Dichloroacetate (DCA) has been used for many years as an investigational drug to treat children born with mitochondrial disorders. Through its inhibition of Pyruvate Dehydrogenase Kinase (PDK), a key component of the pyruvate dehydrogenase complex, DCA has shown promise in facilitating oxidative phosphorylation in cell mitochondria. Recently, DCA has received more attention as a possible treatm...

Lactic acidosis is a clinical condition due to accumulation of H(+) ions from lactic acid, characterized by blood lactate levels >5 mM and arterial pH <7.25. In addition to supportive care, treatment usually consists of intravenous NaHCO(3), with a resultant mortality >60%. Dichloroacetate (DCA) is a compound that lowers blood lactate levels under various conditions in both man and laboratory a...

Oxidative stress and the resulting change in cell redox state are proposed to contribute to pathogenic alterations in ion channels that underlie electrical remodeling of the diseased heart. The present study examined whether K(+) channel remodeling is controlled by endogenous oxidoreductase systems that regulate redox-sensitive cell functions. Diabetes was induced in rats by streptozotocin, and...

Branched chain a-ketoacid dehydrogenase was purified 1,400-fold from a Triton X-100 extract of rabbit liver by polyethylene glycol fractionation, chromatography on hydroxyapatite and Sepharose CL-2B, and high speed centrifugation. The complex eluted from Sepharose CL-2B prior to blue dextran, indicating an apparent M, > 2 x 10‘. Electrophoresis on sodium dodecyl sulfate-polyacrylamide gels indi...