Phenylalanine and phenylpyruvate inhibit ATP diphosphohydrolase from rat brain cortex

International Journal of Developmental Neuroscience - Tập 19 - Trang 649-653 - 2001
Simone Luisa Berti1, Carla Denise Bonan1, Flávio Laporta da Silva1, Ana Maria Oliveira Battastini1, João José Freitas Sarkis1, Clóvis Milton Duval Wannmacher1
1Departamento de Bioquı́mica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-anexo, 90035-003 Porto Alegre, RS, Brazil

Tóm tắt

AbstractThe 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.

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