Product Code Database
Tryptophan (symbol Trp or W)
Like other amino acids, tryptophan is a zwitterion at physiological pH where the amino group is protonated (–; pKa = 9.39) and the carboxylic acid is deprotonation ( –COO−; pKa = 2.38).
Humans and many animals cannot synthesize tryptophan: they need to obtain it through their diet, making it an essential amino acid.
Tryptophan is named after the digestive enzymes trypsin, which were used in its first isolation from casein proteins. It was assigned the one-letter symbol W based on the double ring being visually suggestive to the bulky letter.
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.
| + Tryptophan (Trp) content of various foods |
| 1.23 |
| 1.62 |
| 1.11 |
| 1.62 |
| 1.47 |
| 2.64 |
| 2.17 |
| 1.17 |
| 1.29 |
| 1.74 |
| 1.27 |
| 1.11 |
| 1.14 |
| 1.12 |
| 1.39 |
| 1.12 |
| 1.17 |
| 1.12 |
| 0.96 |
| 1.33 |
| 1.23 |
| 1.23 |
| 2.34 |
| 1.18 |
| 1.20 |
| 1.10 |
| 0.84 |
| 0.64 |
| 0.87 |
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 adjuvant therapy in addition to standard treatment for mood and anxiety disorders is not supported by the scientific evidence.
The industrial production of tryptophan is also biosynthesis 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 Escherichia coli. These strains carry that prevent the reuptake of aromatic amino acids or multiple/overexpressed . The conversion is catalyzed by the enzyme tryptophan synthase.
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. There are also claims that a precursor reached sufficient concentrations to form a toxic dimer.
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.
Insomnia
The American Academy of Sleep Medicine's 2017 clinical practice guidelines recommended against the use of tryptophan in the treatment of insomnia due to poor effectiveness.
Side effects
Potential of tryptophan supplementation include nausea, diarrhea, drowsiness, lightheadedness, headache, Xerostomia, 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 drug interaction with other drugs are not well known.
Isolation
The isolation of tryptophan was first reported by Frederick Hopkins in 1901. Hopkins recovered tryptophan from hydrolysis 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 commonly synthesize tryptophan from shikimic acid or anthranilic acid: 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 catalysis the formation of tryptophan from indole and the amino acid serine.
(2024). 9783540433835 ISBN 9783540433835
Society and culture
Showa Denko contamination scandal
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. (2024). 9780123864550, Elsevier Science. ISBN 9780123864550 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.
Turkey meat and drowsiness hypothesis
A common assertion in the US and the UK is that heavy consumption of turkey meat—as seen during Thanksgiving and Christmas—results in Somnolence, due to high levels of tryptophan contained in turkey. However, the amount of tryptophan in turkey is comparable with that of other meats. Drowsiness after eating may be caused by other foods eaten with the turkey, particularly . 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 the hormone melatonin—which is an important mediator of the circadian rhythm—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
Yeast amino acid metabolism
In 1912 Felix Ehrlich demonstrated that yeast metabolizes the natural amino acids essentially by splitting off carbon dioxide and replacing the Amine with a hydroxyl. By this reaction, tryptophan gives rise to tryptophol.
Serotonin precursor
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.
Psychedelic effects
Tryptophan produces the head-twitch response (HTR) in rodents when administered at sufficiently high doses. (2024). 9783662558782 ISBN 9783662558782 The HTR is induced by serotonergic psychedelics like lysergic acid diethylamide (LSD) and psilocybin and is a behavioral proxy of psychedelic effects. (2024). 9781461441205, Springer New York. ISBN 9781461441205 Tryptophan is converted into the trace amine tryptamine and tryptamine is N-methyl group by indolethylamine N-methyltransferase (INMT) into N-methyltryptamine (NMT) and N, N-dimethyltryptamine ( N, N-DMT), which are known serotonergic psychedelics.
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
Further reading
External links
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