View source for Tryptophan

{{redirect|Tryptan|the type of anti-migraine drug|Triptan|the hydrocarbon|Triptane}}
{{cs1 config|name-list-style=vanc}}
{{Use dmy dates|date=September 2020}}
{{chembox
| Name           = {{sm|l}}-Tryptophan
| ImageFile1     = L-Tryptophan - L-Tryptophan.svg
| ImageName1     = Structure of {{sm|l}}-isomer
| ImageCaption1  = [[Skeletal formula]] of <small>L</small>-tryptophan
| ImageClass1    = skin-invert-image
| ImageFileL2    = Tryptophan-from-xtal-3D-bs-17.png
| ImageClassL2   = bg-transparent  
| ImageSizeL2    = 105px
| ImageCaptionL2 = [[ball-and-stick model]]<ref name="Görbitz">{{ cite journal | title = Single-crystal investigation of L-tryptophan with ''{{prime|Z}}'' = 16 | first1 = C. H. | last1=  Görbitz | first2 = K. W. | last2 = Törnroos | first3 = G. M. | last3 = Day | journal = [[Acta Crystallographica Section B]] | volume = 68 | pages = 549–557 | year = 2012 | issue = Pt 5 | doi = 10.1107/S0108768112033484 | pmid = 22992800 }}</ref>
| ImageFileR2    = Tryptophan-from-xtal-3D-sf.png
| ImageClassR2 = bg-transparent  
| ImageSizeR2    = 120px
| ImageCaptionR2 = [[space-filling model]]<ref name="Görbitz" />
| IUPACName      = Tryptophan
| SystematicName = 2-Amino-3-(1''H''-indol-3-yl)propanoic acid
| OtherNames     = 2-Amino-3-(1''H''-indol-3-yl)propionic acid
| Section1       = {{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 6066
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 8DUH1N11BX
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 54976
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00020
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C11H12N2O2/c12-9(11(14)15)5-7-6-13-10-4-2-1-3-8(7)10/h1-4,6,9,13H,5,12H2,(H,14,15)/t9-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = QIVBCDIJIAJPQS-VIFPVBQESA-N
| CASNo = 73-22-3
| CASNo_Ref = {{cascite|correct|CAS}}
| PubChem = 6305
| IUPHAR_ligand = 717
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00150
| ChEBI_Ref =
| ChEBI = 16828
| SMILES = c1[nH]c2ccccc2c1C[C@H](N)C(=O)O
| SMILES1 = c1[nH]c2ccccc2c1C[C@H]([NH3+])C(=O)[O-]
| SMILES1_Comment = [[Zwitterion]]
}}
| Section2       = {{Chembox Properties
| C=11 | H=12 | N=2 | O=2
| Appearance =
| Density =
| MeltingPt =
| BoilingPt =
| Solubility = Soluble: 0.23 g/L at 0&nbsp;°C,<br />
11.4 g/L at 25&nbsp;°C,<br />
17.1 g/L at 50&nbsp;°C,<br />
27.95 g/L at 75&nbsp;°C
| SolubleOther = Soluble in hot alcohol, alkali hydroxides; insoluble in [[chloroform]].
| pKa=2.38 (carboxyl), 9.39 (amino)<ref name="isbn0-19-855338-2">{{cite book | vauthors = Dawson RM | title = Data for Biochemical Research | url = https://archive.org/details/dataforbiochemic00daws | url-access = registration | publisher = Clarendon Press | location = Oxford | year = 1969 | isbn = 0-19-855338-2 |display-authors=etal}}</ref>
| MagSus = −132.0·10<sup>−6</sup> cm<sup>3</sup>/mol
}}
| Section6       = {{Chembox Pharmacology
| ATCCode_prefix = N06
| ATCCode_suffix = AX02
}}
| Section7       = {{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt = }}
}}
[[File:Tryptophan-spin.gif|thumb|Tryptophan ball and stick model spinning]]
'''Tryptophan''' (symbol '''Trp''' or '''W''')<ref name="IUPAC">
{{
    cite web
  | url=https://iupac.qmul.ac.uk/AminoAcid/AA1n2.html
  | title=Nomenclature and Symbolism for Amino Acids and Peptides
  | year=1983
  | publisher=IUPAC-IUB Joint Commission on Biochemical Nomenclature
  | archive-url=https://web.archive.org/web/20211202124922/https://iupac.qmul.ac.uk/AminoAcid/AA1n2.html
  | archive-date=2021-12-02
  | url-status=live
  | access-date=2022-10-22
}}

</ref> is an α-[[amino acid]] that is used in the [[biosynthesis]] of [[protein]]s. Tryptophan contains an [[Alpha and beta carbon|α]]-amino group, an α-[[carboxylic acid]] group, and a side chain [[indole]], making it a [[polar molecule]] with a non-polar [[Aromatic hydrocarbon|aromatic]] [[Alpha and beta carbon|beta carbon]] substituent. Tryptophan is also a precursor to the [[neurotransmitter]] [[serotonin]], the [[hormone]] [[melatonin]], and [[vitamin B3|vitamin B<sub>3</sub>]] (niacin).<ref>{{cite journal|vauthors=Slominski A, Semak I, Pisarchik A, Sweatman T, Szczesniewski A, Wortsman J|date=2002|title=Conversion of L-tryptophan to serotonin and melatonin in human melanoma cells|journal=FEBS Letters|volume=511|issue=1–3|pages=102–6|doi=10.1016/s0014-5793(01)03319-1|pmid=11821057|s2cid=7820568|doi-access=free|bibcode=2002FEBSL.511..102S }}</ref> It is [[Genetic code|encoded]] by the [[codon]] UGG.

Like other amino acids, tryptophan is a [[zwitterion]] at [[physiological pH]] where the amino group is [[protonated]] (–{{chem|NH|3|+}}; pK<sub>a</sub> = 9.39) and the carboxylic acid is [[deprotonation|deprotonated]] ( –COO<sup>−</sup>; pK<sub>a</sub> = 2.38).<ref name="PubChem">{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/L-tryptophan#section=Ecological-Information|title=L-tryptophan {{!}} C11H12N2O2 - PubChem|website=pubchem.ncbi.nlm.nih.gov|access-date=22 December 2016}}</ref>

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.<ref>{{Citation |last=Curzon |first=G. |title=Hopkins and the Discovery of Tryptophan |date=1987-12-31 |work=Progress in Tryptophan and Serotonin Research 1986 |pages=XXIX–XL |editor-last=Bender |editor-first=David A. |url=https://www.degruyter.com/document/doi/10.1515/9783110854657-004/html |access-date=2024-02-19 |place=Berlin, Boston |publisher=De Gruyter |doi=10.1515/9783110854657-004 |isbn=978-3-11-085465-7 |editor2-last=Joseph |editor2-first=Michael H. |editor3-last=Kochen |editor3-first=Walter |editor4-last=Steinhart |editor4-first=Hans|url-access=subscription }}</ref> It was assigned the [[List of amino acids by one-letter symbol|one-letter symbol]] W based on the double ring being visually suggestive to the bulky letter.<ref name=":0">{{Cite journal |date=10 July 1968 |title=IUPAC-IUB Commission on Biochemical Nomenclature A One-Letter Notation for Amino Acid Sequences |url=https://www.jbc.org/article/S0021-9258(19)34176-6/pdf |journal=Journal of Biological Chemistry |language=en |volume=243 |issue=13 |pages=3557–3559 |doi=10.1016/S0021-9258(19)34176-6|doi-access=free }}</ref>

