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

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6, 18, 202, 7, 11-13, 22...8, 9, 19, 21, 27...15, 38, 404, 17, 31, 34, 361, 3, 5, 8, 14...4, 24, 3110, 42, 44cytosolZn2+ HBB CYB5RsRHAGH2OProtonated CarbaminoDeoxyHbAHCO3-heme H+NAD+O2SLC4A1 HBA1 Cl-MetHbHBB H2OHBA1 CA1,2NADHCO-H+-HBB O2 HCO3-CYB5R4 SLC4A1 dimerheme CYB5R2 CA1 N-seryl-glycosylphosphatidylinositolethanolamine-CA4 CYB5R1 H+HBB CA2 AQP1 H+OxyHbACO2HbAZn2+ CYB5RL CO-H+-HBA1 FeHM Cl-CO2HBA1 AQP1 tetramerheme CA4:Zn2+16, 43, 4647-4930


Description

Carbon dioxide (CO2) in plasma is hydrated to yield protons (H+) and bicarbonate (HCO3-) by carbonic anhydrase IV (CA4) located on the apical plasma membranes of endothelial cells. Plasma CO2 is also taken up by erythrocytes via AQP1 and RhAG. Within erythrocytes CA1 and, predominantly, CA2 hydrate CO2 to HCO3- and protons (reviewed in Geers & Gros 2000, Jensen 2004, Boron 2010). The HCO3- is transferred out of the erythrocyte by the band 3 anion exchange protein (AE1, SLC4A1) which cotransports a chloride ion (Cl-) into the erythrocyte.
Also within the erythrocyte, CO2 combines with the N-terminal alpha amino groups of HbA to form carbamates while protons bind histidine residues in HbA. The net result is the Bohr effect, a conformational change in HbA that reduces its affinity for O2 and hence assists the delivery of O2 to tissues. View original pathway at Reactome.

Comments

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Pathway is converted from Reactome ID: 1237044
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Reactome version: 75
Reactome Author 
Reactome Author: May, Bruce

