Alanine prevents the in vitro inhibition of glycolysis caused by phenylalanine in brain cortex of rats.
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.
Lütz
Maria da Graça
Mda G
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Feksa
Luciane Rosa
LR
Wyse
Angela Terezinha de Souza
AT
Dutra-Filho
Carlos Severo
CS
Wajner
Moacir
M
Wannmacher
Clóvis Milton Duval
CM
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
D004338:Drug Combinations; D019344:Lactic Acid; D010649:Phenylalanine; D000244:Adenosine Diphosphate; D005947:Glucose; D000409:Alanine