Asparagine

Asparagine was first isolated in 1806 in a crystalline form by French chemists Louis Nicolas Vauquelin and Pierre Jean Robiquet (then a young assistant). It was isolated from asparagus juice,{{cite journal |title=La découverte d'un nouveau principe végétal dans le suc des asperges |vauthors=Vauquelin LN, Robiquet PJ |journal=Annales de Chimie |year=1806 |volume=57 |pages=88–93 |language=fr|hdl=2027/nyp.33433062722578 }}{{cite book | vauthors = Plimmer RH |author-link=R. H. A. Plimmer| veditors = Plimmer RH, Hopkins FG |title= The chemical composition of the proteins |url= https://books.google.com/books?id=7JM8AAAAIAAJ&pg=PA112 |access-date= January 18, 2010 |edition= 2nd |series= Monographs on biochemistry |volume= Part I. Analysis |orig-year= 1908 |year= 1912 |publisher= Longmans, Green and Co. |location= London|page= 112}} in which it is abundant, hence the chosen name. It was the first amino acid to be isolated.{{Cite book |title=Advances in Protein Chemistry |vauthors=Anfinsen CB, Edsall JT, Richards FM |year=1972 |pages=[https://archive.org/details/advancesinprotei26anfi/page/99 99, 103] |publisher=Academic Press |location=New York |isbn=978-0-12-034226-6 |url=https://archive.org/details/advancesinprotei26anfi/page/99 }}

Three years later, in 1809, Pierre Jean Robiquet identified a substance from liquorice root with properties which he qualified as very similar to those of asparagine,{{cite journal| vauthors = Robiquet PJ |title=Analyse de la racine de réglisse|journal=Annales de Chimie et de Physique|date=1809|volume=72|issue=1|pages=143–159|url=https://babel.hathitrust.org/cgi/pt?id=mdp.39015065225404;view=1up;seq=143|trans-title=Analysis of licorice root|language=fr}} and which Plisson identified in 1828 as asparagine itself.{{cite journal| vauthors = Plisson A |title=De l'indentité de l'asparagine avec l'agédoïte|journal=Journal de Pharmacie et des Sciences Accessoires|date=1828|volume=14|issue=4|pages=177–182|url=https://books.google.com/books?id=ELgal5J1G5AC&pg=PA177|trans-title=On the identity of asparagine with agédoïte|language=fr}}{{Cite book|chapter-url=http://www.henriettes-herb.com/eclectic/kings/glycyrrhiza.html|chapter=Glycyrrhiza (U. S. P.)—Glycyrrhiza|title=King's American Dispensatory|year=1898|first1=Harvey Wickes|last1=Felter|first2=John Uri|last2=Lloyd|name-list-style=vanc|publisher=Henriette's Herbal Homepage|archive-date=2015-09-24|access-date=2014-12-25|archive-url=https://web.archive.org/web/20150924025756/http://www.henriettes-herb.com/eclectic/kings/glycyrrhiza.html|url-status=live}}

