Alanine prevents the reduction of pyruvate kinase activity in brain cortex of rats subjected to chemically induced hyperphenylalaninemia.
The mechanisms by which phenylalanine is toxic to the brain in phenylketonuria are not fully understood. Considering that brain glucose metabolism is reduced in these patients, our main objective was to determine pyruvate kinase activity in brain cortex of rats subjected to acute and chronic chemically induced hyperphenylalaninemia. The effect of alanine administration on the enzyme activity in the treated rats was also investigated. We also studied the in vitro effect of the two amino acids on pyruvate kinase activity in brain cortex of nontreated rats. The results indicated that phenylalanine inhibits pyruvate kinase in vitro and in vivo and that alanine prevents the inhibitory effect of phenylalanine on the enzyme activity. Considering the crucial role pyruvate kinase plays in glucose metabolism in brain, it is possible that inhibition of this enzyme activity may contribute to the brain damage characteristic of this disease.
Feksa
Luciane Rosa
LR
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
Cornelio
Andrea Renata
AR
Rech
Virginia Cielo
VC
Dutra-Filho
Carlos Severo
CS
Wyse
Angela Terezinha Souza
AT
Wajner
Moacir
M
Wannmacher
Clóvis Milton Duval
CM
D000409:Alanine / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D010649:Phenylalanine / Q000097:blood*; D011770:Pyruvate Kinase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D010649:Phenylalanine; D011770:Pyruvate Kinase; D000409:Alanine