Methylmalonic and propionic acids increase the in vitro incorporation of P-32 into cytoskeletal proteins from cerebral cortex of young rats through NMDA glutamate receptors

In this study we investigated the effects of methylmalonic acid (MMA) and p ropionic acid (PA) on the phosphorylation of cytoskeletal proteins of cereb ral cortex of rats. Slices of tissue were incubated with P-32-orthophosphat e in the presence or absence of glutamate, MMA, PA and ionotropic or metabo tropic glutamate receptor agonists. The cytoskeletal fraction was isolated and the radioactivity incorporated into the cytoskeletal proteins was measu red. Results demonstrated that the acids, glutamate and NMDA increased the phosphorylation of the proteins studied. However, this effect was not obser ved for non-NMDA ionotropic agonists or metabotropic agonists. Experiments using glutamate receptor antagonists confirmed that MMA and PA at the same concentrations as found in tissues from propionic or methylmalonic acidemic children increase the phosphorylation of cytoskeletal proteins, possibly v ia NMDA glutamate receptors. Therefore, it is feasible that these findings may be related to the neurological dysfunction characteristic of these diso rders. (C) 2000 Elsevier Science B.V. All rights reserved.