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).

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Background

Literature (2)

Gene Data

Tryptophan 2,3 dioxygenase Inhibitors
Cat. No.	Product Name / Activity
4392	680C91
	Potent and selective tryptophan 2,3-dioxygenase (TDO) inhibitor

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 :

IUPHAR Receptor Code

BJP Guide

Literature for Tryptophan 2,3 dioxygenase

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