Citrulline: Difference between revisions

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 443676645

| ImageSize = 230

| ImageFile_Ref = {{chemboximage|correct|??}}

| ImageFile1 = L-Citrulline zwitterion ball from xtal.png

| ImageSize1 = 230

| ImageName1 = Ball and stick model of zwitterionic citrulline

| IUPACName = 2-Amino-5-(carbamoylamino)pentanoic acid<ref>{{cite web|title=Citrulline - Compound Summary|url=https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=833&loc=ec_rcs#x291|work=PubChem Compound|publisher=National Center for Biotechnology Information|access-date=1 May 2012|location=USA|date=16 September 2004|at=Identification}}</ref>

|Section1={{Chembox Identifiers

| CASNo = 627-77-0

| CASNo_Ref = {{cascite|correct|CAS}}

| CASNo1 = 13594-51-9

| CASNo1_Ref = {{cascite|correct|CAS}}

| CASNo1_Comment = (<small>''D''</small>)

| CASNo2 = 372-75-8

| CASNo2_Ref = {{cascite|correct|CAS}}

| CASNo2_Comment = (<small>''L''</small>)

| PubChem = 833

| PubChem1 = 637599

| PubChem1_Comment = <small>''D''</small>

| PubChem2 = 9750

| PubChem2_Comment = <small>''L''</small>

| ChemSpiderID = 810

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID1 = 553200

| ChemSpiderID1_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID1_Comment = <small>''D''</small>

| ChemSpiderID2 = 9367

| ChemSpiderID2_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID2_Comment = <small>''L''</small>

| UNII = 1OYO2NV4NM

| UNII1_Ref = {{fdacite|correct|FDA}}

| UNII1 = KNS2VUH6P2

| UNII1_Comment = (''D'')

| UNII2_Ref = {{fdacite|correct|FDA}}

| UNII2 = 29VT07BGDA

| UNII2_Comment = (''L'')

| EINECS = 211-012-2

| DrugBank = DB00155

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| KEGG_Ref = {{keggcite|correct|kegg}}

| MeSHName = Citrulline

| ChEBI = 18211

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| Beilstein = 1725417, 1725415 <small>''D''</small>, 1725416 <small>''L''</small>

| Gmelin = 774677 <small>''L''</small>

| 3DMet = B01217

| SMILES = NC(CCCNC(N)=O)C(O)=O

| StdInChI = 1S/C6H13N3O3/c7-4(5(10)11)2-1-3-9-6(8)12/h4H,1-3,7H2,(H,10,11)(H3,8,9,12)

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = RHGKLRLOHDJJDR-UHFFFAOYSA-N

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

}}

|Section2={{Chembox Properties

| C=6 | H=13 | N=3 | O=3

| Appearance = White crystals

| Odor = Odourless

| LogP = −1.373

| pKa = 2.508

| pKb = 11.489

}}

|Section3={{Chembox Thermochemistry

| Entropy = 254.4 J K⁻¹ mol⁻¹

| HeatCapacity = 232.80 J K⁻¹ mol⁻¹

}}

|Section4={{Chembox Related

| OtherFunction_label = alkanoic acids

| OtherFunction = {{unbulleted list|[[n-Acetylaspartic acid|''N''-Acetylaspartic acid]]|[[Aceglutamide]]|[[n-Acetylglutamic acid|''N''-Acetylglutamic acid]]|[[Pivagabine]]}}

| OtherCompounds = {{unbulleted list|[[Bromisoval]]|[[Carbromal]]}}

The [[organic compound]] '''citrulline''' is an α-[[amino acid]].<ref name=":0">{{Citation|last=Banerjee|first=Aryamitra|title=Chapter 15 - Gastrointestinal toxicity biomarkers|date=2014-01-01|url=http://www.sciencedirect.com/science/article/pii/B9780124046306000154|work=Biomarkers in Toxicology|pages=269–277|editor-last=Gupta|editor-first=Ramesh C.|place=Boston|publisher=Academic Press|language=en|doi=10.1016/b978-0-12-404630-6.00015-4|isbn=978-0-12-404630-6|s2cid=88798984 |access-date=2020-11-10}}</ref> Its name is derived from ''[[citrullus]]'', the [[Latin]] word for [[watermelon]]. Although named and described by [[gastroenterology|gastroenterologists]] since the late 19th century, it was first isolated from watermelon in 1914 by [[Japan]]ese researchers Yatarō Koga (古賀彌太郎) and Ryō Ōtake (大嶽了)<ref name="Koga1914">{{cite journal

