The Kynurenine Pathway and Kynurenine 3-Monooxygenase Inhibitors.

Under normal physiological conditions, the kynurenine pathway (KP) plays a critical role in generating cellular energy and catabolizing tryptophan. Under inflammatory conditions, however, there is an upregulation of the KP enzymes, particularly kynurenine 3-monooxygenase (KMO). KMO has garnered much attention due to its production of toxic metabolites that have been implicated in many diseases and disorders.

Modulation of Enzyme Activity in the Kynurenine Pathway by Kynurenine Monooxygenase Inhibition.

The kynurenine pathway is the major route for tryptophan metabolism in mammals. Several of the metabolites in the kynurenine pathway, however, are potentially toxic, particularly 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and quinolinic acid. Quinolinic acid (QUIN) is an excitotoxic agonist at the NMDA receptor, and has been shown to be elevated in neurodegenerative diseases such as Alzheimer's Disease and Huntington's Disease.