How is kynurenine formed?
l-Kynurenine is a metabolite of the amino acid l-tryptophan used in the production of niacin. Kynurenine is synthesized by the enzyme tryptophan dioxygenase, which is made primarily but not exclusively in the liver, and indoleamine 2,3-dioxygenase, which is made in many tissues in response to immune activation.
What is the role of TDO?
TDO is mainly present in the liver and metabolizes 95% of hepatic Trp. It is a key serotonergic determinant 59 and plays a key role in the emotional and psychiatric status 60. Due to the similar enzymatic function with IDO, it can also suppress inflammation and maintain immune homeostasis 61 by Trp starvation 62.
What is tryptophan oxygenase?
In enzymology, tryptophan 2,3-dioxygenase (EC 1.13. 11.11) is a heme enzyme that catalyzes the oxidation of L-tryptophan (L-Trp) to N-formyl-L-kynurenine, as the first and rate-limiting step of the kynurenine pathway. In humans, tryptophan 2,3-dioxygenase is encoded by the TDO2 gene.
What causes high quinolinic acid?
Quinolinic acid levels are increased in the brains of children infected with a range of bacterial infections of the central nervous system (CNS), of poliovirus patients, and of Lyme disease with CNS involvement patients.
What is tryptophan Pyrrolase?
The regulation and functions of rat liver tryptophan pyrrolase are reviewed. Possible functions of the pyrrolase are the detoxication of tryptophan and the regulation of brain 5-hydroxytryptamine synthesis, liver haem metabolism, synthesis of nicotinamide-adenine dinucleotides (phosphates) and hepatic gluconeogenesis.
What are the effects of overexpression of TDO2?
TDO2 overexpression was related to poor prognosis and associated with cancer cell proliferation and tumor stem cells in esophageal squamous cell carcinoma.
How is TDO different from other dioxygenases?
The data suggest that TDO uses a ring-opening mechanism during N-formylkynurenine formation, rather than Criegee or dioxetane mechanisms as previously proposed. Studies indicate that the heme dioxygenases are differentiated by their ability to catalyze the oxidation of l-tryptophan to N-formylkynurenine.
How is high TDO2 expression associated with colorectal cancer?
High TDO2 expression is associated with Colorectal Cancer. Crystal tryptophan 2,3-dioxygenase structure revealed eight residues playing critical roles in L-tryptophan oxidation. IL-1beta is suggested to stimulate tryptophan catabolism and production of IL-6 and IL-8 by increasing TDO expression in endometriosis.
Where are the polymorphisms located in the TDO2 promoter?
Identification of 12 polymorphisms in the human TDO2 promoter region, 2 of them corresponding to previously unknown single-nucleotide polymorphisms and 3 of them located in putative glucocorticoid-responsive elements. TDO is highly expressed in the brains of Alzheimer disease patients.