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- Title
POSSIBLE ADDITIVE EFFECT BETWEEN GLUTARIC AND 3-HYDROXYGLUTARIC ACIDS ON CEREBRAL ENERGY METABOLISM.
- Authors
Ferreira, Gustavo C.; Schuck, Patrícia F.; Tonin, Anelise; Ceolato, Paula C.; Viegas, Carolina M.; Wajner, Moacir
- Abstract
Increased concentrations of glutaric acid (GA) and 3-hydroxyglutaric acid (3HG) are found in the body fluids and brain tissue of patients affected by glutaric acidemia type I (GAI), which present a markedly striatal and cortical degeneration. In addition, a toxic role was recently postulated for quinolinic acid (QA) in the neuropathology of GAI. Therefore, we investigated whether the combination of QA with GA or 3HG or the mixture GA plus 3HG could alter energy metabolism in cerebral cortex from young. The parameters evaluated were glucose uptake, lactate formation and 14CO2 production from labeled glucose and acetate, as well as the activities of pyruvate dehydrogenase (PDH) and creatine kinase (CK). We first observed that 5 mM GA, 1 mM 3HG and 0.1 µM QA per se did not alter these parameters. Similarly, no change occurred when combining GA with QA or 3HG with QA. In contrast, coincubation of GA plus 3HG increased glucose uptake, decreased 14CO2 generation from glucose, inhibited PDH activity as well as total and mitochondrial CK activities. Furthermore, GA plus 3HG-induced inhibitory effects on CK were prevented by the antioxidants glutathione and catalase plus superoxide dismutase, indicating the participation of reactive oxygen species. our data indicate a synergistic action of GA and 3HG disturbing energy metabolism in cerebral cortex of young rats.
- Subjects
ENERGY metabolism
- Publication
Neurotoxicity Research, 2008, Vol 13, Issue 2, p146
- ISSN
1029-8428
- Publication type
Abstract