Reduced Na+,K+-ATPase Activity in Erythrocyte Membranes from Patients with Phenylketonuria

Na+,K+-ATPase activity was determined in erythrocyte membranes from 12 phenylketonuric patients of both sexes, aged 8.8 ± 5.0 y, with plasma phenylalanine levels of 0.64 ± 0.31 mM. The in vitro effects of phenylalanine and alanine on the enzyme activity in erythrocyte membranes from healthy individuals were also investigated. We observed that Na+,K+-ATPase activity was decreased by 31% in erythrocytes from phenylketonuric patients compared with normal age-matched individuals (p < 0.01). We also observed a significant negative correlation between erythrocyte Na+,K+-ATPase activity and plasma phenylalanine levels (r = −0.65;p < 0.05). All PKU patients with plasma phenylalanine levels higher than 0.3 mM had erythrocyte Na+,K+-ATPase activity below the normal range. Phenylalanine inhibited in vitro erythrocyte Na+,K+-ATPase activity by 22 to 34%, whereas alanine had no effect on this activity. However, when combined with phenylalanine, alanine prevented Na+,K+-ATPase inhibition. Considering that reduction of Na+,K+-ATPase activity occurs in various neurodegenerative disorders leading to neuronal loss , our previous observations showing a significant reduction of Na+,K+-ATPase activity in brain cortex of rats subjected to experimental phenylketonuria and the present results, it is proposed that determination of Na+,K+-ATPase activity in erythrocytes may be a useful peripheral marker for the neurotoxic effect of phenylalanine in phenylketonuria.