Kynureninase (KYNU)

Kynureninase (KYNU) is a PLP-dependent hydrolase enzyme that plays a key role in the kynurenine pathway of tryptophan catabolism[1]. It catalyzes the cleavage of L-kynurenine to anthranilic acid and L-alanine, as well as the cleavage of 3-hydroxy-L-kynurenine to 3-hydroxyanthranilic acid and L-alanine, facilitating the production of NAD+ cofactors from tryptophan[1][3]. The enzyme is encoded by the *KYNU* gene in humans. Biochemically, it belongs to the class V group of the aminotransferase superfamily and requires pyridoxal 5'-phosphate (PLP) as a cofactor[1][3]. Its activity regulates levels of several bioactive metabolites with roles in oxidative stress, neuroprotection, excitotoxicity, and immune modulation[2][3]. Mutations or dysfunction in kynureninase have been linked to neurological and psychiatric disorders, inflammation, immune dysregulation, cancer progression, and NAD deficiency syndromes[2][3]. While *inhibitors and substrate analogues* have been used experimentally to study its function, no current drugs in clinical use directly target kynureninase. Monitoring metabolites of the kynurenine pathway serves as a functional biomarker for KYNU activity and pathway status. Safety concerns with therapeutic modulation center on the balance between beneficial and harmful effects in the nervous and immune systems, given the broad downstream impact of changing tryptophan pathway metabolite levels[2][3].

Other names

KynureninaseL-kynurenine hydrolaseKYNUKYNUUVCRL2KynU

Inhibition or modulation of kynureninase alters tryptophan metabolism; for example, enzyme inhibitors reduce the conversion of kynurenine to anthranilic acid and 3-hydroxykynurenine to 3-hydroxyanthranilic acid, potentially affecting NAD+ biosynthesis and immune signaling[3]