Fructose 2,6-bisphosphate and the control of glycolysis by growth factors, tumor promoters and oncogenes.
Tumor and proliferating cells maintain a high glycolytic rate even under aerobic conditions. The discovery of fructose 2,6-bisphosphate, a potent stimulator of glycolysis, has prompted a re-investigation of this phenomenon. Rat hepatoma cells and fibroblasts stimulated by mitogens or transformed by the Rous sarcoma virus carrying the v-src oncogene were used as models. The results indicate that in established lines of hepatoma cells the biochemical properties of the bifunctional enzyme, PFK-2/FBPase-2, involved in the synthesis and degradation of fructose 2,6-bisphosphate, differ from those of the enzyme from normal liver. In addition, the stimulation of glycolysis induced by phorbol esters and pp60v-src can be explained by an increase in the concentration of fructose 2,6-bisphosphate and an activation of PFK-2. The mechanism of stimulation involves the transcription of a gene whose product activates PFK-2 or is a distinct PFK-2 isozyme. Finally, mercaptopurines were found to block fructose 2,6-bisphosphate synthesis in vitro and in lymphocytes and lymphoblastic cells. In these cells, this resulted in an inhibition of glycolysis.
Hormone and Metabolic Research Unit, University of Louvain Medical School, Brussels, Belgium.
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D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D006597:Fructose-Bisphosphatase / Q000378:metabolism; D005635:Fructosediphosphates / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D009857:Oncogenes; D010732:Phosphofructokinase-1 / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism
D002273:Carcinogens; D005635:Fructosediphosphates; D006133:Growth Substances; C027652:fructose 2,6-diphosphate; D010732:Phosphofructokinase-1; D006597:Fructose-Bisphosphatase