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). fdc dbe AKA DOPAC AKA 5-hydroxyindoleacetaldehyde AKA MHPG, MOPG AKA Dopamine beta-hydrocylase Located membrane-bound and intra-vesicular [PMID: 30372766] AKA MET AKA VLA AKA VMAT2 AKA HVA AKA 5-HTP AKA Phenylethanolamine N-methyltransferase AKA 5-HIAA AKA 3OMD AKA 3MT AKA Tyrosine 3-mono oxygenase, TYH AKA Monoamine oxidase A AKA levodopa AKA Aromatic L-amino acid decarboxylase, DCC AKA Monoamine oxidase A AKA Monoamine oxidase A AKA VMAT2 AKA VMAT2 AKA Tryptophan hydroxylase AKA Tryptophan hydroxylase Expressed in skin, gut and pineal gland (tissues where serotonint is expressed), and also in the CNS. AKA Tryptophan hydroxylase Expressed in neuronal cells, and the predominant isoform of the Central Nervous System (CNS). AKA Pyridoxal phosphate, cofactor AKA tetrahydropterin, cofactor AKA tetrahydropterin, cofactor AKA tetrahydropterin, cofactor AKA tetrahydropterin, cofactor AKA tetrahydropterin, cofactor AKA Catechol-O- metyltransferase AKA Catechol-O- metyltransferase dbe dbe dbe dbe dbe not found in Rhea dbe Transport from synaptic cleft to cytosol dbe Several steps involved dbe Transport from cytosol to synaptic vesicles dbe dbe dbe Several steps involved dbe "During the hydroxylation of tyrosine, tryptophan, and phenylalanine, BH4 is converted to Q-BH2 which can be reduced to BH4 by DHPR. Q-BH2 is rearranged rapidly to the more stable 7,8-BH2 isomer which does not serve as a substrate for DHPR" [PMID:6572916] dc8 b30 dbe Transport from cytosol to synaptic vesicles Transport from cytosol to synaptic vesicles "During the hydroxylation of tyrosine, tryptophan, and phenylalanine, BH4 is converted to Q-BH2 which can be reduced to BH4 by DHPR. Q-BH2 is rearranged rapidly to the more stable 7,8-BH2 isomer which does not serve as a substrate for DHPR" [PMID:6572916] dc8 b30 "During the hydroxylation of tyrosine, tryptophan, and phenylalanine, BH4 is converted to Q-BH2 which can be reduced to BH4 by DHPR. Q-BH2 is rearranged rapidly to the more stable 7,8-BH2 isomer which does not serve as a substrate for DHPR" [PMID:6572916] dc8 b30 dbe dbe dbe AKA Brunner syndrome AKA infantile parkinsonism-dystonia AKA SEGAWA syndrome, DYPT5b, DYT/PARK-TH AKA PARKINSONISM-DYSTONIA 2, INFANTILE-ONSET DISEASE caused by deficiency AKA ORTHOSTATIC HYPOTENSION 1, Norepinephrine deficiency AKA PARKINSONISM-DYSTONIA 2, INFANTILE-ONSET dbe dopamine beta-hydroxylase deficiency DOID:0090145 Disease 9783642403361 ISBN Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases Springer-Verlag Berlin Heidelberg 2014 Nenad Blau Marinus Duran K Michael Gibson Carlo Dionisi-Vici neurotransmitter metabolic pathway PW:0000407 Pathway Ontology Parkinsonism DOID:0080855 Disease Segawa syndrome pathway PW:0001612 Pathway Ontology dystonia DOID:543 Disease tryptophan degradation pathway PW:0001281 Pathway Ontology 30372766 PubMed Inherited Disorders of Neurotransmitters: Classification and Practical Approaches for Diagnosis and Treatment Neuropediatrics . 2019 Heiko Brennenstuhl Sabine Jung-Klawitter Birgit Assmann Thomas Opladen dopamine degradation pathway PW:0002511 Pathway Ontology 21550412 PubMed Synthesis and recycling of tetrahydrobiopterin in endothelial function and vascular disease Nitric Oxide 2011 Mark J Crabtree Keith M Channon serotonin biosynthetic pathway PW:0001237 Pathway Ontology dopamine metabolic pathway PW:0000409 Pathway Ontology aromatic L-amino acid decarboxylase deficiency DOID:0090123 Disease tyrosine degradation pathway PW:0001284 Pathway Ontology tyrosine metabolic pathway PW:0000052 Pathway Ontology dopamine beta hydroxylase deficiency pathway PW:0002208 Pathway Ontology Brunner Syndrome DOID:0060693 Disease epinephrine metabolic pathway PW:0000441 Pathway Ontology epinephrine degradation pathway PW:0002512 Pathway Ontology dopamine biosynthetic pathway PW:0000802 Pathway Ontology epinephrine biosynthetic pathway PW:0000803 Pathway Ontology 6572916 PubMed Biosynthesis of tetrahydrobiopterin by de novo and salvage pathways in adrenal medulla extracts, mammalian cell cultures, and rat brain in vivo Proc Natl Acad Sci U S A . 1983 C A Nichol C L Lee M P Edelstein J Y Chao D S Duch serotonin metabolic pathway PW:0000410 Pathway Ontology aromatic amino acid decarboxylase deficiency pathway PW:0002324 Pathway Ontology tryptophan metabolic pathway PW:0000054 Pathway Ontology