Tryptophan
Tryptophan (symbol Trp or W)[3] 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 polar molecule with a non-polar aromatic beta carbon substituent. Tryptophan is also a precursor to the neurotransmitter serotonin, the hormone melatonin, and vitamin B3.[4] It is encoded by the codon UGG.
"Tryptan" redirects here. For the type of anti-migraine drug, see Triptan. For the hydrocarbon, see Triptane.
Like other amino acids, tryptophan is a zwitterion at physiological pH where the amino group is protonated (–NH+
3; pKa = 9.39) and the carboxylic acid is deprotonated ( –COO−; pKa = 2.38).[5]
Humans and many animals cannot synthesize tryptophan: they need to obtain it through their diet, making it an essential amino acid. In 2023, the emission spectrum of tryptophan was discovered in the interstellar gas of the star cluster IC 348.[6]
Tryptophan is named after the digestive enzymes trypsin, which were used in its first isolation from casein proteins.[7] It was assigned the one-letter symbol W based on the double ring being visually suggestive to the bulky letter.[8]
Amino acids, including tryptophan, are used as building blocks in protein biosynthesis, and proteins are required to sustain life. 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. Tryptophan, along with other aromatic amino acids, is also important in glycan-protein interactions. In addition, tryptophan functions as a biochemical precursor for the following compounds:
The disorder fructose malabsorption causes improper absorption of tryptophan in the intestine, reduced levels of tryptophan in the blood,[16] and depression.[17]
In bacteria that synthesize tryptophan, high cellular levels of this amino acid activate a repressor protein, which binds to the trp operon.[18] 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.
Medical use[edit]
Depression[edit]
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,[28][29] but consuming purified tryptophan increases the serotonin level in the brain, whereas eating foods containing tryptophan does not.[30]
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".[31] 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.[31][32]
Insomnia[edit]
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.[33]
Side effects[edit]
Potential side effects of tryptophan supplementation include nausea, diarrhea, drowsiness, lightheadedness, headache, dry mouth, blurred vision, sedation, euphoria, and nystagmus (involuntary eye movements).[34][35]
Interactions[edit]
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.[35] Because tryptophan supplementation has not been thoroughly studied in a clinical setting, its interactions with other drugs are not well known.[31]
Isolation[edit]
The isolation of tryptophan was first reported by Frederick Hopkins in 1901.[36] Hopkins recovered tryptophan from hydrolysed casein, recovering 4–8 g of tryptophan from 600 g of crude casein.[37]
Society and culture[edit]
Showa Denko contamination scandal[edit]
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.[42] 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,[43][44][45] with other countries following suit.[46][47]
Subsequent studies suggested that EMS was linked to specific batches of L-tryptophan supplied by a single large Japanese manufacturer, Showa Denko.[43][48][49][50] 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.[43][51][52] However, other evidence suggests that tryptophan itself may be a potentially major contributory factor in EMS.[53] There are also claims that a precursor reached sufficient concentrations to form a toxic dimer.[54]
The FDA loosened its restrictions on sales and marketing of tryptophan in February 2001,[43] but continued to limit the importation of tryptophan not intended for an exempted use until 2005.[55]
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".[56] 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.[57]