Marked reduction of Na+, K+-ATPase and creatine kinase activities induced by acute lysine administration in glutaryl-CoA dehydrogenase deficient mice

Alexandre Umpierrez Amaral, Cristiane Cecatto, Bianca Seminotti, Ângela Zanatta, Carolina Gonçalves Fernandes, Estela Natacha Brandt Busanello, Luisa Macedo Braga, César Augusto João Ribeiro, Diogo Onofre Gomes de Souza, Michael Woontner, David M. Koeller, Stephen Goodman, Moacir Wajner

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Glutaric acidemia type I (GA I) is an inherited neurometabolic disorder caused by a severe deficiency of the mitochondrial glutaryl-CoA dehydrogenase activity leading to accumulation of predominantly glutaric (GA) and 3-hydroxyglutaric (3HGA) acids in the brain and other tissues. Affected patients usually present with hypotonia and brain damage and acute encephalopathic episodes whose pathophysiology is not yet fully established. In this study we investigated important parameters of cellular bioenergetics in brain, heart and skeletal muscle from 15-day-old glutaryl-CoA dehydrogenase deficient mice (Gcdh-/-) submitted to a single intra-peritoneal injection of saline (Sal) or lysine (Lys - 8μmol/g) as compared to wild type (WT) mice. We evaluated the activities of the respiratory chain complexes II, II-III and IV, α-ketoglutarate dehydrogenase (α-KGDH), creatine kinase (CK) and synaptic Na+, K+-ATPase. No differences of all evaluated parameters were detected in the Gcdh-/- relatively to the WT mice injected at baseline (Sal). Furthermore, mild increases of the activities of some respiratory chain complexes (II-III and IV) were observed in heart and skeletal muscle of Gcdh-/- and WT mice after Lys administration. However, the most marked effects provoked by Lys administration were marked decreases of the activities of Na+, K+-ATPase in brain and CK in brain and skeletal muscle of Gcdh-/- mice. In contrast, brain α-KGDH activity was not altered in WT and Gcdh-/- injected with Sal or Lys. Our results demonstrate that reduction of Na+, K+-ATPase and CK activities may play an important role in the pathogenesis of the neurodegenerative changes in GA I.

Original languageEnglish (US)
Pages (from-to)81-86
Number of pages6
JournalMolecular Genetics and Metabolism
Issue number1-2
StatePublished - Sep 2012


  • Bioenergetics
  • Brain
  • Creatine kinase activity
  • Glutaric acidemia type I
  • Glutaryl-CoA dehydrogenase deficient mice
  • Na, K-ATPase activity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology


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