{{Short description|Chemical conversion reaction}} '''Carboxylation''' is a chemical reaction in which a carboxylic acid is produced by treating a substrate with carbon dioxide.<ref>"Carboxylation: The introduction of a carboxyl group into a molecule or compound to form a carboxylic acid or a carboxylate; an instance of this."{{cite book|title=Oxford English Dictionary|publisher=Oxford University Press|year=2018|url=http://www.oed.com}}</ref> The opposite reaction is decarboxylation. In chemistry, the term carbonation is sometimes used synonymously with carboxylation, especially when applied to the reaction of carbanionic reagents with CO<sub>2</sub>. More generally, carbonation usually describes the production of carbonates.<ref>"Carbonation: Impregnation or treatment with carbon dioxide; conversion into a carbonate."{{ cite book|title=Oxford English Dictionary|publisher=Oxford University Press|year=2018|url=http://www.oed.com}}</ref>
==Organic chemistry== Carboxylation is a standard conversion in organic chemistry.<ref>{{cite journal|last1=Braunstein|first1=Pierre|last2=Matt|first2=Dominique|last3=Nobel|first3=Dominique|title=Reactions of Carbon Dioxide with Carbon-Carbon Bond Formation Catalyzed by Transition-Metal Complexes|journal=Chemical Reviews|date=August 1988|volume=88|issue=5|pages=747–764|doi=10.1021/cr00087a003}}</ref> Specifically carbonation (i.e., carboxylation) of Grignard reagents, organolithium, and related carbanionic reagents is a classic way to convert organic halides into carboxylic acids.<ref>{{cite journal|author=A. M. Appel |display-authors=et al|title=Frontiers, Opportunities, and Challenges in Biochemical and Chemical Catalysis of CO<sub>2</sub> Fixation|journal=Chem. Rev.|year=2013|volume=113|issue=8|pages=6621–6658|doi=10.1021/cr300463y|pmid=23767781|pmc=3895110}}</ref> This approach give carboxylate salts. Typically, these salts are converted to the carboxylic acid.<ref>{{cite journal |author=Henry Gilman R. H. Kirby|title=''dl''-Methylethylacetic Acid |journal=Organic Syntheses |date=1925 |volume=5 |page=75 |doi=10.15227/orgsyn.005.0075}}</ref><ref>{{cite journal |author=S. V. Puntambeker, E. A. Zoellner, L. T. Sandborn, E. W. Bousquet |title=Trimethylacetic Acid |journal=Organic Syntheses |date=1928 |volume=8 |page=104 |doi=10.15227/orgsyn.008.0104}}</ref><ref>{{cite journal| title=Regio- and Stereoselective Carboxylation of Allylic Barium Reagents: (E)-4,8-Dimethyl-3,7-Nonadienoic Acid |author=Akira Yanagisawa |author2=Katsutaka Yasue |author3=Hisashi Yamamoto|journal=Organic Syntheses |volume=74|pages=178|year=1997|doi=10.15227/orgsyn.074.0178}}</ref>
Sodium salicylate, precursor to aspirin, is commercially produced by treating sodium phenolate (the sodium salt of phenol) with carbon dioxide at high pressure (100 atm) and high temperature (390 K). Acidification of the resulting salicylate salt gives salicylic acid. :400px|class=skin-invert The method, known as the Kolbe-Schmitt reaction, entails nucleophilic attack of the phenoxide on carbon dioxide.
In some cases, alkenes undergo hydrocarboxylation using a mixture of carbon dioxide and {{chem2|H2}}:<ref>{{cite journal |doi=10.1038/s41467-022-35293-3 |title=Catalytic direct hydrocarboxylation of styrenes with CO2 and H2 |date=2022 |last1=Jin |first1=Yushu |last2=Caner |first2=Joaquim |last3=Nishikawa |first3=Shintaro |last4=Toriumi |first4=Naoyuki |last5=Iwasawa |first5=Nobuharu |journal=Nature Communications |volume=13 |issue=1 |article-number=7584 |pmid=36481654 |pmc=9732006 }}</ref> :{{chem2|RCH\dCH2 + H2 + CO2 -> RCH2\sCH2CO2H}}
Other methods, e.g. the Koch reaction, effect "net" carboxylation involve the use of carbon monoxide, either directly or generated in situ. These methods are variants of carbonylation reactions.
