Synthesis and kinetic evaluation of substrates and inhibitors for kynureninase
Abstract
Kynureninase is a pyridoxal-5’-phosphate (PLP) dependent enzyme in the kynurenine
metabolic pathway of L-tryptophan in animals and bacteria. In mammals, this pathway
provides a de novo synthesis of NAD(P)+ . The mammalian kynureninase catalyses the
hydrolytic cleavage of 3-hydroxy-L-kynurenine to 3-hydroxyanthranilic acid and Lalanine.
One of the metabolites in this pathway is quinolininc acid. Quinolinic acid is a
neurotoxin if produced in excess of its biosynthetic requirement. Potent inhibitors of this
enzyme are required as drug targets for several neurological disorders and other
diseases including Alzhemier’s, AIDS related dementia and Huntington’s disease. In the
current work, potent inhibitors and substrates for both human and bacterial
kynureninase have been synthesized and kinetically evaluated for their enzymatic
activity.