Platelet Na+,K+-ATPase activity as a possible peripheral marker for the neurotoxic effects of phenylalanine in phenylketonuria

The in vitro effects of phenylalanine or alanine alone or combined on Na+,K +-ATPase activity in membranes from human platelets were investigated. The enzyme activity was assayed in membranes prepared from platelet-rich plasma of healthy donors. Phenylalanine or alanine were added to the assay to fin al concentrations of 0.3 to 1.2 mM, similar to those found in plasma of phe nylketonuric patients. Phenylalanine inhibited Na+,K+-ATPase activity by 20-50% [F(4,25)=11.47;p<0 .001]. Alanine had no effect on Na+,K+-ATPase activity but when combined wi th phenylalanine prevented the enzyme inhibition. These results, allied to others previously reported on brain Na+,K+-ATPase activity, may reflect a g eneral inhibitory effect of phenylalanine on this important enzyme activity . Therefore, it is possible that measurement of Na+,K+-ATPase activity in p latelets from PKU patients may be a useful peripheral marker for the neurot oxic effects of phenylalanine.