Tryptophan 2,3-dioxygenase

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Tryptophan 2,3-dioxygenase
Properties of human protein
Mass / length primary structure 406 amino acids
Secondary to quaternary structure Homotetramer
Cofactor Hamm
Gene name TDO2
External IDs
Enzyme classification
EC, category dioxygenase
Response type Oxidation with the incorporation of two oxygen atoms
Substrate L-tryptophan + O 2
Products N-formylkynurenine
Homology family Tryptophan 2,3-dioxygenase
Parent taxon Creature

Tryptophan-2,3-Dioxygenase (TDO) is an enzyme that oxidizes L- Tryptophan by binding to two oxygen atoms . This is the first and at the same time rate-determining reaction step in the breakdown of tryptophan. TDO occurs in most living things. In humans, it is mainly produced in the liver . An active TDO enzyme consists of a tetramer and binds two molecules of heme as a cofactor in the catalytic center.

TDO supplements itself in the body with indolamine-2,3-dioxygenase (IDO), which catalyzes the same breakdown; However, the IDO uses superoxide anions instead of oxygen and is localized in the immune system and the placenta .

Catalyzed reaction

L-Trp+ O 2 N-formyl-L-kynurenine

L -ryptophan is oxidized to N -formyl- L -kynurenine . The hamming molecule stabilizes the substrate (tryptophan). As with all dioxygenases , the iron atom of the heme is involved in the oxidation of tryptophan. Other tryptamines such as serotonin are also accepted as a substrate .


The transcription of TDO is influenced by the presence of glucocorticoids and heme . The enzyme activity of TDO is modulated by insulin and can be inhibited by the drugs acyclovir , tolmetin and sulindac .

Individual evidence

  1. a b UniProt P48775
  2. BioGPS entry
  3. Liao M, Pabarcus MK, Wang Y, et al : Impaired dexamethasone-mediated induction of tryptophan 2,3-dioxygenase in heme-deficient rat hepatocytes: translational control by a hepatic eIF2alpha kinase, the heme-regulated inhibitor . In: J. Pharmacol. Exp. Ther. . 323, No. 3, December 2007, pp. 979-89. doi : 10.1124 / jpet.107.124602 . PMID 17761498 .
  4. Isenović ER, Zakula Z, Koricanac G, Ribarac-Stepić N: Comparative analysis of tryptophan oxygenase activity and glucocorticoid receptor under the influence of insulin . In: Physiol Res . 57, No. 1, 2008, pp. 101-7. PMID 17223727 .
  5. Müller AC, Daya S: Acyclovir inhibits rat liver tryptophan-2,3-dioxygenase and induces a concomitant rise in brain serotonin and 5-hydroxyindole acetic acid levels . In: Metab Brain Dis . 23, No. 3, September 2008, pp. 351-60. doi : 10.1007 / s11011-008-9095-4 . PMID 18665439 .
  6. Dairam A, Antunes EM, Saravanan KS, Daya S: Non-steroidal anti-inflammatory agents, tolmetin and sulindac, inhibit liver tryptophan 2,3-dioxygenase activity and alter brain neurotransmitter levels . In: Life Sci. . 79, No. 24, November 2006, pp. 2269-74. doi : 10.1016 / j.lfs.2006.07.028 . PMID 16952380 .

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