The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

TDO2  -  tryptophan 2,3-dioxygenase

Homo sapiens

Synonyms: TDO, TO, TPH2, TRPO, Tryptamin 2,3-dioxygenase, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of TDO2


Psychiatry related information on TDO2


High impact information on TDO2

  • We have examined this question in liver by studying the heme saturation of tryptophan pyrrolase, the heme-dependent enzyme which controls the first and rate-limiting step in the catabolism of L-tryptophan [2].
  • Two sisters with abnormal tryptophan metabolism were given 200 mg L-kynurenine sulfate orally to bypass the effects of tryptophan oxygenase activity [10].
  • The results indicated that the higher tryptophanase activity in the feces of rats fed an all-meat diet is due to the inducibility of this enzyme by tryptophan and is not due to any inhibitor in the feces of rats on a normal diet [1].
  • The tryptophanase of the indole-positive strains of intestinal anaerobes was inducible by tryptophan and was susceptible to glucose repression [1].
  • Triokinase activity is absent in the distal two-fifths of intestine, and tryptophan oxygenase is present only in the distal one-sixth, or most terminal part of the ileum [11].

Chemical compound and disease context of TDO2


Biological context of TDO2


Anatomical context of TDO2

  • For this follow-up study of postmortem anterior cingulate gyrus, we have found evidence of increased TDO2 activity in schizophrenia at three different levels of regulation: mRNA, protein, and metabolic product [7].
  • This resulted in suppression of growth, changes in morphology (microvilli and large cytoplasm with developed organelles), and expression of hepatocyte markers (albumin, tyrosine amino transferase, and tryptophan oxygenase) [19].
  • Whereas TDO is located in the liver cells, IDO is expressed in a large variety of cells and is inducible by the cytokine interferon-gamma [20].
  • Small intestine indole 2,3-dioxygenase (IDO) did not vary significantly among the three groups but was higher in comparison with liver TDO activity [21].
  • TDO is located in liver cells, whereas IDO is expressed in a variety of cells including monocyte-derived macrophages and dendritic cells and is preferentially induced by Th1-type cytokine interferon-gamma [22].

Associations of TDO2 with chemical compounds


Other interactions of TDO2


Analytical, diagnostic and therapeutic context of TDO2

  • Sequence alignment of the rat liver protein with that of known or putative TDO sequences from other organisms reveals that four of the His residues are conserved in eukaryotes, two of which are also conserved in prokaryotes [23].
  • Finally, we present evidence that the expression and activity of liver specific transcription factors, CCAAT/enhancer binding proteins and liver specific key enzymes such as tryptophan 2,3-dioxygenase, are improved in hepatocyte/BMSC co-cultures [31].
  • Liver L-tryptophan 2,3-dioxygenase activity (TDO), a rate-limiting enzyme of the kynurenine pathway, was increased in proportion to blood urea nitrogen and creatinine levels [12].
  • The effects of the administration of oestrogens on the activity of hepatic tryptophan oxygenase have been assessed both directly (by measurement of enzyme activity in vitro) and indirectly (by measurement of urinary excretion of tryptophan metabolites) in rats, and indirectly in menopausal women receiving hormone replacement therapy [32].
  • Both adrenalectomy and ovariectomy led to a reduction in the activity of tryptophan oxygenase in homogenates of liver from mature rats; again there was no effect of giving 500 micrograms of oestradiol/kg body wt by intraperitoneal injection [32].


