title: Alanine prevents the reduction of pyruvate kinase activity in brain cortex of rats subjected to chemically induced hyperphenylalaninemia.
abstract: 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.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Luciane Rosa
authors.initials: LR
authors.lastname: Feksa
authors.forename: Andrea Renata
authors.initials: AR
authors.lastname: Cornelio
authors.forename: Virginia Cielo
authors.initials: VC
authors.lastname: Rech
authors.forename: Carlos Severo
authors.initials: CS
authors.lastname: Dutra-Filho
authors.forename: Angela Terezinha Souza
authors.initials: AT
authors.lastname: Wyse
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Clóvis Milton Duval
authors.initials: CM
authors.lastname: Wannmacher
mesh_terms: 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
chemical_list: D010649:Phenylalanine; D011770:Pyruvate Kinase; D000409:Alanine