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Effects of Dichloroacetate on Brain Tissue Pyruvate Dehydrogenase
Authors:Owen B. Evans
Affiliation:Department of Neurology, Jerry Lewis Neuromuscular Research Center, Vanderbilt University Medical Center, Nashville, Tennessee, U.S.A.
Abstract:The activation of the pyruvate dehydrogenase complex (PDHC) by dichloroacetate (DCA) was studied in brain tissue. Chronic administration of DCA to rats caused no significant change of PDHC activation in brain. DCA brain concentrations were comparable to those of other tissues in which activation is known to occur. No effect of DCA on PDHC could be demonstrated from isolated brain mitochondria, whereas DCA reversed the deactivation of PDHC by ATP, alpha-ketoglutarate plus malate, and succinate in liver mitochondria. This study suggests that the regulation of PDHC activation in neural tissue differs from that in other tissues.
Keywords:ATP    Dichloroacetate    Mitochondria    Pyruvate dehydrogenase
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