Fig. (2).

Tryptophan-kynurenine pathway. The essential amino acid L-tryptophan is converted to 5-hydroxytryptophan by tryptophan hydroxylase (TPH), and this is metabolized to serotonin (5-HT) by 5-hydroxytryptophan decarboxylase. The kynurenine pathway is initiated by the conversion of tryptophan to kynurenine by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). Kynurenine is mostly hydroxylated (kynurenine hydroxylase) to 3-hydroxykynurenine. Kynureninase acts upon both 3-hydroxykynurenine and kynurenine; on 3-hydroxykynurenine to form 3-hydroxyanthranilic acid; and on kynurenine to form anthranilic acid (this latter conversion accounts for only a minority of kynureninase activity). Three-hydroxyanthranilic acid is converted into quinolinic acid, an NMDA receptor agonist by 3-hydroxyanthranilic acid oxygenase. Kynurenine can also be converted into kynurenic acid by kynurenine aminotransferase. By contrast, kynurenic acid is an antagonist at NMDA and α7 nicotinic acetylcholine receptors (nAChRs), both of which play roles in the pathophysiology of psychiatric disease.