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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).
The amino acid hydroxylases (monooxygenases), EC.1.14.16.-, are iron-containing enzymes which utilise molecular oxygen and sapropterin as co-substrate and co-factor, respectively. In humans, as well as in other mammals, there are two distinct L-Tryptophan hydroxylase 2 genes. In humans, these genes are located on chromosomes 11 and 12 and encode two different homologous enzymes, TPH1 and TPH2.
* Key recommended reading is highlighted with an asterisk
* Amireault P, Sibon D, Côté F. (2013) Life without peripheral serotonin: insights from tryptophan hydroxylase 1 knockout mice reveal the existence of paracrine/autocrine serotonergic networks. ACS Chem Neurosci, 4 (1): 64-71. [PMID:23336045]
* Daubner SC, Le T, Wang S. (2011) Tyrosine hydroxylase and regulation of dopamine synthesis. Arch. Biochem. Biophys., 508 (1): 1-12. [PMID:21176768]
Fitzpatrick PF. (2012) Allosteric regulation of phenylalanine hydroxylase. Arch. Biochem. Biophys., 519 (2): 194-201. [PMID:22005392]
* Flydal MI, Martinez A. (2013) Phenylalanine hydroxylase: function, structure, and regulation. IUBMB Life, 65 (4): 341-9. [PMID:23457044]
Lehmann IT, Bobrovskaya L, Gordon SL, Dunkley PR, Dickson PW. (2006) Differential regulation of the human tyrosine hydroxylase isoforms via hierarchical phosphorylation. J. Biol. Chem., 281 (26): 17644-51. [PMID:16644734]
Matthes S, Mosienko V, Bashammakh S, Alenina N, Bader M. (2010) Tryptophan hydroxylase as novel target for the treatment of depressive disorders. Pharmacology, 85 (2): 95-109. [PMID:20130443]
* Roberts KM, Fitzpatrick PF. (2013) Mechanisms of tryptophan and tyrosine hydroxylase. IUBMB Life, 65 (4): 350-7. [PMID:23441081]
* Tekin I, Roskoski Jr R, Carkaci-Salli N, Vrana KE. (2014) Complex molecular regulation of tyrosine hydroxylase. J Neural Transm, 121 (12): 1451-81. [PMID:24866693]
Waider J, Araragi N, Gutknecht L, Lesch KP. (2011) Tryptophan hydroxylase-2 (TPH2) in disorders of cognitive control and emotion regulation: a perspective. Psychoneuroendocrinology, 36 (3): 393-405. [PMID:21257271]
1. Abita JP, Milstien S, Chang N, Kaufman S. (1976) In vitro activation of rat liver phenylalanine hydroxylase by phosphorylation. J. Biol. Chem., 251 (17): 5310-4. [PMID:182695]
2. Daubner SC, Le T, Wang S. (2011) Tyrosine hydroxylase and regulation of dopamine synthesis. Arch. Biochem. Biophys., 508 (1): 1-12. [PMID:21176768]
3. Greengard O, Yoss MS, Del Valle JA. (1976) Alpha-methylphenylalanine, a new inducer of chronic hyperphenylalaninemia in sucling rats. Science, 192 (4243): 1007-8. [PMID:944951]
4. Joh TH, Park DH, Reis DJ. (1978) Direct phosphorylation of brain tyrosine hydroxylase by cyclic AMP-dependent protein kinase: mechanism of enzyme activation. Proc. Natl. Acad. Sci. U.S.A., 75 (10): 4744-8. [PMID:33381]
5. Johansen PA, Jennings I, Cotton RG, Kuhn DM. (1996) Phosphorylation and activation of tryptophan hydroxylase by exogenous protein kinase A. J. Neurochem., 66 (2): 817-23. [PMID:8592157]
6. Kim JJ, Wang H, Terc JD, Zambrowicz B, Yang QM, Khan WI. (2015) Blocking peripheral serotonin synthesis by telotristat etiprate (LX1032/LX1606) reduces severity of both chemical- and infection-induced intestinal inflammation. Am. J. Physiol. Gastrointest. Liver Physiol., 309 (6): G455-65. [PMID:26206858]
7. Nicholson AN, Wright CM. (1981) (+)-6-fluorotryptophan, an inhibitor of tryptophan hydroxylase: sleep and wakefulness in the rat. Neuropharmacology, 20 (4): 335-9. [PMID:6457252]
8. Teigen K, Dao KK, McKinney JA, Gorren AC, Mayer B, Frøystein NA, Haavik J, Martínez A. (2004) Tetrahydrobiopterin binding to aromatic amino acid hydroxylases. Ligand recognition and specificity. J. Med. Chem., 47 (24): 5962-71. [PMID:15537351]
Database page citation:
Amino acid hydroxylases. Accessed on 29/03/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=249.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Enzymes. Br J Pharmacol. 172: 6024-6109.