Reversible hydration of carbon dioxide (Homo sapiens)

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8, 9, 11, 31, 338, 10, 16, 20, 25...4, 8, 22, 402, 8, 17, 19, 23...4, 8, 22, 401, 3, 5-8, 12...1, 3, 5-8, 12...2, 8, 17, 19, 23...8, 10, 16, 20, 25...cytosolmitochondrial matrixH2OCA2 CA1 Zn2+ Zn2+ H+H+CA4,9,14,12:Zn2+HCO3-CA14 HCO3-H+H2OCA7 Zn2+ CA6:ZincCA1,2,3,7,13:ZincCO2CA9 CA12 Zn2+ CA5B CA3 CO2CO2H2ON-seryl-glycosylphosphatidylinositolethanolamine-CA4 CA5A,B:ZincCA6 CA13 CA5A HCO3-26


Description

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. View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 1475029
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: May, Bruce

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Bibliography

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  1. 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.''; PubMed Europe PMC
  2. Baird TT, Waheed A, Okuyama T, Sly WS, Fierke CA.; ''Catalysis and inhibition of human carbonic anhydrase IV.''; PubMed Europe PMC
  3. 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.''; PubMed Europe PMC
  4. Thatcher BJ, Doherty AE, Orvisky E, Martin BM, Henkin RI.; ''Gustin from human parotid saliva is carbonic anhydrase VI.''; PubMed Europe PMC
  5. Pesando JM.; ''Proton magnetic resonance studies of carbonic anhydrase. II. Group controlling catalytic activity.''; PubMed Europe PMC
  6. 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.''; PubMed Europe PMC
  7. Ghannam AF, Tsen W, Rowlett RS.; ''Activation parameters for the carbonic anhydrase II-catalyzed hydration of CO2.''; PubMed Europe PMC
  8. Lindskog S.; ''Structure and mechanism of carbonic anhydrase.''; PubMed Europe PMC
  9. Breton S.; ''The cellular physiology of carbonic anhydrases.''; PubMed Europe PMC
  10. 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.''; PubMed Europe PMC
  11. Esbaugh AJ, Tufts BL.; ''The structure and function of carbonic anhydrase isozymes in the respiratory system of vertebrates.''; PubMed Europe PMC
  12. Ren X, Lindskog S.; ''Buffer dependence of CO2 hydration catalyzed by human carbonic anhydrase I.''; PubMed Europe PMC
  13. 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.''; PubMed Europe PMC
  14. 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.''; PubMed Europe PMC
  15. Carter N, Jeffery S, Shiels A, Edwards Y, Tipler T, Hopkinson DA.; ''Characterization of human carbonic anhydrase III from skeletal muscle.''; PubMed Europe PMC
  16. 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.''; PubMed Europe PMC
  17. Wingo T, Tu C, Laipis PJ, Silverman DN.; ''The catalytic properties of human carbonic anhydrase IX.''; PubMed Europe PMC
  18. 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.''; PubMed Europe PMC
  19. 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.''; PubMed Europe PMC
  20. 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.''; PubMed Europe PMC
  21. Tu C, Qian M, Earnhardt JN, Laipis PJ, Silverman DN.; ''Properties of intramolecular proton transfer in carbonic anhydrase III.''; PubMed Europe PMC
  22. 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.''; PubMed Europe PMC
  23. 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.''; PubMed Europe PMC
  24. Tibell L, Forsman C, Simonsson I, Lindskog S.; ''Anion inhibition of CO2 hydration catalyzed by human carbonic anhydrase II. Mechanistic implications.''; PubMed Europe PMC
  25. Nagao Y, Platero JS, Waheed A, Sly WS.; ''Human mitochondrial carbonic anhydrase: cDNA cloning, expression, subcellular localization, and mapping to chromosome 16.''; PubMed Europe PMC
  26. 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.''; PubMed Europe PMC
  27. 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.''; PubMed Europe PMC
  28. Zhu XL, Sly WS.; ''Carbonic anhydrase IV from human lung. Purification, characterization, and comparison with membrane carbonic anhydrase from human kidney.''; PubMed Europe PMC
  29. 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.''; PubMed Europe PMC
  30. 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.''; PubMed Europe PMC
  31. Boron WF.; ''Evaluating the role of carbonic anhydrases in the transport of HCO3--related species.''; PubMed Europe PMC
  32. 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).''; PubMed Europe PMC
  33. Gilmour KM.; ''Perspectives on carbonic anhydrase.''; PubMed Europe PMC
  34. Silverman DN, Tu C, Chen X, Tanhauser SM, Kresge AJ, Laipis PJ.; ''Rate-equilibria relationships in intramolecular proton transfer in human carbonic anhydrase III.''; PubMed Europe PMC
  35. Khalifah RG.; ''The carbon dioxide hydration activity of carbonic anhydrase. I. Stop-flow kinetic studies on the native human isoenzymes B and C.''; PubMed Europe PMC