The determination of asparagine's structure required decades of research. The empirical formula for asparagine was first determined in 1833 by the French chemists Antoine François Boutron Charlard and Théophile-Jules Pelouze; in the same year, the German chemist Justus Liebig provided a more accurate formula.{{cite journal |last1=Boutron-Charlard |last2=Pelouze |title=Ueber das Asparamid (Asparagin des Herrn Robiquet) und die Asparamidsäure |journal=Annalen der Chemie |date=1833 |volume=6 |pages=75–88 |url=https://babel.hathitrust.org/cgi/pt?id=uva.x002457885;view=1up;seq=467 |trans-title=On asparamide (the asparagine of Mr. Robiquet) and aspartic acid |language=de |doi=10.1002/jlac.18330060111 |archive-date=2022-10-02 |access-date=2018-06-10 |archive-url=https://web.archive.org/web/20221002170459/https://babel.hathitrust.org/cgi/pt?id=uva.x002457885;view=1up;seq=467 |url-status=live }} The empirical formula of asparagine appears on p. 80.{{cite journal |last1=Liebig |first1=Justus |name-list-style=vanc |title=Ueber die Zusammensetzung des Asparamids und der Asparaginsäure |journal=Annalen der Chemie |date=1833 |volume=7 |issue=14 |pages=146–150 |url=https://babel.hathitrust.org/cgi/pt?id=uva.x002457886;view=1up;seq=156 |trans-title=On the composition of asparamide [asparagine] and aspartic acid |language=de |bibcode=1834AnP...107..220L |doi=10.1002/andp.18341071405 |archive-date=2022-10-02 |access-date=2018-06-10 |archive-url=https://web.archive.org/web/20221002134806/https://babel.hathitrust.org/cgi/pt?id=uva.x002457886;view=1up;seq=156 |url-status=live |url-access=subscription }} The empirical formula appears on p. 149 ; the formula is correct if the subscripts are divided by 2. In 1846 the Italian chemist Raffaele Piria treated asparagine with nitrous acid, which removed the molecule's amine (–NH₂) groups and transformed asparagine into malic acid.See:

