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- Title
Enzymatic transamination of d-kynurenine generates kynurenic acid in rat and human brain.
- Authors
Pérez-de la Cruz, Veronica; Amori, Laura; Sathyasaikumar, Korrapati V.; Wang, Xiao-Dan; Notarangelo, Francesca M.; Wu, Hui-Qiu; Schwarcz, Robert
- Abstract
J. Neurochem. (2012) 120, 1026-1035. Abstract In the mammalian brain, the α7 nicotinic and NMDA receptor antagonist kynurenic acid is synthesized by irreversible enzymatic transamination of the tryptophan metabolite l-kynurenine. d-kynurenine, too, serves as a bioprecursor of kynurenic acid in several organs including the brain, but the conversion is reportedly catalyzed through oxidative deamination by d-aminoacid oxidase. Using brain and liver tissue homogenates from rats and humans, and conventional incubation conditions for kynurenine aminotransferases, we show here that kynurenic acid production from d-kynurenine, like the more efficient kynurenic acid synthesis from l-kynurenine, is blocked by the aminotransferase inhibitor amino-oxyacetic acid. In vivo, focal application of 100 μM d-kynurenine by reverse microdialysis led to a steady rise in extracellular kynurenic acid in the rat striatum, causing a 4-fold elevation after 2 h. Attesting to functional significance, this increase was accompanied by a 36% reduction in extracellular dopamine. Both of these effects were duplicated by perfusion of 2 μM l-kynurenine. Co-infusion of amino-oxyacetic acid (2 mM) significantly attenuated the in vivo effects of d-kynurenine and essentially eliminated the effects of l-kynurenine. Thus, enzymatic transamination accounts in part for kynurenic acid synthesis from d-kynurenine in the brain. These results are discussed with regard to implications for brain physiology and pathology.
- Subjects
ENZYMATIC analysis; KYNURENINE; BRAIN research; NICOTINIC receptors; AMINOTRANSFERASES; MICRODIALYSIS; METHYL aspartate receptors; SCHIZOPHRENIA
- Publication
Journal of Neurochemistry, 2012, Vol 120, Issue 6, p1026
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2012.07653.x