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Bibliography

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History

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CompareRevisionActionTimeUserComment
114620view16:08, 25 January 2021ReactomeTeamReactome version 75
113068view11:12, 2 November 2020ReactomeTeamReactome version 74
112303view15:22, 9 October 2020ReactomeTeamReactome version 73
101201view11:10, 1 November 2018ReactomeTeamreactome version 66
100739view20:34, 31 October 2018ReactomeTeamreactome version 65
100283view19:11, 31 October 2018ReactomeTeamreactome version 64
99829view15:55, 31 October 2018ReactomeTeamreactome version 63
99386view14:33, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99084view12:39, 31 October 2018ReactomeTeamreactome version 62
93916view13:44, 16 August 2017ReactomeTeamreactome version 61
93492view11:25, 9 August 2017ReactomeTeamreactome version 61
87441view13:40, 22 July 2016MkutmonOntology Term : 'classic metabolic pathway' added !
86588view09:21, 11 July 2016ReactomeTeamreactome version 56
83189view10:19, 18 November 2015ReactomeTeamVersion54
81766view10:11, 26 August 2015ReactomeTeamVersion53
76982view08:27, 17 July 2014ReactomeTeamFixed remaining interactions
76687view12:05, 16 July 2014ReactomeTeamFixed remaining interactions
76014view10:07, 11 June 2014ReactomeTeamRe-fixing comment source
75722view11:18, 10 June 2014ReactomeTeamReactome 48 Update
75073view14:02, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74719view08:47, 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)
CYB5R1 ProteinQ9UHQ9 (Uniprot-TrEMBL)
CYB5R2 ProteinQ6BCY4 (Uniprot-TrEMBL)
CYB5R4 ProteinQ7L1T6 (Uniprot-TrEMBL)
CYB5RL ProteinQ6IPT4 (Uniprot-TrEMBL)
CYB5RsComplexR-HSA-6806851 (Reactome)
Cl-MetaboliteCHEBI:17996 (ChEBI)
FeHM MetaboliteCHEBI:36144 (ChEBI)
H+MetaboliteCHEBI:15378 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HBA1 ProteinP69905 (Uniprot-TrEMBL)
HBB ProteinP68871 (Uniprot-TrEMBL)
HCO3-MetaboliteCHEBI:17544 (ChEBI)
HbAComplexR-HSA-9033252 (Reactome)
MetHbComplexR-HSA-9033251 (Reactome)
N-seryl-glycosylphosphatidylinositolethanolamine-CA4 ProteinP22748 (Uniprot-TrEMBL)
NAD+MetaboliteCHEBI:57540 (ChEBI)
NADHMetaboliteCHEBI:57945 (ChEBI)
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-1237042 (Reactome)
CA1,2mim-catalysisR-HSA-1475435 (Reactome)
CA4:Zn2+mim-catalysisR-HSA-1237047 (Reactome)
CO2ArrowR-HSA-1237042 (Reactome)
CO2ArrowR-HSA-1237069 (Reactome)
CO2R-HSA-1237042 (Reactome)
CO2R-HSA-1237047 (Reactome)
CO2R-HSA-1237069 (Reactome)
CO2R-HSA-1237325 (Reactome)
CO2R-HSA-1475435 (Reactome)
CYB5Rsmim-catalysisR-HSA-6806831 (Reactome)
Cl-ArrowR-HSA-1237038 (Reactome)
Cl-R-HSA-1237038 (Reactome)
H+ArrowR-HSA-1237047 (Reactome)
H+ArrowR-HSA-1475435 (Reactome)
H+ArrowR-HSA-6806831 (Reactome)
H+R-HSA-1237325 (Reactome)
H2OR-HSA-1237047 (Reactome)
H2OR-HSA-1475435 (Reactome)
HCO3-ArrowR-HSA-1237038 (Reactome)
HCO3-ArrowR-HSA-1237047 (Reactome)
HCO3-ArrowR-HSA-1475435 (Reactome)
HCO3-R-HSA-1237038 (Reactome)
HbAArrowR-HSA-6806831 (Reactome)
MetHbR-HSA-6806831 (Reactome)
NAD+ArrowR-HSA-6806831 (Reactome)
NADHR-HSA-6806831 (Reactome)
O2ArrowR-HSA-1237325 (Reactome)
OxyHbAR-HSA-1237325 (Reactome)
Protonated Carbamino DeoxyHbAArrowR-HSA-1237325 (Reactome)
R-HSA-1237038 (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-1237042 (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-1237047 (Reactome) Carbonic anhydrase IV (CA4) anchored to extracellular face of the plasma membrane (Wistrand et al. 1999) hydrates carbon dioxide (CO2) to yield bicarbonate (HCO3-) and a proton (H+) (Zhu & Sly 1990, Okayuma et al. 1992, Baird et al. 1997, Innocenti et al. 2004). During the reaction a hydroxyl group bound by the zinc ion (Zn2+) of CA4 attacks the CO2 molecule 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.
R-HSA-1237069 (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-1237325 (Reactome) The Bohr effect refers to the observation that carbon dioxide (CO2) decreases the affinity of hemoglobin (HbA) for oxygen (O2) (Rossi-Bernardi & Roughton 1967, Kwant et al. 1988, Dash & Bassingthwaighte 2010). The Bohr effect has two components: protonation of histidines in HbA (Chatake et al. 2007, Kovalevsky et al. 2010, Fang et al. 1999) and chemical reaction (carbamation) of the N-terminal valines of HbA by CO2 (Ferguson & Roughton 1934, Forster et al. 1968, Bauer & Schroder 1972, Morrow et al. 1973, Morrow et al. 1976, Mathew et al. 1977, Acharya et al. 1994). The protons (H+) for this reaction are produced by carbonic anhydrase acting on water and CO2 to produce bicarbonate (HCO3-) and H+ (Kernohan & Roughton 1968).
R-HSA-1475435 (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.
R-HSA-6806831 (Reactome) NADH-Cytochrome b5 reductases (CYB5Rs), flavoproteins consisting of NADH and flavin adenine dinucleotide (FAD) binding domains, catalyse electron transfer from the two-electron carrier NADH to the one-electron carrier ferricytochrome b5 ((Fe(3+)Cb5), forming ferrocytochrome b5 ((Fe(2+)Cb5) (Zhu et al. 1999, Baker et al. 2005, Zhu et al. 2004). CYB5Rs participate in fatty acid synthesis, cholesterol synthesis and xenobiotic oxidation as members of the electron transport chain on the endoplasmic reticulum membrane. In erythrocytes, CYB5Rs participate in the reduction of methemoglobin (MetHb) to hemoglobin A (HbA).
RHAGmim-catalysisR-HSA-1237069 (Reactome)
SLC4A1 dimermim-catalysisR-HSA-1237038 (Reactome)
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