Neurotransmitter clearance (Homo sapiens)

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42, 9, 115371, 8mitochondrial matrixMAOA-FAD complex aldehyde dehydrogenase, mitochondrial, tetramer cytosolH2ONADHH2OAdoMetAcChoFAD NH35HT-N-CH3HIAANa+ALDH2 H2O2AdoMetSLC6A3HCYSNAdH2OacetateNH35HTMAOA-FAD complexCho5HT-N-CH3MAOA 5HTDAH2OCOMTNH3SLC22A2NAD+ACHE oligomerNa+HIALDAdoHcyO2DAHIALDNa+Na+Sodium dependent Serotonin transporterH+CDNBNAdH2O2O2OCT2aldehyde dehydrogenase, mitochondrial, tetramer6, 10


Description

Neurotransmitter released in the synaptic cleft binds to specific receptors on the post-synaptic cell and the excess of the neurotransmitter is cleared to prevent over activation of the post-synaptic cell. The neurotransmitter is cleared by either re-uptake by the pre-synaptic neuron, diffusion in the perisynaptic area, uptake by astrocytes surrounding the synaptic cleft or enzymatic degradation of the neurotransmitter.
This topic will be annotated in a future release. Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=112311

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Ontology Terms

 

Bibliography

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History

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CompareRevisionActionTimeUserComment
114635view16:09, 25 January 2021ReactomeTeamReactome version 75
113083view11:14, 2 November 2020ReactomeTeamReactome version 74
112317view15:23, 9 October 2020ReactomeTeamReactome version 73
101216view11:11, 1 November 2018ReactomeTeamreactome version 66
100754view20:36, 31 October 2018ReactomeTeamreactome version 65
100298view19:13, 31 October 2018ReactomeTeamreactome version 64
99844view15:57, 31 October 2018ReactomeTeamreactome version 63
99401view14:34, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99092view12:39, 31 October 2018ReactomeTeamreactome version 62
94498view09:04, 14 September 2017Mkutmonreactome version 61
87768view10:01, 25 July 2016RyanmillerOntology Term : 'signaling pathway' added !
87767view10:00, 25 July 2016RyanmillerOntology Term : 'signaling pathway pertinent to the brain and nervous system' added !
86397view09:17, 11 July 2016ReactomeTeamreactome version 56
83079view09:53, 18 November 2015ReactomeTeamVersion54
81400view12:55, 21 August 2015ReactomeTeamVersion53
76869view08:14, 17 July 2014ReactomeTeamFixed remaining interactions
76574view11:55, 16 July 2014ReactomeTeamFixed remaining interactions
75907view09:56, 11 June 2014ReactomeTeamRe-fixing comment source
75607view10:46, 10 June 2014ReactomeTeamReactome 48 Update
74962view13:48, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74606view08:39, 30 April 2014ReactomeTeamReactome46
58006view22:02, 5 February 2013AriuttaPeriodical save, work in progress
42088view21:56, 4 March 2011MaintBotAutomatic update
39896view05:55, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
5HT-N-CH3MetaboliteCHEBI:3210 (ChEBI)
5HTMetaboliteCHEBI:28790 (ChEBI)
ACHE oligomerComplexREACT_117773 (Reactome)
ALDH2 ProteinP05091 (Uniprot-TrEMBL)
AcChoMetaboliteCHEBI:15355 (ChEBI)
AdoHcyMetaboliteCHEBI:16680 (ChEBI)
AdoMetMetaboliteCHEBI:15414 (ChEBI)
CDNBMetaboliteCHEBI:34718 (ChEBI)
COMTProteinP21964 (Uniprot-TrEMBL)
ChoMetaboliteCHEBI:15354 (ChEBI)
DAMetaboliteCHEBI:18243 (ChEBI)
FAD MetaboliteCHEBI:16238 (ChEBI)
H+MetaboliteCHEBI:15378 (ChEBI)
H2O2MetaboliteCHEBI:16240 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HCYSMetaboliteCHEBI:17230 (ChEBI)
HIAAMetaboliteCHEBI:27823 (ChEBI)
HIALDMetaboliteCHEBI:50157 (ChEBI)
MAOA ProteinP21397 (Uniprot-TrEMBL)
MAOA-FAD complexComplexREACT_5113 (Reactome)
NAD+MetaboliteCHEBI:15846 (ChEBI)
NADHMetaboliteCHEBI:16908 (ChEBI)
NAdMetaboliteCHEBI:18357 (ChEBI)
NH3MetaboliteCHEBI:16134 (ChEBI)
Na+MetaboliteCHEBI:29101 (ChEBI)
O2MetaboliteCHEBI:15379 (ChEBI)
OCT2ProteinREACT_160574 (Reactome) This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
SLC22A2ProteinO15244 (Uniprot-TrEMBL)
SLC6A3ProteinQ01959 (Uniprot-TrEMBL)
Sodium dependent Serotonin transporterREACT_15766 (Reactome)
acetateMetaboliteCHEBI:30089 (ChEBI)
aldehyde dehydrogenase, mitochondrial, tetramerComplexREACT_2466 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
5HT-N-CH3ArrowREACT_15434 (Reactome)
5HT-N-CH3ArrowREACT_15485 (Reactome)
5HT-N-CH3ArrowREACT_15553 (Reactome)
5HT-N-CH3REACT_15553 (Reactome)
5HTArrowREACT_15458 (Reactome)
5HTREACT_15458 (Reactome)
5HTREACT_1795 (Reactome)
ACHE oligomerREACT_14816 (Reactome)
AcChoREACT_14816 (Reactome)
AdoHcyArrowREACT_15531 (Reactome)
AdoMetREACT_15531 (Reactome)
AdoMetREACT_15553 (Reactome)
CDNBArrowREACT_15434 (Reactome)
CDNBArrowREACT_15531 (Reactome)
CDNBREACT_15434 (Reactome)
COMTREACT_15531 (Reactome)
COMTREACT_15553 (Reactome)
ChoArrowREACT_14816 (Reactome)
DAArrowREACT_15468 (Reactome)
DAREACT_15468 (Reactome)
DAREACT_15485 (Reactome)
DAREACT_15531 (Reactome)
H+ArrowREACT_15407 (Reactome)
H2O2ArrowREACT_15434 (Reactome)
H2O2ArrowREACT_1795 (Reactome)
H2OREACT_14816 (Reactome)
H2OREACT_15434 (Reactome)
H2OREACT_15485 (Reactome)
H2OREACT_1795 (Reactome)
HCYSArrowREACT_15553 (Reactome)
HIAAArrowREACT_15407 (Reactome)
HIALDArrowREACT_1795 (Reactome)
HIALDREACT_15407 (Reactome)
MAOA-FAD complexREACT_15434 (Reactome)
MAOA-FAD complexREACT_15485 (Reactome)
MAOA-FAD complexREACT_1795 (Reactome)
NAD+REACT_15407 (Reactome)
NADHArrowREACT_15407 (Reactome)
NH3ArrowREACT_15434 (Reactome)
NH3ArrowREACT_15485 (Reactome)
NH3ArrowREACT_1795 (Reactome)
Na+ArrowREACT_15458 (Reactome)
Na+ArrowREACT_15468 (Reactome)
Na+REACT_15458 (Reactome)
Na+REACT_15468 (Reactome)
O2REACT_15434 (Reactome)
O2REACT_15485 (Reactome)
O2REACT_1795 (Reactome)
OCT2REACT_15341 (Reactome)
REACT_14816 (Reactome) Acetylcholinesterase (ACHE) oligomers (comprising monomers, dimers and tetramers), anchored to the extracellular side of the plasma membrane, hydrolyze acetylcholine (AcCho) to form choline (Cho) and acetate (Weinstock & Groner 2008, Velan et al. 1991, Kryger et al. 2000).

