tryptophan hydroxylase


Summary: An enzyme that catalyzes the hydroxylation of TRYPTOPHAN to 5-HYDROXYTRYPTOPHAN in the presence of NADPH and molecular oxygen. It is important in the biosynthesis of SEROTONIN.

Top Publications

  1. Grohmann M, Hammer P, Walther M, Paulmann N, Büttner A, Eisenmenger W, et al. Alternative splicing and extensive RNA editing of human TPH2 transcripts. PLoS ONE. 2010;5:e8956 pubmed publisher
    ..b>Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of 5-HT...
  2. Zhang C, Li Z, Shao Y, Xie B, Du Y, Fang Y, et al. Association study of tryptophan hydroxylase-2 gene in schizophrenia and its clinical features in Chinese Han population. J Mol Neurosci. 2011;43:406-11 pubmed publisher
    ..b>Tryptophan hydroxylase 2 (TPH2), a newly identified isoform of tryptophan hydroxylase (the rate limiting enzyme in the ..
  3. Li Z, CHALAZONITIS A, Huang Y, Mann J, Margolis K, Yang Q, et al. Essential roles of enteric neuronal serotonin in gastrointestinal motility and the development/survival of enteric dopaminergic neurons. J Neurosci. 2011;31:8998-9009 pubmed publisher
    ..5-HT biosynthesis depends on tryptophan hydroxylase 1 (TPH1) in EC cells and on TPH2 in neurons; therefore, mice lacking TPH1 and/or TPH2 distinguish EC-..
  4. Scheuch K, Höltje M, Budde H, Lautenschlager M, Heinz A, Ahnert Hilger G, et al. Lithium modulates tryptophan hydroxylase 2 gene expression and serotonin release in primary cultures of serotonergic raphe neurons. Brain Res. 2010;1307:14-21 pubmed publisher
    ..reverse transcriptase polymerase chain reaction and Western blotting, we examined the effect of lithium on tryptophan hydroxylase 2 (TPH2) expression, the rate-limiting enzyme in brain 5-HT biosynthesis...
  5. Scarpa R, Alaggio R, Norberto L, Furmaniak J, Chen S, Smith B, et al. Tryptophan hydroxylase autoantibodies as markers of a distinct autoimmune gastrointestinal component of autoimmune polyendocrine syndrome type 1. J Clin Endocrinol Metab. 2013;98:704-12 pubmed publisher
    Autoantibodies to tryptophan hydroxylase (TPHAbs) directed against serotonin-producing enterochromaffin cells (EC) have been reported in autoimmune-polyendocrine-syndrome type 1 (APS-1) patients with gastrointestinal dysfunction (GID)...
  6. Kim H, Toyofuku Y, Lynn F, Chak E, Uchida T, Mizukami H, et al. Serotonin regulates pancreatic beta cell mass during pregnancy. Nat Med. 2010;16:804-8 pubmed publisher
    ..Expression of serotonin synthetic enzyme tryptophan hydroxylase-1 (Tph1) and serotonin production rose sharply in beta cells during pregnancy or after treatment with ..
  7. Moussaif M, Sze J. Intraflagellar transport/Hedgehog-related signaling components couple sensory cilium morphology and serotonin biosynthesis in Caenorhabditis elegans. J Neurosci. 2009;29:4065-75 pubmed publisher
    ..neurons, resulting in cilium structural remodeling and upregulation of the serotonin-biosynthesis enzyme tryptophan hydroxylase tph-1 in the ADF neurons...
  8. Gentile M, Nawa Y, Lunardi G, Florio T, Matsui H, Colucci D Amato L. Tryptophan hydroxylase 2 (TPH2) in a neuronal cell line: modulation by cell differentiation and NRSF/rest activity. J Neurochem. 2012;123:963-70 pubmed publisher
    ..The synthesis of 5-HT is initiated by the hydroxylation of tryptophan, catalyzed by tryptophan hydroxylase (TPH)...
