Following heme-dependent tryptophan 2,3-dioxygenase (TDO) and a kynureninase, two consecutive metalloenzymes of the kynurenine pathway determine the metabolic partitioning of tryptophan metabolites to quinolinic acid, or further metabolism (Figure 1).The first metalloenzyme is an iron-dependent 3-hydroxyanthranilic acid dioxygenase (HAO);the second is a zinc-dependent 2-amino-3-carboxymuconic-6-semialdehyde decarboxylase (ACMSD).A unique feature of these enzymes is that the substrate of the latter enzyme, i.e., the product of the first enzyme, is unstable and spontaneously decays.