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Neurotoxic effects of copper: Inhibition of glycolysis and glycolytic enzymes

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Abstract

The effects of Cu2+ on glycolysis and several glycolytic enzymes were studied in rat brain extracts in vitro. At concentrations reportedly found in Wilson's disease, Cu2+ significantly inhibited lactate production from glucose or glucose-6-phosphate in rat brain postnuclear supernatant with an IC50 of about 3 μM. Cu2+ also inhibited several glycolytic enzymes. Amongst the latter, Cu2+ was most effective in inhibiting hexokinase (IC50 for Cu2+=7 μM), moderately effective in inhibiting pyruvate kinase (IC50 for Cu2+=56 μM), but least effective in inhibiting lactate dehydrogenase (IC50 for Cu2+=300 μM). These results suggest that inhibition of brain glycolysis may have pathophysiological importance in copper poisoning and in Wilson's disease.

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Authors and Affiliations

  1. Altschul Laboratory for Dementia Research, Cornell University Medical College Burke rehabilitation Center, 785 Mamaroneck Avenue, 10605, White Plains, New York

    James C. K. Lai & John P. Blass

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  1. James C. K. Lai
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  2. John P. Blass
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Lai, J.C.K., Blass, J.P. Neurotoxic effects of copper: Inhibition of glycolysis and glycolytic enzymes. Neurochem Res 9, 1699–1710 (1984). https://doi.org/10.1007/BF00968080

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