Figure 1.

The tricarboxylic acid cycle (TCA) and its interface with the tryptophan (Trp)–kynurenine (KYN) metabolic system. (a) The TCAcycle is initiated with acetyl coenzyme A (acetyl-CoA) reacting with oxaloacetate to form citrate. Citrate is oxidized to alpha (α)-ketoglutarate (2-oxoglutarate) with the formation of nicotinamide adenine dinucleotide (NADH). α-ketoglutarate is oxidized to succinyl coenzyme A (succinyl-CoA) with the formation of NADH. Succinyl-CoA is converted to succinate with the formation of adenosine triphosphate (ATP). Succinate is oxidized to fumarate with the formation of flavin adenine dinucleotide (FADH₂). Fumarate is hydrated to malate which is oxidized to oxaloacetate to end the cycle. (b) Cytosolic kynurenine aminotransferase (KAT) I catalyzes the reaction of an S-substituted L-Cys to pyruvate. KAT I also catalyzes the reaction of L-glutamine to α-ketoglutarate (2-oxoglutarate). (c) Mitochondrial KAT II, KAT III, and KAT IV catalyze the reaction of α-ketoglutarate catalyzes the reaction of L-glutamine to α-ketoglutarate (2-oxoglutarate) to L-glutamate. (d) KAT II catalyzes the reaction of α-ketoglutarate (2-oxoglutarate) to 2-oxoadipate which is eventually degraded to acetyl-CoA. (e) Mitochondrial KAT III catalyzes the reaction of an S-substituted L-Cys to pyruvate. (f) Mitochondrial KAT IV catalyzes the reaction of α-ketoglutarate (2-oxoglutarate) and L-aspartate to α-ketoglutarate (2-oxaloacetate) and L-glutamate.