Asparagine (symbolAsn orN[2]) is an α-amino acid that isused in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH+ 3 form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO− form under biological conditions), and a side chaincarboxamide, classifying it as a polar (at physiological pH),aliphatic amino acid. It is non-essential in humans, meaning the body can synthesize it. It isencoded by thecodons AAU and AAC.
The one-letter symbol N for asparagine was assigned arbitrarily,[3] with the proposed mnemonic asparagiNe;[4]
Asparagine was first isolated in 1806 in a crystalline form by French chemistsLouis Nicolas Vauquelin andPierre Jean Robiquet (then a young assistant). It was isolated fromasparagus juice,[5][6] in which it is abundant, hence the chosen name. It was the first amino acid to be isolated.[7]
Three years later, in 1809, Pierre Jean Robiquet identified a substance fromliquorice root with properties which he qualified as very similar to those of asparagine,[8] and whichPlisson identified in 1828 as asparagine itself.[9][10]
The determination of asparagine's structure required decades of research. Theempirical formula for asparagine was first determined in 1833 by the French chemists Antoine François Boutron Charlard andThéophile-Jules Pelouze; in the same year, the German chemistJustus Liebig provided a more accurate formula.[11][12] In 1846 the Italian chemistRaffaele Piria treated asparagine withnitrous acid, which removed the molecule'samine (–NH2) groups and transformed asparagine intomalic acid.[13] This revealed the molecule's fundamental structure: a chain of four carbon atoms. Piria thought that asparagine was a diamide of malic acid;[14] however, in 1862 the German chemistHermann Kolbe showed that this surmise was wrong; instead, Kolbe concluded that asparagine was anamide of an amine ofsuccinic acid.[15] 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.[16] Since the structure of asparagine was still not fully known – the location of the amine group within the molecule was still not settled[17] – Piutti synthesized asparagine and thus published its true structure in 1888.[18]
Since the asparagine side-chain can form hydrogen bond interactions with the peptide backbone, asparagine residues are often found near the beginning ofalpha-helices asasx turns andasx motifs, and in similar turn motifs, or asamide rings, inbeta sheets. Its role can be thought as "capping" the hydrogen bond interactions that would otherwise be satisfied by the polypeptide backbone.[citation needed]
Asparagine also provides key sites forN-linked glycosylation, modification of the protein chain with the addition ofcarbohydrate 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 ofproline.[19]
Asparagine is notessential for humans, which means that it can be synthesized from central metabolic pathway intermediates and is not required in the diet.[citation needed]
The precursor to asparagine isoxaloacetate, which atransaminase enzyme converts toaspartate. The enzyme transfers the amino group fromglutamate to oxaloacetate producingα-ketoglutarate and aspartate. The enzymeasparagine synthetase produces asparagine,AMP, glutamate, andpyrophosphate from aspartate,glutamine, andATP. 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.[21]
The biosynthesis of asparagine from oxaloacetate
In reaction that is the reverse of its biosynthesis, asparagine is hydrolyzed to aspartate byasparaginase. Aspartate then undergoes transamination to form glutamate and oxaloacetate from alpha-ketoglutarate. Oxaloacetate, which enters thecitric acid cycle (Krebs cycle).[21]
Heating a mixture of asparagine andreducing sugars or other source ofcarbonyls producesacrylamide in food. These products occur in baked goods such as French fries, potato chips, and toasted bread. Acrylamide is converted in the liver toglycidamide, which is a possible carcinogen.[22]
Asparagine synthetase is required for normal development of the brain.[23] Asparagine is also involved inprotein synthesis during replication ofpoxviruses.[24]
^Vauquelin LN, Robiquet PJ (1806). "La découverte d'un nouveau principe végétal dans le suc des asperges".Annales de Chimie (in French).57:88–93.hdl:2027/nyp.33433062722578.
^Plimmer RH (1912) [1908]. Plimmer RH, Hopkins FG (eds.).The chemical composition of the proteins. Monographs on biochemistry. Vol. Part I. Analysis (2nd ed.). London: Longmans, Green and Co. p. 112. RetrievedJanuary 18, 2010.
^Felter HW, Lloyd JU (1898)."Glycyrrhiza (U. S. P.)—Glycyrrhiza".King's American Dispensatory. Henriette's Herbal Homepage.Archived from the original on 2015-09-24. Retrieved2014-12-25.
French translation:Piria R (1848)."Recherches sur la constitution chimique de l'asparagine et de l'acide aspartique" [Investigations into the chemical constitution of asparagine and of aspartic acid].Annales de Chimie et de Physique. 3rd series (in French).22:160–179.Archived from the original on 2023-04-05. Retrieved2018-06-10. 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.)
^The 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).
Grimaux E (1875)."Recherches synthétiques sur le groupe urique" [Synthetic investigations of the uric group].Bulletin de la Société Chimique de Paris. 2nd series (in French).24:337–355.Archived from the original on 2021-03-22. Retrieved2018-06-10. 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, ... )
Guareschi I (1876)."Studi sull' asparagine e sull' acido aspartico" [Studies of asparagine and of aspartic acid].Atti della Reale Academia del Lincei. 2nd series (in Italian). 3 (pt. 2):378–393.Archived from the original on 2021-03-22. Retrieved2018-06-10. 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:Guareschi J (1877)."Asparagine and aspartic acid".Journal of the Chemical Society.31:457–459. See especially p. 458.
^Piutti A (1888)."Sintesi e costituzione delle asparagine" [Synthesis and constitution of asparagine].Gazzetta Chimica Italiana (in Italian).18:457–472.Archived from the original on 2021-03-22. Retrieved2018-06-10.
^Brooker R, Widmaier E, Graham L, Stiling P, Hasenkampf C, Hunter F, Bidochka M, Riggs D (2010). "Chapter 5: Systems Biology of Cell Organization".Biology (Canadian ed.). United States of America: McGraw-Hill Ryerson. pp. 105–106.ISBN978-0-07-074175-1.
^abBerg, Jeremy; Tymoczko, John; Stryer, Lubert (2002).Biochemistry (5th ed.). New York: W. H. Freeman. p. 968.ISBN0716746840.Archived from the original on 14 March 2007. Retrieved27 May 2021.
^Friedman, Mendel (2003). "Chemistry, Biochemistry, and Safety of Acrylamide. A Review".Journal of Agricultural and Food Chemistry.51 (16):4504–4526.doi:10.1021/jf030204+.PMID14705871.
^Burda P, Aebi M (January 1999). "The dolichol pathway of N-linked glycosylation".Biochimica et Biophysica Acta (BBA) - General Subjects.1426 (2):239–57.doi:10.1016/S0304-4165(98)00127-5.PMID9878760.
^Imperiali B, O'Connor SE (December 1999). "Effect of N-linked glycosylation on glycopeptide and glycoprotein structure".Current Opinion in Chemical Biology.3 (6):643–9.doi:10.1016/S1367-5931(99)00021-6.PMID10600722.
^Patterson MC (September 2005). "Metabolic mimics: the disorders of N-linked glycosylation".Seminars in Pediatric Neurology.12 (3):144–51.doi:10.1016/j.spen.2005.10.002.PMID16584073.
