Phenylpyruvic Acid Decreases Glucose-6-Phosphate Dehydrogenase Activity in Rat Brain

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• 作者：Andrea Pereira Rosa (2)
  Carlos Eduardo Dias Jacques (1)
  Tarsila Barros Moraes (2)
  Clóvis M. D. Wannmacher (12)
  ?ngela de Mattos Dutra (3)
  Carlos Severo Dutra-Filho (12) dutra@ufrgs.br
• 关键词：Phenylalanine – Phenyllactic acid – Phenylacetic acid – Phenylpyruvic acid – Glucose ; 6 ; phosphate dehydrogenase – Oxidative stress
• 刊名：Cellular and Molecular Neurobiology
• 出版年：2012
• 出版时间：October 2012
• 年：2012
• 卷：32
• 期：7
• 页码：1113-1118
• 全文大小：291.4 KB
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• 作者单位：1. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 (Anexo), Porto Alegre, RS 90035-003, Brazil2. Programa de Pós-Gradua??o em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil3. Departamento de Ciências Básica da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
• ISSN：1573-6830

文摘

Phenylketonuria is a recessive autosomal disorder that is caused by a deficiency in the activity of phenylalanine-4-hydroxylase, which converts phenylalanine to tyrosine, leading to the accumulation of phenylalanine and its metabolites phenyllactic acid, phenylacetic acid, and phenylpyruvic acid in the blood and tissues of patients. Phenylketonuria is characterized by severe neurological symptoms, but the mechanisms underlying brain damage have not been clarified. Recent studies have shown the involvement of oxidative stress in the neuropathology of hyperphenylalaninemia. Glucose-6-phosphate dehydrogenase plays an important role in antioxidant defense because it is the main source of reduced nicotinamide adenine dinucleotide phosphate (NADPH), providing a reducing power that is essential in protecting cells against oxidative stress. Therefore, the present study investigated the in vitro effect of phenylalanine (0.5, 1, 2.5, and 5 mM) and its metabolites phenyllactic acid, phenylacetic acid, and phenylpyruvic acid (0.2, 0.6, and 1.2 mM) on the activity of enzymes of the pentose phosphate pathway, which is involved in the oxidative phase in rat brain homogenates. 6-Phosphogluconate dehydrogenase activity was not altered by any of the substances tested. Phenylalanine, phenyllactic acid, and phenylacetic acid had no effect on glucose-6-phosphate dehydrogenase activity. Phenylpyruvic acid significantly reduced glucose-6-phosphate dehydrogenase activity without pre-incubation and after 1 h of pre-incubation with the homogenates. The inhibition of glucose-6-phosphate dehydrogenase activity caused by phenylpyruvic acid could elicit an impairment of NADPH production and might eventually alter the cellular redox status. The role of phenylpyruvic acid in the pathophysiological mechanisms of phenylketonuria remains unknown.