Carboxylation of epoxides gives cyclic carbonates. Such reactions are catalyzed by N-Heterocyclic carbenes<ref>{{cite journal | doi = 10.1039/C3SC51070K | volume=4 | title=N-Heterocyclic carbene (NHC)–copper-catalysed transformations of carbon dioxide | year=2013 | journal=Chemical Science | page=3395 | author=Zhang Liang| issue=9 }}</ref> and catalysts based on silver.<ref>{{cite journal|title=Silver-catalyzed carboxylation|author=K. Sekine |author2=T. Yamada|journal=Chem. Soc. Rev.|volume=45 |issue=16 |pages=4524–4532 |year=2016|doi=10.1039/C5CS00895F|pmid=26888406 |doi-access=free}}</ref>
==Carboxylation in biochemistry== Food chains usually originate from carboxylation that couples carbon dioxide to a sugar. The process is usually catalysed by the enzyme RuBisCO. Ribulose-1,5-bisphosphate carboxylase/oxygenase, the enzyme that catalyzes this carboxylation, is possibly the single most abundant protein on Earth.<ref>{{cite journal |vauthors=Dhingra A, Portis AR, Daniell H | title = Enhanced translation of a chloroplast-expressed RbcS gene restores small subunit levels and photosynthesis in nuclear RbcS antisense plants | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 101 | issue = 16 | pages = 6315–20 |date=April 2004 | pmid = 15067115 | pmc = 395966 | doi = 10.1073/pnas.0400981101 | quote = (Rubisco) is the most prevalent enzyme on this planet, accounting for 30–50% of total soluble protein in the chloroplast; |bibcode = 2004PNAS..101.6315D | doi-access = free }}</ref><ref name="Feller_2008">{{cite journal |vauthors=Feller U, Anders I, Mae T | title = Rubiscolytics: fate of Rubisco after its enzymatic function in a cell is terminated | journal = J. Exp. Bot. | volume = 59 | issue = 7 | pages = 1615–24 | year = 2008 | pmid = 17975207 | doi = 10.1093/jxb/erm242| url = https://boris.unibe.ch/30426/1/2008_JExpBot_59_1615.pdf }}</ref><ref>{{cite journal |last1=Raven |first1=John A. |title=Rubisco: still the most abundant protein of Earth? |journal=New Phytologist |date=April 2013 |volume=198 |issue=1 |pages=1–3 |doi = 10.1111/nph.12197|pmid=23432200 |doi-access=free |bibcode=2013NewPh.198....1R }}</ref> [[File:Calvin Cycle 5.svg|left|thumb|400x400px|The Calvin cycle showing the carboxylation of ribulose-1,5-bisphosphate.]] 140px|thumb|right|Carboxyglutamic acid Many carboxylases, including acetyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, propionyl-CoA carboxylase, and pyruvate carboxylase require biotin as a cofactor. These enzymes are involved in various anabolic pathways.<ref name="ods">{{Cite web|url=https://ods.od.nih.gov/factsheets/Biotin-HealthProfessional/|title=Biotin – Fact Sheet for Health Professionals|date=8 December 2017|publisher=Office of Dietary Supplements, US National Institutes of Health|access-date=25 February 2018}}</ref> In the EC scheme, such carboxylases are mostly classed under EC 6.4.1, ligases “forming carbon-carbon bonds,” or sometimes EC 6.3.4, "Other Carbon—Nitrogen Ligases".
Another example is the posttranslational modification of glutamate residues, to γ-carboxyglutamate, in proteins. It occurs primarily in proteins involved in the blood clotting cascade, specifically factors II, VII, IX, and X, protein C, and protein S, and also in some bone proteins. This modification is required for these proteins to function. Carboxylation occurs in the liver and is performed by γ-glutamyl carboxylase (GGCX).<ref>OMIM - gamma-glutamyl carboxylase, contributed by McKusick VA, last updated October 2004 [https://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=137167]{{dead link|date=July 2025|bot=medic}}{{cbignore|bot=medic}}</ref> GGCX requires vitamin K as a cofactor and performs the reaction in a processive manner.<ref>{{cite journal |vauthors=Morris DP, Stevens RD, Wright DJ, Stafford DW |title=Processive post-translational modification. Vitamin K-dependent carboxylation of a peptide substrate |journal=J. Biol. Chem. |volume=270 |issue=51 |pages=30491–8 |year=1995 |pmid=8530480 |doi=10.1074/jbc.270.51.30491|doi-access=free }}</ref> γ-carboxyglutamate binds calcium, which is essential for its activity.<ref>{{cite journal |vauthors=Hauschka PV, Lian JB, Gallop PM |title=Direct identification of the calcium-binding amino acid, gamma-carboxyglutamate, in mineralized tissue |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=72 |issue=10 |pages=3925–9 |year=1975 |pmid=1060074 |doi=10.1073/pnas.72.10.3925 |pmc=433109|bibcode=1975PNAS...72.3925H |doi-access=free }}</ref> For example, in prothrombin, calcium binding allows the protein to associate with the plasma membrane in platelets, bringing it into close proximity with the proteins that cleave prothrombin to active thrombin after injury.<ref>Berg JM, Tymoczko JL, Stryer L. ''Biochemistry'', 5th ed. New York: W. H. Freeman and Company, 2002.</ref>
==See also== * Decarboxylation * Carboxy-lyases
{{clear}} == References == {{reflist|30em}}
{{Protein primary structure}}
Category:Organic reactions Category:Post-translational modification