Erythrocytes take up oxygen and release carbon dioxide (Homo sapiens)

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1, 19, 298, 16, 31, 35, 42...7, 17, 322, 21, 282, 13, 21, 22, 303, 11, 12, 16, 18...4, 6, 9, 20, 24...cytosolCA4:Zn2+Cl-CA1 CO-H+-HBB H2OCl-heme Zn2+ H+CO2OxyHbACO2RHAGHCO3-AQP1 CA2 N-seryl-glycosylphosphatidylinositolethanolamine-CA4 heme CO-H+-HBA1 SLC4A1 dimerHCO3-HBA1 H2OSLC4A1 CA1,2AQP1 tetramerH+Protonated CarbaminoDeoxyHbAO2 O2Zn2+ HBB 10, 15, 365, 14, 3840


Description

Erythrocytes circulating through the capillaries of the lung must exchange carbon dioxide (CO2) for oxygen (O2) during their short (0.5-1 sec.) transit time in pulmonary tissue (Reviewed in Jensen 2004, Esbaugh and Tufts 2006, Boron 2010). CO2 bound as carbamate to the N-terminus of hemoglobin and protons (H+) bound to histidine residues in hemoglobin are released as hemoglobin (HbA) binds O2. Bicarbonate (HCO3-) present in plasma is taken up by erythrocytes via the band3 anion exchanger (AE1, SLC4A1) and combined with H+ by carbonic anhydrases I and II (CA1/CA2) to yield water and CO2 (Reviewed by Esbaugh and Tufts 2006). CO2 is passively transported out of the erythrocyte by AQP1 and RhAG. HCO3- in plasma is also directly dehydrated by extracellular carbonic anhydrase IV (CA4) present on endothelial cells lining the capillaries in the lung. View original pathway at:Reactome.

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Reactome-Converter 
Pathway is converted from Reactome ID: 1247673
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: May, Bruce

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Bibliography

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  1. Esbaugh AJ, Tufts BL.; ''The structure and function of carbonic anhydrase isozymes in the respiratory system of vertebrates.''; PubMed Europe PMC
  2. Musa-Aziz R, Chen LM, Pelletier MF, Boron WF.; ''Relative CO2/NH3 selectivities of AQP1, AQP4, AQP5, AmtB, and RhAG.''; PubMed Europe PMC
  3. 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
  4. Dash RK, Bassingthwaighte JB.; ''Erratum to: Blood HbO2 and HbCO2 dissociation curves at varied O2, CO2, pH, 2,3-DPG and temperature levels.''; PubMed Europe PMC
  5. Walz T, Hirai T, Murata K, Heymann JB, Mitsuoka K, Fujiyoshi Y, Smith BL, Agre P, Engel A.; ''The three-dimensional structure of aquaporin-1.''; PubMed Europe PMC
  6. Kraan J, Rispens P.; ''Contribution of the Haldane effect to the increase in arterial carbon dioxide tension in hypoxaemic subjects treated with oxygen.''; PubMed Europe PMC
  7. Sterling D, Reithmeier RA, Casey JR.; ''A transport metabolon. Functional interaction of carbonic anhydrase II and chloride/bicarbonate exchangers.''; PubMed Europe PMC
  8. Baird TT, Waheed A, Okuyama T, Sly WS, Fierke CA.; ''Catalysis and inhibition of human carbonic anhydrase IV.''; PubMed Europe PMC
  9. Mertzlufft F, Brandt L.; ''Hyperoxic intubation apnoea: an in vivo model for the proof of the Christiansen-Douglas-Haldane effect.''; PubMed Europe PMC
  10. Salhany JM, Cordes KA, Sloan RL.; ''Gel filtration chromatographic studies of the isolated membrane domain of band 3.''; PubMed Europe PMC
  11. Pesando JM.; ''Proton magnetic resonance studies of carbonic anhydrase. II. Group controlling catalytic activity.''; PubMed Europe PMC
  12. Ghannam AF, Tsen W, Rowlett RS.; ''Activation parameters for the carbonic anhydrase II-catalyzed hydration of CO2.''; PubMed Europe PMC
