Neurotoxic effects of copper: Inhibition of glycolysis and glycolytic enzymes

摘要

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 IC50of about 3 μM. Cu2+also inhibited several glycolytic enzymes. Amongst the latter, Cu2+was most effective in inhibiting hexokinase (IC50for Cu2+=7 μM), moderately effective in inhibiting pyruvate kinase (IC50for Cu2+=56 μM), but least effective in inhibiting lactate dehydrogenase (IC50for Cu2+=300 μM). These results suggest that inhibition of brain glycolysis may have pathophysiological importance in copper poisoning and in Wilson's dise