Overexpression of fructose 2,6-bisphosphatase decreases glycolysis and delays cell cycle progression

Am J Physiol Cell Physiol. 2000 Nov;279(5):C1359-65. doi: 10.1152/ajpcell.2000.279.5.C1359.

Abstract

The ability to overexpress 6-phosphofructo-2-kinase/fructose 2, 6-bisphosphatase (PFK-2)/(FBPase-2) or a truncated form of the enzyme with only the bisphosphatase domain allowed us to analyze the relative role of the kinase and the bisphosphatase activities in regulating fructose 2,6-bisphosphate (Fru-2,6-P(2)) concentration and to elucidate their differential metabolic impact in epithelial Mv1Lu cells. The effect of overexpressing PFK-2/FBPase-2 resulted in a small increase in the kinase activity and in the activity ratio of the bifunctional enzyme, increasing Fru-2,6-P(2) levels, but these changes had no major effects on cell metabolism. In contrast, expression of the bisphosphatase domain increased the bisphosphatase activity, producing a significant decrease in Fru-2,6-P(2) concentration. The fall in the bisphosphorylated metabolite correlated with a decrease in lactate production and ATP concentration, as well as a delay in cell cycle. These results provide support for Fru-2,6-P(2) as a regulator of glycolytic flux and point out the role of glycolysis in cell cycle progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Cell Cycle / physiology*
  • Cell Line
  • Epithelial Cells / metabolism
  • Fructokinases / metabolism
  • Glycolysis / physiology*
  • Lactic Acid / metabolism
  • Mink
  • Osmolar Concentration
  • Phosphofructokinase-2
  • Phosphoric Monoester Hydrolases / metabolism*
  • Time Factors

Substances

  • Lactic Acid
  • Adenosine Triphosphate
  • Fructokinases
  • Phosphofructokinase-2
  • Phosphoric Monoester Hydrolases