Acetylcholine from the synaptic cleft is degraded into inactive molecules, Cho and acetate by ACHE, which is located in the synaptic cleft (Weinstock & Groner 2008).
REACT_15341 (Reactome) Noradrenaline is cleared from the synaptic cleft by Noaradrenaline uptake transporter. This reaction is carried out by neurons as well as astrocytes.
REACT_15407 (Reactome) 5-hydroxyindole acetaldehyde is then catalyzed by aldehyde dehydrogenase to form 5-hydroxyindole acetic acid
REACT_15434 (Reactome) 3-methoxytyramine generated by COMT after methylation of dopamine is oxidized into homovanillic acid by monoamine oxidase A
REACT_15458 (Reactome) The human gene SLC6A4 encodes the sodium-dependent serotonin transporter 5HTT which mediates the re-uptake of serotonin from the synaptic cleft thus terminating the action of serotonin (Canli T and Lesch KP, 2007). The serotonin taken up in the cytosol from the synaptic cleft may be recycled into synaptic vesicles or metabolized.
REACT_15468 (Reactome) The human gene SLC6A3 encodes the sodium-dependent dopamine transporter, DAT which mediates the re-uptake of dopamine from the synaptic cleft (Vandenbergh DJ et al, 2000). Dopamine can then be degraded by either COMT or monoamine oxidase.
REACT_15485 (Reactome) Dopamine is oxidized to 3,4-dihydroxyphenylacetic acid by monoamine oxidase.
REACT_15531 (Reactome) Dopamine in the cytosol is metabolized to 3-methoxytyramine by catecholamine o-methyltransferase (COMT), which uses s-adenosylmethionine as a methyl group donor.
REACT_15553 (Reactome) 3,4-dihydroxyphenylacetic acid, generated after oxidation of dopamine by monoamineoxidase, is methylated by catecholamine o-methyltransferase to homovanillic acid.
REACT_1795 (Reactome) At the beginning of this reaction, 1 molecule of 'Oxygen', 1 molecule of 'H2O', and 1 molecule of '5-Hydroxytryptamine' are present. At the end of this reaction, 1 molecule of 'NH3', 1 molecule of '5-Hydroxyindoleacetaldehyde', and 1 molecule of 'H2O2' are present.

This reaction takes place in the 'mitochondrial outer membrane' and is mediated by the 'amine oxidase activity' of 'MAOA-FAD complex'.

SLC6A3REACT_15468 (Reactome)
Sodium dependent Serotonin transporterREACT_15458 (Reactome)
acetateArrowREACT_14816 (Reactome)
aldehyde dehydrogenase, mitochondrial, tetramerREACT_15407 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1870"
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