tryptophan 2 3 dioxygenase


Gene Symbol: tryptophan 2 3 dioxygenase
Description: tryptophan 2,3-dioxygenase
Alias: HYPTRP, TDO, TPH2, TRPO, tryptophan 2,3-dioxygenase, tryptamin 2,3-dioxygenase, tryptophan oxygenase, tryptophan pyrrolase, tryptophanase
Species: human
Products:     tryptophan 2 3 dioxygenase

Top Publications

  1. Dick R, Murray B, Reid M, Correia M. Structure--function relationships of rat hepatic tryptophan 2,3-dioxygenase: identification of the putative heme-ligating histidine residues. Arch Biochem Biophys. 2001;392:71-8 pubmed
    The liver cytosolic enzyme tryptophan 2,3-dioxygenase (TDO) catalyzes the oxidation of L-tryptophan to formylkynurenine and controls the physiological flux of tryptophan into both the serotonergic and kynureninic pathways...
  2. Guillemin G, Smythe G, Takikawa O, Brew B. Expression of indoleamine 2,3-dioxygenase and production of quinolinic acid by human microglia, astrocytes, and neurons. Glia. 2005;49:15-23 pubmed
    ..However, astrocytes and neurons had the ability to catabolize QUIN. This study also provides the first evidence of IDO expression and lack of production of QUIN in culture of primary human neurons. ..
  3. Basran J, Rafice S, Chauhan N, Efimov I, Cheesman M, Ghamsari L, et al. A kinetic, spectroscopic, and redox study of human tryptophan 2,3-dioxygenase. Biochemistry. 2008;47:4752-60 pubmed publisher
    ..These new findings illustrate that significant mechanistic differences exist across the heme dioxygenase family, and the data are discussed within this broader framework. ..
  4. Fukumura E, Sugimoto H, Misumi Y, Ogura T, Shiro Y. Cooperative binding of L-trp to human tryptophan 2,3-dioxygenase: resonance Raman spectroscopic analysis. J Biochem. 2009;145:505-15 pubmed publisher
    Tryptophan 2,3-dioxygenase (TDO) is a tetrameric enzyme that catalyses the oxidative cleavage of l-tryptophan (l-Trp) to N-formylkynurenine by the addition of O(2) across the 2,3-bond of the indole ring...
  5. Capece L, Lewis Ballester A, Batabyal D, Di Russo N, Yeh S, Estrin D, et al. The first step of the dioxygenation reaction carried out by tryptophan dioxygenase and indoleamine 2,3-dioxygenase as revealed by quantum mechanical/molecular mechanical studies. J Biol Inorg Chem. 2010;15:811-23 pubmed publisher
    Tryptophan dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) are two heme-containing enzymes which catalyze the conversion of L: -tryptophan to N-formylkynurenine (NFK)...
  6. Efimov I, Basran J, Thackray S, Handa S, Mowat C, Raven E. Structure and reaction mechanism in the heme dioxygenases. Biochemistry. 2011;50:2717-24 pubmed publisher
  7. Pilotte L, Larrieu P, Stroobant V, Colau D, Dolusic E, Frederick R, et al. Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase. Proc Natl Acad Sci U S A. 2012;109:2497-502 pubmed publisher
    ..Tryptophan 2,3-dioxygenase (TDO) is an unrelated hepatic enzyme that also degrades tryptophan along the kynurenine pathway...
  8. Sas K, Szabó E, Vecsei L. Mitochondria, Oxidative Stress and the Kynurenine System, with a Focus on Ageing and Neuroprotection. Molecules. 2018;23: pubmed publisher
    ..The end product of the route is NAD⁺. The first metabolic reaction is mediated by TRP-2,3-dioxygenase (TDO) or indolamine-2,3-dioxygenases (IDO), the latter being induced by inflammation, and it is thought to have a ..
  9. Chaudhari S, Noh M, Moussian B, Specht C, Kramer K, Beeman R, et al. Knickkopf and retroactive proteins are required for formation of laminar serosal procuticle during embryonic development of Tribolium castaneum. Insect Biochem Mol Biol. 2015;60:1-6 pubmed publisher
    ..Insects treated with dsRNA for chitin synthase-A (TcChs-A) and tryptophan oxygenase (TcVer) were used as positive and negative controls for these experiments, respectively...

More Information

Publications127 found, 100 shown here

  1. Zhong W, Gao L, Zhou Z, Lin H, Chen C, Huang P, et al. Indoleamine 2,3-dioxygenase 1 deficiency attenuates CCl4-induced fibrosis through Th17 cells down-regulation and tryptophan 2,3-dioxygenase compensation. Oncotarget. 2017;8:40486-40500 pubmed publisher
    ..On the other hand, tryptophan 2,3-dioxygenase (TDO), another systemic tryptophan metabolism enzyme, exhibited a compensatory increase as a result of IDO1 deficiency...
  2. Mandic S, Volkoff H. The effects of fasting and appetite regulators on catecholamine and serotonin synthesis pathways in goldfish (Carassius auratus). Comp Biochem Physiol A Mol Integr Physiol. 2018;223:1-9 pubmed publisher
    ..Irisin injections decreased feeding and increased TPH2 and AADC brain expressions and TH and SPR intestinal expressions, and decreased TPH1 brain expression and AADC ..
  3. Fuertig R, Azzinnari D, Bergamini G, Cathomas F, Sigrist H, Seifritz E, et al. Mouse chronic social stress increases blood and brain kynurenine pathway activity and fear behaviour: Both effects are reversed by inhibition of indoleamine 2,3-dioxygenase. Brain Behav Immun. 2016;54:59-72 pubmed publisher
  4. Magnusson J, Cummings K. Central serotonin and the control of arterial blood pressure and heart rate in infant rats: influence of sleep state and sex. Am J Physiol Regul Integr Comp Physiol. 2017;:ajpregu.00321.2017 pubmed publisher
    ..We tested these hypotheses using two week-old, male and female rat pups lacking tryptophan hydroxylase 2 (TPH2-/-) and wildtype littermates (WT)...
