Brain pyruvate oxidation in experimental thiamin-deficiency encephalopathy

Petraki Munujos, Jaume Coll-Cantí, Jorge Beleta, Francesc González-Sastre, F. Javier Gella

Research output: Contribution to journalArticleResearchpeer-review

22 Citations (Scopus)

Abstract

Pyrithiamine-induced thiamin deficiency has been used in rat as an experimental form of Wernicke-Korsakoff encephalopathy, a disease associated with chronic alcoholism. Although the main etiological factor is known to be the lack of thiamin, the biochemical mechanisms involved in the pathogenesis remain unclear. Thiamin-dependent enzymes were studied in brain mitochondria: α-ketoglutarate dehydrogenase activity exhibited 40% reduction, whereas pyruvate dehydrogenase did not change significantly. Polarographic recordings of mitochondrial respiration revealed a decreased State 3, when using pyruvate/malate, α-ketoglutarate or glutamine as a substrate, but the respiration rates remained unchanged with glutamate or succinate. This fall in pyruvate oxidation may be due to the impairment of α-ketoglutarate dehydrogenase, which follows pyruvate dehydrogenase in the metabolic pathway. A time course of lactate concentration showed dramatic increases in thalamus, mid brain, hypothalamus and colliculli, consistent with the anatomopathological findings. No increases were found before the onset of neurological symptoms.
Original languageEnglish
Pages (from-to)13-25
JournalClinica Chimica Acta
Volume255
Issue number1
DOIs
Publication statusPublished - 15 Nov 1996

Keywords

  • Lactic acidosis
  • Mitochondrial respiration
  • Pyrithiamine
  • Pyruvate dehydrogenase
  • Thiamin-deficiency
  • α-Ketoglutarate dehydrogenase

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