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. 2023 Feb 28;16(3):369. doi: 10.3390/ph16030369

Figure 1.

Figure 1

Kynurenine pathway. Tryptophan catabolism through KP leads to nicotinamide adenine dinucleotide (NAD+) formation. The first step is performed by tryptophan dioxygenase (TDO) in the liver or by indoleamine dioxygenase (IDO) in the brain to produce L-kynurenine (L-KYN). L-KYN is a substrate for three enzymes: kynurenine aminotransferase (KAT) to produce kynurenic acid (KYNA); kynureninase (KYNU) to produce anthranilic acid (ANA); and kynurenine monooxygenase (KMO) to produce 3-hydroxykynurenine (3-HK). Then, KYNU takes 3-HK as a substrate to produce 3-hydroxyanthranilic acid (3-HANA), which can also be metabolized by a nonspecific hydroxylation of ANA. 3-hydroxyanthranilate oxidase (3-HAO) opens the ring of 3-HANA, producing the unstable product 2-amino-3-carboxymuconate-semialdehyde, further metabolized to produce picolinic acid (PIC) through α-amino-β-carboxymuconate-semialdehyde-decarboxylase (ACMSC) or quinolinic acid (QUIN) by a nonenzymatic reaction. Finally, quinolinate phosphoribosyltransferase (QPRT) leads to NAD+ production. The overexpressed KP enzymes in glioma are in yellow and down-expressed enzymes are in green.