Carbonic anhydrase dehydrates bicarbonate (plasma membrane)

Stable Identifier
Reaction [transition]
Homo sapiens
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Carbonic anhydrase IV (CA4, Zhu and Sly 1990, Okuyama et al. 1992, Baird et al. 1997, Innocenti et al. 2004), carbonic anhydrase IX (CA9, Wingo et al. 2001, Hilvo et al. 2008), carbonic anhydrase XII (CA12, Ulmasov et al. 2000, Pastorekova et al. 2008), and carbonic anhydrase XIV (CA14, Ozensoy et al. 2005, Temperini et al. 2008) are membrane-bound enzymes that dehydrate bicarbonate to yield water and carbon dioxide. Depending on the concentrations of reactants the reaction is reversible.
CA4 has high catalytic activity. CA9, CA12, and CA14 have moderate activity. CA4 is anchored to the extracellular face of the plasma membrane by glycosylphosphatidylinositol. CA9, CA12, and CA14 are single-pass transmembrane proteins. CA4 is found on the extracellular face of capillaries in kidney, lung, and muscle where it maintains the gradient of carbon dioxide between tissue and blood. CA9 and CA12 are found on basolateral membranes of epithelia. CA9 is inducible by Hypoxia-inducible factor 1 alpha (HIF1alpha) and acidifies the extracellular environment of tumors. In rodents CA15 is membrane anchored and has low activity; in primates CA15 is a pseudogene.

Literature References
PubMed ID Title Journal Year
11121027 Purification and kinetic analysis of recombinant CA XII, a membrane carbonic anhydrase overexpressed in certain cancers

Silverman, DN, Tu, C, Sly, WS, Grubb, JH, Shah, GN, Ulmasov, B, Waheed, A

Proc Natl Acad Sci U S A 2000
16006130 Carbonic anhydrase inhibitors: inhibition of the human transmembrane isozyme XIV with a library of aromatic/heterocyclic sulfonamides

Puccetti, L, Nishimori, I, Supuran, CT, Scozzafava, A, Vullo, D, Ozensoy, O

Bioorg Med Chem 2005
9054574 Catalysis and inhibition of human carbonic anhydrase IV

Sly, WS, Fierke, CA, Okuyama, T, Baird TT, Jr, Waheed, A

Biochemistry 1997
2111324 Carbonic anhydrase IV from human lung. Purification, characterization, and comparison with membrane carbonic anhydrase from human kidney

Sly, WS, Zhu, XL

J Biol Chem 1990
15501038 Carbonic anhydrase inhibitors: inhibition of the membrane-bound human isozyme IV with anions

Innocenti, A, Wurl, M, Supuran, CT, Scozzafava, A, Antel, J, Firnges, MA

Bioorg Med Chem Lett 2004
7625839 Carbonic anhydrase IV: role of removal of C-terminal domain in glycosylphosphatidylinositol anchoring and realization of enzyme activity

Sly, WS, Kusumoto, W, Okuyama, T, Waheed, A, Zhu, XL

Arch Biochem Biophys 1995
11676494 The catalytic properties of human carbonic anhydrase IX

Laipis, PJ, Silverman, DN, Tu, C, Wingo, T

Biochem Biophys Res Commun 2001
18162396 Carbonic anhydrase inhibitors. Interaction of 2-N,N-dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide with 12 mammalian isoforms: kinetic and X-ray crystallographic studies

Cabeza, JE, Supuran, CT, Wentworth P, Jr, Scozzafava, A, Cecchi, A, Blackburn, GM, Boyle, NA, Temperini, C

Bioorg Med Chem Lett 2008
18703501 Biochemical characterization of CA IX, one of the most active carbonic anhydrase isozymes

Supuran, CT, Scaloni, A, Hilvo, M, Matulis, D, Kulomaa, MS, Nordlund, HR, Parkkila, S, Salzano, AM, Innocenti, A, Jänis, J, Pastorek, J, Lindfors, M, Baranauskiene, L, Pastoreková, S, Scozzafava, A, Monti, SM, Di Fiore, A, De Simone, G, Valjakka, J

J Biol Chem 2008
18294854 Carbonic anhydrase activators: activation of the human tumor-associated isozymes IX and XII with amino acids and amines

Pastorekova, S, Pastorek, J, Nishimori, I, Supuran, CT, Scozzafava, A, Vullo, D

Bioorg Med Chem 2008
9336012 Structure and mechanism of carbonic anhydrase

Lindskog, S

Pharmacol Ther 1997
Event Information
Catalyst Activity

carbonate dehydratase activity of CA4,9,14,12:Zn2+ [plasma membrane]

Orthologous Events
Cross References
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