Carboxylation is a

chemical reaction A chemical reaction is a process that leads to the chemistry, chemical transformation of one set of chemical substances to another. When chemical reactions occur, the atoms are rearranged and the reaction is accompanied by an Gibbs free energy, ...

in which a

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...

is produced by treating a substrate with

carbon dioxide Carbon dioxide is a chemical compound with the chemical formula . It is made up of molecules that each have one carbon atom covalent bond, covalently double bonded to two oxygen atoms. It is found in a gas state at room temperature and at norma ...

. The opposite reaction is

decarboxylation Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is ...

. In

chemistry Chemistry is the scientific study of the properties and behavior of matter. It is a physical science within the natural sciences that studies the chemical elements that make up matter and chemical compound, compounds made of atoms, molecules a ...

, the term

carbonation Carbonation is the chemical reaction of carbon dioxide to give carbonates, bicarbonates, and carbonic acid. In chemistry, the term is sometimes used in place of carboxylation, which refers to the formation of carboxylic acids. In inorganic che ...

is sometimes used synonymously with carboxylation, especially when applied to the reaction of

carbanion In organic chemistry, a carbanion is an anion with a lone pair attached to a tervalent carbon atom. This gives the carbon atom a negative charge. Formally, a carbanion is the conjugate base of a carbon acid: : where B stands for the base (chemist ...

ic reagents with CO₂. More generally, carbonation usually describes the production of

carbonate A carbonate is a salt of carbonic acid, (), characterized by the presence of the carbonate ion, a polyatomic ion with the formula . The word "carbonate" may also refer to a carbonate ester, an organic compound containing the carbonate group ...

Organic chemistry

Carboxylation is a standard conversion in

organic chemistry Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic matter, organic materials, i.e., matter in its various forms that contain ...

. Specifically carbonation (i.e. carboxylation) of

Grignard reagent Grignard reagents or Grignard compounds are chemical compounds with the general formula , where X is a halogen and R is an organic group, normally an alkyl or aryl. Two typical examples are methylmagnesium chloride and phenylmagnesium bromi ...

s and organolithium compounds is a classic way to convert organic halides into carboxylic acids. Sodium salicylate, precursor to

aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...

, is commercially prepared by treating sodium phenolate (the sodium salt of

phenol Phenol (also known as carbolic acid, phenolic acid, or benzenol) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile and can catch fire. The molecule consists of a phenyl group () ...

) with

at high pressure (100 atm) and high temperature (390 K) – a method known as the Kolbe-Schmitt reaction. Acidification of the resulting salicylate salt gives salicylic acid. :

Many detailed procedures are described in the journal ''

Organic Syntheses ''Organic Syntheses'' is a peer-reviewed scientific journal that was established in 1921. It publishes detailed and checked procedures for the synthesis of organic compounds. A unique feature of the review process is that all of the data and expe ...

''. Carboxylation catalysts include

N-Heterocyclic carbene A persistent carbene (also known as stable carbene) is an organic molecule whose natural resonance structure has a carbon atom with octet rule, incomplete octet (a carbene), but does not exhibit the tremendous instability typically associated with ...

s and catalysts based on silver.

Carboxylation in biochemistry

Carbon-based life originates from carboxylation that couples atmospheric carbon dioxide to a sugar. The process is usually catalysed by the enzyme

RuBisCO Ribulose-1,5-bisphosphate carboxylase/oxygenase, commonly known by the abbreviations RuBisCo, rubisco, RuBPCase, or RuBPco, is an enzyme () involved in the light-independent (or "dark") part of photosynthesis, including the carbon fixation by wh ...

. Ribulose-1,5-bisphosphate carboxylase/oxygenase, the enzyme that catalyzes this carboxylation, is possibly the single most abundant

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

on Earth.

Many carboxylases, including Acetyl-CoA carboxylase, Methylcrotonyl-CoA carboxylase, Propionyl-CoA carboxylase, and Pyruvate carboxylase require

biotin Biotin (also known as vitamin B7 or vitamin H) is one of the B vitamins. It is involved in a wide range of metabolic processes, both in humans and in other organisms, primarily related to the utilization of fats, carbohydrates, and amino acids. ...

as a cofactor. These enzymes are involved in various biogenic pathways. In the EC scheme, such carboxylases are classed under EC 6.3.4, "Other Carbon—Nitrogen Ligases". Another example is the

posttranslational modification In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translate mRNA ...

glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

residues, to γ-carboxyglutamate, in proteins. It occurs primarily in proteins involved in the

blood clotting Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a thrombus, blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of co ...

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 The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

and is performed by γ-glutamyl carboxylase (GGCX). GGCX requires

vitamin K Vitamin K is a family of structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-translational modification, post-synthesis modification of certain proteins ...

as a cofactor and performs the reaction in a processive manner. γ-carboxyglutamate binds calcium, which is essential for its activity. For example, in

prothrombin Prothrombin (coagulation factor II) is encoded in the human by the F2-gene. It is proteolytically cleaved during the clotting process by the prothrombinase enzyme complex to form thrombin. Thrombin (Factor IIa) (, fibrose, thrombase, throm ...

, calcium binding allows the protein to associate with the

plasma membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

platelets Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cyto ...

, bringing it into close proximity with the proteins that cleave prothrombin to active

thrombin Prothrombin (coagulation factor II) is encoded in the human by the F2-gene. It is proteolytically cleaved during the clotting process by the prothrombinase enzyme complex to form thrombin. Thrombin (Factor IIa) (, fibrose, thrombase, throm ...

after injury.Berg JM, Tymoczko JL, Stryer L. ''Biochemistry'', 5th ed. New York: W. H. Freeman and Company, 2002.

References

{{Protein primary structure Organic reactions Post-translational modification

Organic chemistry

Carboxylation in biochemistry

See also

References