== Function ==

[[Image:Tryptophan metabolism.svg|class=skin-invert-image|thumb|275px|Metabolism of {{sm|l}}-tryptophan into serotonin and melatonin (left) and niacin (right). Transformed functional groups after each chemical reaction are highlighted in red.]]
Amino acids, including tryptophan, are used as building blocks in [[protein biosynthesis]], and [[protein]]s 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 protein]]s within the [[cell membrane]]. Tryptophan, along with other [[aromatic amino acid]]s, is also important in [[glycan-protein interactions]]. In addition, tryptophan functions as a biochemical [[Precursor (chemistry)|precursor]] for the following [[chemical compounds|compounds]]:
* [[Serotonin]] (a [[neurotransmitter]]), synthesized by [[tryptophan hydroxylase]].<ref name="pmid6132421">{{cite journal|vauthors=Fernstrom JD|date=1983|title=Role of precursor availability in control of monoamine biosynthesis in brain|journal=Physiological Reviews|volume=63|issue=2|pages=484–546|doi=10.1152/physrev.1983.63.2.484|pmid=6132421}}</ref><ref name="pmid1704290">{{cite journal|vauthors=Schaechter JD, Wurtman RJ|date=1990|title=Serotonin release varies with brain tryptophan levels|url=http://wurtmanlab.mit.edu/static/pdf/790.pdf|journal=Brain Research|volume=532|issue=1–2|pages=203–10|doi=10.1016/0006-8993(90)91761-5|pmid=1704290|s2cid=8451316|access-date=30 May 2014|archive-date=9 August 2020|archive-url=https://web.archive.org/web/20200809154957/http://wurtmanlab.mit.edu/static/pdf/790.pdf}}</ref>
* [[Melatonin]] (a [[neurohormone]]) is in turn synthesized from serotonin, via [[N-Acetyltransferase|N-acetyltransferase]] and [[5-hydroxyindole-O-methyltransferase]] enzymes.<ref name="pmid4391290">{{cite journal | vauthors = Wurtman RJ, Anton-Tay F | title = The mammalian pineal as a neuroendocrine transducer | journal = Recent Progress in Hormone Research | volume = 25 | pages = 493–522 | year = 1969 | pmid = 4391290 | doi = 10.1016/b978-0-12-571125-8.50014-4 | url = http://wurtmanlab.mit.edu/static/pdf/104.pdf | isbn = 978-0-12-571125-8 | archive-url = https://web.archive.org/web/20140531104922/http://wurtmanlab.mit.edu/static/pdf/104.pdf | archive-date = 31 May 2014 }}</ref>
* [[Kynurenine]], to which tryptophan is mainly (more than 95%) metabolized. Two enzymes, namely [[indoleamine 2,3-dioxygenase]] (IDO) in the immune system and the brain, and [[tryptophan 2,3-dioxygenase]] (TDO) in the liver, are responsible for the synthesis of kynurenine from tryptophan. The [[kynurenine pathway]] of tryptophan catabolism is altered in several diseases, including psychiatric disorders such as [[schizophrenia]],<ref name="Marx-2020">{{Cite journal|last1=Marx|first1=Wolfgang|last2=McGuinness|first2=Amelia J.|last3=Rocks|first3=Tetyana|last4=Ruusunen|first4=Anu|last5=Cleminson|first5=Jasmine|last6=Walker|first6=Adam J.|last7=Gomes-da-Costa|first7=Susana|last8=Lane|first8=Melissa|last9=Sanches|first9=Marsal|last10=Diaz|first10=Alexandre P.|last11=Tseng|first11=Ping-Tao|date=2020-11-23|title=The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a meta-analysis of 101 studies|journal=Molecular Psychiatry|volume=26|issue=8|pages=4158–4178|doi=10.1038/s41380-020-00951-9|issn=1476-5578|pmid=33230205|s2cid=227132820}}</ref> major depressive disorder,<ref name="Marx-2020" /> and [[bipolar disorder]].<ref name="Marx-2020" /><ref name="Bartoli">{{cite journal |last1=Bartoli |first1=F  |last2=Misiak |first2=B |last3=Callovini |first3=T |last4=Cavaleri |first4= D |last5=Cioni |first5=RM |last6=Crocamo |first6=C |last7=Savitz |first7=JB |last8=Carrà |first8=G |title=The kynurenine pathway in bipolar disorder: a meta-analysis on the peripheral blood levels of tryptophan and related metabolites. |journal=Molecular Psychiatry |date=19 October 2020 |volume=26 |issue=7 |pages=3419–3429 |doi=10.1038/s41380-020-00913-1 |pmid=33077852 |s2cid=224314102 }}</ref>
* [[Niacin (substance)|Niacin]], also known as vitamin B<sub>3</sub>, is synthesized from tryptophan via [[kynurenine]] and [[quinolinic acid]]s.<ref name="pmid14284754">{{cite journal|vauthors=Ikeda M, Tsuji H, Nakamura S, Ichiyama A, Nishizuka Y, Hayaishi O|date=1965|title=Studies on the biosynthesis of nicotinamide adenine dinucleotide. II. A role of picolinic carboxylase in the biosynthesis of nicotinamide adenine dinucleotide from tryptophan in mammals|journal=The Journal of Biological Chemistry|volume=240|issue=3|pages=1395–401|doi=10.1016/S0021-9258(18)97589-7|pmid=14284754|doi-access=free}}</ref>
* [[Auxin]]s (a class of [[phytohormone]]s) are synthesized from tryptophan.<ref name="pmid18394986">{{cite journal|vauthors=Palme K, Nagy F|date=2008|title=A new gene for auxin synthesis|journal=Cell|volume=133|issue=1|pages=31–2|doi=10.1016/j.cell.2008.03.014|pmid=18394986|s2cid=9949830|doi-access=free}}</ref>

The disorder [[fructose malabsorption]] causes improper absorption of tryptophan in the intestine, reduced levels of tryptophan in the blood,<ref name="Ledochowski M, Widner B, Murr C, Sperner-Unterweger B, Fuchs D 2001 367–71">{{cite journal|vauthors=Ledochowski M, Widner B, Murr C, Sperner-Unterweger B, Fuchs D|date=2001|title=Fructose malabsorption is associated with decreased plasma tryptophan|url=http://www.lactose.at/pdf/works/11336160.pdf |journal=Scandinavian Journal of Gastroenterology|volume=36|issue=4|pages=367–71|doi=10.1080/003655201300051135|pmid=11336160|archive-url=https://web.archive.org/web/20160419160203/http://www.lactose.at/pdf/works/11336160.pdf|archive-date=19 April 2016}}</ref> and depression.<ref>{{cite journal | vauthors = Ledochowski M, Sperner-Unterweger B, Widner B, Fuchs D | title = Fructose malabsorption is associated with early signs of mental depression | journal = European Journal of Medical Research | volume = 3 | issue = 6 | pages = 295–8 | date = June 1998 | pmid = 9620891 }}</ref>

