Carbonic anhydrases reversibly catalyze the hydration of carbon dioxide and directly produce bicarbonate and protons, bypassing the formation of carbonic acid (reviewed in Lindskog 1997, Breton 2001, Esbaugh and Tufts 2006, Boron 2010, Gilmour 2010). 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. There are currently 12 known active carbonic anhydrases in humans.
Baird TT, Waheed A, Okuyama T, Sly WS, Fierke CA.; ''Catalysis and inhibition of human carbonic anhydrase IV.''; PubMedEurope PMCScholia
Fujikawa-Adachi K, Nishimori I, Taguchi T, Onishi S.; ''Human mitochondrial carbonic anhydrase VB. cDNA cloning, mRNA expression, subcellular localization, and mapping to chromosome x.''; PubMedEurope PMCScholia
Bootorabi F, Jänis J, Smith E, Waheed A, Kukkurainen S, Hytönen V, Valjakka J, Supuran CT, Vullo D, Sly WS, Parkkila S.; ''Analysis of a shortened form of human carbonic anhydrase VII expressed in vitro compared to the full-length enzyme.''; PubMedEurope PMCScholia
Silverman DN, Tu C, Chen X, Tanhauser SM, Kresge AJ, Laipis PJ.; ''Rate-equilibria relationships in intramolecular proton transfer in human carbonic anhydrase III.''; PubMedEurope PMCScholia
Nishimori I, Innocenti A, Vullo D, Scozzafava A, Supuran CT.; ''Carbonic anhydrase inhibitors: the inhibition profiles of the human mitochondrial isoforms VA and VB with anions are very different.''; PubMedEurope PMCScholia
Khalifah RG.; ''The carbon dioxide hydration activity of carbonic anhydrase. I. Stop-flow kinetic studies on the native human isoenzymes B and C.''; PubMedEurope PMCScholia
Nishimori I, Minakuchi T, Onishi S, Vullo D, Scozzafava A, Supuran CT.; ''Carbonic anhydrase inhibitors. DNA cloning, characterization, and inhibition studies of the human secretory isoform VI, a new target for sulfonamide and sulfamate inhibitors.''; PubMedEurope PMCScholia
Temperini C, Cecchi A, Boyle NA, Scozzafava A, Cabeza JE, Wentworth P, Blackburn GM, Supuran CT.; ''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.''; PubMedEurope PMCScholia
Esbaugh AJ, Tufts BL.; ''The structure and function of carbonic anhydrase isozymes in the respiratory system of vertebrates.''; PubMedEurope PMCScholia
Zhu XL, Sly WS.; ''Carbonic anhydrase IV from human lung. Purification, characterization, and comparison with membrane carbonic anhydrase from human kidney.''; PubMedEurope PMCScholia
Boron WF.; ''Evaluating the role of carbonic anhydrases in the transport of HCO3--related species.''; PubMedEurope PMCScholia
Innocenti A, Firnges MA, Antel J, Wurl M, Scozzafava A, Supuran CT.; ''Carbonic anhydrase inhibitors: inhibition of the membrane-bound human isozyme IV with anions.''; PubMedEurope PMCScholia
Nishimori I, Vullo D, Innocenti A, Scozzafava A, Mastrolorenzo A, Supuran CT.; ''Carbonic anhydrase inhibitors. The mitochondrial isozyme VB as a new target for sulfonamide and sulfamate inhibitors.''; PubMedEurope PMCScholia
Domsic JF, Williams W, Fisher SZ, Tu C, Agbandje-McKenna M, Silverman DN, McKenna R.; ''Structural and kinetic study of the extended active site for proton transfer in human carbonic anhydrase II.''; PubMedEurope PMCScholia
Becker HM, Klier M, Schüler C, McKenna R, Deitmer JW.; ''Intramolecular proton shuttle supports not only catalytic but also noncatalytic function of carbonic anhydrase II.''; PubMedEurope PMCScholia
Gitto R, Agnello S, Ferro S, Vullo D, Supuran CT, Chimirri A.; ''Identification of potent and selective human carbonic anhydrase VII (hCA VII) inhibitors.''; PubMedEurope PMCScholia
Mikulski R, Domsic JF, Ling G, Tu C, Robbins AH, Silverman DN, McKenna R.; ''Structure and catalysis by carbonic anhydrase II: role of active-site tryptophan 5.''; PubMedEurope PMCScholia
Elder I, Fisher Z, Laipis PJ, Tu C, McKenna R, Silverman DN.; ''Structural and kinetic analysis of proton shuttle residues in the active site of human carbonic anhydrase III.''; PubMedEurope PMCScholia
