Developmental modulation of cysteine conjugate beta-lyase/glutamine transaminase K/kynurenine aminotransferase mRNA in rat brain.

Cysteine conjugate beta-lyase/glutamine transaminase K/kynurenine aminotransferase (CS-lyase/GTK/KAT) is a tri-functional enzyme found in several organs, including the brain. Kynurenine aminotransferase is important in tryptophan metabolism in the CNS, producing kynurenic acid, a NMDA receptor antagonist and neuroprotective. Tryptophan not metabolised via kynurenine aminotransferase may form quinolinic acid, a NMDA receptor agonist and neurotoxin. Kynurenic acid co-treatment blocks quinolinic acid induced lesions in the CNS in rat. In many conditions exhibiting neurodegeneration (i.e. Huntington's, Parkinsonism, Down's syndrome) quinolinic acid and/or kynurenic acid concentrations are altered, suggesting the ratio of these chemicals may be important in neurodegeneration. We have investigated the developmental modulation of CS-lyase/GTK/KAT mRNA in rat brain. CS-lyase/GTK/KAT mRNA was measured in 14, 21, 28, 35, 42 day post-natal and adult rats. While many regions demonstrated a steady increase to adult levels, two other profiles were seen. Five regions rapidly reached adult levels of the mRNA, while two peaked above the adult level before falling back. This provides evidence that expression of the CS-lyase/GTK/KAT gene is physiologically modulated, and provides the basis for further investigation into the mechanism of control. Artificial modulation could possibly be used to alter levels of the neuroprotectant kynurenic acid in neurodegeneration.