Editing Asparagine (section)

==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). It was isolated from [[asparagus]] juice,<ref>{{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 }}</ref><ref>{{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}}</ref> in which it is abundant, hence the chosen name.  It was the first amino acid to be isolated.<ref name=Anfinsen>{{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 }}</ref>

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,<ref>{{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}}</ref> and which [[Auguste-Arthur Plisson|Plisson]] identified in 1828 as asparagine itself.<ref>{{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}}</ref><ref>{{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}}</ref>

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 von Liebig|Justus Liebig]] provided a more accurate formula.<ref>{{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.</ref><ref>{{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 }}  The empirical formula appears on p. 149 ; the formula is correct if the subscripts are divided by 2.</ref>  In 1846 the Italian chemist [[Raffaele Piria]] treated asparagine with [[nitrous acid]], which removed the molecule's [[amine]] (–NH<sub>2</sub>) groups and transformed asparagine into [[malic acid]].<ref>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.)</ref>  This revealed the molecule's fundamental structure:  a chain of four carbon atoms.  Piria thought that asparagine was a diamide of malic acid;<ref>{{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}}</ref> 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]].<ref>{{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 }}</ref>  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.<ref>{{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 }}</ref>  Since the structure of asparagine was still not fully known – the location of the amine group within the molecule was still not settled<ref>The French chemist Edouard Grimaux thought that the amine group (–NH<sub>2</sub>) was located next to the amide group (–C(O)NH<sub>2</sub>), 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.</ref> – Piutti synthesized asparagine and thus published its true structure in 1888.<ref>{{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 }}</ref>