PROPIONIC-ACID INHIBITS IN-VITRO CO2 PRODUCTION IN CEREBELLUM AND CEREBRAL-CORTEX OF SUCKLING RATS

We investigated the effect of propionic acid (PA) on carbon dioxide pr oduction from C-14-acetate and C-14-citrate in cerebellum and cerebral cortex of young rats. The objective was to detect alterations in brai n energy metabolism due to the influence of this metabolite which may be related to the neurological dysfunction characteristic of propionic acidaemia. PA significantly reduced (CO2)-C-14 formation at concentra tions as low as 1 mM in cerebellum and 2.5 mM in cerebral cortex. Sinc e propionate and acetate use the same membrane transporter, there may be competition by this carrier between these two substances. To elimin ate this factor, we used radiolabelled citrate as substrate. PA signif icantly inhibited CO, formation in both structures at doses of 2.5 Mm and higher. These findings may represent a true blockage at the Krebs cycle site or in the respiratory chain. Scavenging of CoA units by PA in the medium could be another mechanism to explain the inhibition of CO2 production, although this seems unlikely. It is possible that a bl ockage in energy production is an important mechanism underlying the n europathological findings and neurological symptoms of propionic acida emic patients.