  13. Endeward V, Musa-Aziz R, Cooper GJ, Chen LM, Pelletier MF, Virkki LV, Supuran CT, King LS, Boron WF, Gros G.; ''Evidence that aquaporin 1 is a major pathway for CO2 transport across the human erythrocyte membrane.''; PubMed Europe PMC
  14. Murata K, Mitsuoka K, Hirai T, Walz T, Agre P, Heymann JB, Engel A, Fujiyoshi Y.; ''Structural determinants of water permeation through aquaporin-1.''; PubMed Europe PMC
  15. Pinder JC, Pekrun A, Maggs AM, Brain AP, Gratzer WB.; ''Association state of human red blood cell band 3 and its interaction with ankyrin.''; PubMed Europe PMC
  16. Lindskog S.; ''Structure and mechanism of carbonic anhydrase.''; PubMed Europe PMC
  17. Knauf PA, Gasbjerg PK, Brahm J.; ''The asymmetry of chloride transport at 38 degrees C in human red blood cell membranes.''; PubMed Europe PMC
  18. 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
  19. Jensen FB.; ''Red blood cell pH, the Bohr effect, and other oxygenation-linked phenomena in blood O2 and CO2 transport.''; PubMed Europe PMC
  20. Klocke RA.; ''Mechanism and kinetics of the Haldane effect in human erythrocytes.''; PubMed Europe PMC
  21. Endeward V, Cartron JP, Ripoche P, Gros G.; ''Red cell membrane CO2 permeability in normal human blood and in blood deficient in various blood groups, and effect of DIDS.''; PubMed Europe PMC
  22. Nakhoul NL, Davis BA, Romero MF, Boron WF.; ''Effect of expressing the water channel aquaporin-1 on the CO2 permeability of Xenopus oocytes.''; PubMed Europe PMC
  23. 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
  24. Morrow JS, Matthew JB, Wittebort RJ, Gurd FR.; ''Carbon 13 resonances of 13CO2 carbamino adducts of alpha and beta chains in human adult hemoglobin.''; PubMed Europe PMC
  25. Tibell L, Forsman C, Simonsson I, Lindskog S.; ''Anion inhibition of CO2 hydration catalyzed by human carbonic anhydrase II. Mechanistic implications.''; PubMed Europe PMC
  26. Tazawa H, Mochizuki M, Tamura M, Kagawa T.; ''Quantitative analyses of the CO2 dissociation curve of oxygenated blood and the Haldane effect in human blood.''; PubMed Europe PMC
  27. Ren X, Lindskog S.; ''Buffer dependence of CO2 hydration catalyzed by human carbonic anhydrase I.''; PubMed Europe PMC
  28. Endeward V, Cartron JP, Ripoche P, Gros G.; ''RhAG protein of the Rhesus complex is a CO2 channel in the human red cell membrane.''; PubMed Europe PMC
  29. Boron WF.; ''Evaluating the role of carbonic anhydrases in the transport of HCO3--related species.''; PubMed Europe PMC
  30. Blank ME, Ehmke H.; ''Aquaporin-1 and HCO3(-)-Cl- transporter-mediated transport of CO2 across the human erythrocyte membrane.''; PubMed Europe PMC
  31. 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
  32. Dahl NK, Jiang L, Chernova MN, Stuart-Tilley AK, Shmukler BE, Alper SL.; ''Deficient HCO3- transport in an AE1 mutant with normal Cl- transport can be rescued by carbonic anhydrase II presented on an adjacent AE1 protomer.''; PubMed Europe PMC
  33. Kalhoff H, Werkmeister F, Kiwull-Schöne H, Diekmann L, Manz F, Kiwull P.; ''The Haldane effect under different acid-base conditions in premature and adult humans.''; PubMed Europe PMC
  34. Doyle ML, Di Cera E, Robert CH, Gill SJ.; ''Carbon dioxide and oxygen linkage in human hemoglobin tetramers.''; PubMed Europe PMC
  35. Zhu XL, Sly WS.; ''Carbonic anhydrase IV from human lung. Purification, characterization, and comparison with membrane carbonic anhydrase from human kidney.''; PubMed Europe PMC
  36. Taylor AM, Boulter J, Harding SE, Cölfen H, Watts A.; ''Hydrodynamic properties of human erythrocyte band 3 solubilized in reduced Triton X-100.''; PubMed Europe PMC