  5. Dostal C, Gamsby N, Lawson M, McCusker R. Glia- and tissue-specific changes in the Kynurenine Pathway after treatment of mice with lipopolysaccharide and dexamethasone. Brain Behav Immun. 2018;69:321-335 pubmed publisher
    ..These findings demonstrate a plausible interaction between immune activation and glucocorticoids associated with depression. ..
  6. van der Stelt I, Hoevenaars F, Siroká J, de Ronde L, Friedecky D, Keijer J, et al. Metabolic Response of Visceral White Adipose Tissue of Obese Mice Exposed for 5 Days to Human Room Temperature Compared to Mouse Thermoneutrality. Front Physiol. 2017;8:179 pubmed publisher
    ..Markers of thermogenesis were not altered in eWAT. Decreased expression of tryptophan hydroxylase 2 (Tph2) and cholecystokinin (Cck) might represent altered neuroendocrine signaling...
  7. Pan Q, Liu Q, Wan R, Kalavagunta P, Liu L, Lv W, et al. Selective inhibition of intestinal 5-HT improves neurobehavioral abnormalities caused by high-fat diet mice. Metab Brain Dis. 2019;: pubmed publisher
    ..3) LP533401 and SIM reversed the inhibition of Tryptophan Hydroxylase 2, Tph2 gene expression and the activation of Indoleamine 2,3-dioxy-Genase, IDO expression in HFD-treated brain, whereas BZ ..
  8. Pitzer M, Lueras J, Warden A, Weber S, MCBRIDE J. Viral vector mediated expression of mutant huntingtin in the dorsal raphe produces disease-related neuropathology but not depressive-like behaviors in wildtype mice. Brain Res. 2015;1608:177-90 pubmed publisher
    ..showed a 75% reduction in cells that stained positive for the serotonin synthesis enzyme, tryptophan hydroxylase-2 (TPH2) compared to controls (p<0.05)...
  9. Baan M, Kibbe C, Bushkofsky J, Harris T, Sherman D, Davis D. Transgenic expression of the human growth hormone minigene promotes pancreatic β-cell proliferation. Am J Physiol Regul Integr Comp Physiol. 2015;309:R788-94 pubmed publisher
    ..receptor, and expression of its downstream targets tryptophan hydroxylase-1 (Tph1), tryptophan hydroxylase-2 (Tph2), and cytokine-inducible SH2 containing protein (Cish) was increased...
  10. Patrick R, Ames B. Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism. FASEB J. 2014;28:2398-413 pubmed publisher
    ..D hormone (calcitriol) activates the transcription of the serotonin-synthesizing gene tryptophan hydroxylase 2 (TPH2) in the brain at a vitamin D response element (VDRE) and represses the transcription of TPH1 in tissues outside the ..
  11. Fox J, Hassell J, Siebler P, Arnold M, Lamb A, Smith D, et al. Preimmunization with a heat-killed preparation of Mycobacterium vaccae enhances fear extinction in the fear-potentiated startle paradigm. Brain Behav Immun. 2017;66:70-84 pubmed publisher
    ..sectioned for analysis of mRNA expression for genes important in control of brain serotonergic signaling, including tph2, htr1a, slc6a4, and slc22a3, throughout the brainstem dorsal and median raphe nuclei. Immunization with M...
  12. Kindler J, Lim C, Weickert C, Boerrigter D, Galletly C, Liu D, et al. Dysregulation of kynurenine metabolism is related to proinflammatory cytokines, attention, and prefrontal cortex volume in schizophrenia. Mol Psychiatry. 2019;: pubmed publisher
    ..the prefrontal cortex (PFC), kynurenine (KYN)/TRP ratio, KYNA levels, and mRNA for enzymes, tryptophan dioxygenase (TDO) and kynurenine aminotransferases (KATI/II), were significantly increased in the high cytokine schizophrenia ..
  13. Weng R, Shen S, Burton C, Yang L, Nie H, Tian Y, et al. Lipidomic profiling of tryptophan hydroxylase 2 knockout mice reveals novel lipid biomarkers associated with serotonin deficiency. Anal Bioanal Chem. 2016;408:2963-73 pubmed publisher
    ..lipid biomarkers associated with serotonin deficiency by lipidomic profiling of tryptophan hydroxylase 2 knockout (Tph2-/-) mice...
  14. Panosyan E, Lin H, Koster J, Lasky J. In search of druggable targets for GBM amino acid metabolism. BMC Cancer. 2017;17:162 pubmed publisher
    ..Last, AA metabolism is heterogeneous in TCGA subtypes of GBM (as well as medulloblastomas and other pediatric tumors), which may translate to variable responses to AA targeted therapies. ..
  15. Vasudeva R, Hobby A, Kirby L. Ethanol consumption in the Sprague-Dawley rat increases sensitivity of the dorsal raphe nucleus to 5,7-dihydroxytryptamine. Behav Brain Res. 2015;295:35-44 pubmed publisher
    ..Quantification of 5-HT depletion in the dorsal raphe nucleus (DRN) using tryptophan hydroxylase-2 (TPH2) immunohistochemistry resulted in a 76% decrease in staining with 5,7-DHT treatment...
  16. Tu W, Cheng C, Wang S, Tang P, Chen C, Chen H, et al. Profiling of differential gene expression in the hypothalamus of broiler-type Taiwan country chickens in response to acute heat stress. Theriogenology. 2016;85:483-494.e8 pubmed publisher
    ..Conversely, the expression of TPH2 was downregulated at all recovery times...
