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Inhibition of in vitro CO2 production and lipid synthesis by 2-hydroxybutyric acid in rat brain

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Inhibition of in vitro CO2 production and lipid synthesis by 2-hydroxybutyric acid in rat brain

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Título Inhibition of in vitro CO2 production and lipid synthesis by 2-hydroxybutyric acid in rat brain
Autor Silva, Alexandre Rodrigues da
Ruschel, Cristiano
Helegda, Celio
Wyse, Angela Terezinha de Souza
Wannmacher, Clovis Milton Duval
Wajner, Moacir
Dutra Filho, Carlos Severo
Abstract 2-Hydroxybutyric acid appears at high concentrations in situations related to deficient energy metabolism (e.g., birth asphyxia) and also in inherited metabolic diseases affecting the central nervous system during neonatal development, such as "cerebral" lactic acidosis, glutaric aciduria type II, dihydrolipoyl dehydrogenase (E3) deficiency, and propionic acidemia. The present study was carried out to determine the effect of 2-hydroxybutyric acid at various concentrations (1- 10 mM) on CO2 production and lipid synthesis from labeled substrates in cerebral cortex of 30-day-old Wistar rats in vitro. CO2 production was significantly inhibited (30-70%) by 2-hydroxybutyric acid in cerebral cortex prisms, in total homogenates and in the mitochondrial fraction. We also demonstrated a significant inhibition of lipid synthesis (20-45%) in cerebral cortex prisms and total homogenates in the presence of 2-hydroxybutyric acid. However, no inhibition of lipid synthesis occurred in homogenates free of nuclei and mitochondria. The results indicate an impairment of mitochondrial energy metabolism caused by 2-hydroxybutyric acid, a fact that may secondarily lead to reduction of lipid synthesis. It is possible that these findings may be associated with the neuropathophysiology of the situations where 2- hydroxybutyric acid is accumulated.
Contido em Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas. Ribeirão Preto, SP. Vol. 34, no. 5 (May 2001), p. 627-631
Assunto Bioquímica
Origem Nacional
Tipo Artigo de periódico
URI http://hdl.handle.net/10183/21137
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