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

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8, 22, 376, 7, 11, 14, 26...16, 25, 381, 2, 4, 5, 12...16, 18, 21, 23, 3815, 30, 323, 9, 13, 17, 19...CA4:Zn2+ [plasmamembrane]SLC4A1 dimer [plasmamembrane]Protonated CarbaminoHemoglobinalpha:ferroheme b[cytosol]CA1/CA2 [cytosol]CA1:Zn2+ [cytosol]Protonated CarbaminoDeoxyHbA [cytosol]Hemoglobinbeta:ferrohemeb:oxygen [cytosol]OxyHbA [cytosol]CA2:Zn2+ [cytosol]Hemoglobinalpha:ferrohemeb:oxygen [cytosol]Protonated CarbaminoHemoglobin beta:ferroheme b[cytosol]cytosolAQP1 tetramer[plasma membrane]H2OH+SLC4A1 [plasmamembrane]Cl-HCO3-CA2 [cytosol]CO-H+-HBB [cytosol]O2H+CO2AQP1 [plasmamembrane]HBB [cytosol]CA4:Zn2+HCO3-RHAGSLC4A1 dimerH2Oferroheme b[cytosol]O2 [cytosol]AQP1 tetramerZn2+ [cytosol]CA1/CA2CA1 [cytosol]OxyHbAferroheme b[cytosol]CO-H+-HBA1 [cytosol]Zn2+ [extracellularregion]Protonated CarbaminoDeoxyHbAN-seryl-glycosylphosphatidylinositolethanolamine-CA4[plasma membrane]HBA1 [cytosol]Cl-CO21020, 31, 4233, 39, 43


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.Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=1247673

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Bibliography

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History

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114973view16:50, 25 January 2021ReactomeTeamReactome version 75
113417view11:49, 2 November 2020ReactomeTeamReactome version 74
112619view15:59, 9 October 2020ReactomeTeamReactome version 73
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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 [plasma membrane]ProteinP29972 (Uniprot-TrEMBL)
AQP1 tetramerComplexREACT_24230 (Reactome)
CA1 [cytosol]ProteinP00915 (Uniprot-TrEMBL)
CA1/CA2ComplexREACT_124189 (Reactome)
CA2 [cytosol]ProteinP00918 (Uniprot-TrEMBL)
CA4:Zn2+ComplexREACT_123990 (Reactome)
CO-H+-HBA1 [cytosol]ProteinP69905 (Uniprot-TrEMBL)
CO-H+-HBB [cytosol]ProteinP68871 (Uniprot-TrEMBL)
CO2MetaboliteCHEBI:16526 (ChEBI)
Cl-MetaboliteCHEBI:17996 (ChEBI)
H+MetaboliteCHEBI:15378 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HBA1 [cytosol]ProteinP69905 (Uniprot-TrEMBL)
HBB [cytosol]ProteinP68871 (Uniprot-TrEMBL)
HCO3-MetaboliteCHEBI:17544 (ChEBI)
N-seryl-glycosylphosphatidylinositolethanolamine-CA4 [plasma membrane]ProteinP22748 (Uniprot-TrEMBL)
O2 [cytosol]MetaboliteCHEBI:15379 (ChEBI)
O2MetaboliteCHEBI:15379 (ChEBI)
OxyHbAComplexREACT_123853 (Reactome)
Protonated Carbamino DeoxyHbAComplexREACT_125222 (Reactome)
RHAGProteinQ02094 (Uniprot-TrEMBL)
SLC4A1 [plasma membrane]ProteinP02730 (Uniprot-TrEMBL)
SLC4A1 dimerComplexREACT_125443 (Reactome)
Zn2+ [cytosol]MetaboliteCHEBI:29105 (ChEBI)
Zn2+ [extracellular region]MetaboliteCHEBI:29105 (ChEBI)
ferroheme b [cytosol]MetaboliteCHEBI:17627 (ChEBI)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
AQP1 tetramermim-catalysisREACT_121218 (Reactome)
CA1/CA2mim-catalysisREACT_120912 (Reactome)
CA4:Zn2+mim-catalysisREACT_120877 (Reactome)
CO2ArrowREACT_120816 (Reactome)
CO2ArrowREACT_120877 (Reactome)
CO2ArrowREACT_120912 (Reactome)
CO2ArrowREACT_121218 (Reactome)
CO2ArrowREACT_121236 (Reactome)
CO2REACT_121218 (Reactome)
CO2REACT_121236 (Reactome)
Cl-ArrowREACT_120922 (Reactome)
Cl-REACT_120922 (Reactome)
H+ArrowREACT_120816 (Reactome)
H+REACT_120877 (Reactome)
H+REACT_120912 (Reactome)
H2OArrowREACT_120877 (Reactome)
H2OArrowREACT_120912 (Reactome)
HCO3-ArrowREACT_120922 (Reactome)
HCO3-REACT_120877 (Reactome)
HCO3-REACT_120912 (Reactome)
HCO3-REACT_120922 (Reactome)
O2REACT_120816 (Reactome)
OxyHbAArrowREACT_120816 (Reactome)
Protonated Carbamino DeoxyHbAREACT_120816 (Reactome)
REACT_120816 (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.
REACT_120877 (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.
REACT_120912 (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.
REACT_120922 (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).
REACT_121218 (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.
REACT_121236 (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).
RHAGmim-catalysisREACT_121236 (Reactome)
SLC4A1 dimermim-catalysisREACT_120922 (Reactome)
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