kynurenine 3-monooxygenase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: L-kynurenine + H+ + NADPH + O2 = 3-hydroxy-L-kynurenine + H2O + NADP+. [EC:1.14.13.9, RHEA:20545]

Kynurenine 3-monooxygenase (KMO) is an enzyme that catalyzes the conversion of L-kynurenine to 3-hydroxykynurenine, a key step in the kynurenine pathway of tryptophan catabolism. This reaction involves the incorporation of one atom of molecular oxygen into the substrate, leading to the formation of a hydroxyl group at the 3-position of the kynurenine molecule. The active site of KMO contains a non-heme iron center that is essential for its catalytic activity. This iron center is coordinated by two histidine residues, one glutamate residue, and a water molecule. Upon binding of the substrate, the iron center undergoes a redox cycle, alternating between Fe(II) and Fe(III) states, facilitating the oxygen activation and subsequent hydroxylation reaction. The hydroxylation step is highly stereospecific, leading to the formation of the (S)-enantiomer of 3-hydroxykynurenine. The enzymatic activity of KMO is regulated by various factors, including the availability of its substrate, kynurenine, and the presence of inhibitors. Furthermore, the expression and activity of KMO are influenced by various physiological and pathological conditions, including inflammation, neurodegenerative diseases, and cancer. The kynurenine pathway, and specifically the activity of KMO, has been implicated in the pathogenesis of various diseases. For instance, increased KMO activity is observed in inflammatory conditions, leading to elevated levels of 3-hydroxykynurenine, which can contribute to oxidative stress and tissue damage. In neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, KMO activity is dysregulated, potentially contributing to neuronal dysfunction and cell death. Moreover, KMO activity has been linked to the growth and progression of certain types of cancer.'
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Proteins (2)

Compounds (5)