Inhibitory effects of Zn2+ on muscle glycolysis and their reversal by histidine.
Of a number of divalent cations investigated, Zn2+ strongly inhibited lactate production from glucose 6-phosphate in rat muscle cytosol fraction. The I50 value for lactate production influenced by Zn2+ was 10 microM and was increased to 200 microM and 18 microM by the addition of 10mM histidine and 10mM carnosine, respectively. The inhibitory effect of 50 microM Zn2+ on lactate production was completely reversed by the addition of 1.2mM histidine and the apparent Km was found to be 0.34mM. The inhibitory site for Zn2+ was investigated by the estimation of glycolytic intermediates. It occurred at point between fructose 6-phosphate and fructose 1,6-bisphosphate. Purified rat muscle phosphofructokinase was inhibited by Zn2+. The I50 values for Zn2+ were calculated to be 12, 5.5 and 1.5 microM in the presence of 3, 0.3 and 0.06mM fructose 6-phosphate, respectively. The addition of histidine removed the inhibitory effect of Zn2+ on the glycolytic key enzyme. These studies indicate that in rat skeletal muscle the inhibitory effect of Zn2+ on lactate production might result from the inhibition of phosphofructokinase and that histidine could remove the effect.
D000818:Animals; D002336:Carnosine / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects*; D006639:Histidine / Q000494:pharmacology*; D007773:Lactates / Q000096:biosynthesis; D008297:Male; D009132:Muscles / Q000378:metabolism*; D010732:Phosphofructokinase-1 / Q000037:antagonists & inhibitors; D051381:Rats; D015032:Zinc / Q000494:pharmacology*
D007773:Lactates; D006639:Histidine; D002336:Carnosine; D010732:Phosphofructokinase-1; D015032:Zinc