Franchi M, Vullo D, Gallori E, Antel J, Wurl M, Scozzafava A, Supuran CT.; ''Carbonic anhydrase inhibitors: inhibition of human and murine mitochondrial isozymes V with anions.''; PubMedEurope PMCScholia
Nagao Y, Platero JS, Waheed A, Sly WS.; ''Human mitochondrial carbonic anhydrase: cDNA cloning, expression, subcellular localization, and mapping to chromosome 16.''; PubMedEurope PMCScholia
Wingo T, Tu C, Laipis PJ, Silverman DN.; ''The catalytic properties of human carbonic anhydrase IX.''; PubMedEurope PMCScholia
Tu CK, Paranawithana SR, Jewell DA, Tanhauser SM, LoGrasso PV, Wynns GC, Laipis PJ, Silverman DN.; ''Buffer enhancement of proton transfer in catalysis by human carbonic anhydrase III.''; PubMedEurope PMCScholia
Okuyama T, Waheed A, Kusumoto W, Zhu XL, Sly WS.; ''Carbonic anhydrase IV: role of removal of C-terminal domain in glycosylphosphatidylinositol anchoring and realization of enzyme activity.''; PubMedEurope PMCScholia
Tu C, Qian M, Earnhardt JN, Laipis PJ, Silverman DN.; ''Properties of intramolecular proton transfer in carbonic anhydrase III.''; PubMedEurope PMCScholia
Simonsson I, Jonsson BH, Lindskog S.; ''A 13C nuclear magnetic resonance study of CO2/HCO-3 exchange catalyzed by human carbonic anhydrase I.''; PubMedEurope PMCScholia
Ghannam AF, Tsen W, Rowlett RS.; ''Activation parameters for the carbonic anhydrase II-catalyzed hydration of CO2.''; PubMedEurope PMCScholia
Tibell L, Forsman C, Simonsson I, Lindskog S.; ''Anion inhibition of CO2 hydration catalyzed by human carbonic anhydrase II. Mechanistic implications.''; PubMedEurope PMCScholia
Nishimori I, Onishi S, Vullo D, Innocenti A, Scozzafava A, Supuran CT.; ''Carbonic anhydrase activators: the first activation study of the human secretory isoform VI with amino acids and amines.''; PubMedEurope PMCScholia
Ulmasov B, Waheed A, Shah GN, Grubb JH, Sly WS, Tu C, Silverman DN.; ''Purification and kinetic analysis of recombinant CA XII, a membrane carbonic anhydrase overexpressed in certain cancers.''; PubMedEurope PMCScholia
Carter N, Jeffery S, Shiels A, Edwards Y, Tipler T, Hopkinson DA.; ''Characterization of human carbonic anhydrase III from skeletal muscle.''; PubMedEurope PMCScholia
Ren X, Lindskog S.; ''Buffer dependence of CO2 hydration catalyzed by human carbonic anhydrase I.''; PubMedEurope PMCScholia
Pesando JM.; ''Proton magnetic resonance studies of carbonic anhydrase. II. Group controlling catalytic activity.''; PubMedEurope PMCScholia
Pastorekova S, Vullo D, Nishimori I, Scozzafava A, Pastorek J, Supuran CT.; ''Carbonic anhydrase activators: activation of the human tumor-associated isozymes IX and XII with amino acids and amines.''; PubMedEurope PMCScholia
Thatcher BJ, Doherty AE, Orvisky E, Martin BM, Henkin RI.; ''Gustin from human parotid saliva is carbonic anhydrase VI.''; PubMedEurope PMCScholia
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.; ''Biochemical characterization of CA IX, one of the most active carbonic anhydrase isozymes.''; PubMedEurope PMCScholia
Jones GL, Shaw DC.; ''A chemical and enzymological comparison of the common major human erythrocyte carbonic anhydrase II, its minor component, and a new genetic variant, CA II Melbourne (237 Pro leads to His).''; PubMedEurope PMCScholia
Tu C, Chen X, Ren X, LoGrasso PV, Jewell DA, Laipis PJ, Silverman DN.; ''Interactions of active-site residues and catalytic activity of human carbonic anhydrase III.''; PubMedEurope PMCScholia
Ozensoy O, Nishimori I, Vullo D, Puccetti L, Scozzafava A, Supuran CT.; ''Carbonic anhydrase inhibitors: inhibition of the human transmembrane isozyme XIV with a library of aromatic/heterocyclic sulfonamides.''; PubMedEurope PMCScholia