• {{cite journal |last1=Piria |first1=Raffaele |s2cid=177614807 |name-list-style=vanc |title=Studi sulla costituzione chimica dell' asparagina e dell' acido aspartico |journal=Il Cimento |date=January 1846 |volume=4 |pages=55–73 |url=https://books.google.com/books?id=5ptZAAAAYAAJ&pg=PA55 |trans-title=Studies of the chemical constitution of asparagine and aspartic acid |language=it |doi=10.1007/BF02532918 }}
• French translation: {{cite journal |last1=Piria |first1=Raffaele |name-list-style=vanc |title=Recherches sur la constitution chimique de l'asparagine et de l'acide aspartique |journal=Annales de Chimie et de Physique |date=1848 |volume=22 |pages=160–179 |url=https://babel.hathitrust.org/cgi/pt?id=hvd.hx3dy1;view=1up;seq=164 |series=3rd series |trans-title=Investigations into the chemical constitution of asparagine and of aspartic acid |language=fr |archive-date=2023-04-05 |access-date=2018-06-10 |archive-url=https://web.archive.org/web/20230405235216/https://babel.hathitrust.org/cgi/pt?id=hvd.hx3dy1;view=1up;seq=164 |url-status=live }} From p. 175: " ... on voit, en outre, que l'asparagine et l'acide aspartique lui-même se décomposent avec une facilité remarquable, sous l'influence de l'acide hyponitrique, en fournissant du gaz azote et de l'acide malique." ( ... one sees, in addition, that asparagine and aspartic acid itself are decomposed with a remarkable ease under the influence of nitrous acid, rendering nitrogen gas and malic acid.) This revealed the molecule's fundamental structure: a chain of four carbon atoms. Piria thought that asparagine was a diamide of malic acid;{{cite book |last1=Plimmer |first1=Robert Henry Aders | name-list-style = vanc |title=The Chemical Constitution of the Proteins. Part I: Analysis |date=1912 |publisher=Longmans, Green and Co. |location=London, England |page=112 |edition=2nd |url=https://books.google.com/books?id=EaAhAQAAMAAJ&pg=PA112}} however, in 1862 the German chemist Hermann Kolbe showed that this surmise was wrong; instead, Kolbe concluded that asparagine was an amide of an amine of succinic acid.{{cite journal |last1=Kolbe |first1=Hermann |name-list-style=vanc |title=Ueber die chemische Constitution des Asparagins und der Asparaginsäure |journal=Annalen der Chemie |date=1862 |volume=121 |issue=2 |pages=232–236 |url=https://babel.hathitrust.org/cgi/pt?id=uva.x002457960;view=1up;seq=244 |trans-title=On the chemical constitution of asparagine and aspartic acid |language=de |doi=10.1002/jlac.18621210209 |archive-date=2022-10-02 |access-date=2018-06-10 |archive-url=https://web.archive.org/web/20221002170504/https://babel.hathitrust.org/cgi/pt?id=uva.x002457960;view=1up;seq=244 |url-status=live }} In 1886, the Italian chemist Arnaldo Piutti (1857–1928) discovered a mirror image or "enantiomer" of the natural form of asparagine, which shared many of asparagine's properties, but which also differed from it.{{cite journal |vauthors=Piutti A |title=Ein neues Asparagin |journal=Berichte der Deutschen Chemischen Gesellschaft |date=1886 |volume=19 |issue=2 |pages=1691–1695 |url=https://babel.hathitrust.org/cgi/pt?id=osu.32435060218146;view=1up;seq=903 |trans-title=A new asparagine |language=de |doi=10.1002/cber.18860190211 |archive-date=2021-03-22 |access-date=2018-06-10 |archive-url=https://web.archive.org/web/20210322222731/https://babel.hathitrust.org/cgi/pt?id=osu.32435060218146;view=1up;seq=903 |url-status=live }} Since the structure of asparagine was still not fully known – the location of the amine group within the molecule was still not settledThe French chemist Edouard Grimaux thought that the amine group (–NH₂) was located next to the amide group (–C(O)NH₂), whereas the Italian chemist Icilio Guareschi thought that the amine group was located next to the carboxyl group (–COOH).
• {{cite journal |last1=Grimaux |first1=Edouard |name-list-style=vanc |title=Recherches synthétiques sur le groupe urique |journal=Bulletin de la Société Chimique de Paris |date=1875 |volume=24 |pages=337–355 |url=https://babel.hathitrust.org/cgi/pt?id=hvd.hc1j15;view=1up;seq=345 |series=2nd series |trans-title=Synthetic investigations of the uric group |language=fr |archive-date=2021-03-22 |access-date=2018-06-10 |archive-url=https://web.archive.org/web/20210322023926/https://babel.hathitrust.org/cgi/pt?id=hvd.hc1j15;view=1up;seq=345 |url-status=live }} On p. 352, Grimaux presented two putative structures for asparagine, and on p. 353, he favored structure (I.), which is incorrect. From p. 353: " ... ce sont les formules marquées du chiffre I qui me semblent devoir être adoptées pour l'asparagine, ... " ( ... it is the formulas marked by the figure I which, it seems to me, should be adopted for asparagine, ... )
• {{cite journal |last1=Guareschi |first1=Icilio |name-list-style=vanc |title=Studi sull' asparagine e sull' acido aspartico |journal=Atti della Reale Academia del Lincei |date=1876 |volume=3 (pt. 2) |pages=378–393 |url=https://babel.hathitrust.org/cgi/pt?id=mdp.39015080328845;view=1up;seq=406 |series=2nd series |trans-title=Studies of asparagine and of aspartic acid |language=it |archive-date=2021-03-22 |access-date=2018-06-10 |archive-url=https://web.archive.org/web/20210322183322/https://babel.hathitrust.org/cgi/pt?id=mdp.39015080328845;view=1up;seq=406 |url-status=live }} On p. 388, Guareschi proposed two structures (α and β) for asparagine; he favored α, the correct one. From p. 388: "La formola α mi sembra preferibile per seguente ragione: ... " (The formula α seems preferable to me for the following reason: ... )
• English abstract in: {{cite journal |vauthors=Guareschi J |title=Asparagine and aspartic acid |journal=Journal of the Chemical Society |date=1877 |volume=31 |pages=457–459 |url=https://babel.hathitrust.org/cgi/pt?id=chi.47400175;view=1up;seq=473 }} See especially p. 458. – Piutti synthesized asparagine and thus published its true structure in 1888.{{cite journal |vauthors=Piutti A |title=Sintesi e costituzione delle asparagine |journal=Gazzetta Chimica Italiana |date=1888 |volume=18 |pages=457–472 |url=https://babel.hathitrust.org/cgi/pt?id=mdp.39015036973934;view=1up;seq=495 |trans-title=Synthesis and constitution of asparagine |language=it |archive-date=2021-03-22 |access-date=2018-06-10 |archive-url=https://web.archive.org/web/20210322090253/https://babel.hathitrust.org/cgi/pt?id=mdp.39015036973934;view=1up;seq=495 |url-status=live }}

