Tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase 1 make separate, tissue-specific contributions to basal and inflammation-induced kynurenine pathway metabolism in mice.
Biochim Biophys Acta
; 1860(11 Pt A): 2345-2354, 2016 11.
Article
en En
| MEDLINE
| ID: mdl-27392942
ABSTRACT
BACKGROUND:
In mammals, the majority of the essential amino acid tryptophan is degraded via the kynurenine pathway (KP). Several KP metabolites play distinct physiological roles, often linked to immune system functions, and may also be causally involved in human diseases including neurodegenerative disorders, schizophrenia and cancer. Pharmacological manipulation of the KP has therefore become an active area of drug development. To target the pathway effectively, it is important to understand how specific KP enzymes control levels of the bioactive metabolites in vivo.METHODS:
Here, we conducted a comprehensive biochemical characterization of mice with a targeted deletion of either tryptophan 2,3-dioxygenase (TDO) or indoleamine 2,3-dioxygenase (IDO), the two initial rate-limiting enzymes of the KP. These enzymes catalyze the same reaction, but differ in biochemical characteristics and expression patterns. We measured KP metabolite levels and enzyme activities and expression in several tissues in basal and immune-stimulated conditions. RESULTS ANDCONCLUSIONS:
Although our study revealed several unexpected downstream effects on KP metabolism in both knockout mice, the results were essentially consistent with TDO-mediated control of basal KP metabolism and a role of IDO in phenomena involving stimulation of the immune system.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Triptófano Oxigenasa
/
Indolamina-Pirrol 2,3,-Dioxigenasa
/
Quinurenina
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Biochim Biophys Acta
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos