Neurotransmitter clearance in synaptic cleft (Bos taurus)

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21, 10756, 9, 114aldehydedehydrogenase,mitochondrial,tetramer[mitochondrialmatrix]mitochondrial matrixMAOA-FAD complex[mitochondrial outermembrane]cytosol5HT-N-CH3Na+5HT-N-CH3Sodium dependentSerotonintransporterChoH2O25HTAcChoNa+NAdHIAAAdoHcyH2OMAOA-FAD complexDASLC22A2SLC6A3CDNBNH35HTNH3NAD+HIALDH2OO2NADHNa+ACHE oligomerFAD [mitochondrialouter membrane]HIALDDAH2O2COMTH2ONH3O2AdoMetNAdOCT2HCYSAdoMetH+acetateMAOAALDH2H2ONa+aldehydedehydrogenase,mitochondrial,tetramer3, 8


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

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP1870(76869) with a 83.0% conversion rate.

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Bibliography

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  1. Beck O, Helander A, Carlsson S, Borg S.; ''Changes in serotonin metabolism during treatment with the aldehyde dehydrogenase inhibitors disulfiram and cyanamide.''; PubMed Europe PMC Scholia
  2. Vandenbergh DJ, Thompson MD, Cook EH, Bendahhou E, Nguyen T, Krasowski MD, Zarrabian D, Comings D, Sellers EM, Tyndale RF, George SR, O'Dowd BF, Uhl GR.; ''Human dopamine transporter gene: coding region conservation among normal, Tourette's disorder, alcohol dependence and attention-deficit hyperactivity disorder populations.''; PubMed Europe PMC Scholia
  3. Greenfield NJ, Pietruszko R.; ''Two aldehyde dehydrogenases from human liver. Isolation via affinity chromatography and characterization of the isozymes.''; PubMed Europe PMC Scholia
  4. Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, Quester S, Baumann C, Lang F, Busch AE, Koepsell H.; ''Cloning and characterization of two human polyspecific organic cation transporters.''; PubMed Europe PMC Scholia
  5. Canli T, Lesch KP.; ''Long story short: the serotonin transporter in emotion regulation and social cognition.''; PubMed Europe PMC Scholia
  6. Weinstock M, Groner E.; ''Rational design of a drug for Alzheimer's disease with cholinesterase inhibitory and neuroprotective activity.''; PubMed Europe PMC Scholia
  7. O'Carroll AM, Fowler CJ, Phillips JP, Tobbia I, Tipton KF.; ''The deamination of dopamine by human brain monoamine oxidase. Specificity for the two enzyme forms in seven brain regions.''; PubMed Europe PMC Scholia
  8. Hempel J, Kaiser R, Jörnvall H.; ''Mitochondrial aldehyde dehydrogenase from human liver. Primary structure, differences in relation to the cytosolic enzyme, and functional correlations.''; PubMed Europe PMC Scholia
  9. Kryger G, Harel M, Giles K, Toker L, Velan B, Lazar A, Kronman C, Barak D, Ariel N, Shafferman A, Silman I, Sussman JL.; ''Structures of recombinant native and E202Q mutant human acetylcholinesterase complexed with the snake-venom toxin fasciculin-II.''; PubMed Europe PMC Scholia
  10. Fernandez E, Koek W, Ran Q, Gerhardt GA, France CP, Strong R.; ''Monoamine metabolism and behavioral responses to ethanol in mitochondrial aldehyde dehydrogenase knockout mice.''; PubMed Europe PMC Scholia
  11. Velan B, Grosfeld H, Kronman C, Leitner M, Gozes Y, Lazar A, Flashner Y, Marcus D, Cohen S, Shafferman A.; ''The effect of elimination of intersubunit disulfide bonds on the activity, assembly, and secretion of recombinant human acetylcholinesterase. Expression of acetylcholinesterase Cys-580----Ala mutant.''; PubMed Europe PMC Scholia

History

CompareRevisionActionTimeUserComment
117564view11:20, 21 May 2021EweitzModified title
87906view12:57, 25 July 2016ElisaOntology Term : 'signaling pathway' added !
87905view12:57, 25 July 2016ElisaOntology Term : 'signaling pathway pertinent to the brain and nervous system' added !
80737view15:24, 30 June 2015MkutmonNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
5HT-N-CH3MetaboliteCHEBI:3210 (ChEBI)
5HTMetaboliteCHEBI:28790 (ChEBI)
ACHE oligomerComplexREACT_117773 (Reactome)
ALDH2ProteinENSBTAG00000008743 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P05091
AcChoMetaboliteCHEBI:15355 (ChEBI)
AdoHcyMetaboliteCHEBI:16680 (ChEBI)
AdoMetMetaboliteCHEBI:15414 (ChEBI)
CDNBMetaboliteCHEBI:34718 (ChEBI)
COMTProteinENSBTAG00000019516 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P21964
ChoMetaboliteCHEBI:15354 (ChEBI)
DAMetaboliteCHEBI:18243 (ChEBI)
FAD [mitochondrial outer membrane]MetaboliteCHEBI:16238 (ChEBI)
H+MetaboliteCHEBI:15378 (ChEBI)
H2O2MetaboliteCHEBI:16240 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HCYSMetaboliteCHEBI:17230 (ChEBI)
HIAAMetaboliteCHEBI:27823 (ChEBI)
HIALDMetaboliteCHEBI:50157 (ChEBI)
MAOA-FAD complexComplexREACT_5113 (Reactome)
MAOAProteinENSBTAG00000016206 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P21397
NAD+MetaboliteCHEBI:15846 (ChEBI)
NADHMetaboliteCHEBI:16908 (ChEBI)
NAdMetaboliteCHEBI:18357 (ChEBI)
NH3MetaboliteCHEBI:16134 (ChEBI)
Na+MetaboliteCHEBI:29101 (ChEBI)
O2MetaboliteCHEBI:15379 (ChEBI)
OCT2ProteinThis 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.
SLC22A2ProteinENSBTAG00000009583 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:O15244
SLC6A3ProteinENSBTAG00000015843 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q01959
Sodium dependent

Serotonin

transporter		REACT_15766 (Reactome)
acetateMetaboliteCHEBI:30089 (ChEBI)
aldehyde

dehydrogenase, mitochondrial,

tetramer		ComplexREACT_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 oligomermim-catalysisREACT_14816 (Reactome)
AcChoREACT_14816 (Reactome)
AdoHcyArrowREACT_15531 (Reactome)
AdoMetREACT_15531 (Reactome)
AdoMetREACT_15553 (Reactome)
CDNBArrowREACT_15434 (Reactome)
CDNBArrowREACT_15531 (Reactome)
CDNBREACT_15434 (Reactome)
COMTmim-catalysisREACT_15531 (Reactome)
COMTmim-catalysisREACT_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 complexmim-catalysisREACT_15434 (Reactome)
MAOA-FAD complexmim-catalysisREACT_15485 (Reactome)
MAOA-FAD complexmim-catalysisREACT_1795 (Reactome)
NAD+REACT_15407 (Reactome)
NADHArrowREACT_15407 (Reactome)
NAdArrowREACT_15341 (Reactome)
NAdREACT_15341 (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)
OCT2mim-catalysisREACT_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'.

SLC6A3mim-catalysisREACT_15468 (Reactome)
Sodium dependent

Serotonin

transporter		mim-catalysisREACT_15458 (Reactome)
acetateArrowREACT_14816 (Reactome)
aldehyde

dehydrogenase, mitochondrial,

tetramer		mim-catalysisREACT_15407 (Reactome)
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