| last1 = Koga

| first1 = Yatarō

| last2 = Ōtake

| first2 = Ryō

| title = Study report on the constituents of squeezed watermelon

| journal = Tokyo Kagaku Kaishi [Journal of the Tokyo Chemical Society]

| volume = 35

| number = 5

| pages = 519-528

| doi = 10.1246/nikkashi1880.35.519

| year = 1914

}}</ref><ref name="Fragkos2011">{{cite journal

|last1 = Fragkos

|first1 = Konstantinos C.

|last2 = Forbes

|first2 = Alastair

| title = Was citrulline first a laxative substance? The truth about modern citrulline and its isolation

| journal = Nihon Ishigaku Zasshi [Journal of the Japanese Society for the History of Medicine]

| volume = 57

| number = 3

| pages = 275-292

| url = http://jshm.or.jp/journal/57-3/57-3_275.pdf

| pmid = 22397107

| year = 2011

}}</ref> and further codified by Mitsunori Wada of [[Tokyo Imperial University]] in 1930.<ref name="Wada1930a">{{cite journal

| last = Wada

| first = Mitsunori

| title = On the occurrence of a new amino acid in watermelon. Citrullus vulgaris, Schrad.

| journal = Proceedings of the Imperial Academy

| volume = 6

| number = 1

| pages = 15-17

| doi = 10.2183/pjab1912.6.15

| year = 1930

}}</ref><ref name="Wada1930b">{{cite journal

| last = Wada

| first = Mitsunori

| title = On the occurrence of a new amino acid in watermelon, Citrullus vulgaris, Schrad.

| journal = Bulletin of the Agricultural Chemical Society of Japan

| volume = 6

| number = 1-5

| pages = 32-34

| doi = 10.1271/bbb1924.6.32

| year = 1930

}}</ref><ref name="Wada1930c">{{cite journal

| author = Wada, Mitsunori

| title = Über Citrullin, eine neue Aminosäure im Preßsaft der Wassermelone, Citrullus vulgaris, Schrad.

| journal = Biochemische Zeitschrift

| volume = 224

| pages = 420-429

| year = 1930

| language = de

}}</ref>

It has the [[chemical formula|formula]] H₂NC(O)NH(CH₂)₃CH(NH₂)CO₂H. It is a key intermediate in the [[urea cycle]], the pathway by which mammals excrete [[ammonia]] by converting it into urea. Citrulline is also produced as a byproduct of the [[enzyme|enzymatic]] production of [[nitric oxide]] from the amino acid [[arginine]], catalyzed by [[nitric oxide synthase]].<ref>{{cite web|title=Nos2 - Nitric Oxide Synthase|url=https://www.uniprot.org/uniprot/P29477|website=Uniprot.org|publisher=Uniprot Consortium|access-date=10 February 2015}}</ref>

Citrulline can be derived from:

* from arginine via [[nitric oxide synthase]], as a byproduct of the production of nitric oxide for [[Second messenger system|signaling]] purposes

* from [[ornithine]] through the breakdown of [[proline]] or [[glutamine]]/[[glutamate]]

* from [[asymmetric dimethylarginine]] via DDAH

Citrulline is made from [[ornithine]] and [[carbamoyl phosphate]] in one of the central reactions in the urea cycle. It is also produced from [[arginine]] as a byproduct of the reaction catalyzed by [[nitric oxide synthase|NOS]] family (NOS; [https://enzyme.expasy.org/EC/1.14.13.39 EC 1.14.13.39]).<ref>{{cite book |vauthors=Cox M, Lehninger AL, Nelson DR |title=Lehninger principles of biochemistry |publisher=Worth Publishers |location=New York |year=2000 |page= [https://archive.org/details/lehningerprincip01lehn/page/449 449] |isbn=978-1-57259-153-0 |edition=3rd |access-date= 13 March 2020 |url=https://archive.org/details/lehningerprincip01lehn }}</ref> It is also prevalent in [[TCHH|trichohyalin]] at the inner root [[Root sheath (hair)|sheath]] and medulla of hair follicles, where it is synthesized from arginine.<ref>{{Cite journal

| last1 = Rogers | first1 = G. E.