In bacteria that synthesize tryptophan, high cellular levels of this amino acid activate a [[repressor]] protein, which binds to the [[trp operon]].<ref name="pmid16285852">{{cite journal | vauthors = Gollnick P, Babitzke P, Antson A, Yanofsky C | title = Complexity in regulation of tryptophan biosynthesis in Bacillus subtilis | journal = Annual Review of Genetics | volume = 39 | pages = 47–68 | year = 2005 | pmid = 16285852 | doi = 10.1146/annurev.genet.39.073003.093745 }}</ref> Binding of this repressor to the tryptophan operon prevents [[transcription (genetics)|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 metabolism by human microbiota|align=left}}{{clear}}

==Recommended dietary allowance==
In 2002, the [[U.S. Institute of Medicine]] set a [[Recommended Dietary Allowance]] (RDA) of 5&nbsp;mg/kg body weight/day of tryptophan for adults 19 years and over.<ref name="DRItext">{{cite book | last1 = Institute of Medicine | title = Dietary Reference Intakes for Energy, Carbohydrates, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids | chapter = Protein and Amino Acids | publisher = The National Academies Press | year = 2002 | location = Washington, DC | pages = 589–768 | doi = 10.17226/10490 | isbn = 978-0-309-08525-0 | chapter-url = https://www.nap.edu/read/10490/chapter/12| author1-link = Institute of Medicine }}</ref>

===Dietary sources===
Tryptophan is present in most protein-based foods or dietary proteins. It is particularly plentiful in [[chocolate]], [[oat]]s, dried [[Date Palm|date]]s, [[milk]], [[yogurt]], [[cottage cheese]], [[red meat]], [[egg (food)|eggs]], [[fish]], [[poultry]], [[sesame]], [[chickpea]]s, [[almonds]], [[sunflower seeds]], [[pumpkin seeds]], [[hemp]] seeds, [[buckwheat]], [[Spirulina (dietary supplement)|spirulina]], and [[peanut]]s. Contrary to the popular belief<ref name="scientificamerican">{{cite magazine|title=Does Turkey Make You Sleepy? | vauthors = Ballantyne C | date=2007-11-21 | url = http://www.scientificamerican.com/article.cfm?id=fact-or-fiction-does-turkey-make-you-sleepy | magazine = Scientific American | access-date = 2013-06-06 }}</ref><ref name = "McCue"/> that cooked [[turkey meat|turkey]] contains an abundance of tryptophan, the tryptophan content in turkey is typical of poultry.<ref name="USDA">{{cite web|url=https://www.ars.usda.gov/northeast-area/beltsville-md-bhnrc/beltsville-human-nutrition-research-center/methods-and-application-of-food-composition-laboratory/|title=USDA National Nutrient Database for Standard Reference, Release 22|last=Holden|first=Joanne|publisher=Nutrient Data Laboratory, Agricultural Research Service, United States Department of Agriculture|access-date=29 November 2009}}</ref>

{| class="wikitable sortable" style="text-align: center;"
|+ Tryptophan (Trp) content of various foods<ref name = "USDA" /><ref name="Rambali">{{cite journal | vauthors = Rambali B, Van Andel I, Schenk E, Wolterink G, van de Werken G, Stevenson H, Vleeming W | title=[The contribution of cocoa additive to cigarette smoking addiction] | journal=RIVM | year=2002 | url = http://rivm.nl/bibliotheek/rapporten/650270002.pdf | issue = report 650270002/2002 | publisher = The National Institute for Public Health and the Environment (Netherlands) | archive-url=https://web.archive.org/web/20051108071725/http://rivm.nl/bibliotheek/rapporten/650270002.pdf | archive-date=8 November 2005 }}</ref>
|-
! scope="col" | Food
! scope="col" | Tryptophan <br />[g/100 g of food]
! scope="col" | Protein <br />[g/100 g of food]
! scope="col" | Tryptophan/protein <br />[%]
|-
| style="text-align: left;" | [[Egg white]], dried || 1.00 || 81.10 || 1.23
|-
| style="text-align: left;" | [[Spirulina (dietary supplement)|Spirulina]], dried || 0.92 || 57.47 || 1.62
|-
| style="text-align: left;" | [[Atlantic cod|Cod, Atlantic]], dried || 0.70 || 62.82 || 1.11
|-
| style="text-align: left;" | [[Soybeans]], raw || 0.59 || 36.49 || 1.62
|-
| style="text-align: left;" | Cheese, [[Parmigiano-Reggiano|Parmesan]] || 0.56 || 37.90 || 1.47
|-
| style="text-align: left;" | [[Chia seed]]s, dried || 0.44 || 16.50 || 2.64
|-
| style="text-align: left;" | [[Sesame seed]] || 0.37 || 17.00 || 2.17
|-
| style="text-align: left;" | [[Hemp]] seed, hulled || 0.37 || 31.56 || 1.17
|-
| style="text-align: left;" | [[Cheddar cheese|Cheese, Cheddar]] || 0.32 || 24.90 || 1.29
|-
| style="text-align: left;" | [[Sunflower seed]] || 0.30 || 17.20 || 1.74
|-
| style="text-align: left;" | Pork, chop || 0.25 || 19.27 || 1.27
|-
| style="text-align: left;" | [[Turkey meat|Turkey]] || 0.24 || 21.89 || 1.11
|-
| style="text-align: left;" | [[Chicken (food)|Chicken]] || 0.24 || 20.85 || 1.14
|-
| style="text-align: left;" | [[Beef]] || 0.23 || 20.13 || 1.12
|-
| style="text-align: left;" | [[Oat]]s || 0.23 || 16.89 || 1.39
|-
| style="text-align: left;" | [[Salmon]] || 0.22 || 19.84 || 1.12
|-
| style="text-align: left;" | [[Lamb and mutton|Lamb, chop]] || 0.21 || 18.33 || 1.17
|-
| style="text-align: left;" | [[Perch|Perch, Atlantic]] || 0.21 || 18.62 || 1.12
|-
| style="text-align: left;" | [[Chickpea]]s, raw || 0.19 || 19.30 || 0.96
|-
| style="text-align: left;" | [[Egg (food)|Egg]] || 0.17 || 12.58 || 1.33
|-
| style="text-align: left;" | Wheat flour, white || 0.13 || 10.33 || 1.23
|-
| style="text-align: left;" | [[Baking chocolate]], unsweetened || 0.13 || 12.90 || 1.23
|-
| style="text-align: left;" | [[Milk]] || 0.08 || 3.22 || 2.34
|-
| style="text-align: left;" | Rice, white, medium-grain, cooked || 0.03 || 2.38 || 1.18
|-
| style="text-align: left;" | [[Quinoa]], uncooked || 0.17 || 14.12 || 1.20
|-
| style="text-align: left;" | Quinoa, cooked || 0.05 || 4.40 || 1.10
|-
| style="text-align: left;" | Potatoes, russet || 0.02 || 2.14 || 0.84
|-
| style="text-align: left;" | [[Tamarind]] || 0.02 || 2.80 || 0.64
|-
| style="text-align: left;" | [[Banana]] || 0.01 || 1.03 || 0.87
|}

