ATP diphosphohydrolase activity in synaptosomes from cerebral cortex of rats subjected to chemically induced phenylketonuria.
ATP diphosphohydrolase (apyrase) (EC 3.6.1.5) activity was measured in synaptosomes from cerebral cortex of Wistar rats of both sexes subjected to experimental phenylketonuria, i.e., chemical hyperphenylalaninemia induced by subcutaneous administration of 5.2 mumol phenylalanine/g body weight (twice a day) plus 0.9 mumol p-chlorophenylalanine/g body weight (once a day). ATP diphosphohydrolase specific activity (nmol Pi min-1 mg protein-1) of synaptosomes was significantly decreased compared to controls for both ATP (from 147.6 to 129.9) and ADP (from 70.2 to 63.1) hydrolysis one hour after single administration of the drugs to 35-day old rats. Chronic treatment was performed from the 6th to the 28th postpartum day. The enzyme specific activity of synaptosomes was measured one week after the last administration of the drugs and was significantly reduced compared to controls for both ATP (from 164.1 to 150.2) and ADP (from 76.3 to 62.1) hydrolysis. The in vitro effects of the drugs on the synaptosome enzyme specific activity were also investigated. Phenylalanine alone or associated with p-chlorophenylalanine significantly reduced enzyme specific activity for both ATP (from 150.2 to 136.0) and ADP (from 70.5 to 59.3) nucleotides as substrates. Since ADP diphosphohydrolase seems to play an important role in neurotransmission, these findings may be related to the neurological dysfunction characteristic of human phenylketonuria.
Wyse
A T
AT
Departamento de Ciências Fisiológicas, Fundação Universidade do Rio Grande, Brasil.
Sarkis
J J
JJ
Cunha-Filho
J S
JS
Teixeira
M V
MV
Schetinger
M R
MR
Wajner
M
M
Wannmacher
C M
CM
D000818:Animals; D001081:Apyrase / Q000378:metabolism*; D002540:Cerebral Cortex / Q000201:enzymology*; D005260:Female; D008297:Male; D010649:Phenylalanine; D010661:Phenylketonurias / Q000139:chemically induced* / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000201:enzymology*
D010649:Phenylalanine; D001081:Apyrase