Metabolic control of kynurenic acid formation in the rat brain

Excitotoxic neuronal loss can be precipitated by defects in cerebral energy metabolism. Antagonists of excitatory amino acid receptors, such as the endogenous metabolite kynurenic acid, can effectively block excitotoxic lesions. Using brain tissue slices, the present study was designed to examine a potential link between metabolic status and cerebral kynurenic acid formation in adult rats. The results demonstrate that fluctuations in cerebral energy metabolism are closely associated with changes in kynurenic acid synthesis. Taken together, the data are compatible with the idea that the production of kynurenic acid in the brain is critically affected by the availability of pyruvate or other 2-oxoacids (i.e. co-substrates for the enzymatic transamination of the bioprecursor of kynurenic acid, L-kynurenine). Such metabolic control of kynurenic acid function may play a role in excitotoxic brain diseases