  9. Must A, Tasa G, Lang A, Vasar E, Koks S, Maron E, et al. Variation in tryptophan hydroxylase-2 gene is not associated to male completed suicide in Estonian population. Neurosci Lett. 2009;453:112-4 pubmed publisher
    ..b>Tryptophan hydroxylase isoform 2 (TPH2) is the rate-limiting enzyme in the biosynthetic pathway of serotonin, being expressed in ..

More Information


  1. Lin Y, Ko H, Chang F, Yeh T, Sun H. Population-specific functional variant of the TPH2 gene 2755C>A polymorphism contributes risk association to major depression and anxiety in Chinese peripartum women. Arch Womens Ment Health. 2009;12:401-8 pubmed publisher
    The rate-limiting enzyme of serotonin biosynthesis, tryptophan hydroxylase 2 (TPH2), is one of the most promising candidate genes for psychiatric disorders...
  2. Tsai S, Hong C, Liou Y, Yu Y, Chen T, Hou S, et al. Tryptophan hydroxylase 2 gene is associated with major depression and antidepressant treatment response. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:637-41 pubmed publisher
    b>Tryptophan hydroxylase-2 (TPH2) is the rate-limiting biosynthetic isoenzyme for serotonin that is preferentially expressed in the brain and has been implicated in the pathogenesis of major depressive disorder (MDD) and in the mechanism of ..
  3. Clark J, Alves S, Gundlah C, Rocha B, Birzin E, Cai S, et al. Selective estrogen receptor-beta (SERM-beta) compounds modulate raphe nuclei tryptophan hydroxylase-1 (TPH-1) mRNA expression and cause antidepressant-like effects in the forced swim test. Neuropharmacology. 2012;63:1051-63 pubmed publisher
    ..are brain penetrant and display dose dependent efficacy in the murine dorsal raphe assays for induction of tryptophan hydroxylase mRNA and progesterone receptor protein...
  4. Wrzosek M, Łukaszkiewicz J, Wrzosek M, Serafin P, Jakubczyk A, Klimkiewicz A, et al. Association of polymorphisms in HTR2A, HTR1A and TPH2 genes with suicide attempts in alcohol dependence: a preliminary report. Psychiatry Res. 2011;190:149-51 pubmed publisher
    ..No differences in genotype distribution in HTR1A and TPH2 SNPs were found between patients with and without suicide attempts. ..
  5. Rothman R, Cadet J, Dersch C, McCoy M, Lehrmann E, Becker K, et al. Altered gene expression in pulmonary tissue of tryptophan hydroxylase-1 knockout mice: implications for pulmonary arterial hypertension. PLoS ONE. 2011;6:e17735 pubmed publisher
    ..A recent study reported that female mice lacking the gene for tryptophan hydroxylase-1 (Tph1(-/-) mice) were protected from PAH caused by chronic dexfenfluramine, suggesting a pivotal role ..
  6. Serretti A, Chiesa A, Porcelli S, Han C, Patkar A, Lee S, et al. Influence of TPH2 variants on diagnosis and response to treatment in patients with major depression, bipolar disorder and schizophrenia. Psychiatry Res. 2011;189:26-32 pubmed publisher
    The present study is aimed at exploring whether some single nucleotide polymorphisms (SNPs) within the tryptophan hydroxylase 2 gene (TPH2) could be associated with major depression (MD), bipolar disorder (BD) and schizophrenia and ..
  7. Matthes S, Mosienko V, Bashammakh S, Alenina N, Bader M. Tryptophan hydroxylase as novel target for the treatment of depressive disorders. Pharmacology. 2010;85:95-109 pubmed publisher
    ..This paper summarizes the data which support TPH2 as novel drug target and discusses strategies for its pharmacological exploitation. ..
  8. Jacobsen J, Siesser W, Sachs B, Peterson S, Cools M, Setola V, et al. Deficient serotonin neurotransmission and depression-like serotonin biomarker alterations in tryptophan hydroxylase 2 (Tph2) loss-of-function mice. Mol Psychiatry. 2012;17:694-704 pubmed publisher
    ..We employed a naturalistic model of 5-HT deficiency, the tryptophan hydroxylase 2 (Tph2) R439H knockin mouse, to address this question...