  17. Kaneko I, Sabir M, Dussik C, Whitfield G, Karrys A, Hsieh J, et al. 1,25-Dihydroxyvitamin D regulates expression of the tryptophan hydroxylase 2 and leptin genes: implication for behavioral influences of vitamin D. FASEB J. 2015;29:4023-35 pubmed publisher
    ..Brain TPH2 mRNA, encoding the rate-limiting enzyme in serotonin synthesis, was induced 2...
  18. Zhao H, Mohamed N, Chan S, Tan C, Tao R, Yu V, et al. Absence of Stress Response in Dorsal Raphe Nucleus in Modulator of Apoptosis 1-Deficient Mice. Mol Neurobiol. 2019;56:2185-2201 pubmed publisher
    ..Repeated forced swimming stress causes an up-regulation of tryptophan hydroxylase 2 (TPH2) and a down-regulation of brain-derived neurotrophic factor (BDNF) in the dorsal raphe nucleus (DRN) in young wild-..
  19. Lukkes J, Norman K, Meda S, Andersen S. Sex differences in the ontogeny of CRF receptors during adolescent development in the dorsal raphe nucleus and ventral tegmental area. Synapse. 2016;70:125-32 pubmed publisher
    ..The serotonin and catecholamine enzymes in the DR and VTA, tryptophan hydroxylase 2 (TPH2) and tyrosine hydroxylase, respectively, were also analyzed for maturational differences...
  20. Hasni Ebou M, Singh Estivalet A, Launay J, Callebert J, Tronche F, Ferre P, et al. Glucocorticoids Inhibit Basal and Hormone-Induced Serotonin Synthesis in Pancreatic Beta Cells. PLoS ONE. 2016;11:e0149343 pubmed publisher
    ..expression and activity of the two key enzymes of serotonin synthesis, Tryptophan Hydroxylase 1 (Tph1) and 2 (Tph2), leading to reduced serotonin contents...
  21. Jiang P, Zhang L, Cai H, Li H, Liu Y, Tang M, et al. Neurochemical effects of chronic administration of calcitriol in rats. Nutrients. 2014;6:6048-59 pubmed publisher
    ..Additionally, calcitriol treatment promoted tyrosine hydroxylase (TH) and tryptophan hydroxylase 2 (TPH2) expression without changing dopamine and serotonin status...
  22. WHITNEY M, Shemery A, Yaw A, Donovan L, Glass J, Deneris E. Adult Brain Serotonin Deficiency Causes Hyperactivity, Circadian Disruption, and Elimination of Siestas. J Neurosci. 2016;36:9828-42 pubmed publisher
    ..Cre recombinase (AAV-Cre) into the midbrain/pons of mice carrying a loxP-conditional tryptophan hydroxylase 2 (Tph2) allele...
  23. Vacher S, Castagnet P, Chemlali W, Lallemand F, Meseure D, Pocard M, et al. High AHR expression in breast tumors correlates with expression of genes from several signaling pathways namely inflammation and endogenous tryptophan metabolism. PLoS ONE. 2018;13:e0190619 pubmed publisher
    ..The breast cancer ER status likely influences AhR activity involved in these signaling pathways. The mechanisms involved in AhR activation and target gene expression in breast cancers are also discussed. ..
  24. Angoa Perez M, Kane M, Herrera Mundo N, Francescutti D, Kuhn D. Effects of combined treatment with mephedrone and methamphetamine or 3,4-methylenedioxymethamphetamine on serotonin nerve endings of the hippocampus. Life Sci. 2014;97:31-6 pubmed publisher
    ..measures of 5HT by HPLC and by immunoblot analysis of serotonin transporter (SERT) and tryptophan hydroxylase 2 (TPH2), selective markers of 5HT nerve endings...
  25. Boros F, Bohar Z, Vecsei L. Genetic alterations affecting the genes encoding the enzymes of the kynurenine pathway and their association with human diseases. Mutat Res. 2018;776:32-45 pubmed publisher
    ..pathway (KP), which involves several enzymes, including indoleamine 2,3-dioxygenase, tryptophan 2,3 dioxygenase (TDO), kynurenine aminotransferases (KATs), kynurenine monooxygenase (KMO) etc...
  26. Harding K, Lonstein J. Extensive juvenile "babysitting" facilitates later adult maternal responsiveness, decreases anxiety, and increases dorsal raphe tryptophan hydroxylase-2 expression in female laboratory rats. Dev Psychobiol. 2016;58:492-508 pubmed publisher
    ..22-36) on adult maternal responsiveness, anxiety-related behaviors, and dorsal raphe tryptophan hydroxylase-2 (TPH2) and serotonin transporter (SERT) levels in nulliparous rats...
  27. Drew J, Farquharson A, Horgan G, Williams L. Tissue-specific regulation of sirtuin and nicotinamide adenine dinucleotide biosynthetic pathways identified in C57Bl/6 mice in response to high-fat feeding. J Nutr Biochem. 2016;37:20-29 pubmed publisher
    ..Novel molecular targets identified above could direct strategies for dietary/therapeutic interventions to limit metabolic dysfunction and development of T2D. ..
  28. Ma J, Wang F, Yang J, Dong Y, Su G, Zhang K, et al. Xiaochaihutang attenuates depressive/anxiety-like behaviors of social isolation-reared mice by regulating monoaminergic system, neurogenesis and BDNF expression. J Ethnopharmacol. 2017;208:94-104 pubmed publisher
    ..In addition, we found XCHT enhanced monoamine neurotransmitter synthesis enzymes (TPH2 and TH) expressions, inhibited serotonin transporter (SERT) expression and decreased monoamine neurotransmitter ..
  29. Vila M, Pazos M, Iglesias C, Veiga N, Seoane G, Carrera I. Toluene Dioxygenase-Catalysed Oxidation of Benzyl Azide to Benzonitrile: Mechanistic Insights for an Unprecedented Enzymatic Transformation. Chembiochem. 2016;17:291-5 pubmed publisher
    Enzymatic dioxygenation of benzyl azide by toluene dioxygenase (TDO) produces significant amounts of the cis-cyclohexadienediol derived from benzonitrile, along with the expected azido diols...
