Lütz Maria da Graça, Feksa Luciane Rosa, Wyse Angela Terezinha de Souza, Dutra-Filho Carlos Severo, Wajner Moacir, Wannmacher Clóvis Milton Duval
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Metab Brain Dis. 2003 Mar;18(1):87-94. doi: 10.1023/a:1021986820562.
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.
糖酵解是为大脑功能提供能量的主要途径。在本研究中，我们调查了苯丙酮尿症中已知会积累的主要代谢产物苯丙氨酸和/或丙氨酸对30日龄Wistar大鼠大脑皮层匀浆中丙酮酸激酶活性、葡萄糖利用、乳酸释放和ADP浓度的体外影响。我们发现苯丙氨酸降低了丙酮酸激酶活性、葡萄糖利用和乳酸释放，并提高了大脑中ADP的水平。我们还证实，丙氨酸本身不会改变这些参数，但能阻止苯丙氨酸的影响。我们的数据表明，苯丙氨酸对丙酮酸激酶的抑制作用会降低糖酵解和能量产生，而丙氨酸作为苯丙氨酸在酶活性上的已知竞争者，可能通过防止氨基酸引起的酶抑制作用，阻止了苯丙氨酸导致的糖酵解和能量产生的减少。这些结果表明，苯丙氨酸对大脑丙酮酸激酶活性的抑制可能与苯丙酮尿症患者大脑中观察到的葡萄糖代谢减少有关，并且可能是这些患者神经功能障碍的机制之一。
