Inhibition of energy production in vitro by glutaric acid in cerebral cortex of young rats

The present study investigated the effects of glutaric acid (GA), which pre dominantly accumulates in glutaric acidemia type I (GA-I), on some in vitro parameters of energy metabolism in cerebral cortex of rats. We first evalu ated CO2 production from [U-C-14] acetate, as well as ATP levels in brain o f young Wistar rats. The effect of the acid on the activities of the respir atory chain complexes were also investigated. GA was tested at final concen trations ranging from 0.5 to 5.0 mM. GA significantly reduced brain CO2 pro duction by 50 % at the concentrations of 0.5 to 3.0 mM, ATP levels by 25 % at the concentration of 3.0 mM, succinate:cytochrome C oxireductase (comple x II plus CoQ plus complex III) by 25 % at 5 mM concentration, and NADH:cyt ochrome C oxireductase (complex I plus CoQ plus complex III) by 25 % at 2.5 and 5 mM concentrations. The results strongly indicate that GA impairs bra in energy production. If these effects also occur in humans, it is possible that they may contribute to the neuropathology of patients affected by GA- I.