  30. Badawy A. Tryptophan availability for kynurenine pathway metabolism across the life span: Control mechanisms and focus on aging, exercise, diet and nutritional supplements. Neuropharmacology. 2017;112:248-263 pubmed publisher
    ..determinant of kynurenine metabolite formation and is more effective than induction of hepatic Trp 2,3-dioxygenase (TDO) or extrahepatic indoleamine 2,3-dioxygenase (IDO)...
  31. Raven E. A short history of heme dioxygenases: rise, fall and rise again. J Biol Inorg Chem. 2017;22:175-183 pubmed publisher
    It is well established that there are two different classes of enzymes-tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO)-that catalyse the O2-dependent oxidation of L-tryptophan to N-formylkynurenine...
  32. Low J, Capozzi B, Cui J, Wei S, Venkataraman L, Campos L. Tuning the polarity of charge carriers using electron deficient thiophenes. Chem Sci. 2017;8:3254-3259 pubmed publisher
    Thiophene-1,1-dioxide (TDO) oligomers have fascinating electronic properties...
  33. Pompili M, Gentile G, Scassellati C, Bonvicini C, Innamorati M, Erbuto D, et al. Genetic association analysis of serotonin and signal transduction pathways in suicide attempters from an Italian sample of psychiatric patients. Neurosci Lett. 2017;656:94-102 pubmed publisher eight genes (serotonin transporter, SLC6A4; receptors, 5HTR1A, 1B, 5HTR2A; Tryptophan Hydroxylase, TPH1, TPH2; Monoamine Oxidase, MAOA and G Protein Subunit Beta 3, GNB3) to investigate their predictive value for suicide...
  34. Wang F, Fang M, Hinton D, Chernick M, Jia S, Zhang Y, et al. Increased coiling frequency linked to apoptosis in the brain and altered thyroid signaling in zebrafish embryos (Danio rerio) exposed to the PBDE metabolite 6-OH-BDE-47. Chemosphere. 2018;198:342-350 pubmed publisher
    ..5-HT, serotonin)-immunoreactive (5-HT-ir) neurons and the mRNA expression of tryptophan hydroxylase 2 (TPH2)...
  35. Hiroi R, Carbone D, Zuloaga D, Bimonte Nelson H, Handa R. Sex-dependent programming effects of prenatal glucocorticoid treatment on the developing serotonin system and stress-related behaviors in adulthood. Neuroscience. 2016;320:43-56 pubmed publisher
    ..a synthetic GC) during prenatal life on stress-related behaviors in adulthood and on the tryptophan hydroxylase-2 (TpH2) gene expression in the adult dorsal raphe nucleus (DRN)...
  36. Karanović J, Ivkovic M, Jovanović V, Sviković S, Pantović Stefanović M, Brkušanin M, et al. Effect of childhood general traumas on suicide attempt depends on TPH2 and ADARB1 variants in psychiatric patients. J Neural Transm (Vienna). 2017;124:621-629 pubmed publisher
    ..We examined whether the interaction of child abuse, TPH2 (tryptophan hydroxylase 2) variant rs4290270, affecting alternative splicing and editing of TPH2 pre-mRNAs, and ..
  37. Bazhenova E, Sinyakova N, Kulikova E, Kazarinova I, Bazovkina D, Gainetdinov R, et al. No effect of C1473G polymorphism in the tryptophan hydroxylase 2 gene on the response of the brain serotonin system to chronic fluoxetine treatment in mice. Neurosci Lett. 2017;653:264-268 pubmed publisher
    ..The interaction between SERT and the key enzyme of 5-HT synthesis in the brain, tryptophan hydroxylase 2 (TPH2), is essential to maintain the brain 5-HT level...
  38. Scherer T, Allegri G, Sarkissian C, Ying M, Grisch Chan H, Rassi A, et al. Tetrahydrobiopterin treatment reduces brain L-Phe but only partially improves serotonin in hyperphenylalaninemic ENU1/2 mice. J Inherit Metab Dis. 2018;41:709-718 pubmed publisher
    ..and 3-methoxy-4-hydroxyphenylglycol (MHPG) content, and brain TH protein, as well as tryptophan hydroxylase type 2 (TPH2) protein levels and activity were reduced in comparison to wild-type mice...
  39. Carli M, Kostoula C, Sacchetti G, Mainolfi P, Anastasia A, Villani C, et al. Tph2 gene deletion enhances amphetamine-induced hypermotility: effect of 5-HT restoration and role of striatal noradrenaline release. J Neurochem. 2015;135:674-85 pubmed publisher
    Variants of tryptophan hydroxylase-2 (Tph2), the gene encoding enzyme responsible for the synthesis of brain serotonin (5-HT), have been associated with neuropsychiatric disorders, substance abuse and addiction...
  40. Montgomery J, Wiggin T, Rivera Perez L, Lillesaar C, Masino M. Intraspinal serotonergic neurons consist of two, temporally distinct populations in developing zebrafish. Dev Neurobiol. 2016;76:673-87 pubmed publisher
    ..Because the pet1 and tph2 promoters drive transgene expression in the spinal cord, we hypothesized that tph2 is expressed in spinal cords of ..
  41. Lemay F, Doré F, Beaulieu J. Increased ethanol consumption despite taste aversion in mice with a human tryptophan hydroxylase 2 loss of function mutation. Neurosci Lett. 2015;609:194-7 pubmed publisher
    Polymorphisms in the gene encoding the brain serotonin synthesis enzyme Tph2 have been identified in mental illnesses, with co-morbidity of substance use disorder...
