Methylmalonate administration decreases Na+,K+-ATPase activity in cerebralcortex of rats

Buffered methylmalonate (MMA) was injected s.c. into rats twice a day at 8 h intervals from 5 to 25 days of age (chronic treatment), or into 10-day-ol d rats three times a day at 1 h intervals (acute treatment). Control rats r eceived saline in the same volumes. Na+,K+-ATPase and Mg2+-ATPase activitie s were determined in the synaptic plasma membranes from cerebral cortex of rats. Na+,K+-ATPase activity was reduced by 30-40% in MMA-treated rats, whe reas Mg2+-ATPase activity was not. In contrast, MMA at final concentrations ranging from 0.1 to 2.0 mM had no in vitro effect on these enzyme activiti es. However, when brain homogenates were incubated with 2 mM MMA before mem brane preparation, Na+,K+-ATPase activity was decreased by 44%. Furthermore , this reduction was totally prevented by the simultaneous addition of glut athione and MMA, suggesting that oxidation of thiol groups or other oxidati ve damage to the enzyme could be responsible for this effect. NeuroReport 1 1:2331-2334 (C) 2000 Lippincott Williams & Wilkins.