  9. MacGillivray L, Lagrou L, Reynolds K, Rosebush P, Mazurek M. Role of serotonin transporter inhibition in the regulation of tryptophan hydroxylase in brainstem raphe nuclei: time course and regional specificity. Neuroscience. 2010;171:407-20 pubmed publisher
    ..We studied the time course of changes in tryptophan hydroxylase (TPH) in four raphe nuclei after initiation of two different SERT inhibitors, citalopram and fluoxetine...
  10. Armbruster D, Mueller A, Strobel A, Kirschbaum C, Lesch K, Brocke B. Influence of functional tryptophan hydroxylase 2 gene variation and sex on the startle response in children, young adults, and older adults. Biol Psychol. 2010;83:214-21 pubmed publisher
    Serotonin, a key regulator of emotional behavior, is synthesized by tryptophan hydroxylase (TPH). Allelic variation of TPH2 gene expression influences serotonin synthesis in the brain and therefore may modulate emotional processing...
  11. Liu Q, Wong Riley M. Postnatal changes in tryptophan hydroxylase and serotonin transporter immunoreactivity in multiple brainstem nuclei of the rat: implications for a sensitive period. J Comp Neurol. 2010;518:1082-97 pubmed publisher
    ..recently been implicated in SIDS, we conducted a large-scale investigation of the 5-HT-synthesizing enzyme tryptophan hydroxylase (TPH) and serotonin transporter (SERT) with semiquantitative immunohistochemistry in multiple brainstem ..
  12. Schallreuter K, Salem M, Gibbons N, Martinez A, Slominski R, Lüdemann J, et al. Blunted epidermal L-tryptophan metabolism in vitiligo affects immune response and ROS scavenging by Fenton chemistry, part 1: Epidermal H2O2/ONOO(-)-mediated stress abrogates tryptophan hydroxylase and dopa decarboxylase activities, leading to low se. FASEB J. 2012;26:2457-70 pubmed publisher
    ..acid L-tryptophan (Trp) affects immune response mechanisms, we here looked at epidermal Trp metabolism via tryptophan hydroxylase (TPH) with its downstream cascade, including serotonin and melatonin...
  13. Liu Y, Jiang Y, Si Y, Kim J, Chen Z, Rao Y. Molecular regulation of sexual preference revealed by genetic studies of 5-HT in the brains of male mice. Nature. 2011;472:95-9 pubmed publisher
    ..A role for 5-HT was demonstrated by the phenotype of mice lacking tryptophan hydroxylase 2 (Tph2), which is required for the first step of 5-HT synthesis in the brain...
  14. Fasching P, Faschingbauer F, Goecke T, Engel A, Haberle L, Seifert A, et al. Genetic variants in the tryptophan hydroxylase 2 gene (TPH2) and depression during and after pregnancy. J Psychiatr Res. 2012;46:1109-17 pubmed publisher
    ..This underlines the relevance of these functional polymorphisms for depression in general and the importance of longitudinal assessments in research on postpartum depression. ..
  15. Kawabata Y, Hiraki T, Takeuchi A, Okubo K. Sex differences in the expression of vasotocin/isotocin, gonadotropin-releasing hormone, and tyrosine and tryptophan hydroxylase family genes in the medaka brain. Neuroscience. 2012;218:65-77 pubmed publisher
  16. Utge S, Soronen P, Partonen T, Loukola A, Kronholm E, Pirkola S, et al. A population-based association study of candidate genes for depression and sleep disturbance. Am J Med Genet B Neuropsychiatr Genet. 2010;153B:468-476 pubmed publisher
    ..These differences may partially explain the broad spectrum of depressive symptoms, and their systematic monitoring could potentially be used for diagnostic purposes. ..
  17. Inoue H, Yamasue H, Tochigi M, Takei K, Suga M, Abe O, et al. Effect of tryptophan hydroxylase-2 gene variants on amygdalar and hippocampal volumes. Brain Res. 2010;1331:51-7 pubmed publisher
    b>Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin (5-HT)...