  42. Karami A, Goh Y, Jahromi M, Lazorchak J, Abdullah M, Courtenay S. Diploid and triploid African catfish (Clarias gariepinus) differ in biomarker responses to the pesticide chlorpyrifos. Sci Total Environ. 2016;557-558:204-11 pubmed publisher, exposure to CPF did not change brain 11?-hsd2, ftz-f1, foxl2, GnRH or cyp19a2 mRNA levels, while reduced tph2 transcript levels compared to the control group...
  43. Villalba K, Devieux J, Rosenberg R, Cadet J. Serotonin-Related Gene Polymorphisms and Asymptomatic Neurocognitive Impairment in HIV-Infected Alcohol Abusers. Genet Res Int. 2016;2016:7169172 pubmed publisher
    ..Single nucleotide polymorphisms in the SLC6A4, TPH2, and GALM genes may affect the activity of serotonin and increase the risk of HAND...
  44. Larkin P, Sathyasaikumar K, Notarangelo F, Funakoshi H, Nakamura T, Schwarcz R, et al. Tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase 1 make separate, tissue-specific contributions to basal and inflammation-induced kynurenine pathway metabolism in mice. Biochim Biophys Acta. 2016;1860:2345-2354 pubmed publisher
    ..a comprehensive biochemical characterization of mice with a targeted deletion of either tryptophan 2,3-dioxygenase (TDO) or indoleamine 2,3-dioxygenase (IDO), the two initial rate-limiting enzymes of the KP...
  45. Lim L, Shrestha S, Or Y, Tan S, Chung H, Sun Y, et al. Tetratricopeptide repeat domain 9A modulates anxiety-like behavior in female mice. Sci Rep. 2016;6:37568 pubmed publisher be the key neuromodulator involved in anxiety behaviors, the mRNA levels of tryptophan hydroxylase (TPH) 1, TPH2 (both are involved in serotonin synthesis), and serotonin transporter (5-HTT) were measured in the ventromedial ..
  46. Murthi P, Wallace E, Walker D. Altered placental tryptophan metabolic pathway in human fetal growth restriction. Placenta. 2017;52:62-70 pubmed publisher
    ..IDO and TDO mRNA and protein expression, responsible for kynurenine production from tryptophan, were significantly lower in ..
  47. Cheong J, Sun L. Targeting the IDO1/TDO2-KYN-AhR Pathway for Cancer Immunotherapy - Challenges and Opportunities. Trends Pharmacol Sci. 2018;39:307-325 pubmed publisher
    ..We review recent progress and future perspectives in targeting the IDO1/TDO2-KYN-AhR signaling pathway for the development of novel cancer immunotherapies. ..
  48. Winn S, Scherer T, Thony B, Ying M, Martinez A, Weber S, et al. Blood phenylalanine reduction corrects CNS dopamine and serotonin deficiencies and partially improves behavioral performance in adult phenylketonuric mice. Mol Genet Metab. 2018;123:6-20 pubmed publisher
    ..protein abundance and maximally stimulated activities of tyrosine hydroxylase (TH) and tryptophan hydroxylase 2 (TPH2), the rate limiting enzymes catalyzing neuronal dopamine and serotonin synthesis respectively, in comparison to ..
  49. Glotov A, Sinitsyna E, Danilova M, Vashukova E, Walter J, Stahl F, et al. Detection of human genome mutations associated with pregnancy complications using 3-D microarray based on macroporous polymer monoliths. Talanta. 2016;147:537-46 pubmed publisher
    ..G/A, rs6025), MTHFR (C/T, rs1801133) and ITGB3 (T/C, rs5918), involved in coagulation, and COMT (C/G, rs4818), TPH2 (T/A, rs11178997), PON1 (T/A rs854560), AGTR2 (C/A, rs11091046) and SERPINE1 (5G/4G, rs1799889), associated with ..
  50. Amobi A, Qian F, Lugade A, Odunsi K. Tryptophan Catabolism and Cancer Immunotherapy Targeting IDO Mediated Immune Suppression. Adv Exp Med Biol. 2017;1036:129-144 pubmed publisher
    ..driven by the key and rate-limiting enzymes indoleamine-2,3-dioxygenase 1 (IDO1) and tryptophan-2,3-dioxygenase 2 (TDO), resulting in local depletion of tryptophan, while tryptophan catabolites accumulate, including kynurenine and its ..
  51. Obayashi Y, Ozaki Y, Goto S, Obayashi S, Suzumori N, Ohyama F, et al. Role of Indoleamine 2,3-Dioxygenase and Tryptophan 2,3-Dioxygenase in Patients with Recurrent Miscarriage. Am J Reprod Immunol. 2016;75:69-77 pubmed publisher
    An indoleamine 2,3-dioxygenase (IDO) and a tryptophan 2,3-dioxygenase (TDO) lead to dysfunction of T cell and immunological tolerance between fetus and mother in early pregnancy...
  52. Różycka A, Słopień R, Słopień A, Dorszewska J, Seremak Mrozikiewicz A, Lianeri M, et al. The MAOA, COMT, MTHFR and ESR1 gene polymorphisms are associated with the risk of depression in menopausal women. Maturitas. 2016;84:42-54 pubmed publisher
    ..The following candidate genes were selected for the study: 5HTR2A, 5HTR1B, 5HTR2C, TPH1, TPH2, MAOA, COMT, NET, GABRB1, ESR1, MTHFR, MTR and MTHFD1...
  53. Su Y, Li J, Dai W, Liao X, Dong L, Lu T, et al. Genetic variation in the tryptophan hydroxylase 2 gene moderates depressive symptom trajectories and remission over 8 weeks of escitalopram treatment. Int Clin Psychopharmacol. 2016;31:127-33 pubmed publisher
    ..the relationship between genotypic variation in six candidate serotonergic genes (ADCY9, HTR1B, GNB3, HTR2A, TPH2, SLC6A4) and depressive and anxiety symptom severity trajectories as well as remission following escitalopram ..
