Carbonic anhydrase hydrates carbon dioxide (plasma membrane)

Stable Identifier
R-HSA-1475025
Type
Reaction
Species
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 (CA14Ozensoy et al. 2005, Temperini et al. 2008) are membrane-bound enzymes that hydrate extracellular carbon dioxide to yield bicarbonate and a proton.Carbonic anhydrase deprotonates water to yield a zinc-hydroxyl group and a proton which is transferred to external buffer molecules via histidine or glutamate residues in carbonic anhydrase. The hydroxyl group reacts with carbon dioxide in the active site to yield bicarbonate. A water molecule displaces the bicarbonate and the reaction cycle begins again (reviewed in Lindskog 1997). 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
16006130 Carbonic anhydrase inhibitors: inhibition of the human transmembrane isozyme XIV with a library of aromatic/heterocyclic sulfonamides

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

Bioorg Med Chem 2005
11121027 Purification and kinetic analysis of recombinant CA XII, a membrane carbonic anhydrase overexpressed in certain cancers

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

Proc Natl Acad Sci U S A 2000
9054574 Catalysis and inhibition of human carbonic anhydrase IV

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

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

Zhu, XL, Sly, WS

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

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

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

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

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

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

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

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

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

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

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

Bioorg Med Chem 2008
9336012 Structure and mechanism of carbonic anhydrase

Lindskog, S

Pharmacol Ther 1997
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Catalyst Activity
Title
carbonate dehydratase activity of CA4,9,14,12:Zn2+ [plasma membrane]
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