Neurotransmitter disorders (WP4220)

Homo sapiens

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Neurotransmitters are chemical messengers which mediate, amplify, or modulate synaptic transmissions between neurons, meaning that many are involved in primary brain functions such as movement, pain threshold, memory, and so on. The are various disorders associated with neurotransmitter dysfunction, which may also be caused by defects in the neurotransmitter transporters. This pathway describes various defects including deficiencies of tyrosine hydrolyse (TH), aromatic l-amino acid decarboxylase (AADC), dopamine Beta-Hydroxylase (DBH), monoamine oxidase A, as well as the heredity dopamine transporter syndrome and the brain dopamine-serotonin vesicular transporter (VMAT2) disease. This pathway was inspired by Edition 5, Chapter 19 of the book of Blau (ISBN 9783030677268) (Ed.4 Chapter 31).

Authors

Ann Friesacher , Denise Slenter , Egon Willighagen , Kristina Hanspers , Irene Hemel , Martina Summer-Kutmon , Eric Weitz , and Finterly Hu

Activity

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Organisms

Homo sapiens

Communities

Diseases Inherited Metabolic Disorders (IMD) Pathways Rare Diseases

Annotations

Disease Ontology

Parkinsonism dystonia dopamine beta-hydroxylase deficiency aromatic L-amino acid decarboxylase deficiency Brunner Syndrome

Pathway Ontology

neurotransmitter metabolic pathway tyrosine degradation pathway epinephrine biosynthetic pathway dopamine beta-hydroxylase deficiency pathway dopamine degradation pathway serotonin metabolic pathway epinephrine metabolic pathway tryptophan metabolic pathway aromatic L-amino acid decarboxylase deficiency pathway dopamine biosynthetic pathway serotonin biosynthetic pathway tyrosine metabolic pathway Segawa syndrome pathway dopamine metabolic pathway tryptophan degradation pathway epinephrine degradation pathway

Participants
Query Drugst.One

Label Type Compact Identifier Comment
melatonin Metabolite chebi:16796
Dihydroxyphenylacetic acid Metabolite chebi:41941 AKA DOPAC
5-HIAL Metabolite pubchem.compound:74688 AKA 5-hydroxyindoleacetaldehyde
Vanillylmandelic acid Metabolite chebi:27622
Epinephrine Metabolite wikidata:Q132621
3-methoxy-4-hydroxyphenylglycol Metabolite wikidata:Q223097 AKA MHPG, MOPG
Norepinephrine Metabolite chebi:72587
Dopamine Metabolite chebi:59905
L-Tyrosine Metabolite chebi:58315
Serotonin Metabolite chebi:28790
Normetanephrine Metabolite wikidata:Q517109
Metanephrine Metabolite hmdb:HMDB0004063 AKA MET
Vanillactic acid Metabolite hmdb:HMDB0000913 AKA VLA
Homovanillic acid Metabolite chebi:545959 AKA HVA
L-Tryptophan Metabolite chebi:16828
5-Hydroxytryptophan Metabolite chebi:17780 AKA 5-HTP
5-Hydroxyindoleacetic acid Metabolite chebi:27823 AKA 5-HIAA
3-O-methyldopa Metabolite chebi:82913 AKA 3OMD
3-Methoxytyramine Metabolite chebi:1582 AKA 3MT
L-Dopa Metabolite chebi:57504 AKA levodopa
Dopamine Metabolite chebi:59905
Serotonin Metabolite chebi:28790
Norepinephrine Metabolite chebi:72587
PLP Metabolite chebi:18405 AKA Pyridoxal phosphate, cofactor
BH4 Metabolite chebi:30436 AKA tetrahydropterin, cofactor
qBH2 Metabolite chebi:43120 AKA tetrahydropterin, cofactor
BH4 Metabolite chebi:30436 AKA tetrahydropterin, cofactor
qBH2 Metabolite chebi:43120 AKA tetrahydropterin, cofactor
BH4 Metabolite chebi:30436 AKA tetrahydropterin, cofactor
SLC18A2 GeneProduct ncbigene:6571 AKA VMAT2
SLC18A2 GeneProduct ncbigene:6571 AKA VMAT2
SLC18A2 GeneProduct ncbigene:6571 AKA VMAT2
DBH Protein uniprot:P09172 AKA Dopamine beta-hydrocylase
Located membrane-bound and intra-vesicular [PMID: 30372766]
Aldehyde dehydrogenase Protein eccode:1.2.1.3
SLC6A3 Protein uniprot:Q01959
PNMT Protein uniprot:P11086 AKA Phenylethanolamine N-methyltransferase
TH Protein uniprot:P07101 AKA Tyrosine 3-mono oxygenase, TYH
MAOA Protein ncbigene:4128 AKA Monoamine oxidase A
AADC Protein uniprot:P20711 AKA Aromatic L-amino acid decarboxylase, DCC
MAOA Protein ncbigene:4128 AKA Monoamine oxidase A
MAOA Protein ncbigene:4128 AKA Monoamine oxidase A
TPH Protein eccode:1.14.16.4 AKA Tryptophan hydroxylase
TPH1 Protein uniprot:P17752 AKA Tryptophan hydroxylase
Expressed in skin, gut and pineal gland (tissues where serotonint is expressed), and also in the CNS.
TPH2 Protein uniprot:Q8IWU9 AKA Tryptophan hydroxylase
Expressed in neuronal cells, and the predominant isoform of the Central Nervous System (CNS).
COMT Protein uniprot:P21964 AKA Catechol-O- metyltransferase
COMT Protein uniprot:P21964 AKA Catechol-O- metyltransferase

References

  1. Biosynthesis of tetrahydrobiopterin by de novo and salvage pathways in adrenal medulla extracts, mammalian cell cultures, and rat brain in vivo. Nichol CA, Lee CL, Edelstein MP, Chao JY, Duch DS. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1546–50. PubMed Europe PMC Scholia
  2. Synthesis and recycling of tetrahydrobiopterin in endothelial function and vascular disease. Crabtree MJ, Channon KM. Nitric Oxide. 2011 Aug 1;25(2):81–8. PubMed Europe PMC Scholia
  3. Inherited Disorders of Neurotransmitters: Classification and Practical Approaches for Diagnosis and Treatment. Brennenstuhl H, Jung-Klawitter S, Assmann B, Opladen T. Neuropediatrics. 2019 Feb;50(1):2–14. PubMed Europe PMC Scholia