modified from : Tryptophan is an essential amino acid and a precursor for the synthesis of serotonin. Alternatively, tryptophan can be metabolized in glial cells via the kynurenine pathway to create kynurenic acid (synthesized by kynurenine aminotransferase, KAT) or quinolinic acid (QUIN). These substances are endogenous modulators of NMDA glutamate receptors. A key enzyme of the kynurenine pathway, indoleamine 2,3-dioxygenase (IDO), and the enzyme that catalyses the production of 3-OH-kynurenine, kynurenine monoxygenase (KMO), are activated by proinflammatory cytokines, including interleukin-1 and -6 (IL-1, IL-6), tumor necrosis factor a (TNFa), or interferon g (IFNg). These enzymes are inhibited by anti-inflammatory cytokines, including IL-4. Serotonin is normally broken down into 5-hydroxyindoleacetic acid (5-HIAA), but the indole ring of serotonin can also be cleaved by IDO to form formyl-5-hydroxykynurenamine (f-5-KYM). Annotation: grey arrows: activation; dotted grey lines with bar at the end: inhibition; black font: potentially neurotoxic; purple font: neutral or not known; bright blue: potentially neuroprotective.