  18. Yadav V, Balaji S, Suresh P, Liu X, Lu X, Li Z, et al. Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. Nat Med. 2010;16:308-12 pubmed publisher
    ..We synthesized and used LP533401, a small molecule inhibitor of tryptophan hydroxylase-1 (Tph-1), the initial enzyme in GDS biosynthesis...
  19. Booij L, Turecki G, Leyton M, Gravel P, Lopez de Lara C, Diksic M, et al. Tryptophan hydroxylase(2) gene polymorphisms predict brain serotonin synthesis in the orbitofrontal cortex in humans. Mol Psychiatry. 2012;17:809-17 pubmed publisher
    ..related to polymorphisms of the gene that encodes for the indoleamine's rate-limiting enzyme in the brain, tryptophan hydroxylase-2 (TPH(2))...
  20. Calvo A, Scherer T, Pey A, Ying M, Winge I, McKinney J, et al. Effect of pharmacological chaperones on brain tyrosine hydroxylase and tryptophan hydroxylase 2. J Neurochem. 2010;114:853-63 pubmed publisher
  21. Kriegebaum C, Song N, Gutknecht L, Huang Y, Schmitt A, Reif A, et al. Brain-specific conditional and time-specific inducible Tph2 knockout mice possess normal serotonergic gene expression in the absence of serotonin during adult life. Neurochem Int. 2010;57:512-7 pubmed publisher
    Several lines of evidence implicate a dysregulation of tryptophan hydroxylase (TPH)-dependent serotonin (5-HT) synthesis in emotional behaviour and stress, and point to its relevance for the etiology and pathogenesis of various ..
  22. Nowak E, de Vries V, Wasiuk A, Ahonen C, Bennett K, Le Mercier I, et al. Tryptophan hydroxylase-1 regulates immune tolerance and inflammation. J Exp Med. 2012;209:2127-35 pubmed publisher
    ..Here we report the novel finding that Tph-1 (tryptophan hydroxylase-1), a synthase which catalyses the conversion of tryptophan to serotonin and exhausts tryptophan, is a ..
  23. Viikki M, Kampman O, Illi A, Setälä Soikkeli E, Anttila S, Huuhka M, et al. TPH1 218A/C polymorphism is associated with major depressive disorder and its treatment response. Neurosci Lett. 2010;468:80-4 pubmed publisher
    The association between the tryptophan hydroxylase 1 (TPH1) 218A/C polymorphism and (1) severity of major depressive disorder (MDD) and (2) response to treatment was studied...
  24. Chen G, Novak M, Meyer J, Kelly B, Vallender E, Miller G. The effect of rearing experience and TPH2 genotype on HPA axis function and aggression in rhesus monkeys: a retrospective analysis. Horm Behav. 2010;57:184-91 pubmed publisher
    Gene-environment (GxE) interactions contribute to the development of many neuropsychiatric disorders. Tryptophan hydroxylase-2 (TPH2) synthesizes neuronal serotonin and is closely related to the hypothalamic-pituitary-adrenal (HPA) axis, ..
  25. Gao J, Pan Z, Jiao Z, Li F, Zhao G, Wei Q, et al. TPH2 gene polymorphisms and major depression--a meta-analysis. PLoS ONE. 2012;7:e36721 pubmed publisher
    b>Tryptophan hydroxylase-2 (TPH2) is the rate-limiting enzyme in the synthetic pathway for brain serotonin and is considered key factor for maintaining normal serotonin transmission in the central neuron system (CNS)...
  26. Amireault P, Hatia S, Bayard E, Bernex F, Collet C, Callebert J, et al. Ineffective erythropoiesis with reduced red blood cell survival in serotonin-deficient mice. Proc Natl Acad Sci U S A. 2011;108:13141-6 pubmed publisher
    ..Availability of 5-HT depends on the expression of the enzyme tryptophan hydroxylase (TPH), and the recent discovery of a dual system for 5-HT synthesis in the brain (TPH2) and periphery (..
