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.