  1. Tryptophanase of fecal flora as a possible factor in the etiology of colon cancer. Chung, K.T., Fulk, G.E., Slein, M.W. J. Natl. Cancer Inst. (1975) [Pubmed]
  2. Sn-protoporphyrin rapidly and markedly enhances the heme saturation of hepatic tryptophan pyrrolase. Evidence that this synthetic metalloporphyrin increases the functional content of heme in the liver. Kappas, A., Drummond, G.S., Sardana, M.K. J. Clin. Invest. (1985) [Pubmed]
  3. Molecular insights into substrate recognition and catalysis by tryptophan 2,3-dioxygenase. Forouhar, F., Anderson, J.L., Mowat, C.G., Vorobiev, S.M., Hussain, A., Abashidze, M., Bruckmann, C., Thackray, S.J., Seetharaman, J., Tucker, T., Xiao, R., Ma, L.C., Zhao, L., Acton, T.B., Montelione, G.T., Chapman, S.K., Tong, L. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  4. Tryptophanase in sRNA control of the Escherichia coli cell cycle. Chattoraj, D.K. Mol. Microbiol. (2007) [Pubmed]
  5. Exclusion of the 5-HT1A serotonin neuroreceptor and tryptophan oxygenase genes in a large British kindred multiply affected with Tourette's syndrome, chronic motor tics, and obsessive-compulsive behavior. Brett, P.M., Curtis, D., Robertson, M.M., Gurling, H.M. The American journal of psychiatry. (1995) [Pubmed]
  6. Association of tryptophan 2,3 dioxygenase gene polymorphism with autism. Nabi, R., Serajee, F.J., Chugani, D.C., Zhong, H., Huq, A.H. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2004) [Pubmed]
  7. Upregulation of the initiating step of the kynurenine pathway in postmortem anterior cingulate cortex from individuals with schizophrenia and bipolar disorder. Miller, C.L., Llenos, I.C., Dulay, J.R., Weis, S. Brain Res. (2006) [Pubmed]
  8. Predisposition to alcoholism, tryptophan oxygenase activity, and structure of intron 6 in the corresponding gene of C57BL/6J, CC57BR/Mv, and BALB/cJ mice. Kaledin, V.I., Klimova, N.V., Vasil'ev, G.V., Ivanova, E.A., Vasil'eva, E.D., Il'nitskaya, S.I. Bull. Exp. Biol. Med. (2003) [Pubmed]
  9. TPH2: an answer for unipolar depression? Slow, E. Clin. Genet. (2005) [Pubmed]
  10. Abnormal tryptophan metabolism in a family with a history of bladder cancer. Leklem, J.E., Brown, R.R. J. Natl. Cancer Inst. (1976) [Pubmed]
  11. Distribution of intrinsic factor-vitamin B12 receptors in human intestine. Hagedorn, C.H., Alpers, D.H. Gastroenterology (1977) [Pubmed]
  12. Mechanism of increases in L-kynurenine and quinolinic acid in renal insufficiency. Saito, K., Fujigaki, S., Heyes, M.P., Shibata, K., Takemura, M., Fujii, H., Wada, H., Noma, A., Seishima, M. Am. J. Physiol. Renal Physiol. (2000) [Pubmed]
  13. Increase in tryptophan oxygenase activity in alcoholic patients. Buydens-Branchey, L., Branchey, M., Worner, T.M., Zucker, D., Aramsombatdee, E., Lieber, C.S. Alcohol. Clin. Exp. Res. (1988) [Pubmed]
  14. Biosynthesis of new indigoid inhibitors of protein kinases using recombinant cytochrome P450 2A6. Wu, Z.L., Aryal, P., Lozach, O., Meijer, L., Guengerich, F.P. Chem. Biodivers. (2005) [Pubmed]
  15. Dioxygenase-catalysed oxidation of disubstituted benzene substrates: benzylic monohydroxylation versus aryl cis-dihydroxylation and the meta effect. Boyd, D.R., Sharma, N.D., Bowers, N.I., Dalton, H., Garrett, M.D., Harrison, J.S., Sheldrake, G.N. Org. Biomol. Chem. (2006) [Pubmed]
  16. Sequence of human tryptophan 2,3-dioxygenase (TDO2): presence of a glucocorticoid response-like element composed of a GTT repeat and an intronic CCCCT repeat. Comings, D.E., Muhleman, D., Dietz, G., Sherman, M., Forest, G.L. Genomics (1995) [Pubmed]