  27. Chen G, Miller G. Advances in tryptophan hydroxylase-2 gene expression regulation: new insights into serotonin-stress interaction and clinical implications. Am J Med Genet B Neuropsychiatr Genet. 2012;159B:152-71 pubmed publisher
    ..b>Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in 5-HT biosynthesis, and the recent identification of a second, neuron-..
  28. Shen X, Wu Y, Qian M, Wang X, Hou Z, Liu Y, et al. Tryptophan hydroxylase 2 gene is associated with major depressive disorder in a female Chinese population. J Affect Disord. 2011;133:619-24 pubmed publisher
    ..In this study, we aimed to investigate the association of tryptophan hydroxylase 2 gene with MDD and its treatment response in the Chinese Han population...
  29. Angoa Perez M, Kane M, Briggs D, Sykes C, Shah M, Francescutti D, et al. Genetic depletion of brain 5HT reveals a common molecular pathway mediating compulsivity and impulsivity. J Neurochem. 2012;121:974-84 pubmed publisher
    ..Mice lacking the gene encoding brain tryptophan hydroxylase 2 (Tph2-/-), the initial and rate-limiting enzyme in the synthesis of serotonin, were tested in numerous ..
  30. Demarque M, Spitzer N. Activity-dependent expression of Lmx1b regulates specification of serotonergic neurons modulating swimming behavior. Neuron. 2010;67:321-34 pubmed publisher
    ..The results link activity-dependent regulation of a transcription factor to transmitter specification and altered behavior...
  31. Dzirasa K, Kumar S, Sachs B, Caron M, Nicolelis M. Cortical-amygdalar circuit dysfunction in a genetic mouse model of serotonin deficiency. J Neurosci. 2013;33:4505-13 pubmed publisher
    ..Together, our findings establish a functional link between functional hyposerotonergia and altered mPFC-AMY network dynamics. ..
  32. Chen G, Miller G. 5'-Untranslated region of the tryptophan hydroxylase-2 gene harbors an asymmetric bidirectional promoter but not internal ribosome entry site in vitro. Gene. 2009;435:53-62 pubmed publisher
    b>Tryptophan hydroxylase-2 (TPH2) catalyzes the synthesis of neuronal serotonin, a major neurotransmitter involved in many brain functions and psychiatric disorders...
  33. Paulmann N, Grohmann M, Voigt J, Bert B, Vowinckel J, Bader M, et al. Intracellular serotonin modulates insulin secretion from pancreatic beta-cells by protein serotonylation. PLoS Biol. 2009;7:e1000229 pubmed publisher
    ..We combined biochemical and electrophysiological analyses of mice selectively deficient in peripheral tryptophan hydroxylase (Tph1-/-) and 5-HT to show that intracellular 5-HT regulates insulin secretion...
  34. Waider J, Araragi N, Gutknecht L, Lesch K. Tryptophan hydroxylase-2 (TPH2) in disorders of cognitive control and emotion regulation: a perspective. Psychoneuroendocrinology. 2011;36:393-405 pubmed publisher
    Based on genetic variation, there is accumulating evidence that altered function of tryptophan hydroxylase-2 (TPH2), the enzyme critical for synthesis of serotonin (5-HT) in the brain, plays a role in anxiety-, aggression- and depression-..
  35. Song N, Xiu J, Huang Y, Chen J, Zhang L, Gutknecht L, et al. Adult raphe-specific deletion of Lmx1b leads to central serotonin deficiency. PLoS ONE. 2011;6:e15998 pubmed publisher
    ..of 5-HT in the brain of Lmx1b iCKO mice was reduced to 60% of that in control mice, and the expression of tryptophan hydroxylase 2 (Tph2), serotonin transporter (Sert) and vesicular monoamine transporter 2 (Vmat2) was greatly down-..
