'Carboxylation' in
chemistry is a
chemical reaction in which a
carboxylic acid group is introduced in a
substrate. The opposite reaction is
decarboxylation.
Carboxylation in organic chemistry
In
organic chemistry many different protocols exist for carboxylation. One general approach is by reaction of
nucleophiles with
dry ice (solid
carbon dioxide)
[1] or
formic acid [2] [3]
Carboxylation in biochemistry
Carboxylation in
biochemistry is a
posttranslational modification of
glutamate residues 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.
[4]
The carboxylase requires
vitamin K as a cofactor and performs the reaction in a processive manner.
[5] γ-carboxyglutamate binds calcium, which is essential for its activity.
[6] 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.
[7]
References
1. ''REGIO- AND STEREOSELECTIVE CARBOXYLATION OF
ALLYLIC BARIUM REAGENTS: (E)-4,8-DIMETHYL-3,7-NONADIENOIC ACID'' Akira Yanagisawa, Katsutaka Yasue, and Hisashi Yamamoto1 Organic Syntheses, Coll. Vol. 9, p.317 (1998); Vol. 74, p.178 (1997) link.
2. ''1-ADAMANTANECARBOXYLIC ACID'' H. Koch and W. Haaf Organic Syntheses, Coll. Vol. 5, p.20 (1973); Vol. 44, p.1 (1964) Link.
3. ''1-METHYLCYCLOHEXANECARBOXYLIC ACID'' W. Haaf Organic Syntheses, Coll. Vol. 5, p.739 (1973); Vol. 46, p.72 (1966).
4. OMIM - gamma-glutamyl carboxylase, contributed by McKusick VA, last updated October 2004 [1]
5. Processive post-translational modification. Vitamin K-dependent carboxylation of a peptide substrate, Morris DP, Stevens RD, Wright DJ, Stafford DW, , , J. Biol. Chem., 1995
6. Direct identification of the calcium-binding amino acid, gamma-carboxyglutamate, in mineralized tissue, Hauschka PV, Lian JB, Gallop PM, , , Proc. Natl. Acad. Sci. U.S.A., 1975
7. Berg JM, Tymoczko JL, Stryer L. ''Biochemistry'', 5th ed. New York: W. H. Freeman and Company, 2002.