Editing Tryptophan (section)

== 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|url-status=dead}}</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|url=https://pubmed.ncbi.nlm.nih.gov/33230205|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}}