==Medical use==

===Depression===
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 [[#Showa Denko contamination scandal|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,<ref name="DOI10.1111/j.1601-5215.2010.00508.x">{{cite journal | vauthors = Soh NL, Walter GT | title = Tryptophan and depression: can diet alone be the answer? | journal = Acta Neuropsychiatrica | volume = 23 | issue = 1 | pages = 1601–5215 | year = 2011 | doi = 10.1111/j.1601-5215.2010.00508.x | s2cid = 145779393 }}</ref><ref name="Fernstrom">{{cite journal|vauthors=Fernstrom JD|date=2012|title=Effects and side effects associated with the non-nutritional use of tryptophan by humans|journal=The Journal of Nutrition|volume=142|issue=12|pages=2236S–2244S|doi=10.3945/jn.111.157065|pmid=23077193|doi-access=free}}</ref> but consuming purified tryptophan increases the serotonin level in the brain, whereas eating foods containing tryptophan does not.<ref name="Wurtman_1980">{{cite journal|vauthors=Wurtman RJ, Hefti F, Melamed E|date=1980|title=Precursor control of neurotransmitter synthesis|journal=Pharmacological Reviews|volume=32|issue=4|pages=315–35|doi=10.1016/S0031-6997(25)06841-3 |pmid=6115400}}</ref>

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".<ref name="pmid11687048">{{cite journal | vauthors = Shaw K, Turner J, Del Mar C | title = Tryptophan and 5-hydroxytryptophan for depression | journal = The Cochrane Database of Systematic Reviews | issue = 1 | article-number = CD003198 | year = 2002 | volume = 2010 | pmid = 11869656 | doi = 10.1002/14651858.CD003198 | editor1-last = Shaw | editor1-first = Kelly A | url = https://espace.library.uq.edu.au/view/UQ:209937/UQ209937_OA.pdf }}</ref> The use of tryptophan as an [[adjuvant therapy|adjunctive therapy]] in addition to standard treatment for mood and anxiety disorders is not supported by the scientific evidence.<ref name=pmid11687048/><ref name=Ravindran>{{cite journal | vauthors = Ravindran AV, da Silva TL | title = Complementary and alternative therapies as add-on to pharmacotherapy for mood and anxiety disorders: a systematic review | journal = Journal of Affective Disorders | volume = 150 | issue = 3 | pages = 707–19 | date = September 2013 | pmid = 23769610 | doi = 10.1016/j.jad.2013.05.042 }}</ref>

===Insomnia===
The [[American Academy of Sleep Medicine]]'s 2017 [[clinical practice guideline]]s recommended against the use of tryptophan in the treatment of insomnia due to poor effectiveness.<ref name="pmid27998379">{{cite journal | vauthors = Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL | title = Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline | journal = J Clin Sleep Med | volume = 13 | issue = 2 | pages = 307–349 | date = February 2017 | pmid = 27998379 | pmc = 5263087 | doi = 10.5664/jcsm.6470 | url = }}</ref>

== Side effects ==
Potential [[side effect]]s of tryptophan supplementation include [[nausea]], [[diarrhea]], [[drowsiness]], [[lightheadedness]], [[headache]], [[Xerostomia|dry mouth]], [[blurred vision]], [[sedation]], [[euphoria]], and [[nystagmus]] (involuntary eye movements).<ref name=pmid23077196>{{cite journal | vauthors = Kimura T, Bier DM, Taylor CL | title = Summary of workshop discussions on establishing upper limits for amino acids with specific attention to available data for the essential amino acids leucine and tryptophan | journal = The Journal of Nutrition | volume = 142 | issue = 12 | pages = 2245S–2248S | date = December 2012 | pmid = 23077196 | doi = 10.3945/jn.112.160846 | doi-access = free }}</ref><ref name=pmid22589230>{{cite journal | vauthors = Howland RH | title = Dietary supplement drug therapies for depression | journal = Journal of Psychosocial Nursing and Mental Health Services | volume = 50 | issue = 6 | pages = 13–6 | date = June 2012 | pmid = 22589230 | doi = 10.3928/02793695-20120508-06 }}</ref>

== 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 [[Monoamine oxidase inhibitor|MAOI]] or [[Selective serotonin reuptake inhibitor|SSRI]] class or other strongly serotonergic drugs.<ref name=pmid22589230 /> Because tryptophan supplementation has not been thoroughly studied in a clinical setting, its [[drug interaction|interactions]] with other drugs are not well known.<ref name="pmid11687048"/>

==Isolation==
The isolation of tryptophan was first reported by [[Frederick Hopkins]] in 1901.<ref name="pmid16992614">{{cite journal | vauthors = Hopkins FG, Cole SW | title = A contribution to the chemistry of proteids: Part I. A preliminary study of a hitherto undescribed product of tryptic digestion | journal = The Journal of Physiology | volume = 27 | issue = 4–5 | pages = 418–428 | date = December 1901 | pmid = 16992614 | pmc = 1540554 | doi = 10.1113/jphysiol.1901.sp000880 }}</ref> Hopkins recovered tryptophan from [[hydrolysis|hydrolysed]] [[casein]], recovering 4–8 g of tryptophan from 600 g of crude casein.<ref name="Cox_1943">{{cite journal|doi=10.15227/orgsyn.010.0100 |last1=Cox|first1=G.J.|last2=King|first2=H. | title = L-Tryptophane | volume= 10 | page = 100 | year = 1930 | url=http://www.orgsyn.org/demo.aspx?prep=CV2P0612|journal=Org. Synth.|url-access=subscription }}</ref>

== 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 [[microorganism]]s commonly synthesize tryptophan from [[shikimic acid]] or [[anthranilic acid|anthranilate]]:<ref name="pmid7640526">{{cite journal|vauthors=Radwanski ER, Last RL|date=1995|title=Tryptophan biosynthesis and metabolism: biochemical and molecular genetics|journal=The Plant Cell|volume=7|issue=7|pages=921–34|doi=10.1105/tpc.7.7.921|pmc=160888|pmid=7640526}}</ref> anthranilate condenses with [[phosphoribosylpyrophosphate]] (PRPP), generating [[pyrophosphate]] as a by-product. The ring of the [[ribose]] [[Moiety (chemistry)|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|catalyzes]] the formation of tryptophan from indole and the amino acid [[serine]].

