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

ABSTRACT: 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. Thus, inhibitors of enzymes in the kynurenine pathway may be valuable to treat these diseases. Kynurenine monooxygenase (KMO) is the ideal target for an inhibitor, since inhibition of it would be expected to decrease the toxic metabolites and increase kynurenic acid (KynA), which is neuroprotective. The first generation of KMO inhibitors was based on structural

SUBMITTER: Phillips RS 

PROVIDER: S-EPMC6376250 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature