Editing Ornithine

{{Chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 408781245
| Name = ''<small>L</small>''-Ornithine
| ImageFile = L-Ornithin2.svg
| ImageFile1 = Ornithine ball-and-stick.png
| IUPACName = (''2S'')-2,5-diaminopentanoic acid
| OtherNames = (+)-(''S'')-2,5-Diaminovaleric acid<br>(+)-(''S'')-2,5-Diaminopentanoic acid
| Section1 = {{Chembox Identifiers
 | IUPHAR_ligand = 725
 | UNII = E524N2IXA3
 | InChI = 1/C5H12N2O2/c6-3-1-2-4(7)5(8)9/h4H,1-3,6-7H2,(H,8,9)/t4-/m0/s1
 | InChIKey = AHLPHDHHMVZTML-BYPYZUCNSA-N
 | ChEMBL = 446143
 | StdInChI = 1S/C5H12N2O2/c6-3-1-2-4(7)5(8)9/h4H,1-3,6-7H2,(H,8,9)/t4-/m0/s1
 | StdInChIKey = AHLPHDHHMVZTML-BYPYZUCNSA-N
 | CASNo = 70-26-8
 | EC_number = 200-731-7
 | ChemSpiderID = 6026
 | PubChem = 389
 | KEGG = D08302
 | DrugBank = DB00129
 | ChEBI = 15729
 | SMILES = O=C(O)[C@@H](N)CCCN
 | MeSHName = Ornithine
}}
| Section2 = {{Chembox Properties
 | Properties_ref = <ref>{{cite book |title=CRC Handbook of Chemistry and Physics |edition=62nd |publisher=CRC Press |year=1981 |page=C-408}}</ref>
 | Formula = C<sub>5</sub>H<sub>12</sub>N<sub>2</sub>O<sub>2</sub>
 | MolarMass = 132.16 g/mol
 | MeltingPtC = 140
 | Solubility = Soluble
 | SolubleOther = Soluble in [[ethanol]]
 | SpecRotation = +11.5 (H<sub>2</sub>O, ''c'' = 6.5)
 | pKa = 1.94
}}
}}

'''Ornithine''' is a [[non-proteinogenic]] α-amino acid that plays a role in the [[urea cycle]]. It is not incorporated into proteins during translation. Ornithine is abnormally accumulated in the body in [[ornithine transcarbamylase deficiency]], a disorder of the urea cycle. The [[Moiety (chemistry)|moiety]] derived from ornithine is called '''ornithyl'''.<ref name="Sivashanmugam2017">{{cite journal |last=Sivashanmugam |first=M |title=Ornithine and its role in metabolic diseases: An appraisal |journal=Biomedicine & Pharmacotherapy |volume=86 |pages=185–194 |date=February 2017 |pmid=27978498 |doi=10.1016/j.biopha.2016.12.024}}</ref>

==Role in urea cycle==
<small>L</small>-Ornithine is one of the products of the action of the enzyme [[arginase]] on <small>L</small>-[[arginine]], creating [[urea]]. Therefore, ornithine is a central component of the [[urea cycle]], which enables the disposal of excess [[nitrogen]]. Ornithine itself is recycled and, in a sense, acts as a catalyst.

First, ammonia is converted into [[carbamoyl phosphate]] ({{chem|H|2|NC(O)OPO|3|2−}}) by [[carbamoyl phosphate synthetase]]. [[Ornithine transcarbamylase]] then catalyzes the reaction between carbamoyl phosphate and ornithine to form [[citrulline]] and phosphate (P<sub>i</sub>). Another [[amino group]] is contributed by [[aspartate]], leading to the formation of arginine and the byproduct [[fumarate]]. The resulting arginine, a [[guanidinium]] compound, is subsequently hydrolyzed by arginase to regenerate ornithine and release urea.

The two nitrogen atoms in urea are derived from ammonia and aspartate, while the nitrogen atoms in ornithine remain unchanged.

[[Image:OTC reaction.png|thumb|left|458px|'''Reaction mechanism:'''. The [[Side chain|side-chain]] amino group of ornithine (Orn) nucleophilically attacks the carbonyl carbon of carbamoyl phosphate (CP), ''left'', forming a tetrahedral transition state, ''middle''. Charge rearrangement then releases citrulline (Cit) and phosphate (P<sub>i</sub>), ''right''.<ref name="pmid10747936">{{cite journal |vauthors=Langley DB, Templeton MD, Fields BA, Mitchell RE, Collyer CA |title=Mechanism of inactivation of ornithine transcarbamoylase by Ndelta-(N'-Sulfodiaminophosphinyl)-L-ornithine, a true transition state analogue? Crystal structure and implications for catalytic mechanism |journal=The Journal of Biological Chemistry |volume=275 |issue=26 |pages=20012–9 |date=June 2000 |pmid=10747936 |doi=10.1074/jbc.M000585200 |doi-access=free }}</ref>]] {{clear|left}}

Ornithine is not an amino acid directly coded for by [[DNA]]; that is, it is not a [[proteinogenic amino acid]]. However, in mammalian non-hepatic tissues, the primary role of the urea cycle is often the biosynthesis of arginine. As an intermediate in metabolic pathways, ornithine is thus quite important.<ref>{{cite journal |vauthors=Weber AL, Miller SL |title=Reasons for the occurrence of the twenty coded protein amino acids |journal=Journal of Molecular Evolution |volume=17 |issue=5 |pages=273–284 |year=1981 |pmid=7277510 |doi=10.1007/BF01795749 |bibcode=1981JMolE..17..273W |s2cid=27957755 |url=http://physwww.mcmaster.ca/~higgsp/3D03/WeberReasons.pdf }}</ref> {{clear|left}}

==Other reactions==
Ornithine, through the action of [[ornithine decarboxylase]] (EC 4.1.1.17), serves as the starting point for the synthesis of [[polyamines]] such as [[putrescine]].