Carbonic anhydrase I (CA1, Khalifah 1971, Simonsson et al. 1982, Ren and Lindskog 1992), carbonic anyhydrase II (CA2, Tibell et al. 1984, Jones and Shaw 1983, Pesando 1975, Ghannam et al. 1986), carbonic anhydrase III (CA3, Carter et al. 1979, Tu et al. 1990, Tu et al. 1994, Tu et al. 1998, Silverman et al. 1993), carbonic anhydrase VII (CA7, Bootorabi et al. 2010, Gitto et al. 2010) dehydrate cytosolic bicarbonate to yield water and carbon dioxide (reviewed in Lindskog 1997). Depending on the concentrations of reactants the reaction is reversible. CA2 and CA7 have high catalytic activity, CA1 has low activity (10% of the activity of CA2), and CA3 has very low activity (1% of the activity of CA2). CA1 and CA2 are found in erythrocytes. CA2 is also found in kidney, lung, and white muscle where it facilitates diffusion of carbon dioxide. CA3 is found in red muscle where it participates in resistance against oxidative stress.
Carbonic anhydrase VI (CA6) dehydrates bicarbonate to yield water and carbon dioxide (Thatcher et al. 1998, Nishimori et al. 2007). Depending on the concentrations of reactants the reaction is reversible. CA6 is a major protein of saliva and is also known as gustin.
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.
Carbonic anhydrase VI (CA6) hydrates carbon dioxide to yield bicarbonate and a proton (Thatcher et al. 1998, Nishimori et al. 2007).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. CA6 is a major protein of saliva and is also known as gustin.
Carbonic anhydrase VA (CA5A, Nagao et al. 1993, Franchi et al. 2003, Nishimori et al. 2007) and carbonic anhydrase VB (CA5B, Fujikawa-Adachi et al. 1999, Nishimori et al. 2005, Nishimori et al. 2007) hydrate carbon dioxide in mitochondria 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.
Carbonic anhydrase VA (CA5A, Nagao et al. 1993, Franchi et al. 2003, Nishimori et al. 2007) and carbonic anhydrase VB (CA5B, Fujikawa-Adachi et al. 1999, Nishimori et al. 2005, Nishimori et al. 2007) dehydrate bicarbonate in mitochondria to yield water and carbon dioxide (reviewed in Lindskog 1997). Depending on the concentrations of reactants the reaction is reversible.
Carbonic anhydrase I (CA1, Khalifah 1971, Simonsson et al. 1982, Ren and Lindskog 1992), carbonic anyhydrase II (CA2, Tibell et al. 1984, Jones and Shaw 1983, Pesando 1975, Ghannam et al. 1986), carbonic anhydrase III (CA3, Carter et al. 1979, Tu et al. 1990, Tu et al. 1994, Tu et al. 1998, Silverman et al. 1993), carbonic anhydrase VII (CA7, Bootorabi et al. 2010, Gitto et al. 2010) hydrate 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. CA2 and CA7 have high catalytic activity, CA1 has low activity (10% of the activity of CA2), and CA3 has very low activity (1% of the activity of CA2). CA1 and CA2 are found in erythrocytes. CA2 is also found in kidney, lung, and white muscle where it facilitates diffusion of carbon dioxide. CA3 is found in red muscle where it participates in resistance against oxidative stress.
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.
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CA2 and CA7 have high catalytic activity, CA1 has low activity (10% of the activity of CA2), and CA3 has very low activity (1% of the activity of CA2). CA1 and CA2 are found in erythrocytes. CA2 is also found in kidney, lung, and white muscle where it facilitates diffusion of carbon dioxide. CA3 is found in red muscle where it participates in resistance against oxidative stress.
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.
CA2 and CA7 have high catalytic activity, CA1 has low activity (10% of the activity of CA2), and CA3 has very low activity (1% of the activity of CA2). CA1 and CA2 are found in erythrocytes. CA2 is also found in kidney, lung, and white muscle where it facilitates diffusion of carbon dioxide. CA3 is found in red muscle where it participates in resistance against oxidative stress.
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.