Propionic and methylmalonic acids inhibit the in vitro phosphorylation of a 85 kDa cytoskeletal protein from cerebral cortex of rats

In this study we examine the action of methylmalonic (MMA) and propionic (P A) acids, metabolites which accumulate in methylmalonic and propionic acide mias respectively, on the endogenous phosphorylating system associated with the cytoskeletal fraction of cerebral cortex of young rats. Chronic treatm ent with PA and treatment of tissue slices with MMA or PA are effective in decreasing the in vitro phosphorylation into a Si kDa cytoskeletal associat ed protein. We tested the effect of the acids on the endogenous kinase acti vities by using specific kinase activators and inhibitors. Results demonstr ated that the acids interfere with the endogenous cAMP-dependent and Ca2+/c almodulin-dependent kinase activities. Furthermore, in vitro dephosphorylat ion of the 85 kDa protein was totally inhibited in brain slices treated wit h the acids. Considering the importance of protein phosphorylation to cellu lar function, we speculate that alteration in the phosphorylating level of cytoskeletal associated phosphoproteins induced by MMA and PA treatments ma y somehow be involved in steps leading to brain damage. (C) 1998 Elsevier S cience Ltd. All rights reserved.