Figure 1.

Kynurenine metabolites and the blood brain barrier (BBB) Skorobogatov et al. Tryptophan (TRP) and kynurenine (KYN), and to a lesser degree 3-hydrox kynurenine (3-HK) are actively transported into the brain over LAT1 transporters. Downstream metabolites of the kynurenine pathway (KP), like quinolinic acid (QUINO) and kynurenic acid (KA), cannot make use of these transporters, but (probably limited) passive diffusion of these metabolites over the BBB is possible. Anthranilic acid AA and 3-hydroxy anthranilic acid (not shown in figure) may equally pass the blood brain barrier through passive diffusion, much like QUINO. In the brain, microglia are responsible for the production of metabolites 3-HK and QUINO, whereas astrocytes produce KA. Peripheral production of these KP metabolites is done by blood immune cells, such as blood monocytes (PBMC) and other organs, including liver and kidney. The gut microbiome, which plays a role in psychiatric illness through the gut-brain axis, also affects KP metabolization.