Relevance of Alternative Routes of Kynurenic Acid Production in the Brain

Figure 5

D-Trp can produce KYNA by two different ways: (1) D-Kyn formation by indoleamine dioxygenase (IDO) (since D-Kyn is a poor substrate of tryptophan dioxygenase (TDO). Once D-Kyn is formed, it can be taken as substrate by DAAO and KATs or to interact with ROS to produce KYNA and (2) the inversion of D-Trp to L-Trp, which occurs in two steps: the first one requires oxygen and it is suggested that DAAO can be the enzyme responsible to produce the intermediate IPA and the second step involves the reamination of IPA to yield L-Trp by means of a transaminase. L-Trp can follow the canonical pathway, that is, to produce L-Kyn, which is taken by the kynurenine aminotransferases (KATs) to produce KYNA. However, L-Kyn can also interact with ROS or with peroxidases and promote KYNA formation. The other important way to produce KYNA is through IPA, which in its enolic form can react with ROS producing KYNA.