EFFECT OF PHENYLALANINE AND ITS METABOLITES ON ATP-DIPHOSPHOHYDROLASEACTIVITY IN SYNAPTOSOMES FROM RAT CEREBRAL-CORTEX

The in vitro effects of phenylalanine and some of its metabolites on A TP diphosphohydrolase (apyrase, EC 3.6.1.5) activity in synaptosomes f rom rat cerebral cortex were investigated. The enzyme activity in syna ptosomes from rats subjected to experimental hyperphenylalaninemia (al pha-methylphenylalanine plus phenylalanine) was also studied. In the i n vitro studies, a biphasic effect of phenylalanine on both enzyme sub strates (ATP and ADP) was observed, with maximal inhibition at 2.0 mM and maximal activation at 5.0 mM. Inhibition of the enzyme activity wa s not due to calcium chelation. Moreover, phenylpyruvate, when compare d with phenylalanine showed opposite effects on the enzyme activity, s uggesting that phenylalanine and phenylpyruvate bind to two different sites on the enzyme. The other tested phenylalanine metabolites (pheny llactate, phenylacetate and phenylethylamine) had no effect on ATP dip hosphohydrolase activity. In addition, we found that ATP diphosphohydr olase activity in synaptosomes from cerebral cortex of rats with chemi cally induced hyperphenylalaninemia was significantly enhanced by acut e or chronic treatment. Since it is conceivable that ATPase-ADPase act ivities play an important role in neurotransmitter (ATP) metabolism, i t is tempting to speculate that our results on the deleterious effects of phenylalanine and phenylpyruvate on ATP diphosphohydrolase activit y may be related to the neurological dysfunction characteristics of na turally and chemically induced hyperphenylalaninemia.