Polyamines stimulate the binding of hexokinase type II to mitochondria.
Spermine and spermidine enhanced the binding of hexokinase isoenzyme type II to mitochondria, both of which were prepared from Ehrlich-Lettre hyperdiploid ascites tumor cells, at much lower concentrations than Mg2+. Chymotrypsin-treated hexokinase II could not bind to the mitochondrial membrane in the presence of either spermine or Mg2+, indicating that the effect of spermine is not a nonspecific action, since the treatment of chymotrypsin cleaves only the region essential for the binding without any significant effect of the catalytic activity. Both spermine and Mg2+ antagonized the glucose 6-phosphate-induced release of mitochondria-bound hexokinase, and promoted the binding of the solubilized hexokinase II even in the presence of glucose 6-phosphate. However, inhibition of the activity of soluble hexokinase by glucose 6-phosphate was not reversed by spermine and Mg2+. Hexokinase II rebound to mitochondria with spermine and Mg2+ produced glucose 6-phosphate using ATP generated inside the mitochondria, and no difference was observed between the spermine- and Mg2+-rebound systems. Significance of the binding of hexokinase to mitochondria, especially with polyamines, is discussed with reference to high glycolytic rate in tumor cells.
D000818:Animals; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000494:pharmacology; D006593:Hexokinase / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D011073:Polyamines / Q000494:pharmacology*; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology
D005958:Glucosephosphates; D007527:Isoenzymes; D011073:Polyamines; D013096:Spermine; D019298:Glucose-6-Phosphate; D006593:Hexokinase; D008274:Magnesium; D013095:Spermidine