苯丙氨酸和苯丙酮酸抑制大鼠大脑皮层的ATP二磷酸水解酶。

Phenylalanine and phenylpyruvate inhibit ATP diphosphohydrolase from rat brain cortex.

作者信息

Berti S L, Bonan C D, da Silva F L, Battastini A M, Sarkis J J, Wannmacher C M

机构信息

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.

出版信息

Int J Dev Neurosci. 2001 Nov;19(7):649-53. doi: 10.1016/s0736-5748(01)00048-x.

DOI:10.1016/s0736-5748(01)00048-x

PMID:11705669

Abstract

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.

摘要

本研究的主要目的是表征苯丙氨酸和苯丙酮酸对大鼠大脑皮质突触体中ATP二磷酸水解酶活性的抑制作用。该酶与5'-核苷酸酶一起参与神经递质ATP在突触间隙中形成腺苷的过程。ATP二磷酸水解酶的抑制作用对核苷酸水解具有竞争性，但5'-核苷酸酶不受这些代谢物的影响。此外，这两种物质通过作用于相同的结合位点来抑制酶活性。如果在体外观察到的酶抑制作用也发生在苯丙酮尿症（PKU）患者的大脑中，可能会导致突触间隙中ATP水平升高。在这种情况下，ATP的神经毒性可能是导致苯丙酮尿症特征性脑损伤的机制之一。