  36. Juhasz G, Downey D, Hinvest N, Thomas E, Chase D, Toth Z, et al. Risk-taking behavior in a gambling task associated with variations in the tryptophan hydroxylase 2 gene: relevance to psychiatric disorders. Neuropsychopharmacology. 2010;35:1109-19 pubmed publisher
    ..In conclusion, our study demonstrates the role of the TPH2 gene and the serotonin system in risk taking and suggests that TPH2 gene may contribute to the expression of psychiatric phenotypes through altered decision making. ..
  37. Thomas D, Angoa Perez M, Francescutti Verbeem D, Shah M, Kuhn D. The role of endogenous serotonin in methamphetamine-induced neurotoxicity to dopamine nerve endings of the striatum. J Neurochem. 2010;115:595-605 pubmed publisher
    ..e., increased release of 5HT, loss of function in tryptophan hydroxylase and the serotonin transporter, long-term depletion of 5HT stores)...
  38. Zill P, Büttner A, Eisenmenger W, Muller J, Moller H, Bondy B. Predominant expression of tryptophan hydroxylase 1 mRNA in the pituitary: a postmortem study in human brain. Neuroscience. 2009;159:1274-82 pubmed publisher
    Although the predominant role of tryptophan hydroxylase 2 (TPH2) in the CNS and its influence on the vulnerability to psychiatric disorders have clearly been demonstrated in several studies, the role of TPH1 on neuronal mechanisms, ..
  39. Gutknecht L, Kriegebaum C, Waider J, Schmitt A, Lesch K. Spatio-temporal expression of tryptophan hydroxylase isoforms in murine and human brain: convergent data from Tph2 knockout mice. Eur Neuropsychopharmacol. 2009;19:266-82 pubmed publisher
    Dysregulation of tryptophan hydroxylase (TPH)-dependent serotonin (5-HT) synthesis, has been implicated in various neuropsychiatric disorders, although the differential expression pattern of the two isoforms is controversial...
  40. Marshall A, Nommsen Rivers L, Hernandez L, Dewey K, Chantry C, Gregerson K, et al. Serotonin transport and metabolism in the mammary gland modulates secretory activation and involution. J Clin Endocrinol Metab. 2010;95:837-46 pubmed publisher
    ..Mothers taking serotonergic drugs may need additional support to achieve their breastfeeding goals. ..
  41. Lohoff F. Overview of the genetics of major depressive disorder. Curr Psychiatry Rep. 2010;12:539-46 pubmed publisher
    ..Future large-scale studies are needed to dissect this complex phenotype and to identify pathways involved in the etiology of MDD. ..
  42. Siesser W, Sachs B, Ramsey A, Sotnikova T, Beaulieu J, Zhang X, et al. Chronic SSRI treatment exacerbates serotonin deficiency in humanized Tph2 mutant mice. ACS Chem Neurosci. 2013;4:84-8 pubmed publisher
    ..A rare mutation in tryptophan hydroxylase 2 (Tph2), the rate limiting enzyme for 5-HT synthesis, was identified in several patients with major ..
  43. Rotberg B, Kronenberg S, Carmel M, Frisch A, Brent D, Zalsman G, et al. Additive effects of 5-HTTLPR (serotonin transporter) and tryptophan hydroxylase 2 G-703T gene polymorphisms on the clinical response to citalopram among children and adolescents with depression and anxiety disorders. J Child Adolesc Psychopharmacol. 2013;23:117-22 pubmed publisher
    ..The purpose of this study was to evaluate the association between polymorphisms in two serotonin pathway genes and the clinical response to citalopram among children and adolescents with depression and/or anxiety disorders...
  44. Halmøy A, Johansson S, Winge I, McKinney J, Knappskog P, Haavik J. Attention-deficit/hyperactivity disorder symptoms in offspring of mothers with impaired serotonin production. Arch Gen Psychiatry. 2010;67:1033-43 pubmed publisher
    ..synthesis on the developing human brain, we studied the effects of nonsynonymous mutations affecting tryptophan hydroxylase (TPH) enzymes responsible for serotonin production in maternal reproductive tissues (TPH1) and the brain (..