  37. Kernohan JC, Roughton FJ.; ''Thermal studies of the rates of the reactions of carbon dioxide in concentrated haemoglobin solutions and in red blood cells. A. The reactions catalysed by carbonic anhydrase. B. The carbamino reactions of oxygenated and deoxygenated haemoglobin.''; PubMed Europe PMC
  38. de Groot BL, Engel A, Grubmüller H.; ''A refined structure of human aquaporin-1.''; PubMed Europe PMC
  39. Morrow JS, Keim P, Visscher RB, Marshall RC, Gurd FR.; ''Interaction of 13 CO 2 and bicarbonate with human hemoglobin preparations.''; PubMed Europe PMC
  40. 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
  41. Ferguson JK, Roughton FJ.; ''The chemical relationships and physiological importance of carbamino compounds of CO(2) with haemoglobin.''; PubMed Europe PMC
  42. Okuyama T, Sato S, Zhu XL, Waheed A, Sly WS.; ''Human carbonic anhydrase IV: cDNA cloning, sequence comparison, and expression in COS cell membranes.''; PubMed Europe PMC
  43. Wistrand PJ, Carter ND, Conroy CW, Mahieu I.; ''Carbonic anhydrase IV activity is localized on the exterior surface of human erythrocytes.''; PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
101535view11:40, 1 November 2018ReactomeTeamreactome version 66
101070view21:22, 31 October 2018ReactomeTeamreactome version 65
100600view19:56, 31 October 2018ReactomeTeamreactome version 64
100151view16:42, 31 October 2018ReactomeTeamreactome version 63
99701view15:10, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99285view12:46, 31 October 2018ReactomeTeamreactome version 62
93845view13:40, 16 August 2017ReactomeTeamreactome version 61
93402view11:22, 9 August 2017ReactomeTeamreactome version 61
87442view13:40, 22 July 2016MkutmonOntology Term : 'classic metabolic pathway' added !
86488view09:19, 11 July 2016ReactomeTeamreactome version 56
83368view11:01, 18 November 2015ReactomeTeamVersion54
81750view09:50, 26 August 2015ReactomeTeamVersion53
76878view08:15, 17 July 2014ReactomeTeamFixed remaining interactions
76583view11:56, 16 July 2014ReactomeTeamFixed remaining interactions
75916view09:57, 11 June 2014ReactomeTeamRe-fixing comment source
75616view10:48, 10 June 2014ReactomeTeamReactome 48 Update
74971view13:49, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74615view08:40, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AQP1 ProteinP29972 (Uniprot-TrEMBL)
AQP1 tetramerComplexR-HSA-432246 (Reactome)
CA1 ProteinP00915 (Uniprot-TrEMBL)
CA1,2ComplexR-HSA-1475437 (Reactome)
CA2 ProteinP00918 (Uniprot-TrEMBL)
CA4:Zn2+ComplexR-HSA-1237308 (Reactome)
CO-H+-HBA1 ProteinP69905 (Uniprot-TrEMBL)
CO-H+-HBB ProteinP68871 (Uniprot-TrEMBL)
CO2MetaboliteCHEBI:16526 (ChEBI)
Cl-MetaboliteCHEBI:17996 (ChEBI)
H+MetaboliteCHEBI:15378 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HBA1 ProteinP69905 (Uniprot-TrEMBL)
HBB ProteinP68871 (Uniprot-TrEMBL)
HCO3-MetaboliteCHEBI:17544 (ChEBI)
N-seryl-glycosylphosphatidylinositolethanolamine-CA4 ProteinP22748 (Uniprot-TrEMBL)
O2 MetaboliteCHEBI:15379 (ChEBI)
O2MetaboliteCHEBI:15379 (ChEBI)
OxyHbAComplexR-HSA-1237320 (Reactome)
Protonated Carbamino DeoxyHbAComplexR-HSA-1237312 (Reactome)
RHAGProteinQ02094 (Uniprot-TrEMBL)
SLC4A1 ProteinP02730 (Uniprot-TrEMBL)
SLC4A1 dimerComplexR-HSA-1244330 (Reactome)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)
heme MetaboliteCHEBI:17627 (ChEBI)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
AQP1 tetramermim-catalysisR-HSA-1247649 (Reactome)