  36. 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.''; PubMed Europe PMC
  37. 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.''; PubMed Europe PMC
  38. Gitto R, Agnello S, Ferro S, Vullo D, Supuran CT, Chimirri A.; ''Identification of potent and selective human carbonic anhydrase VII (hCA VII) inhibitors.''; PubMed Europe PMC
  39. 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.''; PubMed Europe PMC
  40. 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.''; PubMed Europe PMC
  41. Simonsson I, Jonsson BH, Lindskog S.; ''A 13C nuclear magnetic resonance study of CO2/HCO-3 exchange catalyzed by human carbonic anhydrase I.''; PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
101357view11:24, 1 November 2018ReactomeTeamreactome version 66
100895view20:59, 31 October 2018ReactomeTeamreactome version 65
100436view19:33, 31 October 2018ReactomeTeamreactome version 64
99985view16:17, 31 October 2018ReactomeTeamreactome version 63
99539view14:52, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99174view12:42, 31 October 2018ReactomeTeamreactome version 62
93748view13:33, 16 August 2017ReactomeTeamreactome version 61
93267view11:18, 9 August 2017ReactomeTeamreactome version 61
89078view06:09, 22 August 2016EgonwOntology Term : 'classic metabolic pathway' added !
86344view09:15, 11 July 2016ReactomeTeamreactome version 56
83176view10:17, 18 November 2015ReactomeTeamVersion54
81773view10:22, 26 August 2015ReactomeTeamVersion53
77043view08:34, 17 July 2014ReactomeTeamFixed remaining interactions
76748view12:11, 16 July 2014ReactomeTeamFixed remaining interactions
76073view10:13, 11 June 2014ReactomeTeamRe-fixing comment source
75783view11:31, 10 June 2014ReactomeTeamReactome 48 Update
75133view14:08, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74780view08:52, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
CA1 ProteinP00915 (Uniprot-TrEMBL)
CA1,2,3,7,13:ZincComplexR-HSA-1475034 (Reactome)
CA12 ProteinO43570 (Uniprot-TrEMBL)
CA13 ProteinQ8N1Q1 (Uniprot-TrEMBL)
CA14 ProteinQ9ULX7 (Uniprot-TrEMBL)
CA2 ProteinP00918 (Uniprot-TrEMBL)
CA3 ProteinP07451 (Uniprot-TrEMBL)
CA4,9,14,12:Zn2+ComplexR-HSA-1475027 (Reactome)
CA5A ProteinP35218 (Uniprot-TrEMBL)
CA5A,B:ZincComplexR-HSA-1475016 (Reactome)
CA5B ProteinQ9Y2D0 (Uniprot-TrEMBL)
CA6 ProteinP23280 (Uniprot-TrEMBL)
CA6:ZincComplexR-HSA-1237316 (Reactome)
CA7 ProteinP43166 (Uniprot-TrEMBL)
CA9 ProteinQ16790 (Uniprot-TrEMBL)
CO2MetaboliteCHEBI:16526 (ChEBI)
H+MetaboliteCHEBI:15378 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HCO3-MetaboliteCHEBI:17544 (ChEBI)
N-seryl-glycosylphosphatidylinositolethanolamine-CA4 ProteinP22748 (Uniprot-TrEMBL)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
CA1,2,3,7,13:Zincmim-catalysisR-HSA-1475022 (Reactome)
CA1,2,3,7,13:Zincmim-catalysisR-HSA-1475026 (Reactome)
CA4,9,14,12:Zn2+mim-catalysisR-HSA-1475017 (Reactome)
CA4,9,14,12:Zn2+mim-catalysisR-HSA-1475025 (Reactome)
CA5A,B:Zincmim-catalysisR-HSA-1475028 (Reactome)
CA5A,B:Zincmim-catalysisR-HSA-1475032 (Reactome)
CA6:Zincmim-catalysisR-HSA-1237045 (Reactome)
CA6:Zincmim-catalysisR-HSA-1237081 (Reactome)
CO2ArrowR-HSA-1237081 (Reactome)
CO2ArrowR-HSA-1475017 (Reactome)
CO2ArrowR-HSA-1475022 (Reactome)
CO2ArrowR-HSA-1475028 (Reactome)
CO2R-HSA-1237045 (Reactome)
CO2R-HSA-1475025 (Reactome)
CO2R-HSA-1475026 (Reactome)
CO2R-HSA-1475032 (Reactome)
H+ArrowR-HSA-1237045 (Reactome)
H+ArrowR-HSA-1475025 (Reactome)
H+ArrowR-HSA-1475026 (Reactome)
H+ArrowR-HSA-1475032 (Reactome)
H+R-HSA-1237081 (Reactome)
H+R-HSA-1475017 (Reactome)
H+R-HSA-1475022 (Reactome)
H+R-HSA-1475028 (Reactome)
H2OArrowR-HSA-1237081 (Reactome)
H2OArrowR-HSA-1475017 (Reactome)
H2OArrowR-HSA-1475022 (Reactome)
H2OArrowR-HSA-1475028 (Reactome)
H2OR-HSA-1237045 (Reactome)
H2OR-HSA-1475025 (Reactome)
H2OR-HSA-1475026 (Reactome)
H2OR-HSA-1475032 (Reactome)
HCO3-ArrowR-HSA-1237045 (Reactome)
HCO3-ArrowR-HSA-1475025 (Reactome)
HCO3-ArrowR-HSA-1475026 (Reactome)
HCO3-ArrowR-HSA-1475032 (Reactome)
HCO3-R-HSA-1237081 (Reactome)
HCO3-R-HSA-1475017 (Reactome)
HCO3-R-HSA-1475022 (Reactome)
HCO3-R-HSA-1475028 (Reactome)
R-HSA-1237045 (Reactome) 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.
R-HSA-1237081 (Reactome) 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.
R-HSA-1475017 (Reactome) 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.
R-HSA-1475022 (Reactome) 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.
R-HSA-1475025 (Reactome) 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.
R-HSA-1475026 (Reactome) 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.
R-HSA-1475028 (Reactome) 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.
R-HSA-1475032 (Reactome) 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.
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