:[[Image:Tryptophan biosynthesis (en).svg|class=skin-invert-image|900px]]

The industrial production of tryptophan is also [[biosynthesis|biosynthetic]] and is based on the [[Industrial fermentation|fermentation]] of [[serine]] and [[indole]] using either wild-type or [[genetically modified bacterium|genetically modified bacteria]] such as ''[[Bacillus amyloliquefaciens|B. amyloliquefaciens]]'', ''[[Bacillus subtilis|B. subtilis]]'', ''[[Corynebacterium glutamicum|C. glutamicum]]'' or ''[[Escherichia coli|E. coli]]''. These strains carry [[mutation]]s that prevent the reuptake of [[aromatic amino acids]] or multiple/overexpressed [[trp operon]]s. The conversion is catalyzed by the enzyme [[tryptophan synthase]].<ref name="pmid12523387">{{cite book | vauthors = Ikeda M | chapter = Amino acid production processes | volume = 79 | pages = 1–35 | year = 2002 | pmid = 12523387 | doi = 10.1007/3-540-45989-8_1 | isbn = 978-3-540-43383-5 | series = Advances in Biochemical Engineering/Biotechnology | title = Microbial Production of l-Amino Acids }}</ref><ref name="pmid22138494">{{cite journal|vauthors=Becker J, Wittmann C|date=2012|title=Bio-based production of chemicals, materials and fuels -Corynebacterium glutamicum as versatile cell factory|journal=Current Opinion in Biotechnology|volume=23|issue=4|pages=631–40|doi=10.1016/j.copbio.2011.11.012|pmid=22138494}}</ref><ref name="pmid18725290">{{cite journal|vauthors=Conrado RJ, Varner JD, DeLisa MP|date=2008|title=Engineering the spatial organization of metabolic enzymes: mimicking nature's synergy|journal=Current Opinion in Biotechnology|volume=19|issue=5|pages=492–9|doi=10.1016/j.copbio.2008.07.006|pmid=18725290}}</ref>

==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 [[Centers for Disease Control and Prevention|CDC]] and at least 37 deaths.<ref>{{cite book|last1=Allen|first1=J.A.|last2=Varga|first2=J|editor1-last=Wexler|editor1-first=Philip|title=Encyclopedia of Toxicology|date=2014|publisher=Elsevier Science|location=Burlington|isbn=978-0-12-386455-0|edition=3rd|chapter=Eosinophilia–Myalgia Syndrome}}</ref> 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,<ref name= FDA_Tryptophan_Info>{{cite web | url = http://www.cfsan.fda.gov/~dms/ds-tryp1.html | archive-url = https://web.archive.org/web/20050225100757/http://www.cfsan.fda.gov/~dms/ds-tryp1.html | archive-date = 2005-02-25 | title = Information Paper on L-tryptophan and 5-hydroxy-L-tryptophan | date = 2001-02-01 | publisher = FU. S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Nutritional Products, Labeling, and Dietary Supplements | access-date = 2012-02-08 }}</ref><ref>{{cite web |url=http://www.webmd.com/vitamins-and-supplements/l-tryptophan-uses-and-risks#1 |title=L-tryptophan: Uses and Risks |website=[[WebMD]] |date=2017-05-12 |access-date=2017-06-05}}</ref><ref>{{cite news|last1=Altman|first1=Lawrence K.|title=Studies Tie Disorder to Maker of Food Supplement|url=https://www.nytimes.com/1990/04/27/us/studies-tie-disorder-to-maker-of-food-supplement.html|work=The New York Times|date=27 April 1990}}</ref> with other countries following suit.<ref>{{cite journal|last1=Castot|first1=A|last2=Bidault|first2=I|last3=Bournerias|first3=I|last4=Carlier|first4=P|last5=Efthymiou|first5=ML|title=["Eosinophilia-myalgia" syndrome due to L-tryptophan containing products. Cooperative evaluation of French Regional Centers of Pharmacovigilance. Analysis of 24 cases].|journal=Thérapie|date=1991|volume=46|issue=5|pages=355–65|pmid=1754978}}</ref><ref>{{cite web|title=COT Statement on Tryptophan and the Eosinophilia-Myalgia Syndrome|url=https://cot.food.gov.uk/sites/default/files/cot/tryptophanamend200401.pdf|publisher=UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment|date=June 2004}}</ref>

Subsequent studies suggested that EMS was linked to specific batches of <small>L</small>-tryptophan supplied by a single large Japanese manufacturer, [[Showa Denko]].<ref name= FDA_Tryptophan_Info /><ref name="pmid2355442">{{cite journal | vauthors = Slutsker L, Hoesly FC, Miller L, Williams LP, Watson JC, Fleming DW | title = Eosinophilia-myalgia syndrome associated with exposure to tryptophan from a single manufacturer | journal = JAMA | volume = 264 | issue = 2 | pages = 213–7 | date = July 1990 | pmid = 2355442 | doi = 10.1001/jama.264.2.213 }}</ref><ref name="pmid8496862">{{cite journal | vauthors = Back EE, Henning KJ, Kallenbach LR, Brix KA, Gunn RA, Melius JM | title = Risk factors for developing eosinophilia myalgia syndrome among L-tryptophan users in New York | journal = The Journal of Rheumatology | volume = 20 | issue = 4 | pages = 666–72 | date = April 1993 | pmid = 8496862 }}</ref><ref name="pmid8895184">{{cite journal | vauthors = Kilbourne EM, Philen RM, Kamb ML, Falk H | title = Tryptophan produced by Showa Denko and epidemic eosinophilia-myalgia syndrome | journal = The Journal of Rheumatology. Supplement | volume = 46 | pages = 81–8; discussion 89–91 | date = October 1996 | pmid = 8895184 }}</ref> It eventually became clear that recent batches of Showa Denko's <small>L</small>-tryptophan were contaminated by trace impurities, which were subsequently thought to be responsible for the 1989 EMS outbreak.<ref name= FDA_Tryptophan_Info /><ref name="pmid2270484">{{cite journal | vauthors = Mayeno AN, Lin F, Foote CS, Loegering DA, Ames MM, Hedberg CW, Gleich GJ | title = Characterization of "peak E," a novel amino acid associated with eosinophilia-myalgia syndrome | journal = Science | volume = 250 | issue = 4988 | pages = 1707–8 | date = December 1990 | pmid = 2270484 | doi = 10.1126/science.2270484 | bibcode = 1990Sci...250.1707M }}</ref><ref name="pmid1544609">{{cite journal | vauthors = Ito J, Hosaki Y, Torigoe Y, Sakimoto K | title = Identification of substances formed by decomposition of peak E substance in tryptophan | journal = Food and Chemical Toxicology | volume = 30 | issue = 1 | pages = 71–81 | date = January 1992 | pmid = 1544609 | doi = 10.1016/0278-6915(92)90139-C }}</ref> However, other evidence suggests that tryptophan itself may be a potentially major contributory factor in EMS.<ref name = "pmid16307217">{{cite journal | vauthors = Smith MJ, Garrett RH | title = A heretofore undisclosed crux of eosinophilia-myalgia syndrome: compromised histamine degradation | journal = Inflammation Research | volume = 54 | issue = 11 | pages = 435–50 | date = November 2005 | pmid = 16307217 | doi = 10.1007/s00011-005-1380-7 | s2cid = 7785345 }}</ref> There are also claims that a precursor reached sufficient concentrations to form a toxic [[Dimer (chemistry)|dimer]].<ref name="pred">{{cite web |author = Michael Predator Carlton |title = Molecular Biology and Genetic Engineering explained by someone who's done it |url = http://conway.cat.org.au/%7Epredator/mol.html  |archive-url=https://web.archive.org/web/20070624165916/http://conway.cat.org.au/%7Epredator/mol.html |archive-date=24 June 2007 }}</ref>