Since the asparagine side-chain can form hydrogen bond interactions with the peptide backbone, asparagine residues are often found near the beginning of alpha-helices as asx turns and asx motifs, and in similar turn motifs, or as amide rings, in beta sheets. Its role can be thought as "capping" the hydrogen bond interactions that would otherwise be satisfied by the polypeptide backbone.{{cn|date=March 2025}}

Asparagine also provides key sites for N-linked glycosylation, modification of the protein chain with the addition of carbohydrate chains. Typically, a carbohydrate tree can solely be added to an asparagine residue if the latter is flanked on the C side by X-serine or X-threonine, where X is any amino acid with the exception of proline.{{cite book |last1=Brooker |first1=Robert |last2=Widmaier |first2=Eric |last3=Graham |first3=Linda |last4=Stiling |first4=Peter |last5=Hasenkampf |first5=Clare |last6=Hunter |first6=Fiona |last7=Bidochka |first7=Michael |last8=Riggs |first8=Daniel | name-list-style = vanc |title=Biology|date=2010|publisher=McGraw-Hill Ryerson|location=United States of America|isbn=978-0-07-074175-1|pages=105–106|edition=Canadian|chapter=Chapter 5: Systems Biology of Cell Organization}}

Asparagine can be hydroxylated in the HIF1 hypoxia-inducible transcription factor. This modification inhibits HIF1-mediated gene activation.{{cite journal | vauthors = Lando D, Peet DJ, Gorman JJ, Whelan DA, Whitelaw ML, Bruick RK | title = FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor | journal = Genes & Development | volume = 16 | issue = 12 | pages = 1466–71 | date = June 2002 | pmid = 12080085 | pmc = 186346 | doi = 10.1101/gad.991402 }}

Asparagine is not essential for humans, which means that it can be synthesized from central metabolic pathway intermediates and is not required in the diet.{{cn|date=March 2025}}

Asparagine is found in:

• Animal sources: dairy, whey, beef, poultry, eggs, fish, lactalbumin, seafood{{cn|date=March 2025}}
• Plant sources: seaweed (spirulina), potatoes, soy protein isolate, tofu{{cn|date=April 2024}}

The precursor to asparagine is oxaloacetate, which a transaminase enzyme converts to aspartate. The enzyme transfers the amino group from glutamate to oxaloacetate producing α-ketoglutarate and aspartate. The enzyme asparagine synthetase produces asparagine, AMP, glutamate, and pyrophosphate from aspartate, glutamine, and ATP. Asparagine synthetase uses ATP to activate aspartate, forming β-aspartyl-AMP. Glutamine donates an ammonium group, which reacts with β-aspartyl-AMP to form asparagine and free AMP.

Image:Asn biosynthesis.svg

In reaction that is the reverse of its biosynthesis, asparagine is hydrolyzed to aspartate by asparaginase. Aspartate then undergoes transamination to form glutamate and oxaloacetate from alpha-ketoglutarate. Oxaloacetate, which enters the citric acid cycle (Krebs cycle).{{cite book |last1=Berg |first1=Jeremy |last2=Tymoczko |first2=John |last3=Stryer |first3=Lubert |title=Biochemistry |date=2002 |publisher=W. H. Freeman |location=New York |isbn=0716746840 |page=968 |edition=5th |url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=stryer.TOC |access-date=27 May 2021 |archive-date=14 March 2007 |archive-url=https://web.archive.org/web/20070314110156/http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=stryer.TOC |url-status=live }}