| last2 = Rothnagel | first2 = J. A.

| title = A sensitive assay for the enzyme activity in hair follicles and epidermis that catalyses the peptidyl-arginine-citrulline post-translational modification

| journal = Current Problems in Dermatology

| volume = 11

| pages = 171–184

| year = 1983

| pmid = 6653155

| doi = 10.1159/000408673

| isbn = 978-3-8055-3752-0

}}</ref> [[Arginine]] is first oxidized into ''N''-hydroxyl-arginine, which is then further oxidized to citrulline concomitant with release of nitric oxide.

Citrulline is also made by [[enterocytes]] of the small intestine.<ref name=":0" /><ref>{{Citation|last=DeLegge|first=Mark H.|title=Chapter 7 - Enteral Access and Enteral Nutrition in Patients With Short Bowel Syndrome|date=2019-01-01|url=http://www.sciencedirect.com/science/article/pii/B978012814330800007X|work=Adult Short Bowel Syndrome|pages=81–96|editor-last=Corrigan|editor-first=Mandy L.|publisher=Academic Press|language=en|doi=10.1016/b978-0-12-814330-8.00007-x|isbn=978-0-12-814330-8|s2cid=81295089|access-date=2020-11-10|editor2-last=Roberts|editor2-first=Kristen|editor3-last=Steiger|editor3-first=Ezra}}</ref>

==Function==

Citrulline is a metabolic intermediate within the [[urea cycle]], which is the pathway by which mammals excrete ammonia by converting it into urea. Citrulline is also produced as a byproduct of the enzymatic production of nitric oxide from the amino acid arginine, catalyzed by nitric oxide synthase. In the yeast species Saccharomyces cerevisiae, citrulline is a metabolic intermediate in the latter, cytosolic half of the arginine biosynthesis pathway.<ref>{{cite web | url=https://pathway.yeastgenome.org/YEAST/new-image?object=CITRUL-BIO2-PWY | title=Saccharomyces cerevisiae citrulline biosynthesis }}</ref>

Several proteins contain citrulline as a result of a [[post-translational modification]]. These citrulline residues are generated by a family of enzymes called [[peptidylarginine deiminase]]s (PADs), which convert arginine into citrulline in a process called [[citrullination]] or deimination with the help of calcium ions. Proteins that normally contain citrulline residues include [[myelin basic protein]] (MBP), [[filaggrin]], and several [[histone]] proteins, whereas other proteins, such as [[fibrin]] and [[vimentin]] are susceptible to citrullination during cell death and tissue [[inflammation]].

Circulating citrulline concentration is a [[biomarker]] of intestinal functionality.<ref>{{Cite journal|last1=Fragkos|first1=Konstantinos C.|last2=Forbes|first2=Alastair|date=2017-10-12|title=Citrulline as a marker of intestinal function and absorption in clinical settings: A systematic review and meta-analysis|journal=United European Gastroenterology Journal|volume=6|issue=2|pages=181–191|language=en|doi=10.1177/2050640617737632|pmid=29511548|pmc=5833233}}</ref><ref>{{cite journal | last1 = Crenn | first1 = P. | display-authors = etal | year = 2000 | title = Post-absorptive plasma citrulline concentration is a marker of intestinal failure in short bowel syndrome patients | journal = Gastroenterology | volume = 119 | issue = 6| pages = 1496–505 | doi=10.1053/gast.2000.20227| pmid = 11113071 | doi-access = free }}</ref>

{{reflist|20em}}

{{Non-proteinogenic amino acids}}

{{Amino acid metabolism intermediates}}

[[Category:Alpha-Amino acids]]

[[Category:Non-proteinogenic amino acids]]

[[Category:Biomarkers]]