The FDA loosened its restrictions on sales and marketing of tryptophan in February 2001,<ref name=FDA_Tryptophan_Info /> but continued to limit the importation of tryptophan not intended for an exempted use until 2005.<ref>{{cite journal|last1=Allen|first1=JA|last2=Peterson|first2=A|last3=Sufit|first3=R|last4=Hinchcliff|first4=ME|last5=Mahoney|first5=JM|last6=Wood|first6=TA|last7=Miller|first7=FW|last8=Whitfield|first8=ML|last9=Varga|first9=J|title=Post-epidemic eosinophilia-myalgia syndrome associated with L-tryptophan.|journal=Arthritis and Rheumatism|date=November 2011|volume=63|issue=11|pages=3633–9|pmid=21702023|pmc=3848710|doi=10.1002/art.30514}}</ref>

The fact that the Showa Denko facility used [[genetically engineered]] bacteria to produce the contaminated batches of <small>L</small>-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".<ref name="pmid7765187">{{cite journal | vauthors = Mayeno AN, Gleich GJ | title = Eosinophilia-myalgia syndrome and tryptophan production: a cautionary tale | journal = Trends in Biotechnology | volume = 12 | issue = 9 | pages = 346–52 | date = September 1994 | pmid = 7765187 | doi = 10.1016/0167-7799(94)90035-3 }}</ref> Those calling for purity monitoring have, in turn, been criticized as anti-[[Genetically modified organism|GMO]] activists who overlook possible non-GMO causes of contamination and threaten the development of biotech.<ref name=Science2000>{{cite journal | vauthors = Raphals P | title = Does medical mystery threaten biotech? | journal = Science | volume = 250 | issue = 4981 | page = 619 | date = November 1990 | pmid = 2237411 | doi = 10.1126/science.2237411 | bibcode = 1990Sci...250..619R }}</ref>

===Turkey meat and drowsiness hypothesis===
{{See also|Postprandial somnolence#Turkey and tryptophan}}

A common assertion in the US and the UK<ref>{{Cite news |last=Harding |first=Nick |date=2023-12-21 |title=How to stop Christmas food from ruining your sleep |language=en-GB |work=The Telegraph |url=https://www.telegraph.co.uk/health-fitness/wellbeing/sleep/why-christmas-foods-negatively-affect-sleep-quality/ |access-date=2023-12-25 |issn=0307-1235}}</ref> is that heavy consumption of [[turkey meat]]—as seen during [[Thanksgiving (United States)|Thanksgiving]] and [[Christmas]]—results in [[Somnolence|drowsiness]], due to high levels of tryptophan contained in turkey.<ref name = "McCue">{{cite web | vauthors = McCue K | title = Chemistry.org: Thanksgiving, Turkey, and Tryptophan | url = http://www.chemistry.org/portal/a/c/s/1/feature_ent.html?DOC=enthusiasts%5Cent_tryptophan.html | access-date = 2007-08-17 | archive-url = https://web.archive.org/web/20070404111342/http://www.chemistry.org/portal/a/c/s/1/feature_ent.html?DOC=enthusiasts%5cent_tryptophan.html | archive-date = 2007-04-04 }}</ref> However, the amount of tryptophan in turkey is comparable with that of other meats.<ref name = "scientificamerican" /><ref name = "USDA" /> [[Postprandial somnolence|Drowsiness after eating]] may be caused by other foods eaten with the turkey, particularly [[carbohydrate]]s.<ref name="HighBeam Research Interview">{{cite journal | title = Food & mood. (neuroscience professor Richard Wurtman) (Interview) | journal = Nutrition Action Healthletter | url = https://www.questia.com/read/1G1-12520128 |date=September 1992 }}{{dead link|date=July 2021}}</ref> Ingestion of a meal rich in carbohydrates triggers the release of [[insulin]].<ref name="pmid3279747">{{cite journal | vauthors = Lyons PM, Truswell AS | title = Serotonin precursor influenced by type of carbohydrate meal in healthy adults | journal = The American Journal of Clinical Nutrition | volume = 47 | issue = 3 | pages = 433–9 | date = March 1988 | pmid = 3279747 | doi =  10.1093/ajcn/47.3.433| doi-access = free }}</ref><ref name="pmid12499331">{{cite journal | vauthors = Wurtman RJ, Wurtman JJ, Regan MM, McDermott JM, Tsay RH, Breu JJ | title = Effects of normal meals rich in carbohydrates or proteins on plasma tryptophan and tyrosine ratios | journal = The American Journal of Clinical Nutrition | volume = 77 | issue = 1 | pages = 128–32 | date = January 2003 | pmid = 12499331 | doi =  10.1093/ajcn/77.1.128| doi-access = free }}</ref><ref name="pmid17284739">{{cite journal | vauthors = Afaghi A, O'Connor H, Chow CM | title = High-glycemic-index carbohydrate meals shorten sleep onset | journal = The American Journal of Clinical Nutrition | volume = 85 | issue = 2 | pages = 426–30 | date = February 2007 | pmid = 17284739 | doi =  10.1093/ajcn/85.2.426| doi-access = free }}</ref><ref name="Banks-2012">{{Cite journal|vauthors=Banks WA, Owen JB, Erickson MA|date=2012|title=Insulin in the Brain: There and Back Again|journal=Pharmacology & Therapeutics|volume=136|issue=1|pages=82–93|doi=10.1016/j.pharmthera.2012.07.006|issn=0163-7258|pmc=4134675|pmid=22820012}}</ref> 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).<ref name="Banks-2012" /><ref name="pmid1148286">{{cite journal | vauthors = Pardridge WM, [[William H. Oldendorf|Oldendorf WH]] | title = Kinetic analysis of blood-brain barrier transport of amino acids | journal = Biochimica et Biophysica Acta (BBA) - Biomembranes | volume = 401 | issue = 1 | pages = 128–36 | date = August 1975 | pmid = 1148286 | doi = 10.1016/0005-2736(75)90347-8 }}</ref><ref name="pmid6538743">{{cite journal | vauthors = Maher TJ, Glaeser BS, Wurtman RJ | title = Diurnal variations in plasma concentrations of basic and neutral amino acids and in red cell concentrations of aspartate and glutamate: effects of dietary protein intake | journal = The American Journal of Clinical Nutrition | volume = 39 | issue = 5 | pages = 722–9 | date = May 1984 | pmid = 6538743 | doi =  10.1093/ajcn/39.5.722}}</ref> Once in the CSF, tryptophan is converted into [[serotonin]] in the [[raphe nuclei]] by the normal enzymatic pathway.<ref name="pmid12499331" /><ref name="pmid5120086">{{cite journal|vauthors=Fernstrom JD, Wurtman RJ|date=1971|title=Brain serotonin content: increase following ingestion of carbohydrate diet|journal=Science|volume=174|issue=4013|pages=1023–5|doi=10.1126/science.174.4013.1023|pmid=5120086|bibcode=1971Sci...174.1023F|s2cid=14345137}}</ref> The resultant serotonin is further metabolised into the hormone [[melatonin]]—which is an important mediator of the [[circadian rhythm]]<ref>{{Cite journal |last=Atul Khullar |first=M. D. |date=2012-07-10 |title=The Role of Melatonin in the Circadian Rhythm Sleep-Wake Cycle |url=https://www.psychiatrictimes.com/view/role-melatonin-circadian-rhythm-sleep-wake-cycle |journal =Psychiatric Times | issue = 7 |language=en |volume=29}}</ref>—by the [[pineal gland]].<ref name="pmid4391290" /> 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.<ref name="pmid3279747" /><ref name="pmid12499331" /><ref name="pmid17284739" /><ref name="pmid5120086" />

