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Kynurenine formamidase (EC 3.5.1.9), also known as arylformamidase, is a key enzyme in the kynurenine pathway, which is the primary metabolic route for the essential amino acid tryptophan [3, 7]. It catalyzes the hydrolysis of N-formyl-L-kynurenine to L-kynurenine, a pivotal intermediate that serves as a precursor for several bioactive metabolites, including the neuroprotectant kynurenic acid and the excitotoxin quinolinic acid [1, 15]. This enzyme is also vital for the de novo biosynthesis of nicotinamide adenine dinucleotide (NAD+), which is essential for cellular energy metabolism and DNA repair [3, 14]. Imbalances in the kynurenine pathway are associated with a wide range of conditions, including neurodegenerative diseases like Alzheimer's and Huntington's, as well as cancer and depression [20, 21]. Although it is less frequently targeted than other enzymes in the pathway like IDO or KMO, kynurenine formamidase is a known target for organophosphorus compounds, and its inhibition can lead to developmental defects and metabolic disruption [13, 20]. Therapeutic interest in this enzyme focuses on its potential to modulate the levels of neuroactive kynurenines and restore metabolic homeostasis in inflammatory and neurological disorders [1, 20].
Inhibition of arylformamidase activity, preventing the hydrolysis of N-formyl-L-kynurenine to L-kynurenine.
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