In bacteria such as ''[[Escherichia coli|E. coli]]'', ornithine can be synthesized from [[L-glutamate|<small>L</small>-glutamate]].<ref>{{Cite web |url=http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/AminoAcid/Orn.html |title=Ornithine Biosynthesis |access-date=2007-08-17 |publisher=School of Biological and Chemical Sciences, Queen Mary, University of London |archive-url=https://web.archive.org/web/20120414191013/http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/AminoAcid/Orn.html |archive-date=2012-04-14 |url-status=dead }}</ref>

[[File:Ornithine lactamization.svg|center|thumb|600px|Ornithine lactamization]]

==Research==
===Exercise fatigue===
<small>L</small>-Ornithine supplementation has been shown to attenuate fatigue in subjects in placebo-controlled studies using a cycle ergometer. The results suggest that <small>L</small>-ornithine may exert an antifatigue effect by increasing the efficiency of energy consumption and promoting the excretion of ammonia.<ref>{{cite journal |vauthors=Sugino T, Shirai T, Kajimoto Y, Kajimoto O |title=L-ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism |journal=Nutrition Research |volume=28 |issue=11 |pages=738–743 |date=November 2008 |pmid=19083482 |doi=10.1016/j.nutres.2008.08.008}}</ref><ref>{{cite journal |vauthors=Demura S, Yamada T, Yamaji S, Komatsu M, Morishita K |title=The effect of L-ornithine hydrochloride ingestion on performance during incremental exhaustive ergometer bicycle exercise and ammonia metabolism during and after exercise |journal=European Journal of Clinical Nutrition |volume=64 |issue=10 |pages=1166–1171 |date=October 2010 |pmid=20717126 |doi=10.1038/ejcn.2010.149 |doi-access=free |hdl=2297/25434 |hdl-access=free}}</ref>

===Weightlifting supplement===
Amino acid supplements, including <small>L</small>-ornithine, are frequently marketed to bodybuilders and weightlifters with claims of increasing levels of [[human growth hormone]] (HGH), muscle mass, and strength. A short, four-day clinical study conducted in 1993 reported that <small>L</small>-ornithine, in combination with <small>L</small>-arginine and <small>L</small>-lysine at 2 g/day each, did not increase HGH levels.<ref>{{cite journal |vauthors=Fogelholm GM, Näveri HK, Kiilavuori KT, Härkönen MH |title=Low-dose amino acid supplementation: no effects on serum human growth hormone and insulin in male weightlifters |journal=International Journal of Sport Nutrition |volume=3 |issue=3 |pages=290–297 |date=September 1993 |pmid=8220394 |doi=10.1123/ijsn.3.3.290}}</ref> A review published in 2002 concluded, "The use of specific amino acids to stimulate GH release by athletes is not recommended."<ref>{{cite journal |vauthors=Chromiak JA, Antonio J |title=Use of amino acids as growth hormone-releasing agents by athletes |journal=Nutrition |volume=18 |issue=7–8 |pages=657–661 |year=2002 |pmid=12093449 |doi=10.1016/s0899-9007(02)00807-9}}</ref>

===Cirrhosis===
[[Hepatic encephalopathy#L-ornithine and L-aspartate|<small>L</small>-ornithine <small>L</small>-aspartate]] (LOLA), a stable salt of ornithine and aspartic acid, has been used in the treatment of [[cirrhosis]]<ref>{{cite journal |vauthors=Sikorska H, Cianciara J, Wiercińska-Drapało A |title=Physiological functions of L-ornithine and L-aspartate in the body and the efficacy of administration of L-ornithine-L-aspartate in conditions of relative deficiency |journal=Polski Merkuriusz Lekarski |volume=28 |issue=168 |pages=490–495 |date=June 2010 |pmid=20642112 |url=https://www.researchgate.net/publication/45273344 |language=pl |via=ResearchGate |access-date=10 March 2025}}</ref> and [[hepatic encephalopathy]].<ref name="pmid30706425">{{cite journal |vauthors=Butterworth R, McPhail M |title=L-Ornithine L-Aspartate (LOLA) for Hepatic Encephalopathy in Cirrhosis: Results of Randomized Controlled Trials and Meta-Analyses |journal=Drugs |volume=79 |issue=Suppl 1 |pages=31–37 |date=February 2019 |pmid=30706425 |pmc=6416237 |doi=10.1007/s40265-018-1024-1 |doi-access=free}}</ref>

==See also==
* [[Bisorcic]]
* [[3-Methylornithine]]

== References ==
{{reflist}}

== External links ==
{{Commons category|L-Ornithine}}
* [http://gmd.mpimp-golm.mpg.de/Spectrums/13d582bc-51b1-4b92-8edf-cb1e31ca64c6.aspx Ornithine mass Spectrum]
{{Amino acid metabolism intermediates}}
{{Non-proteinogenic amino acids}}
[[Category:Alpha-Amino acids]]
[[Category:Basic amino acids]]
[[Category:Urea cycle]]
[[Category:Diamines]]
[[Category:Non-proteinogenic amino acids]]