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]

Bauer IE, Graham DP, Soares JC, Nielsen DA. (2015) Serotonergic gene variation in substance use pharmacotherapy: a systematic review. Pharmacogenomics, 16 (11): 1307-14. [PMID:26265436]

* 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]

* 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]

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10. Specker E, Wesolowski R, Schutz A, Matthes S, Mallow K, Wasinska-Kalwa M, Winkleer L, Oder A, Alenina N, Pleimes D et al.. (2023) Structure-Based Design of Xanthine-Imidazopyridines and -Imidazothiazoles as Highly Potent and In Vivo Efficacious Tryptophan Hydroxylase Inhibitors. J Med Chem, [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.3c01454