Catecholamine turnover C
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Overview
Catecholamines are defined by the presence of two adjacent hydroxyls on a benzene ring with a sidechain containing an amine. The predominant catacholamines in mammalian biology are the neurotransmitter/hormones dopamine, (-)-noradrenaline (norepinephrine) and (-)-adrenaline (epinephrine). These hormone/transmitters are synthesized by sequential metabolism from L-phenylalanine via L-tyrosine. Hydroxylation of L-tyrosine generates levodopa, which is decarboxylated to form dopamine. Hydroxylation of the ethylamine sidechain generates (-)-noradrenaline (norepinephrine), which can be methylated to form (-)-adrenaline (epinephrine). In particular neuronal and adrenal chromaffin cells, the catecholamines dopamine, (-)-noradrenaline and (-)-adrenaline are accumulated into vesicles under the influence of the vesicular monoamine transporters (VMAT1/SLC18A1 and VMAT2/SLC18A2). After release into the synapse or the bloodstream, catecholamines are accumulated through the action cell-surface transporters, primarily the dopamine (DAT/SLC6A3) and norepinephrine transporter (NET/SLC6A2). The primary routes of metabolism of these catecholamines are oxidation via monoamine oxidase activities of methylation via catechol O-methyltransferase.
Enzymes
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L-Phenylalanine hydroxylase
C
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TAT (Tyrosine aminotransferase) C Show summary »« Hide summary
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L-Tyrosine hydroxylase
C
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AADC (L-Aromatic amino-acid decarboxylase )
C
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DBH (Dopamine beta-hydroxylase (dopamine beta-monooxygenase)) C Show summary »« Hide summary
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PNMT (Phenylethanolamine N-methyltransferase) C Show summary »« Hide summary
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MAO-A (Monoamine oxidase A)
C
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MAO-B (Monoamine oxidase B)
C
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COMT (Catechol-O-methyltransferase)
C
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Further reading
* Key recommended reading is highlighted with an asterisk
Al-Nuaimi SK, Mackenzie EM, Baker GB. (2012) Monoamine oxidase inhibitors and neuroprotection: a review. Am J Ther, 19 (6): 436-48. [PMID:22960850]
Daubner SC, Le T, Wang S. (2011) Tyrosine hydroxylase and regulation of dopamine synthesis. Arch. Biochem. Biophys., 508 (1): 1-12. [PMID:21176768]
* Dauvilliers Y, Tafti M, Landolt HP. (2015) Catechol-O-methyltransferase, dopamine, and sleep-wake regulation. Sleep Med Rev, 22: 47-53. [PMID:25466290]
* Deshwal S, Di Sante M, Di Lisa F, Kaludercic N. (2017) Emerging role of monoamine oxidase as a therapeutic target for cardiovascular disease. Curr Opin Pharmacol, 33: 64-69. [PMID:28528298]
Dixon Clarke SE, Ramsay RR. (2011) Dietary inhibitors of monoamine oxidase A. J Neural Transm, 118 (7): 1031-41. [PMID:21190052]
Fitzpatrick PF. (2010) Oxidation of amines by flavoproteins. Arch. Biochem. Biophys., 493 (1): 13-25. [PMID:19651103]
Fitzpatrick PF. (2012) Allosteric regulation of phenylalanine hydroxylase. Arch. Biochem. Biophys., 519 (2): 194-201. [PMID:22005392]
* Fišar Z. (2016) Drugs related to monoamine oxidase activity. Prog. Neuropsychopharmacol. Biol. Psychiatry, 69: 112-24. [PMID:26944656]
Flydal MI, Martinez A. (2013) Phenylalanine hydroxylase: function, structure, and regulation. IUBMB Life, 65 (4): 341-9. [PMID:23457044]
Kaludercic N, Carpi A, Menabò R, Di Lisa F, Paolocci N. (2011) Monoamine oxidases (MAO) in the pathogenesis of heart failure and ischemia/reperfusion injury. Biochim. Biophys. Acta, 1813 (7): 1323-32. [PMID:20869994]
Ma Z, Liu H, Wu B. (2014) Structure-based drug design of catechol-O-methyltransferase inhibitors for CNS disorders. Br J Clin Pharmacol, 77 (3): 410-20. [PMID:23713800]
* Ramsay RR. (2016) Molecular aspects of monoamine oxidase B. Prog. Neuropsychopharmacol. Biol. Psychiatry, 69: 81-9. [PMID:26891670]
Shih JC, Wu JB, Chen K. (2011) Transcriptional regulation and multiple functions of MAO genes. J Neural Transm, 118 (7): 979-86. [PMID:21359973]
Sánchez-Jiménez F, Ruiz-Pérez MV, Urdiales JL, Medina MA. (2013) Pharmacological potential of biogenic amine-polyamine interactions beyond neurotransmission. Br. J. Pharmacol., 170 (1): 4-16. [PMID:23347064]
* Waløen K, Kleppe R, Martinez A, Haavik J. (2017) Tyrosine and tryptophan hydroxylases as therapeutic targets in human disease. Expert Opin. Ther. Targets, 21 (2): 167-180. [PMID:27973928]
Wang CC, Billett E, Borchert A, Kuhn H, Ufer C. (2013) Monoamine oxidases in development. Cell. Mol. Life Sci., 70 (4): 599-630. [PMID:22782111]
Witte AV, Flöel A. (2012) Effects of COMT polymorphisms on brain function and behavior in health and disease. Brain Res. Bull., 88 (5): 418-28. [PMID:22138198]
References
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3. Binda C, Wang J, Li M, Hubalek F, Mattevi A, Edmondson DE. (2008) Structural and mechanistic studies of arylalkylhydrazine inhibition of human monoamine oxidases A and B. Biochemistry, 47 (20): 5616-25. [PMID:18426226]
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19. Yoshida S, Rosen TC, Meyer OG, Sloan MJ, Ye S, Haufe G, Kirk KL. (2004) Fluorinated phenylcyclopropylamines. Part 3: Inhibition of monoamine oxidase A and B. Bioorg. Med. Chem., 12 (10): 2645-52. [PMID:15110846]
20. Youdim MB, Gross A, Finberg JP. (2001) Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. Br. J. Pharmacol., 132 (2): 500-6. [PMID:11159700]
How to cite this family page
Database page citation:
Catecholamine turnover. Accessed on 21/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=766.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Marrion NV, Peters JA, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2017) The Concise Guide to PHARMACOLOGY 2017/18: Enzymes. Br J Pharmacol. 174 Suppl 1: S272-S359.