== 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|amino group]] with a [[hydroxyl|hydroxyl group]]. By this [[chemical reaction|reaction]], tryptophan gives rise to [[tryptophol]].<ref>{{cite journal | url = http://www.jbc.org/content/88/3/659.full.pdf | title = A synthesis of tryptophol | vauthors = Jackson RW | journal = Journal of Biological Chemistry | volume = 88 | issue = 3 | pages = 659–662 | year = 1930 | doi = 10.1016/S0021-9258(18)76755-0 | doi-access = free }}</ref>

=== Serotonin precursor ===
Tryptophan affects brain serotonin synthesis when given orally in a purified form and is used to modify serotonin levels for research.<ref name="Wurtman_1980"/> Low brain serotonin level is induced by administration of tryptophan-poor protein in a technique called [[acute tryptophan depletion]].<ref name="pmid23428157">{{cite journal | vauthors = Young SN | title = Acute tryptophan depletion in humans: a review of theoretical, practical and ethical aspects | journal = Journal of Psychiatry & Neuroscience | volume = 38 | issue = 5 | pages = 294–305 | date = September 2013 | pmid = 23428157 | pmc = 3756112 | doi = 10.1503/jpn.120209 }}</ref> Studies using this method have evaluated the effect of serotonin on mood and social behavior, finding that serotonin reduces aggression and increases agreeableness.<ref name="pmid23440461">{{cite journal | vauthors = Young SN | title = The effect of raising and lowering tryptophan levels on human mood and social behaviour | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 368 | issue = 1615 | article-number = 20110375 | year = 2013 | pmid = 23440461 | pmc = 3638380 | doi = 10.1098/rstb.2011.0375 }}</ref>

=== Psychedelic effects ===
{{See also|5-Hydroxytryptophan#Psychedelic effects}}

Tryptophan produces the [[head-twitch response]] (HTR) in rodents when administered at sufficiently high doses.<ref name="HalberstadtGeyer2018">{{cite book | vauthors = Halberstadt AL, Geyer MA | title = Behavioral Neurobiology of Psychedelic Drugs | chapter = Effect of Hallucinogens on Unconditioned Behavior | series = Current Topics in Behavioral Neurosciences | volume = 36 | pages = 159–199 | date = 2018 | pmid = 28224459 | pmc = 5787039 | doi = 10.1007/7854_2016_466 | isbn = 978-3-662-55878-2 | chapter-url = }}</ref> The HTR is induced by [[serotonergic psychedelic]]s like [[lysergic acid diethylamide]] (LSD) and [[psilocybin]] and is a behavioral proxy of psychedelic effects.<ref name="CanalMorgan2012">{{cite journal | vauthors = Canal CE, Morgan D | title = Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model | journal = Drug Test Anal | volume = 4 | issue = 7–8 | pages = 556–576 | date = 2012 | pmid = 22517680 | pmc = 3722587 | doi = 10.1002/dta.1333 | url = }}</ref><ref name="KozlenkovGonzález-Maeso2013">{{cite book | last1=Kozlenkov | first1=Alexey | last2=González-Maeso | first2=Javier | title=The Neuroscience of Hallucinations | chapter=Animal Models and Hallucinogenic Drugs | publisher=Springer New York | publication-place=New York, NY | date=2013 | isbn=978-1-4614-4120-5 | doi=10.1007/978-1-4614-4121-2_14 | pages=253–277}}</ref> Tryptophan is converted into the [[trace amine]] [[tryptamine]] and tryptamine is ''N''-[[methyl group|methylated]] by [[indolethylamine N-methyltransferase|indolethylamine ''N''-methyltransferase]] (INMT) into [[N-methyltryptamine|''N''-methyltryptamine]] (NMT) and [[dimethyltryptamine|''N'',''N''-dimethyltryptamine]] (''N'',''N''-DMT), which are known serotonergic psychedelics.<ref name="HalberstadtGeyer2018" /><ref name="CarbonaroGatch2016">{{cite journal | vauthors = Carbonaro TM, Gatch MB | title = Neuropharmacology of N,N-dimethyltryptamine | journal = Brain Res Bull | volume = 126 | issue = Pt 1 | pages = 74–88 | date = September 2016 | pmid = 27126737 | pmc = 5048497 | doi = 10.1016/j.brainresbull.2016.04.016 | url = | quote = Endogenous DMT is synthesized from the essential amino acid tryptophan, which is decarboxylated to tryptamine. Tryptamine is then transmethylated by the enzyme indolethylamine-N-methyltransferase (INMT) (using S-adenosyl methionine as a substrate), which catalyzes the addition of methyl groups resulting in the production of N-methyltryptamine (NMT) and DMT. NMT can also act as a substrate for INMT-dependent DMT biosynthesis (Barker et al., 1981).}}</ref><ref name="Barker2018">{{cite journal | vauthors = Barker SA | title = N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function | journal = Front Neurosci | volume = 12 | issue = | article-number = 536 | date = 2018 | pmid = 30127713 | pmc = 6088236 | doi = 10.3389/fnins.2018.00536 | doi-access = free | url = | quote = After the discovery of an indole-N-methyl transferase (INMT; Axelrod, 1961) in rat brain, researchers were soon examining whether the conversion of tryptophan (2, Figure 2) to tryptamine (TA; 3, Figure 2) could be converted to DMT in the brain and other tissues from several mammalian species. Numerous studies subsequently demonstrated the biosynthesis of DMT in mammalian tissue preparations in vitro and in vivo (Saavedra and Axelrod, 1972; Saavedra et al., 1973). In 1972, Juan Saavedra and Julius Axelrod reported that intracisternally administered TA was converted to N-methyltryptamine (NMT; 4, Figure 2) and DMT in the rat, the first demonstration of DMT's formation by brain tissue in vivo.}}</ref><ref name="CameronOlson2018">{{cite journal | vauthors = Cameron LP, Olson DE | title = Dark Classics in Chemical Neuroscience: N, N-Dimethyltryptamine (DMT) | journal = ACS Chem Neurosci | volume = 9 | issue = 10 | pages = 2344–2357 | date = October 2018 | pmid = 30036036 | doi = 10.1021/acschemneuro.8b00101 | url = https://shaunlacob.com/wp-content/uploads/2020/12/Dark-Classics-DMT.pdf | quote=Like serotonin and melatonin, DMT is a product of tryptophan metabolism.25 Following tryptophan decarboxylation, tryptamine is methylated by an N-methyltransferase (i.e., INMT) with S-adenosylmethionine serving as the methyl donor. A second enzymatic methylation produces DMT (Figure 3A).26 [...] The enzyme indolethylamine N-methyltransferase (INMT) catalyzes the methylation of a variety of biogenic amines, and is responsible for converting tryptamine into DMT in mammals.140}}</ref><ref name="ColosimoBorsellinoKrider2024">{{cite journal | last1=Colosimo | first1=Frankie A. | last2=Borsellino | first2=Philip | last3=Krider | first3=Reese I. | last4=Marquez | first4=Raul E. | last5=Vida | first5=Thomas A. | title=The Clinical Potential of Dimethyltryptamine: Breakthroughs into the Other Side of Mental Illness, Neurodegeneration, and Consciousness | journal=Psychoactives | publisher=MDPI AG | volume=3 | issue=1 | date=26 February 2024 | issn=2813-1851 | doi=10.3390/psychoactives3010007 | doi-access=free | pages=93–122 | quote=The metabolism of DMT within the body begins with its synthesis. Endogenous DMT is made from tryptophan after decarboxylation transforms it into tryptamine [22,25]. Tryptamine then undergoes transmethylation mediated by indolethylamine-N-methyltransferase (INMT) with S-adenosyl methionine (SAM) as a substrate, morphing into N-methyltryptamine (NMT) and eventually producing N,N-DMT [26]. Intriguingly, INMT is distributed widely across the body, predominantly in the lungs, thyroid, and adrenal glands, with a dense presence in the anterior horn of the spinal cord. Within the cerebral domain, regions such as the uncus, medulla, amygdala, frontal cortex, fronto-parietal lobe, and temporal lobe exhibit INMT activity, primarily localized in the soma [26]. INMT transcripts are found in specific brain regions, including the cerebral cortex, pineal gland, and choroid plexus, in both rats and humans. Although the rat brain is capable of synthesizing and releasing DMT at concentrations similar to established monoamine neurotransmitters like serotonin [27], the possibility that DMT is an authentic neurotransmitter is still speculative. This issue has been controversial for decades [28] and requires the demonstration of an activity-dependent release (i.e., Ca2+-stimulated) of DMT at a synaptic cleft to be fully established in the human brain.}}</ref><ref name="AraújoCarvalhoBastosMde2015">{{cite journal | vauthors = Araújo AM, Carvalho F, Bastos Mde L, Guedes de Pinho P, Carvalho M | title = The hallucinogenic world of tryptamines: an updated review | journal = Arch Toxicol | volume = 89 | issue = 8 | pages = 1151–1173 | date = August 2015 | pmid = 25877327 | doi = 10.1007/s00204-015-1513-x | bibcode = 2015ArTox..89.1151A | url = }}</ref>

