Asparagine

l-Asparagine
Skeletal formula of L-asparagine
Skeletal formula of L-asparagine
Ball-and-stick model of the L-asparagine molecule as a zwitterion
Ball-and-stick model
Space-filling model
Names
IUPAC name
Asparagine
Other names
2-Amino-3-carbamoylpropanoic acid
Identifiers
CAS Number
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.019.565 Edit this at Wikidata
EC Number
  • 200-735-9
KEGG
PubChem CID
UNII
InChI
  • InChI=1S/C4H8N2O3/c5-2(4(8)9)1-3(6)7/h2H,1,5H2,(H2,6,7)(H,8,9)/t2-/m0/s1 checkY
    Key: DCXYFEDJOCDNAF-REOHCLBHSA-N checkY
  • InChI=1/C4H8N2O3/c5-2(4(8)9)1-3(6)7/h2H,1,5H2,(H2,6,7)(H,8,9)/t2-/m0/s1
    Key: DCXYFEDJOCDNAF-REOHCLBHBD
SMILES
  • O=C(N)C[C@H](N)C(=O)O
  • Zwitterion: O=C(N)C[C@H]([NH3+])C(=O)[O-]
  • C([C@@H](C(=O)O)N)C(=O)N
  • Zwitterion: C([C@@H](C(=O)[O-])[NH3+])C(=O)N
Properties
Chemical formula
 C4H8N2O3
Molar mass 132.119 g·mol−1
Appearance white crystals
Density 1.543 g/cm3
Melting point 234 °C (453 °F; 507 K)
Boiling point 438 °C (820 °F; 711 K)
Solubility in water
 2.94 g/100 mL
Solubility soluble in acids, bases, negligible in methanol, ethanol, ether, benzene
log P −3.82
Acidity (pKa)
  • 2.1 (carboxyl; 20 °C, H2O)
  • 8.80 (amino; 20 °C, H2O)[1]
Magnetic susceptibility (χ)
 -69.5·10−6 cm3/mol
Structure
Crystal structure
 orthorhombic
Thermochemistry
Std enthalpy of
formation (ΔfH⦵298)
 −789.4 kJ/mol
Hazards
NFPA 704 (fire diamond)
1
0
0
Flash point 219 °C (426 °F; 492 K)
Safety data sheet (SDS) Sigma-Alrich
Supplementary data page
Asparagine (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)
Infobox references

Asparagine (symbol Asn or N[2]), 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.

History

Asparagine was first isolated in 1806 in a crystalline form by French chemists Louis Nicolas Vauquelin and Pierre Jean Robiquet (then a young assistant) from asparagus juice,[3][4] in which it is abundant, hence the chosen name. It was the first amino acid to be isolated.[5]

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,[6] and which Plisson identified in 1828 as asparagine itself.[7][8]

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.[9][10] 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.[11] This revealed the molecule's fundamental structure: a chain of four carbon atoms. Piria thought that asparagine was a diamide of malic acid;[12] 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.[13] 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.[14] Since the structure of asparagine was still not fully known – the location of the amine group within the molecule was still not settled[15] – Piutti synthesized asparagine and thus published its true structure in 1888.[16]

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.[17]

Asparagine can be hydroxylated in the HIF1 hypoxia inducible transcription factor. This modification inhibits HIF1-mediated gene activation.[18]

Sources

Dietary sources

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 is found in:

  • Animal sources: dairy, whey, beef, poultry, eggs, fish, lactalbumin, seafood
  • Plant sources: asparagus, potatoes, legumes, nuts, seeds, soy, whole grains

Biosynthesis

The precursor to asparagine is oxaloacetate. Oxaloacetate is converted to aspartate using a transaminase enzyme. 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. In the asparagine synthetase reaction, ATP is used to activate aspartate, forming β-aspartyl-AMP. Glutamine donates an ammonium group, which reacts with β-aspartyl-AMP to form asparagine and free AMP.

The biosynthesis of asparagine from oxaloacetate

Degradation

Asparagine usually enters the citric acid cycle in humans as oxaloacetate.[19] 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.

Function

Asparagine is required for development and function of the brain.[20] The availability of asparagine is also important for protein synthesis during replication of poxviruses.[21]

The addition of N-acetylglucosamine to asparagine is performed by oligosaccharyltransferase enzymes in the endoplasmic reticulum.[22] This glycosylation is important both for protein structure[23] and protein function.[24]

Zwitterion structure

(S)-Asparagine (left) and (R)-asparagine (right) in zwitterionic form at neutral pH.

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.[25][26] The article noted that similar studies had not been conducted in humans.

