Nformylkynurenine

N-formylkynurenine, also known as N-formyl-L-kynurenine, is an intermediate in the kynurenine pathway, the principal route for tryptophan degradation in mammals. It is produced when the dioxygenase enzymes indoleamine 2,3-dioxygenase (IDO) or tryptophan 2,3-dioxygenase (TDO) catalyze the insertion of two oxygen atoms into the indole ring of L-tryptophan, yielding N-formylkynurenine.

The formylated product is then rapidly hydrolyzed by formamidase (arylformamidase) to generate kynurenine and formate. Thus, N-formylkynurenine is a short-lived intermediate that links tryptophan oxidation to downstream kynurenine metabolism. From kynurenine, the pathway can proceed to several other metabolites, including kynurenic acid and 3-hydroxykynurenine, and ultimately to nicotinamide adenine dinucleotide (NAD+) via quinolinic acid.

Physiological and clinical context: The kynurenine pathway handles a large fraction of dietary tryptophan, with flux through the pathway tightly regulated by immune and metabolic cues. IDO, in particular, is inducible by inflammatory mediators such as interferon-γ, linking tryptophan catabolism to immune regulation and tolerance. Metabolites downstream of N-formylkynurenine, including kynurenine, kynurenic acid, and quinolinic acid, have diverse neuroactive and immunomodulatory effects. Aberrant flux through this pathway has been associated with conditions such as cancer, chronic infections, neurodegenerative diseases, and mood disorders, making the regulation of N-formylkynurenine formation a focus of ongoing research.