Effects of phenylalanine and phenylpyruvate on ATP-ADP hydrolysis by rat blood serum.

The nucleotide (ATP-ADP)/nucleoside (adenosine) ratio in the circulation can modulate the processes of vasoconstriction, vasodilatation and platelet aggregation. The main objective of the present study with rat blood serum was to evaluate the possibility of changes in nucleotide hydrolysis by phenylalanine (Phe) and phenylpyruvate (PP), the levels of which could increase in the circulation of individuals with phenylketonuria. Results demonstrated that Phe in the range 1.0-5.0 mM inhibited the ADP hydrolysis by rat serum. The effect of inhibition by Phe on ATP hydrolysis appeared only at a concentration of 5.0 mM. PP had no significant effect upon nucleotide hydrolysis. Kinetic analysis indicated that the inhibition of ADP and ATP hydrolysis by Phe in rat blood serum is uncompetitive. Conversely, Phe and PP did not affect the hydrolysis of p-nitrophenyl-5'-TMP by rat serum.

Phenylalanine and phenylpyruvate inhibit ATP diphosphohydrolase from rat brain cortex.

The main objective of the present study was to characterize the inhibition by phenylalanine and phenylpyruvate of ATP diphosphohydrolase activity in synaptosomes from the brain cortex of rats. This enzyme participates together with a 5'-nucleotidase in adenosine formation from the neurotransmitter, ATP, in the synaptic cleft. The inhibition of ATP diphosphohydrolase was competitive for nucleotide hydrolysis but 5'-nucleotidase was not affected by these metabolites. Furthermore, the two substances inhibited enzyme activity by acting at the same binding site. If the enzyme inhibition observed in vitro also occurs in the brain of PKU patients, it may promote an increase in ATP levels in the synaptic cleft. In this case, the neurotoxicity of ATP could possibly be one of the mechanisms leading to the characteristic brain damage of phenylketonuria.