Brain mitochondrial metabolism in experimental thiamine deficiency

W. Davis Parker*, Richard Haas, David A. Stumpf, Janice Parks, Luis A. Eguren, Carey Jackson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Thiamine deficiency causes Wernicke’s encephalopathy, although the precise mechanism is unknown. We used a low-thiamine diet in conjunction with a thiamine analog, pyrithiamine, as a model of severe thiamine deficiency in rats. We investigated the function of intact, coupled mitochondria isolated from both brain and liver. State 4 respiration did not change in the thiamine-deficient animals. Brain state 3 rates fell in thiamine-deficient animals when pyruvate/malate, alpha-ketoglutarate, or glutamate were used as substrate. Liver state 3 rates were depressed only when pyruvate/malate was substrate. Activities of brain and liver pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase complex were depressed in the thiamine-deficient group. We conclude that the mitochondrial abnormalities resulting from thiamine deficiency are secondary to depression of thiamine-mediated enzyme activity, rather than from a putative role of thiamine in chemiosmotic coupling, and that the resulting abnormalities in ATP synthesis and perhaps in glutamate catabolism result in the irreversible neurologic defect seen in this disease.

Original languageEnglish (US)
Pages (from-to)1477-1481
Number of pages5
JournalNeurology
Volume34
Issue number11
DOIs
StatePublished - Nov 1984

ASJC Scopus subject areas

  • Clinical Neurology

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