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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COMT (Catechol-O-methyltransferase)
C
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MAO-A (Monoamine oxidase A)
C
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MAO-B (Monoamine oxidase B)
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]
* Bastos P, Gomes T, Ribeiro L. (2017) Catechol-O-Methyltransferase (COMT): An Update on Its Role in Cancer, Neurological and Cardiovascular Diseases. Rev Physiol Biochem Pharmacol, 173: 1-39. [PMID:28456872]
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]
* Kolla NJ, Bortolato M. (2020) The role of monoamine oxidase A in the neurobiology of aggressive, antisocial, and violent behavior: A tale of mice and men. Prog Neurobiol, 194: 101875. [PMID:32574581]
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]
* Manzoor S, Hoda N. (2020) A comprehensive review of monoamine oxidase inhibitors as Anti-Alzheimer's disease agents: A review. Eur J Med Chem, 206: 112787. [PMID:32942081]
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]
* Silva TB, Borges F, Serrão MP, Soares-da-Silva P. (2020) Liver says no: the ongoing search for safe catechol O-methyltransferase inhibitors to replace tolcapone. Drug Discov Today, 25 (10): 1846-1854. [PMID:32687872]
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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2. Binda C, Hubálek F, Li M, Herzig Y, Sterling J, Edmondson DE, Mattevi A. (2004) Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class. J Med Chem, 47 (7): 1767-74. [PMID:15027868]
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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17. Stanley WC, Li B, Bonhaus DW, Johnson LG, Lee K, Porter S, Walker K, Martinez G, Eglen RM, Whiting RL et al.. (1997) Catecholamine modulatory effects of nepicastat (RS-25560-197), a novel, potent and selective inhibitor of dopamine-beta-hydroxylase. Br J Pharmacol, 121 (8): 1803-9. [PMID:9283721]
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How to cite this family page
Database page citation:
Catecholamine turnover. Accessed on 13/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=766.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.