  54. Kohli S, Mohanty S, Singh S, Sandeep -, Dabas J, Patel R. The autogenous graft versus transport distraction osteogenesis for reconstruction of the ramus-condyle unit: a prospective comparative study. Int J Oral Maxillofac Surg. 2017;46:1106-1117 pubmed publisher
    ..following condylar reconstruction using sternoclavicular grafts (SCG) versus transport distraction osteogenesis (TDO) in temporomandibular joint (TMJ) ankylosis patients...
  55. Angoa Perez M, Kane M, Sykes C, Perrine S, Church M, Kuhn D. Brain serotonin determines maternal behavior and offspring survival. Genes Brain Behav. 2014;13:579-91 pubmed publisher
    ..of serotonin to maternal care, we used mice with a null mutation in the gene for tryptophan hydroxylase-2 (TPH2), which results in a genetic depletion of brain serotonin, and tested them in a wide range of maternal behavior ..
  56. Kronenberg G, Mosienko V, Gertz K, Alenina N, Hellweg R, Klempin F. Increased brain-derived neurotrophic factor (BDNF) protein concentrations in mice lacking brain serotonin. Eur Arch Psychiatry Clin Neurosci. 2016;266:281-4 pubmed publisher
    ..hippocampus and cortex of two mouse models of altered serotonin signaling: tryptophan hydroxylase (Tph)2-deficient (Tph2 (-/-)) mice lacking brain serotonin and serotonin transporter (SERT)-deficient (SERT(-/-)) mice lacking serotonin ..
  57. Ragan C, Harding K, Lonstein J. Associations among within-litter differences in early mothering received and later emotional behaviors, mothering, and cortical tryptophan hydroxylase-2 expression in female laboratory rats. Horm Behav. 2016;77:62-71 pubmed publisher
    ..Medial prefrontal cortex expression of tryptophan hydroxylase-2 (TPH2; enzyme necessary for serotonin synthesis) was negatively associated with early maternal licking received...
  58. Badawy A. Tryptophan metabolism, disposition and utilization in pregnancy. Biosci Rep. 2015;35: pubmed publisher
    ..demand for protein synthesis and fetal development, most probably mediated by maternal liver Trp 2,3-dioxygenase (TDO) inhibition by progesterone and oestrogens...
  59. Yu C, Pan Z, Luo D. TDO as a therapeutic target in brain diseases. Metab Brain Dis. 2016;31:737-47 pubmed publisher
    Tryptophan-2, 3-dioxygenase (TDO) is a heme-containing protein catalyzing the first reaction in the kynurenine pathway, which incorporates oxygen into the indole moiety of tryptophan and catalyzes it into kynurenine (KYN)...
  60. Sordillo P, Sordillo L, Helson L. The Kynurenine Pathway: A Primary Resistance Mechanism in Patients with Glioblastoma. Anticancer Res. 2017;37:2159-2171 pubmed
    ..Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are produced, accelerating metabolism along the kynurenine pathway and resulting in excess levels of quinolinic ..
  61. Hainer C, Mosienko V, Koutsikou S, Crook J, Gloss B, Kasparov S, et al. Beyond Gene Inactivation: Evolution of Tools for Analysis of Serotonergic Circuitry. ACS Chem Neurosci. 2015;6:1116-29 pubmed publisher
    ..This includes a comparative analysis of several mouse and rat lines expressing Cre or Flp recombinases under Tph2, Sert, or Pet1 promoters with a focus on specificity and recombination efficiency...
  62. Hehar H, Yeates K, Kolb B, Esser M, Mychasiuk R. Impulsivity and Concussion in Juvenile Rats: Examining Molecular and Structural Aspects of the Frontostriatal Pathway. PLoS ONE. 2015;10:e0139842 pubmed publisher
    ..and the prefrontal cortex (PFC), the expression patterns of 8 genes (Comt, Drd2, Drd3, Drd4, Maoa, Sert, Tph1, and Tph2) from these two regions were examined...
  63. Mas S, Blázquez A, Rodriguez N, Boloc D, Lafuente A, Arnaiz J, et al. Pharmacogenetic study focused on fluoxetine pharmacodynamics in children and adolescent patients: impact of the serotonin pathway. Pharmacogenet Genomics. 2016;26:487-496 pubmed
    ..related to the serotonergic system: the 5-hydroxytryptamine receptor 1B (HTR1B) and the tryptophan 5-hydroxylase 2 (TPH2)...
  64. Navrotskaya V, Oxenkrug G, Vorobyova L, Summergrad P. Attenuation of high sucrose diet-induced insulin resistance in tryptophan 2,3-dioxygenase deficient Drosophila melanogaster vermilion mutants. Integr Obes Diabetes. 2015;1:93-95 pubmed
    ..Rate-limiting enzyme of TRP - KYN pathway in Drosophila is TRP 2,3-dioxygenase (TDO), an evolutionary conserved ortholog of human TDO. In insects TDO is encoded by vermilion gene...
  65. Ma J, Xiao H, Yang Y, Cao D, Wang L, Yang X, et al. Interaction of tryptophan hydroxylase 2 gene and life events in susceptibility to major depression in a Chinese Han population. J Affect Disord. 2015;188:304-9 pubmed publisher
    ..The aim of this study is to analyze the interaction of tryptophan hydroxylase 2 gene (TPH2) variation and negative life events in the pathogenesis of MD...
  66. Montalbano A, Waider J, Barbieri M, Baytas O, Lesch K, Corradetti R, et al. Cellular resilience: 5-HT neurons in Tph2(-/-) mice retain normal firing behavior despite the lack of brain 5-HT. Eur Neuropsychopharmacol. 2015;25:2022-35 pubmed publisher
    ..e. tryptophan hydroxylase-2 null mice (Tph2(-/-)) and their littermates, Tph2(+/-) and Tph2(+/+), by using whole-cell patch-clamp recordings in a brainstem ..
