Tryptophan 2,3 dioxygenase

Tryptophan 2,3 dioxygenase (TDO, EC 1.13.11.11) is a heme-containing oxidoreductase which catalyzes the rate-limiting first step of the kynurenine pathway; the oxidative cleavage of L-tryptophan (L-Trp) into N-formyl-kynurenine (Nfk).

Products
Background
Literature
Gene Data

Inhibitors

Cat No Product Name / Activity
4392 680C91
Potent and selective tryptophan 2,3-dioxygenase (TDO) inhibitor
5794 LM 10
Selective tryptophan 2,3-dioxygenase (TDO) inhibitor

Other

Cat No Product Name / Activity
4393 L-Kynurenine
Tryptophan catabolite generated by TDO; also endogenous aryl hydrocarbon receptor ligand

Tryptophan 2,3 dioxygenase (TDO, EC 1.13.11.11) is a heme-containing oxidoreductase which catalyzes the rate-limiting first step of the kynurenine pathway; the oxidative cleavage of L-tryptophan (L-Trp) into N-formyl-kynurenine (Nfk).

Primarily localized to the liver, where its main function is to regulate L-Trp homeostasis in the blood, TDO is responsible for the majority of L-Trp degradation via the kynurenine pathway. This leads to the production of L-Trp metabolites and the synthesis of the redox cofactor nicotinamide adenine dinucleotide. In extrahepatic tissues, the cleavage of L-Trp is catalyzed by indoleamine 2,3 dioxygenase (IDO).

TDO exists as a 134 kDa homotetramer of alpha-helical monomers, which are folded in a similar way to the large domain of IDO. The tetrameric structure of TDO is dependent upon the presence of four heme cofactors, which are situated at each of the four monomer interfaces. These hemes must be reduced for substrate binding and enzymatic activity.

Although TDO expression is mainly restricted to the liver, it is also present in certain cancer cells and is therefore a target of cancer research. The expression of TDO by tumor cells results in immunosuppression, as the depletion of L-Trp caused by TDO inactivates T-cells preventing an antitumor response.

TDO may also be involved in Alzheimer's disease as TDO expression has been associated with senile plaques in the brains of AD patients. As many kynurenine pathway intermediates are neuroactive, increased TDO activity in the brain may exacerbate neurodegeneration.

External sources of pharmacological information for Tryptophan 2,3 dioxygenase :

Literature for Tryptophan 2,3 dioxygenase

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Tryptophan 2,3 dioxygenase Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
TDO2 Human TDO2 NM_005651 P48775
Mouse Tdo2 NM_019911 P48776
Rat Tdo2 NM_022403 P21643