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. 2020 Dec 8;21(24):9338. doi: 10.3390/ijms21249338

Figure 1.

Figure 1

Tryptophan metabolism and the kynurenine pathway. The kynurenine pathway (KP) is the main degradation route of tryptophan (TRP) metabolism producing the end-product nicotinamide adenine dinucleotide (NAD). The indoleamine-2,3-dioxygenase-1 and 2 (IDO-1 and IDO-2), and the tryptophan 2,3-dioxygenase (TDO) (1) are the first rate-liming enzymes that convert the l-TRP to N-formyl-l-kynurenine. N-formyl-l-kynurenine is converted by formamidase (2) to l-kynurenine (l-KYN) (gray box). l-KYN is metabolized into various bioactive compounds: the neuroprotective metabolites are kynurenic acid and picolinic acid (green boxes), while the neurotoxic ones are 3-hydroxy-l-kynurenine (3-HK) and quinolinic acid (red boxes). The main enzymes of the KP are following: 1: tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase 1 and 2 (IDO-1 and IDO-2), 2: formamidase, 3: kynurenine aminotransferases (KATs), 4: kynurenine-3-monooxygenase (KMO), 5: kynureninase, 6: non-specific hydroxylation, 7: 2-amino-3-carboxy-muconate-semialdehyde decarboxylase, 8: 3-hydroxyanthranilate oxidase, 9: quinolinic acid phosphoribosyltransferase.