# Carboxylation

> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Carboxylation
> Markdown URL: https://mediated.wiki/source/Carboxylation.md
> Source: https://en.wikipedia.org/wiki/Carboxylation
> Source revision: 1353378300
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)

{{Short description|Chemical conversion reaction}}
'''Carboxylation''' is a [chemical reaction](/source/chemical_reaction) in which a [carboxylic acid](/source/carboxylic_acid) is produced by treating a [substrate](/source/Substrate_(chemistry)) with [carbon dioxide](/source/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](/source/decarboxylation). In [chemistry](/source/chemistry), the term [carbonation](/source/carbonation) is sometimes used synonymously with carboxylation, especially when applied to the reaction of [carbanion](/source/carbanion)ic reagents with CO<sub>2</sub>. More generally, carbonation usually describes the production of [carbonate](/source/carbonate)s.<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](/source/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 reagent](/source/Grignard_reagent)s, 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](/source/Sodium_salicylate), precursor to [aspirin](/source/aspirin), is commercially produced by treating [sodium phenolate](/source/sodium_phenolate) (the sodium salt of [phenol](/source/phenol)) with [carbon dioxide](/source/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](/source/Kolbe-Schmitt_reaction), entails nucleophilic attack of the phenoxide on [carbon dioxide](/source/carbon_dioxide).

In some cases, alkenes undergo [hydrocarboxylation](/source/hydrocarboxylation) using a mixture of [carbon dioxide](/source/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](/source/Koch_reaction), effect "net" carboxylation involve the use of [carbon monoxide](/source/carbon_monoxide), either directly or generated in situ.  These methods are variants of [carbonylation](/source/carbonylation) reactions.

Carboxylation of epoxides gives cyclic carbonates.  Such reactions are catalyzed by [N-Heterocyclic carbene](/source/N-Heterocyclic_carbene)s<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 chain](/source/Food_chain)s usually originate from carboxylation that couples carbon dioxide to a sugar.  The process is usually [catalysed](/source/Catalysis) by the enzyme [RuBisCO](/source/RuBisCO). [Ribulose-1,5-bisphosphate carboxylase/oxygenase](/source/RuBisCO), the enzyme that catalyzes this carboxylation, is possibly the single most abundant [protein](/source/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](/source/Calvin_cycle) showing the carboxylation of ribulose-1,5-bisphosphate.]]
140px|thumb|right|Carboxyglutamic acid
Many carboxylases, including [acetyl-CoA carboxylase](/source/acetyl-CoA_carboxylase), [methylcrotonyl-CoA carboxylase](/source/methylcrotonyl-CoA_carboxylase), [propionyl-CoA carboxylase](/source/propionyl-CoA_carboxylase), and [pyruvate carboxylase](/source/pyruvate_carboxylase) require [biotin](/source/biotin) as a [cofactor](/source/Cofactor_(biochemistry)). These enzymes are involved in various [anabolic pathway](/source/anabolic_pathway)s.<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](/source/National_Institutes_of_Health)|access-date=25 February 2018}}</ref> In the [EC scheme](/source/Enzyme_Commission_number), such carboxylases are mostly classed under [EC 6.4.1](/source/EC_6.4.1), [ligase](/source/ligase)s “forming carbon-carbon bonds,” or sometimes EC 6.3.4, "Other Carbon—Nitrogen Ligases".

Another example is the [posttranslational modification](/source/posttranslational_modification) of [glutamate](/source/glutamate) residues, to [γ-carboxyglutamate](/source/carboxyglutamic_acid), in proteins.  It occurs primarily in proteins involved in the [blood clotting](/source/blood_clotting) cascade, specifically factors [II](/source/Prothrombin), [VII](/source/Factor_VII), [IX](/source/Factor_IX), and [X](/source/Factor_X), [protein C](/source/protein_C), and [protein S](/source/protein_S), and also in some bone proteins.  This modification is required for these proteins to function.  Carboxylation occurs in the [liver](/source/liver) and is performed by [γ-glutamyl carboxylase](/source/gamma-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](/source/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](/source/calcium_in_biology), 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](/source/prothrombin), calcium binding allows the protein to associate with the [plasma membrane](/source/plasma_membrane) in [platelets](/source/platelets), bringing it into close proximity with the proteins that cleave prothrombin to active [thrombin](/source/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](/source/Decarboxylation)
* [Carboxy-lyases](/source/Carboxy-lyases)

{{clear}}
== References ==
{{reflist|30em}}

{{Protein primary structure}}

Category:Organic reactions
Category:Post-translational modification

---
Adapted from the Wikipedia article [Carboxylation](https://en.wikipedia.org/wiki/Carboxylation) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Carboxylation?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.