Indole-3-Pyruvic Acid as a Direct Precursor of Kynurenic Acid

Abstract

Kynurenic acid (KYNA) is found in large amounts after tryptophan load, because tryptophan-2, 3-dioxygenase (EC 1.13.11.11), present in the liver, opens its indole ring, while kynurenine transaminase (EC 2.6.1.7) is able to catalyze the transformation of kynurenine to KYNA. In the last few years, it was demonstrated that KYNA is an important endogenous antagonist of excitatory amino acid receptors (Ganong et al., 1983; Stone and Burton, 1988) and that it reduces cerebral ischemic effects when administered at high dosages in vivo (Germano et al., 1987). Unfortunately, tryptophan is not a good precursor of cerebral KYNA, because it simultaneously increases kynurenine and quinolinic acid, two well-known pro-convulsant agents (Lapin, 1983; Foster et al., 1984). On the other hand, indole-3-pyruvic acid (IPA), the keto-analog of tryptophan, increases KYNA content in several rat organs after i.p. injection (Russi et al., 1989). Inside the brain, conversion to KYNA appears more effective for IPA than for tryptophan, suggesting a different metabolic pathway. Experiments were therefore performed in order to find the new pathway leading from IPA to KYNA.