Neurotoxic effects of copper: inhibition of glycolysis and glycolytic enzymes.
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 microM. Cu2+ also inhibited several glycolytic enzymes. Amongst the latter, Cu2+ was most effective in inhibiting hexokinase (IC50 for Cu2+ = 7 microM), moderately effective in inhibiting pyruvate kinase (IC50 for Cu2+ = 56 microM), but least effective in inhibiting lactate dehydrogenase (IC50 for Cu2+ = 300 microM). These results suggest that inhibition of brain glycolysis may have pathophysiological importance in copper poisoning and in Wilson's disease.
D000818:Animals; D001921:Brain / Q000201:enzymology*; D001923:Brain Chemistry / Q000187:drug effects*; D003300:Copper / Q000633:toxicity*; D003600:Cytosol / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors; D006019:Glycolysis / Q000187:drug effects*; D006527:Hepatolenticular Degeneration / Q000378:metabolism; D006593:Hexokinase / Q000037:antagonists & inhibitors; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D008297:Male; D010732:Phosphofructokinase-1 / Q000037:antagonists & inhibitors; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains
D007773:Lactates; D019344:Lactic Acid; D003300:Copper; D007770:L-Lactate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D006593:Hexokinase; D010732:Phosphofructokinase-1; D011770:Pyruvate Kinase