  17. Point mutations within 663-666 bp of intron 6 of the human TDO2 gene, associated with a number of psychiatric disorders, damage the YY-1 transcription factor binding site. Vasiliev, G.V., Merkulov, V.M., Kobzev, V.F., Merkulova, T.I., Ponomarenko, M.P., Kolchanov, N.A. FEBS Lett. (1999) [Pubmed]
  18. Human tryptophan oxygenase localized to 4q31: possible implications for alcoholism and other behavioral disorders. Comings, D.E., Muhleman, D., Dietz, G.W., Donlon, T. Genomics (1991) [Pubmed]
  19. Oncostatin M inhibits proliferation of rat oval cells, OC15-5, inducing differentiation into hepatocytes. Okaya, A., Kitanaka, J., Kitanaka, N., Satake, M., Kim, Y., Terada, K., Sugiyama, T., Takemura, M., Fujimoto, J., Terada, N., Miyajima, A., Tsujimura, T. Am. J. Pathol. (2005) [Pubmed]
  20. Interferon-gamma-induced conversion of tryptophan: immunologic and neuropsychiatric aspects. Wirleitner, B., Neurauter, G., Schröcksnadel, K., Frick, B., Fuchs, D. Current medicinal chemistry. (2003) [Pubmed]
  21. Tryptophan metabolism along the kynurenine pathway in diet-induced and genetic hypercholesterolemic rabbits. Allegri, G., Ragazzi, E., Costa, C.V., Caparrotta, L., Biasiolo, M., Comai, S., Bertazzo, A. Clin. Chim. Acta (2004) [Pubmed]
  22. Monitoring tryptophan metabolism in chronic immune activation. Schröcksnadel, K., Wirleitner, B., Winkler, C., Fuchs, D. Clin. Chim. Acta (2006) [Pubmed]
  23. Structure--function relationships of rat hepatic tryptophan 2,3-dioxygenase: identification of the putative heme-ligating histidine residues. Dick, R., Murray, B.P., Reid, M.J., Correia, M.A. Arch. Biochem. Biophys. (2001) [Pubmed]
  24. Mutation of an active site residue of tryptophan synthase (beta-serine 377) alters cofactor chemistry. Jhee, K.H., Yang, L.H., Ahmed, S.A., McPhie, P., Rowlett, R., Miles, E.W. J. Biol. Chem. (1998) [Pubmed]
  25. Expression of the kynurenine pathway enzyme tryptophan 2,3-dioxygenase is increased in the frontal cortex of individuals with schizophrenia. Miller, C.L., Llenos, I.C., Dulay, J.R., Barillo, M.M., Yolken, R.H., Weis, S. Neurobiol. Dis. (2004) [Pubmed]
  26. Serotonin neurons derived from rhesus monkey embryonic stem cells: similarities to CNS serotonin neurons. Salli, U., Reddy, A.P., Salli, N., Lu, N.Z., Kuo, H.C., Pau, F.K., Wolf, D.P., Bethea, C.L. Exp. Neurol. (2004) [Pubmed]
  27. Repression of GR-mediated expression of the tryptophan oxygenase gene by the SWI/SNF complex during liver development. Inayoshi, Y., Kaneoka, H., Machida, Y., Terajima, M., Dohda, T., Miyake, K., Iijima, S. J. Biochem. (2005) [Pubmed]
  28. Cancer cachexia and depressive states: a neuro-endocrine-immunological disease? Iwagaki, H., Hizuta, A., Uomoto, M., Takeuchi, Y., Saito, S., Tanaka, N. Acta Med. Okayama (1997) [Pubmed]
  29. A new metabolic pathway for N,N-dimethyltryptamine. Hryhorczuk, L.M., Rainey, J.M., Frohman, C.E., Novak, E.A. Biol. Psychiatry (1986) [Pubmed]
  30. Cloning and characterization of the Tribolium castaneum eye-color genes encoding tryptophan oxygenase and kynurenine 3-monooxygenase. Lorenzen, M.D., Brown, S.J., Denell, R.E., Beeman, R.W. Genetics (2002) [Pubmed]
  31. Enhanced proliferation and differentiation of rat hepatocytes cultured with bone marrow stromal cells. Mizuguchi, T., Hui, T., Palm, K., Sugiyama, N., Mitaka, T., Demetriou, A.A., Rozga, J. J. Cell. Physiol. (2001) [Pubmed]
  32. The effects of oestrogen administration on tryptophan metabolism in rats and in menopausal women receiving hormone replacement therapy. Bender, D.A., Laing, A.E., Vale, J.A., Papadaki, L., Pugh, M. Biochem. Pharmacol. (1983) [Pubmed]
WikiGenes - Universities