Asparagine (symbol Asn or N), is an α-amino acid that is used 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 chain carboxamide, classifying it as a polar (at physiological pH), aliphatic amino acid. It is non-essential in humans, meaning the body can synthesize it. It is encoded by the codons AAU and AAC.
A reaction between asparagine and reducing sugars or other source of carbonyls produces acrylamide in food when heated to sufficient temperature. These products occur in baked goods such as French fries, potato chips, and toasted bread.
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, and which Plisson identified in 1828 as asparagine itself.
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. 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. This revealed the molecule's fundamental structure: a chain of four carbon atoms. Piria thought that asparagine was a diamide of malic acid; 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. 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. Since the structure of asparagine was still not fully known – the location of the amine group within the molecule was still not settled – Piutti synthesized asparagine and thus determined its true structure.
Structural function in proteins
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.
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.
Asparagine can be hydroxylated in the HIF1 hypoxia inducible transcription factor. This modification inhibits HIF1-mediated gene activation.
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.
Asparagine usually enters the citric acid cycle in humans as oxaloacetate. In bacteria, the degradation of asparagine leads to the production of oxaloacetate which is the molecule which combines with citrate in the citric acid cycle (Krebs cycle). Asparagine is hydrolyzed to aspartate by asparaginase. Aspartate then undergoes transamination to form glutamate and oxaloacetate from alpha-ketoglutarate.
Asparagine is required for development and function of the brain. It also plays an important role in the synthesis of ammonia.
(S)-Asparagine (left) and (R)-asparagine (right) in zwitterionic form at neutral pH.
Alleged cancer link in laboratory mice
According to a 2018 article in The Guardian, a study found that decreasing levels of asparagine "dramatically" reduced the spread of breast cancer in laboratory mice. The article noted that similar studies had not been conducted in humans.
^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.
^R.H.A. Plimmer (1912) . R.H.A. Plimmer; F.G. Hopkins, eds. The chemical composition of the proteins. Monographs on biochemistry. Part I. Analysis (2nd ed.). London: Longmans, Green and Co. p. 112. Retrieved January 18, 2010.
French translation: Piria, Raffaele (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. 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.)
^Piutti, A. (1886). "Ein neues Asparagin" [A new asparagine]. Berichte der Deutschen Chemischen Gesellschaft (in German). 19: 1691–1695.
^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, Edouard (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. 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, Icilio (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. 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: … )
^Burda, Patricie; Aebi, Markus (1999). "The dolichol pathway of N-linked glycosylation". Biochimica et Biophysica Acta (BBA) - General Subjects. 1426 (2): 239–257. doi:10.1016/S0304-4165(98)00127-5.
^Imperiali, Barbara; o’Connor, Sarah E (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.