjunctive therapy
in addition to standard treatment for mood and anxiety disorders is not supported by
the scientific evidence.==Side effects==
Potential side effects of tryptophan supplementation include nausea, diarrhea, drowsiness, lightheadedness,
headache, dry mouth, blurred vision, sedation, euphoria, and nystagmus (involuntary eye movements).==Interactions==
Tryptophan taken as a dietary supplement (such as in tablet form) has the potential to cause
serotonin syndrome when combined with antidepressants of the MAOI or SSRI class or other strongly
serotonergic drugs. Because tryptophan supplementation has not
been thoroughly studied in a clinical setting, its interactions with other drugs are not
well known.==Isolation==
The isolation of tryptophan was first reported by Frederick Hopkins in 1901. Hopkins recovered tryptophan from hydrolysed
casein, recovering 4–8 g of tryptophan from 600 g of crude casein.==Biosynthesis and industrial production
==As an essential amino acid, tryptophan is
not synthesized from simpler substances in humans and other animals, so it needs to be
present in the diet in the form of tryptophan-containing proteins. Plants and microorganisms commonly synthesize
tryptophan from shikimic acid or anthranilate: anthranilate condenses with phosphoribosylpyrophosphate
(PRPP), generating pyrophosphate as a by-product. The ring of the ribose moiety is opened and
subjected to reductive decarboxylation, producing indole-3-glycerol phosphate; this, in turn,
is transformed into indole. In the last step, tryptophan synthase catalyzes
the formation of tryptophan from indole and the amino acid serine. 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, C. glutamicum
or E. coli. These strains carry mutations that prevent
the reuptake of aromatic amino acids or multiple/overexpressed trp operons. The conversion is catalyzed by the enzyme
tryptophan synthase.==Society and culture=====Eosinophilia–myalgia syndrome===
There was a large outbreak of eosinophilia-myalgia syndrome (EMS) in the U.S. in 1989, with more
than 1,500 cases reported to the CDC and at least 37 deaths. After preliminary investigation revealed that
the outbreak was linked to intake of tryptophan, the U.S. Food and Drug Administration (FDA)
recalled tryptophan supplements in 1989 and banned most public sales in 1990, with other
countries following suit.Subsequent studies suggested that EMS was linked to specific
batches of L-tryptophan supplied by a single large Japanese manufacturer, Showa Denko. It eventually became clear that recent batches
of Showa Denko’s L-tryptophan were contaminated by trace impurities, which were subsequently
thought to be responsible for the 1989 EMS outbreak. However, other evidence suggests that tryptophan
itself may be a potentially major contributory factor in EMS.The FDA loosened its restrictions
on sales and marketing of tryptophan in February 2001, but continued to limit the importation
of tryptophan not intended for an exempted use until 2005.The fact that the Showa Denko
facility used genetically engineered bacteria to produce the contaminated batches of L-tryptophan
later found to have caused the outbreak of eosinophilia-myalgia syndrome has been cited
as evidence of a need for “close monitoring of the chemical purity of biotechnology-derived
products”. Those calling for purity monitoring have,
in turn, been criticized as anti-GMO activists who overlook possible non-GMO causes of contamination
and threaten the development of biotech.===Turkey meat and drowsiness===A common assertion in the US is that heavy
consumption of turkey meat results in drowsiness, due to high levels of tryptophan contained
in turkey. However, the amount of tryptophan in turkey
is comparable to that contained in other meats. Drowsiness after eating may be caused by other
foods eaten with the turkey, particularly carbohydrates. Ingestion of a meal rich in carbohydrates
triggers the release of insulin. Insulin in turn stimulates the uptake of large
neutral branched-chain amino acids (BCAA), but not tryptophan, into muscle, increasing
the ratio of tryptophan to BCAA in the blood stream. The resulting increased tryptophan ratio reduces
competition at the large neutral amino acid transporter (which transports both BCAA and
aromatic amino acids), resulting in more uptake of tryptophan across the blood–brain barrier
into the cerebrospinal fluid (CSF). Once in the CSF, tryptophan is converted into
serotonin in the raphe nuclei by the normal enzymatic pathway. The resultant serotonin is further metabolised
into melatonin by the pineal gland. Hence, these data suggest that “feast-induced
drowsiness”—or postprandial somnolence—may be the result of a heavy meal rich in carbohydrates,
which indirectly increases the production of melatonin in the brain, and thereby promotes
sleep.==Research==
In 1912 Felix Ehrlich demonstrated that yeast attacks the natural amino acids essentially
by splitting off carbon dioxide and replacing the amino group with hydroxyl. By this reaction, tryptophan gives rise to
tryptophol.Tryptophan affects brain serotonin synthesis when given orally in a purified
form and is used to modify serotonin levels for research. Low brain serotonin level is induced by administration
of tryptophan-poor protein in a technique called “acute tryptophan depletion”. Studies using this method have evaluated the
effect of serotonin on mood and social behavior, finding that serotonin reduces aggression
and increases agreeableness.===Fluorescence===Tryptophan is an important intrinsic fluorescent
probe (amino acid), which can be used to estimate the nature of the microenvironment around
the tryptophan residue. Most of the intrinsic fluorescence emissions
of a folded protein are due to excitation of tryptophan residues.==See also==
5-Hydroxytryptophan (5-HTP) Acree–Rosenheim reaction
Adamkiewicz reaction Attenuator (genetics)
N,N-Dimethyltryptamine Hopkins–Cole reaction
Serotonin Tryptamine

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