CA1,2mim-catalysisR-HSA-1475436 (Reactome)
CA4:Zn2+mim-catalysisR-HSA-1237059 (Reactome)
CO2ArrowR-HSA-1237059 (Reactome)
CO2ArrowR-HSA-1247645 (Reactome)
CO2ArrowR-HSA-1247649 (Reactome)
CO2ArrowR-HSA-1247668 (Reactome)
CO2ArrowR-HSA-1475436 (Reactome)
CO2R-HSA-1247645 (Reactome)
CO2R-HSA-1247649 (Reactome)
Cl-ArrowR-HSA-1247665 (Reactome)
Cl-R-HSA-1247665 (Reactome)
H+ArrowR-HSA-1247668 (Reactome)
H+R-HSA-1237059 (Reactome)
H+R-HSA-1475436 (Reactome)
H2OArrowR-HSA-1237059 (Reactome)
H2OArrowR-HSA-1475436 (Reactome)
HCO3-ArrowR-HSA-1247665 (Reactome)
HCO3-R-HSA-1237059 (Reactome)
HCO3-R-HSA-1247665 (Reactome)
HCO3-R-HSA-1475436 (Reactome)
O2R-HSA-1247668 (Reactome)
OxyHbAArrowR-HSA-1247668 (Reactome)
Protonated Carbamino DeoxyHbAR-HSA-1247668 (Reactome)
R-HSA-1237059 (Reactome) Carbonic anhydrase IV (CA4) located on the extracellular face of the plasma membrane (Wistrand et al. 1999) dehydrates bicarbonate (HCO3--) to yield water and carbon dioxide (CO2) (Zhu & Sly 1990, Okayuma et al. 1992, Baird et al. 1997, Innocenti et al. 2004, reviewed in Lindskog 1997). Depending on the concentrations of reactants the reaction is reversible.
R-HSA-1247645 (Reactome) The Rhesus blood group type A glycoprotein (RhAG) passively transports carbon dioxide (CO2) across the plasma membrane according to the concentration gradient (Endeward et al. 2006, Endeward et al. 2008, Musa-Aziz et al. 2009).
R-HSA-1247649 (Reactome) Aquaporin-1 (AQP1) passively transports carbon dioxide (CO2) across the plasma membrane according to the concentration gradient (Nakhoul et al. 1998, Blank & Ehmke et al. 2003, Endeward et al. 2006, Musa-Aziz et al. 2009). The pore in AQP1 that conducts CO2 may be distinct from the pore that conducts water.
R-HSA-1247665 (Reactome) The band 3 anion exchange protein (AE1, SLC4A1) exchanges chloride (Cl-) for bicarbonate (HCO3-) across the plasma membrane according to the concentration gradients of the anions (Knauf et al. 1996, Dahl et al. 2003). SLC4A1 may be part of a complex ("metabolon") with carbonic anhydrase II (CA2) which would facilitate the transport of HCO3- (Sterling et al. 2001).
R-HSA-1247668 (Reactome) The binding of oxygen (O2) to hemoglobin (HbA) decreases the affinity of HbA for protons (H+) bound at histidine residues and carbon dioxide (CO2) bound chemically as a carbamate at the N-terminus of the HbA (Ferguson and Roughton 1934, Kernohan & Roughton 1968, Klocke 1973, Morrow et al. 1973, Morrow et al. 1976, Tazawa et al. 1983, Kraan & Rispens 1985, Doyle et al. 1987, Mertzlufft & Brandt 1989, Kalhoff et al.1994, Dash & Bassingthwaighte 2010, reviewed in Jensen 2004). This property of HbA is known as the Haldane Effect and facilitates the exchange of CO2 for O2 in the lungs.
R-HSA-1475436 (Reactome) Carbonic anhydrase I (CA1, Khalifah 1971, Pesando 1975, Simonsson et al. 1982, Ren & Lindskog 1992) and carbonic anhydrase II (CA2, Tibell et al. 1984, Jones & Shaw 1983, Ghannam et al. 1986) hydrate carbon dioxide (CO2) to yield bicarbonate (HCO3-) and a proton (H+). During the reaction a hydroxyl group bound by the zinc ion (Zn2+) attacks the CO2 molecule in the active site to directly form HCO3- (reviewed in Lindskog 1997). The HCO3- is displaced by water, which is then deprotonated by a histidine residue to recreate the Zn2+:hydroxyl group. Depending on the concentrations of reactants the reaction is reversible.
RHAGmim-catalysisR-HSA-1247645 (Reactome)
SLC4A1 dimermim-catalysisR-HSA-1247665 (Reactome)
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