Reduced Na+,K+-ATPase activity in erythrocyte membranes from patients withphenylketonuria

Na+,K+-ATPase activity was determined in erythrocyte membranes from 12 phen ylketonuric patients of both sexes, aged 8.8 +/- 5.0 y, with plasma phenyla lanine levels of 0.64 +/- 0.31 mM. The in vitro effects of phenylalanine an d alanine on the enzyme activity in erythrocyte membranes from healthy indi viduals were also investigated. We observed that Na+,K+-ATPase activity was decreased by 31% in erythrocytes from phenylketonuric patients compared wi th normal age-matched individuals (p < 0.01). We also observed a significan t negative correlation between erythrocyte Na+,K+-ATPase activity and plasm a 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 activ ity below the normal range. Phenylalanine inhibited in vitro erythrocyte Na +,K+-ATPase activity by 22 to 34%, whereas alanine had no effect on this ac tivity. 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 act ivity in brain cortex of rats subjected to experimental phenylketonuria and the present results, it is proposed that determination of Na+,K+-ATPase ac tivity in erythrocytes may be a useful peripheral marker for the neurotoxic effect of phenylalanine in phenylketonuria.