=== Fluorescence ===
{{Main|Fluorescence spectroscopy#Tryptophan 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)
* [[α-Methyltryptophan]]
* [[Acree–Rosenheim reaction]]
* [[Adamkiewicz reaction]]
* [[Attenuator (genetics)]]
* [[N,N-Dimethyltryptamine|''N'',''N''-Dimethyltryptamine]]
* [[Hopkins–Cole reaction]]
* [[Serotonin]]
* [[Tryptamine]]

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Wood RM, Rilling JK, Sanfey AG, Bhagwagar Z, Rogers RD | title = Effects of tryptophan depletion on the performance of an iterated Prisoner's Dilemma game in healthy adults | journal = Neuropsychopharmacology | volume = 31 | issue = 5 | pages = 1075–84 | date = May 2006 | pmid = 16407905 | doi = 10.1038/sj.npp.1300932 | doi-access = free }}
* {{cite journal | vauthors = Huang Y, Zhao M, Chen X, Zhang R, Le A, Hong M, Zhang Y, Jia L, Zang W, Jiang C, Wang J, Fan X, Wang J | title = Tryptophan Metabolism in Central Nervous System Diseases: Pathophysiology and Potential Therapeutic Strategies | journal = Aging Dis | volume = 14 | issue = 3 | pages = 858–878 | date = June 2023 | pmid = 37191427 | doi = 10.14336/AD.2022.0916 | doi-access = free | pmc = 10187711 }}
{{refend}}

== External links ==
{{refbegin}}
* {{cite web | url = http://www.genome.jp/dbget-bin/www_bget?path:hsa00380 | title = KEGG PATHWAY: Tryptophan metabolism - Homo sapiens | date = 2006-08-23 | publisher = KEGG: Kyoto Encyclopedia of Genes and Genomes | access-date = 2008-04-20}}
* {{cite web | url = http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/AminoAcid/TrpCat1.html | title = Tryptophan Catabolism (early stages) | author = G. P. Moss | publisher = Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) | archive-url =https://web.archive.org/web/20030913143004/http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/AminoAcid/TrpCat1.html| archive-date =2003-09-13| access-date = 2008-04-20}}
* {{cite web | url = http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/AminoAcid/TrpCat2.html | title = Tryptophan Catabolism (later stages) | author = G. P. Moss | publisher = Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) | archive-url =https://web.archive.org/web/20030913191403/http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/AminoAcid/TrpCat2.html| archive-date =2003-09-13| access-date = 2008-04-20}}
* {{cite web | url = http://www.snopes.com/food/ingredient/turkey.asp | title = Turkey Causes Sleepiness |author1=B. Mikkelson |author2=D. P. Mikkelson | date = 2007-11-22 | work = Urban Legends Reference Pages | publisher = Snopes.com | access-date = 2008-04-20}}
{{refend}}

{{Amino acids}}
{{Amino acid metabolism intermediates}}
{{Neurotransmitter metabolism intermediates}}
{{Serotonergics}}
{{Tryptamines}}
{{Chocolate}}

{{Authority control}}

<!--https://www.ncbi.nlm.nih.gov/pubmed/29478330-->

[[Category:Alpha-Amino acids]]
[[Category:Proteinogenic amino acids]]
[[Category:Indole alkaloids]]
[[Category:Glucogenic amino acids]]
[[Category:Ketogenic amino acids]]
[[Category:Aromatic amino acids]]
[[Category:Essential amino acids]]
[[Category:Tryptamine alkaloids]]
[[Category:Dietary supplements]]
[[Category:Carbonic anhydrase activators]]
[[Category:Monoamine precursors]]
[[Category:Serotonin]]