References

  1. ↑ Haynes WM, ed. (2016). CRC Handbook of Chemistry and Physics (97th ed.). CRC Press. pp. 5–89. ISBN 978-1498754286.
  2. ↑ "Nomenclature and Symbolism for Amino Acids and Peptides". IUPAC-IUB Joint Commission on Biochemical Nomenclature. 1983. Archived from the original on 9 October 2008. Retrieved 5 March 2018.
  3. ↑ 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.
  4. ↑ 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. Retrieved January 18, 2010.
  5. ↑ Anfinsen CB, Edsall JT, Richards FM (1972). Advances in Protein Chemistry. New York: Academic Press. pp. 99, 103. ISBN 978-0-12-034226-6.
  6. ↑ Robiquet PJ (1809). "Analyse de la racine de réglisse" [Analysis of licorice root]. Annales de Chimie et de Physique (in French). 72 (1): 143–159.
  7. ↑ Plisson A (1828). "De l'indentité de l'asparagine avec l'agédoïte" [On the identity of asparagine with agédoïte]. Journal de Pharmacie et des Sciences Accessoires (in French). 14 (4): 177–182.
  8. ↑ Felter HW, Lloyd JU (1898). "Glycyrrhiza (U. S. P.)—Glycyrrhiza". King's American Dispensatory. Henriette's Herbal Homepage.
  9. ↑ Boutron-Charlard; Pelouze (1833). "Ueber das Asparamid (Asparagin des Herrn Robiquet) und die Asparamidsäure" [On asparamide (the asparagine of Mr. Robiquet) and aspartic acid]. Annalen der Chemie (in German). 6: 75–88. doi:10.1002/jlac.18330060111. The empirical formula of asparagine appears on p. 80.
  10. ↑ Liebig J (1833). "Ueber die Zusammensetzung des Asparamids und der Asparaginsäure" [On the composition of asparamide [asparagine] and aspartic acid]. Annalen der Chemie (in German). 7 (14): 146–150. Bibcode:1834AnP...107..220L. doi:10.1002/andp.18341071405. The empirical formula appears on p. 149 ; the formula is correct if the subscripts are divided by 2.
  11. ↑ See:
    • Piria R (January 1846). "Studi sulla costituzione chimica dell' asparagina e dell' acido aspartico" [Studies of the chemical constitution of asparagine and aspartic acid]. Il Cimento (in Italian). 4: 55–73. doi:10.1007/BF02532918. S2CID 177614807.
    • 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. 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.)
  12. ↑ Plimmer RH (1912). The Chemical Constitution of the Proteins. Part I: Analysis (2nd ed.). London, England: Longmans, Green and Co. p. 112.
  13. ↑ Kolbe H (1862). "Ueber die chemische Constitution des Asparagins und der Asparaginsäure" [On the chemical constitution of asparagine and aspartic acid]. Annalen der Chemie (in German). 121 (2): 232–236. doi:10.1002/jlac.18621210209.
  14. ↑ Piutti A (1886). "Ein neues Asparagin" [A new asparagine]. Berichte der Deutschen Chemischen Gesellschaft (in German). 19 (2): 1691–1695. doi:10.1002/cber.18860190211.
  15. ↑ 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. 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. 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.
  16. ↑ Piutti A (1888). "Sintesi e costituzione delle asparagine" [Synthesis and constitution of asparagine]. Gazzetta Chimica Italiana (in Italian). 18: 457–472.
  17. ↑ 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. ISBN 978-0-07-074175-1.
  18. ↑ Lando D, Peet DJ, Gorman JJ, Whelan DA, Whitelaw ML, Bruick RK (June 2002). "FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor". Genes & Development. 16 (12): 1466–71. doi:10.1101/gad.991402. PMC 186346. PMID 12080085.
  19. ↑ Berg, Jeremy; Tymoczko, John; Stryer, Lubert (2002). Biochemistry (5th ed.). New York: W. H. Freeman. p. 968. ISBN 0716746840. Retrieved 27 May 2021.
  20. ↑ Ruzzo EK, Capo-Chichi JM, Ben-Zeev B, Chitayat D, Mao H, Pappas AL, et al. (October 2013). "Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy". Neuron. 80 (2): 429–41. doi:10.1016/j.neuron.2013.08.013. PMC 3820368. PMID 24139043.
  21. ↑ Pant A, Cao S, Yang Z (July 2019). Shisler JL (ed.). "Asparagine Is a Critical Limiting Metabolite for Vaccinia Virus Protein Synthesis during Glutamine Deprivation". Journal of Virology. 93 (13): e01834–18, /jvi/93/13/JVI.01834–18.atom. doi:10.1128/JVI.01834-18. PMC 6580962. PMID 30996100.
  22. ↑ 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. PMID 9878760.
  23. ↑ 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. PMID 10600722.
  24. ↑ 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. PMID 16584073.
  25. ↑ Sample I (2018-02-07). "Spread of breast cancer linked to compound in asparagus and other foods". The Guardian. Retrieved 2018-05-30.
  26. ↑ Knott SR, Wagenblast E, Khan S, Kim SY, Soto M, Wagner M, et al. (February 2018). "Asparagine bioavailability governs metastasis in a model of breast cancer". Nature. 554 (7692): 378–381. Bibcode:2018Natur.554..378K. doi:10.1038/nature25465. PMC 5898613. PMID 29414946.
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