kynureninase

Kynureninase is a pyridoxal phosphate–dependent enzyme that participates in the kynurenine pathway of tryptophan catabolism. It catalyzes the hydrolytic cleavage of L-kynurenine to anthranilic acid and alanine, enabling downstream steps that feed into nicotinamide adenine dinucleotide (NAD+) biosynthesis and the generation of other neuroactive metabolites.

In the pathway, kynureninase functions after the formation of kynurenine from tryptophan and before later steps that produce 3-hydroxyanthranilic acid and quinolinic acid. The enzyme therefore contributes to the balance of kynurenine pathway flux and to the production of metabolites that influence various physiological processes, including inflammation, neuronal signaling, and energy metabolism. Kynureninase is typically a PLP-dependent enzyme and is encoded by the KYNU gene in humans. Tissue distribution includes liver, kidney, brain, and other organs, reflecting its role in systemic tryptophan metabolism.

Clinical and research aspects: rare hereditary deficiencies of kynureninase can lead to elevated kynurenine levels and altered levels of downstream metabolites. Mutations in KYNU have been linked in case studies to neurodevelopmental and neurological conditions, though the full spectrum of effects remains to be clarified. Because several kynurenine pathway metabolites are neuroactive, kynureninase is a target of interest in studies of neurodegenerative and inflammatory diseases. Research often focuses on how modulating kynureninase activity influences the balance of pathway flux and related clinical outcomes.