Kynurenine

Kynurenine is an endogenous metabolite in the kynurenine pathway of tryptophan degradation. It is formed mainly from tryptophan by the action of the enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO), via the intermediate N-formylkynurenine. Kynurenine sits at a central branch point in the pathway, from which several downstream metabolites are produced.

Downstream metabolism of kynurenine yields a variety of compounds, including kynurenic acid, produced by kynurenine aminotransferases; 3-hydroxykynurenine, produced by kynurenine 3-monooxygenase; and further downstream products such as 3-hydroxyanthranilic acid and quinolinic acid, which eventually contribute to the biosynthesis of nicotinamide adenine dinucleotide (NAD+). Another route yields anthranilic acid via kynureninase. Kynurenine can also interact with receptors such as the aryl hydrocarbon receptor (AhR). It is capable of crossing the blood-brain barrier and can influence brain chemistry.

Biological and clinical significance: The kynurenine pathway plays a role in immune regulation; inflammatory signals, notably interferon-gamma, induce IDO and raise kynurenine levels, which can modulate T cell function and promote immune tolerance. Alterations in the pathway have been linked to infections, cancer, autoimmune diseases, neurodegenerative disorders, and major depressive disorder. Some metabolites are neuroprotective (kynurenic acid) while others are neurotoxic (quinolinic acid), influencing neuronal health. Clinically, kynurenine and its pathway metabolites are studied as biomarkers, and the pathway is a therapeutic target, with approaches including IDO/TDO inhibitors in cancer immunotherapy and strategies to shift downstream metabolite balance.

Notes: L-kynurenine is the biologically dominant form in humans; D-kynurenine is less common. Measurements are typically in plasma or CSF.