  45. Schraenen A, Lemaire K, de Faudeur G, Hendrickx N, Granvik M, Van Lommel L, et al. Placental lactogens induce serotonin biosynthesis in a subset of mouse beta cells during pregnancy. Diabetologia. 2010;53:2589-99 pubmed publisher
    ..mRNA encoding both isoforms of the rate-limiting enzyme of serotonin biosynthesis, tryptophan hydroxylase (TPH), i.e. Tph1 and Tph2, were strongly induced (fold change 25- to 200-fold) during pregnancy...
  46. Perez Rodriguez M, Weinstein S, New A, Bevilacqua L, Yuan Q, Zhou Z, et al. Tryptophan-hydroxylase 2 haplotype association with borderline personality disorder and aggression in a sample of patients with personality disorders and healthy controls. J Psychiatr Res. 2010;44:1075-81 pubmed publisher
    ..We found an association between the previously described TPH2 "risk" haplotype and BPD diagnosis, affective lability, suicidal/parasuicidal behavior, and aggression scores. ..
  47. Alenina N, Kikic D, Todiras M, Mosienko V, Qadri F, Plehm R, et al. Growth retardation and altered autonomic control in mice lacking brain serotonin. Proc Natl Acad Sci U S A. 2009;106:10332-7 pubmed publisher
    ..These data confirm that the majority of central serotonin is generated by TPH2. TPH2-derived serotonin is involved in the regulation of behavior and autonomic pathways but is not essential for adult life. ..
  48. Kim Y, Lee H, Yang J, Hwang J, Yoon H. A tryptophan hydroxylase 2 gene polymorphism is associated with panic disorder. Behav Genet. 2009;39:170-5 pubmed publisher
    ..The novel brain-specific serotonin synthesizing enzyme, tryptophan hydroxylase 2 (TPH2), which represents the rate-limiting enzyme of serotonin production in the brain, may therefore be ..
  49. Claes S, Myint A, Domschke K, Del Favero J, Entrich K, Engelborghs S, et al. The kynurenine pathway in major depression: haplotype analysis of three related functional candidate genes. Psychiatry Res. 2011;188:355-60 pubmed publisher
    ..The three genes, namely, tryptophan hydroxylase 2 (TPH2), kynurenine 3 monooxygenase (KMO) and kynurenine amino transferase 3 (KAT III) SNPs and haplotype ..
  50. Andreou D, Saetre P, Werge T, Andreassen O, Agartz I, Sedvall G, et al. Tryptophan hydroxylase gene 1 (TPH1) variants associated with cerebrospinal fluid 5-hydroxyindole acetic acid and homovanillic acid concentrations in healthy volunteers. Psychiatry Res. 2010;180:63-7 pubmed publisher
    b>Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin synthesis...
  51. Lee B, Lee H, Lee B, Pae C, Yoon B, Ryu S, et al. Impact of the tryptophan hydroxylase 1 gene A218C polymorphism on amygdala activity in response to affective facial stimuli in patients with major depressive disorder. Genes Brain Behav. 2009;8:512-8 pubmed publisher
    b>Tryptophan hydroxylase-1 (TPH1) is the rate-limiting enzyme in serotonin biosynthesis, and allelic variations at the TPH1 locus have been implicated in the pathophysiology of depression. Using 1...
  52. Duerschmied D, Suidan G, Demers M, Herr N, Carbo C, Brill A, et al. Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice. Blood. 2013;121:1008-15 pubmed publisher
    ..b>Tryptophan hydroxylase (Tph)1–deficient mice, lacking non-neuronal serotonin, showed mild leukocytosis compared with wild-type (..
  53. Lowry C, Hale M, Evans A, Heerkens J, Staub D, Gasser P, et al. Serotonergic systems, anxiety, and affective disorder: focus on the dorsomedial part of the dorsal raphe nucleus. Ann N Y Acad Sci. 2008;1148:86-94 pubmed publisher
    Depressed suicide patients have elevated expression of neuronal tryptophan hydroxylase 2 (TPH2) mRNA and protein in midbrain serotonergic neurons, as well as increases in brain serotonin turnover...