title: Alanine prevents the in vitro inhibition of glycolysis caused by phenylalanine in brain cortex of rats.
abstract: Glycolysis is the main route that provides energy to brain functioning. In this study we investigated the in vitro effects of phenylalanine, the main metabolite known to accumulate in phenylketonuria, and/or alanine, on pyruvate kinase activity, glucose utilization, lactate release, and ADP concentration in brain cortex homogenates from 30-day-old Wistar rats. We found that phenylalanine decreased PK activity, glucose utilization, and lactate release, and increased ADP brain levels. We also verified that alanine per se did not modify these parameters, but prevented the effects of phenylalanine. Our data suggest that the inhibition of pyruvate kinase by phenylalanine decreases glycolysis and energy production, and that alanine, a known competitor of phenylalanine on the enzyme activity, prevents the reduction of glycolysis and energy production caused by phenylalanine, probably by preventing the enzyme inhibition provoked by the amino acid. These results suggest that inhibition of brain PK activity by phenylalanine may be related to the diminution of glucose metabolism observed in the brain of phenylketonuric patients and may be one of the mechanisms responsible for the neurological dysfunction found in these patients.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Maria da Graça
authors.initials: Mda G
authors.lastname: Lütz
authors.forename: Luciane Rosa
authors.initials: LR
authors.lastname: Feksa
authors.forename: Angela Terezinha de Souza
authors.initials: AT
authors.lastname: Wyse
authors.forename: Carlos Severo
authors.initials: CS
authors.lastname: Dutra-Filho
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Clóvis Milton Duval
authors.initials: CM
authors.lastname: Wannmacher
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000409:Alanine / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D004338:Drug Combinations; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D019344:Lactic Acid / Q000378:metabolism; D010649:Phenylalanine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004338:Drug Combinations; D019344:Lactic Acid; D010649:Phenylalanine; D000244:Adenosine Diphosphate; D005947:Glucose; D000409:Alanine