Target intelligence / Profile preview

Kynurenine formamidase (AFMID)

Target
AFMID
Molecular classification
Enzyme, Hydrolase, Alpha/beta hydrolase
01

Overview

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].

Other names
ArylformamidaseN-formylkynurenine formamidaseFormylaseFormylkynureninaseFormamidase IFormamidase IIKFaseKFAFKF
02

Mechanism of action

Inhibition of arylformamidase activity, preventing the hydrolysis of N-formyl-L-kynurenine to L-kynurenine.

03

Biological functions

Tryptophan catabolismNAD+ biosynthesisMetabolic detoxification
04

Disease associations

Neurodegenerative diseaseCancerInflammationInfectionPsychiatric disorderOrganophosphorus poisoning
05

Safety considerations

TeratogenicityNeurotoxicityDisruption of NAD+ biosynthesis
06

Interacting drugs

Phenylmethylsulfonyl fluoride

3 more in the full profile.

07

Biomarkers

N-formyl-L-kynurenine levelsKynurenine levelsKynurenine/N-formyl-L-kynurenine ratio

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