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Summary
DescriptionBiosynthesis and breakdown of serotonin and the catecholamines, and the metabolic block in AADC deficiency.png
English: Biosynthesis and breakdown of serotonin and the catecholamines, and the metabolic block in AADC deficiency. Simplified scheme of the biosynthesis and breakdown of serotonin and the catecholamines (dopamine, norepinephrine and epinephrine), and melatonin synthesis. Cofactors (BH4, PLP, Cu) and methyldonor (SAM) are connected to the respective enzyme with dashed lines. Dashed arrows do not show intermediate steps. The metabolic block caused by AADC deficiency is shown as a red bar. Metabolites above the block are increased, metabolites below the block are decreased, indicated by red arrows. The implication of 5-MTHF in L-dopa to 3-OMD metabolism is shown in a simplified manner. Norepinephrine and epinephrine are broken down to NMET and MET only in the periphery. In CSF, the main metabolite of norepinephrine and epinephrine is MHPG. Abbreviations: AADC: aromatic l-amino acid decarboxylase; BH4: tetrahydrobiopterin; COMT: catechol O-methyl transferase; CSF: cerebrospinal fluid; Cu: cupper; DβH: dopamine beta hydroxylase; DOPAC: dihydroxyphenylacetic acid; HCys: homocysteine; 5-HIAA: 5-hydroxyindoleacetic acid; 5-HTP: 5-hydroxytryptophan; HVA: homovanillic acid; L-Dopa: 3,4-dihydroxyphenylalanine; MAO: monoamine oxidase; MET: metanephrine; Met: metionine; MHPG: 3-methoxy 4-hydroxyphenylglycol; 3MT: 3-Metyramine; 5-MTHF: methyltetrahydrofolate; NMET: normetanephrine; 3-OMD: 3-O-methyldopa (=3-methoxytyrosine); Phe: phenylalanine; PhH: phenylalanine hydroxylase; PNMT: phenylethanolamine N-methyltransferase; SAH: S-adenosylhomocysteine; SAM: s-adenosylmethionine; TH: tyrosine hydroxylase; TrH: tryptophan hydroxylase; Tryp: tryptophan; Tyr: tyrosine; VLA: vanillactic acid; VMA: vanillmandelic acid: Vit B6 vitamin B6 (pyridoxine)
Tessa Wassenberg, Marta Molero-Luis, Kathrin Jeltsch, Georg F. Hoffmann, Birgit Assmann, Nenad Blau, Angeles Garcia-Cazorla, Rafael Artuch, Roser Pons, Toni S. Pearson, Vincenco Leuzzi, Mario Mastrangelo, Phillip L. Pearl, Wang Tso Lee, Manju A. Kurian, Simon Heales, Lisa Flint, Marcel Verbeek, Michèl Willemsen & Thomas Opladen
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Captions
Biosynthesis and breakdown of serotonin and the catecholamines, and the metabolic block in AADC deficiency.