Heating a mixture of asparagine and reducing sugars or other source of carbonyls produces acrylamide in food. These products occur in baked goods such as French fries, potato chips, and toasted bread. Acrylamide is converted in the liver to glycidamide, which is a possible carcinogen.{{cite journal |doi= 10.1021/jf030204+ |year= 2003 |volume= 51 |issue= 16 |last1= Friedman| first1=Mendel |title=Chemistry, Biochemistry, and Safety of Acrylamide. A Review|journal=Journal of Agricultural and Food Chemistry| pages=4504–4526 |pmid= 14705871}}

Asparagine synthetase is required for normal development of the brain.{{cite journal | vauthors = Ruzzo EK, Capo-Chichi JM, Ben-Zeev B, Chitayat D, Mao H, Pappas AL, Hitomi Y, Lu YF, Yao X, Hamdan FF, Pelak K, Reznik-Wolf H, Bar-Joseph I, Oz-Levi D, Lev D, Lerman-Sagie T, Leshinsky-Silver E, Anikster Y, Ben-Asher E, Olender T, Colleaux L, Décarie JC, Blaser S, Banwell B, Joshi RB, He XP, Patry L, Silver RJ, Dobrzeniecka S, Islam MS, Hasnat A, Samuels ME, Aryal DK, Rodriguiz RM, Jiang YH, Wetsel WC, McNamara JO, Rouleau GA, Silver DL, Lancet D, Pras E, Mitchell GA, Michaud JL, Goldstein DB | display-authors = 6 | title = Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy | journal = Neuron | volume = 80 | issue = 2 | pages = 429–41 | date = October 2013 | pmid = 24139043 | pmc = 3820368 | doi = 10.1016/j.neuron.2013.08.013 }} Asparagine is also involved in protein synthesis during replication of poxviruses.{{cite journal | vauthors = Pant A, Cao S, Yang Z | title = Asparagine Is a Critical Limiting Metabolite for Vaccinia Virus Protein Synthesis during Glutamine Deprivation | journal = Journal of Virology | volume = 93 | issue = 13 | pages = e01834–18, /jvi/93/13/JVI.01834–18.atom | date = July 2019 | pmid = 30996100 | pmc = 6580962 | doi = 10.1128/JVI.01834-18 | veditors = Shisler JL }}

The addition of N-acetylglucosamine to asparagine is performed by oligosaccharyltransferase enzymes in the endoplasmic reticulum.{{cite journal | vauthors = Burda P, Aebi M | title = The dolichol pathway of N-linked glycosylation | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1426 | issue = 2 | pages = 239–57 | date = January 1999 | pmid = 9878760 | doi = 10.1016/S0304-4165(98)00127-5 }} This glycosylation is involved in protein structure{{cite journal | vauthors = Imperiali B, O'Connor SE | title = Effect of N-linked glycosylation on glycopeptide and glycoprotein structure | journal = Current Opinion in Chemical Biology | volume = 3 | issue = 6 | pages = 643–9 | date = December 1999 | pmid = 10600722 | doi = 10.1016/S1367-5931(99)00021-6 }} and function.{{cite journal | vauthors = Patterson MC | title = Metabolic mimics: the disorders of N-linked glycosylation | journal = Seminars in Pediatric Neurology | volume = 12 | issue = 3 | pages = 144–51 | date = September 2005 | pmid = 16584073 | doi = 10.1016/j.spen.2005.10.002 }}

• Potassium asparaginate

{{Reflist}}

• [http://gmd.mpimp-golm.mpg.de/Spectrums/4811C88D-ACE8-467A-AFC8-09B7089DEF2C.aspx GMD MS Spectrum]

{{Amino acids}}

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Category:Proteinogenic amino acids

Category:Glucogenic amino acids

Category:Carboxamides

Category:Alpha-Amino acids