  67. Timosenko E, Ghadbane H, Silk J, Shepherd D, Gileadi U, Howson L, et al. Nutritional Stress Induced by Tryptophan-Degrading Enzymes Results in ATF4-Dependent Reprogramming of the Amino Acid Transporter Profile in Tumor Cells. Cancer Res. 2016;76:6193-6204 pubmed
    ..a shortage of tryptophan caused by expression of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) resulted in ATF4-dependent upregulation of several amino acid transporters, including SLC1A5 and its truncated ..
  68. Latsko M, Gilman T, Matt L, Nylocks K, Coifman K, Jasnow A. A Novel Interaction between Tryptophan Hydroxylase 2 (TPH2) Gene Polymorphism (rs4570625) and BDNF Val66Met Predicts a High-Risk Emotional Phenotype in Healthy Subjects. PLoS ONE. 2016;11:e0162585 pubmed publisher
    ..We examined the novel interaction between BDNF (Val66Met) and TPH2 (rs4570625) polymorphisms and their influence on behavioral inhibition of negative emotion in two independent ..
  69. D Amato N, Rogers T, Gordon M, Greene L, Cochrane D, Spoelstra N, et al. A TDO2-AhR signaling axis facilitates anoikis resistance and metastasis in triple-negative breast cancer. Cancer Res. 2015;75:4651-64 pubmed publisher
  70. Tanaka T, Hasegawa Baba Y, Watanabe Y, Mizukami S, Kangawa Y, Yoshida T, et al. Maternal exposure to ochratoxin A targets intermediate progenitor cells of hippocampal neurogenesis in rat offspring via cholinergic signal downregulation and oxidative stress responses. Reprod Toxicol. 2016;65:113-122 pubmed publisher
    ..glutamatergic receptors (Gria1, Gria2, and Grin2a), serotonin-synthesizing enzyme, and serotonergic receptors (Tph2, Htr1a, and Htr4) increased in the dentate gyrus, suggesting multiple neuroprotective actions against OTA-induced ..
  71. Karami A, Omar D, Lazorchak J, Yap C, Hashim Z, Courtenay S. A comparison of biomarker responses in juvenile diploid and triploid African catfish, Clarias gariepinus, exposed to the pesticide butachlor. Environ Res. 2016;151:313-320 pubmed publisher
    ..plasma testosterone, 17-β estradiol (E2), cortisol, cholesterol, or mRNA levels of brain tryptophan hydroxylase (tph2), forkhead box L2 (foxl2), and 11 β-hydroxysteroid dehydrogenase type 2 (11β-hsd2)...
  72. Alter S, Stout K, Lohr K, Taylor T, Shepherd K, Wang M, et al. Reduced vesicular monoamine transport disrupts serotonin signaling but does not cause serotonergic degeneration. Exp Neurol. 2016;275 Pt 1:17-24 pubmed publisher
    ..the substantia nigra and locus ceruleus, aged VMAT2 LO mice do not exhibit a change in the number of serotonergic (TPH2+) neurons within the dorsal raphe, as measured by unbiased stereology at 26-30 months...
  73. Markett S, de Reus M, Reuter M, Montag C, Weber B, Schoene Bake J, et al. Serotonin and the Brain's Rich Club-Association Between Molecular Genetic Variation on the TPH2 Gene and the Structural Connectome. Cereb Cortex. 2017;27:2166-2174 pubmed publisher
    ..We assessed the impact of normal variation of the tryptophane hydroxylase 2 gene's promotor region (TPH2 rs4570625) on structural connectivity of the rich club pathways by means of a candidate gene association design...
  74. Xu Z, Reynolds G, Yuan Y, Shi Y, Pu M, Zhang Z. TPH-2 Polymorphisms Interact with Early Life Stress to Influence Response to Treatment with Antidepressant Drugs. Int J Neuropsychopharmacol. 2016;19: pubmed publisher
    ..initial study of monoaminergic coding region single nucleotide polymorphisms identified significant associations of TPH2 and HTR1B single nucleotide polymorphisms with treatment response that showed interactions with childhood and ..
  75. Urata Y, Koga K, Hirota Y, Akiyama I, Izumi G, Takamura M, et al. IL-1? increases expression of tryptophan 2,3-dioxygenase and stimulates tryptophan catabolism in endometrioma stromal cells. Am J Reprod Immunol. 2014;72:496-503 pubmed publisher
    Immune tolerance to endometriotic cells is important to promote endometriosis. Tryptophan 2,3-dioxygenase (TDO) enhances immune tolerance by catabolizing tryptophan to kynurenine...
  76. Laurent L, Deroy K, St Pierre J, Cote F, Sanderson J, Vaillancourt C. Human placenta expresses both peripheral and neuronal isoform of tryptophan hydroxylase. Biochimie. 2017;140:159-165 pubmed publisher
    ..Moreover, it is not known if the two tryptophan hydroxylase isoforms (TPH1 and TPH2), the rate-limiting enzymes in serotonin biosynthesis, are expressed in placenta...
  77. Nabi R, Serajee F, Chugani D, Zhong H, Huq A. Association of tryptophan 2,3 dioxygenase gene polymorphism with autism. Am J Med Genet B Neuropsychiatr Genet. 2004;125B:63-8 pubmed
    ..0027). Our results suggest the presence of a susceptibility mutation in the TDO2 or a nearby gene, but may also represent a chance finding. ..
  78. Baharvand H, Hashemi S, Kazemi Ashtiani S, Farrokhi A. Differentiation of human embryonic stem cells into hepatocytes in 2D and 3D culture systems in vitro. Int J Dev Biol. 2006;50:645-52 pubmed
  79. Meng B, Wu D, Gu J, Ouyang S, Ding W, Liu Z. Structural and functional analyses of human tryptophan 2,3-dioxygenase. Proteins. 2014;82:3210-6 pubmed publisher
    Tryptophan 2,3-dioxygenase (TDO), one of the two key enzymes in the kynurenine pathway, catalyzes the indole ring cleavage at the C2-C3 bond of L-tryptophan...
