Effect of phenylalanine and its metabolites on ATP diphosphohydrolase activity in synaptosomes from rat cerebral cortex.
The in vitro effects of phenylalanine and some of its metabolites on ATP diphosphohydrolase (apyrase, EC 3.6.1.5) activity in synaptosomes from rat cerebral cortex were investigated. The enzyme activity in synaptosomes from rats subjected to experimental hyperphenylalaninemia (alpha-methylphenylalanine plus phenylalanine) was also studied. In the in vitro studies, a biphasic effect of phenylalanine on both enzyme substrates (ATP and ADP) was observed, with maximal inhibition at 2.0 mM and maximal activation at 5.0 mM. Inhibition of the enzyme activity was not due to calcium chelation. Moreover, phenylpyruvate, when compared with phenylalanine showed opposite effects on the enzyme activity, suggesting that phenylalanine and phenylpyruvate bind to two different sites on the enzyme. The other tested phenylalanine metabolites phenyllactate, phenylacetate and phenylethylamine) had no effect on ATP diphosphohydrolase activity. In addition, we found that ATP diphosphohydrolase activity in synaptosomes from cerebral cortex of rats with chemically induced hyperphenylalaninemia was significantly enhanced by acute or chronic treatment. Since it is conceivable that ATPase-ADPase activities play an important role in neurotransmitter (ATP) metabolism, it is tempting to speculate that our results on the deleterious effects of phenylalanine and phenylpyruvate on ATP diphosphohydrolase activity may be related to the neurological dysfunction characteristics of naturally and chemically induced hyperphenylalaninemia.
Wyse
A T
AT
Departamento de Clências Fisiológicas, Fundacão Universidade do Rio Grande, RS, Brazil.
Sarkis
J J
JJ
Cunha-Filho
J S
JS
Teixeira
M V
MV
Schetinger
M R
MR
Wajner
M
M
Milton
C
C
Wannmacher
D
D
D000818:Animals; D001081:Apyrase / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D010651:Phenylalanine Hydroxylase / Q000037:antagonists & inhibitors; D010661:Phenylketonurias / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
C012436:alpha-methylphenylalanine; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase; D001081:Apyrase