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.
Berti
S L
SL
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-anexo, 90035-003, Porto Alegre, RS, Brazil.
Bonan
C D
CD
da Silva
F L
FL
Battastini
A M
AM
Sarkis
J J
JJ
Wannmacher
C M
CM
D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000241:Adenosine / Q000096:biosynthesis; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001081:Apyrase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D006868:Hydrolysis / Q000187:drug effects; D007700:Kinetics; D010649:Phenylalanine / Q000378:metabolism* / Q000494:pharmacology; D010661:Phenylketonurias / Q000201:enzymology* / Q000503:physiopathology; D010667:Phenylpyruvic Acids / Q000378:metabolism* / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes
D010667:Phenylpyruvic Acids; D010649:Phenylalanine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D015720:5'-Nucleotidase; D001081:Apyrase; D000241:Adenosine; C031606:phenylpyruvic acid