  80. Lewis Ballester A, Forouhar F, Kim S, Lew S, Wang Y, Karkashon S, et al. Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase. Sci Rep. 2016;6:35169 pubmed publisher
    Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) play a central role in tryptophan metabolism and are involved in many cellular and disease processes...
  81. Young J, Geurts A, Hodges M, Cummings K. Active sleep unmasks apnea and delayed arousal in infant rat pups lacking central serotonin. J Appl Physiol (1985). 2017;123:825-834 pubmed publisher
    ..Two-week-old tryptophan hydroxylase 2-deficient (TPH2-/-) and wild-type (WT) rat pups were placed in plethysmographic chambers supplied with room air...
  82. Réus G, Becker I, Scaini G, Petronilho F, Oses J, Kaddurah Daouk R, et al. The inhibition of the kynurenine pathway prevents behavioral disturbances and oxidative stress in the brain of adult rats subjected to an animal model of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2018;81:55-63 pubmed publisher
    ..However, the inhibitors of tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase (IDO) and kynurenine-3-monooxygenase (KMO) were able to reverse these changes...
  83. Tidemand K, Peters G, Harris P, Stensgaard E, Christensen H. Isoform-Specific Substrate Inhibition Mechanism of Human Tryptophan Hydroxylase. Biochemistry. 2017;56:6155-6164 pubmed publisher
    ..TPH exists in two isoforms: TPH1 and TPH2. TPH1 catalyzes the initial step in the synthesis of serotonin in the peripheral tissues, while TPH2 catalyzes this ..
  84. Schmidt S, Müller A, Heseler K, Woite C, Spekker K, Mackenzie C, et al. Antimicrobial and immunoregulatory properties of human tryptophan 2,3-dioxygenase. Eur J Immunol. 2009;39:2755-64 pubmed publisher
    ..we show for the first time that another tryptophan-degrading enzyme, the liver-specific tryptophan 2,3-dioxygenase (TDO), is also capable of mediating antimicrobial and immunoregulatory effects...
  85. Opitz C, Litzenburger U, Sahm F, Ott M, Tritschler I, Trump S, et al. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature. 2011;478:197-203 pubmed publisher
    ..ligand of the human AHR that is constitutively generated by human tumour cells via tryptophan-2,3-dioxygenase (TDO), a liver- and neuron-derived Trp-degrading enzyme not yet implicated in cancer biology...
  86. Soichot M, Vaast A, Vignau J, Guillemin G, Lhermitte M, Broly F, et al. Characterization of functional polymorphisms and glucocorticoid-responsive elements in the promoter of TDO2, a candidate gene for ethanol-induced behavioural disorders. Alcohol Alcohol. 2013;48:415-25 pubmed publisher
    In response to acute ethanol consumption, tryptophan 2,3-dioxygenase (TDO) induces the kynurenine pathway (KP) through a glucocorticoid-mediated mechanism, which could lead to a dramatic accumulation of neurotoxic metabolites in ..
  87. Neufang S, Akhrif A, Herrmann C, Drepper C, Homola G, Nowak J, et al. Serotonergic modulation of 'waiting impulsivity' is mediated by the impulsivity phenotype in humans. Transl Psychiatry. 2016;6:e940 pubmed publisher
    ..Subjects were genotyped for the tryptophan hydroxylase-2 (TPH2; G-703T; rs4570625) variant, an enzyme specific for brain serotonin synthesis...
  88. Song N, Zhang Q, Huang Y, Chen L, Ding Y, Zhang L. Enhanced dendritic morphogenesis of adult hippocampal newborn neurons in central 5-HT-deficient mice. Stem Cell Res. 2017;19:6-11 pubmed publisher
    ..Here, we address this question using two central 5-HT-deficient mouse models, Tph2 conditional knockout mice (CKO) losing central 5-HT from embryonic stage, and Pet1-Cre;Rosa26-DTR (diphtheria toxin ..
  89. Comings D, Muhleman D, Dietz G, Donlon T. Human tryptophan oxygenase localized to 4q31: possible implications for alcoholism and other behavioral disorders. Genomics. 1991;9:301-8 pubmed
    A human tryptophan oxygenase clone was isolated by screening a liver cDNA library with a rat tryptophan oxygenase cDNA clone. Analysis showed extensive homology between the rat and the human DNA and protein sequences...
  90. Basran J, Efimov I, Chauhan N, Thackray S, Krupa J, Eaton G, et al. The mechanism of formation of N-formylkynurenine by heme dioxygenases. J Am Chem Soc. 2011;133:16251-7 pubmed publisher
    ..These data suggest that the dioxygenases use a ring-opening mechanism during NFK formation, rather than Criegee or dioxetane mechanisms as previously proposed. ..
  91. Näslund J, Studer E, Johansson E, Eriksson E. Effects of gonadectomy and serotonin depletion on inter-individual differences in anxiety-like behaviour in male Wistar rats. Behav Brain Res. 2016;308:160-5 pubmed publisher
    ..high anxiety-like behaviour and high expression of the serotonin-synthesizing enzyme tryptophan hydroxylase 2 (Tph2) in the raphe was confirmed in sham-operated animals but absent in gonadectomised rats, an ANCOVA revealing a ..
  92. Komnenov D, Solarewicz J, Afzal F, Nantwi K, Kuhn D, Mateika J. Intermittent hypoxia promotes recovery of respiratory motor function in spinal cord-injured mice depleted of serotonin in the central nervous system. J Appl Physiol (1985). 2016;121:545-57 pubmed publisher
    ..activity, ventilation, core body temperature, and limb mobility were measured in spontaneously breathing wild-type (Tph2(+/+)) and tryptophan hydroxylase 2 knockout (Tph2(-/-)) mice...