Fructose 2,6-bisphosphate and the control of glycolysis by glucocorticoids and by other agents in rat hepatoma cells.
The rate, key enzymes, and several metabolites of glycolysis in rat hepatoma (HTC) cells have been compared to those in rat hepatocytes. At 5 to 10 mM glucose, lactate release was greater in HTC cells. This could be explained in part by the absence of key gluconeogenic enzymes, by the substitution of glucokinase by hexokinase, and by an increase in phosphofructokinase 1 and pyruvate kinase activity. In addition, fructose 2,6-bisphosphate, the most potent stimulator of phosphofructokinase 1, was identified in HTC cells and shown to stimulate phosphofructokinase 1 partially purified from these cells. Dexamethasone increased the release of lactate in HTC cells. This glucocorticoid increased the concentration of fructose 2,6-bisphosphate and the Vmax of the enzyme that catalyzes its synthesis, phosphofructokinase 2. The data were consistent with an indirect effect at the gene level, mediated by glucocorticoid receptors. Dexamethasone had no effect on the other rate-limiting glycolytic enzymes. Several agents (adenosine, dibutyryl cyclic adenosine 3':5'-monophosphate, ethanol, antimycin) known to decrease fructose 2,6-bisphosphate in hepatocytes were without effect on this stimulator in HTC cells. DL-Glyceraldehyde inhibited glycolysis in HTC cells and eventually killed them. Although this substance decreased fructose 2,6-bisphosphate inhibition of glycolysis through an action at another level could not be ruled out.
Loiseau
A M
AM
Rousseau
G G
GG
Hue
L
L
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005635:Fructosediphosphates / Q000032:analysis* / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D005985:Glyceraldehyde / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects*; D006598:Hexosediphosphates / Q000032:analysis*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D010732:Phosphofructokinase-1 / Q000032:analysis; D051381:Rats
D005635:Fructosediphosphates; D005938:Glucocorticoids; D006598:Hexosediphosphates; D005985:Glyceraldehyde; C027652:fructose 2,6-diphosphate; D003907:Dexamethasone; D010732:Phosphofructokinase-1; D000241:Adenosine