Fructose 2,6-bisphosphate and the control of glycolysis by growth factors, tumor promoters and oncogenes. 1993

L Hue, and G G Rousseau
Hormone and Metabolic Research Unit, University of Louvain Medical School, Brussels, Belgium.

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.

UI MeSH Term Description Entries
D009857 Oncogenes Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene. Transforming Genes,Oncogene,Transforming Gene,Gene, Transforming,Genes, Transforming
D010732 Phosphofructokinase-1 An allosteric enzyme that regulates glycolysis by catalyzing the transfer of a phosphate group from ATP to fructose-6-phosphate to yield fructose-1,6-bisphosphate. D-tagatose- 6-phosphate and sedoheptulose-7-phosphate also are acceptors. UTP, CTP, and ITP also are donors. In human phosphofructokinase-1, three types of subunits have been identified. They are PHOSPHOFRUCTOKINASE-1, MUSCLE TYPE; PHOSPHOFRUCTOKINASE-1, LIVER TYPE; and PHOSPHOFRUCTOKINASE-1, TYPE C; found in platelets, brain, and other tissues. 6-Phosphofructokinase,6-Phosphofructo-1-kinase,Fructose-6-P 1-Kinase,Fructose-6-phosphate 1-Phosphotransferase,6 Phosphofructokinase,Phosphofructokinase 1
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D005635 Fructosediphosphates Diphosphoric acid esters of fructose. The fructose-1,6- diphosphate isomer is most prevalent. It is an important intermediate in the glycolysis process.
D006019 Glycolysis A metabolic process that converts GLUCOSE into two molecules of PYRUVIC ACID through a series of enzymatic reactions. Energy generated by this process is conserved in two molecules of ATP. Glycolysis is the universal catabolic pathway for glucose, free glucose, or glucose derived from complex CARBOHYDRATES, such as GLYCOGEN and STARCH. Embden-Meyerhof Pathway,Embden-Meyerhof-Parnas Pathway,Embden Meyerhof Parnas Pathway,Embden Meyerhof Pathway,Embden-Meyerhof Pathways,Pathway, Embden-Meyerhof,Pathway, Embden-Meyerhof-Parnas,Pathways, Embden-Meyerhof
D006133 Growth Substances Signal molecules that are involved in the control of cell growth and differentiation. Mitogens, Endogenous,Endogenous Mitogens
D006597 Fructose-Bisphosphatase An enzyme that catalyzes the conversion of D-fructose 1,6-bisphosphate and water to D-fructose 6-phosphate and orthophosphate. EC 3.1.3.11. Fructose-1,6-Bisphosphatase,Fructose-1,6-Diphosphatase,Fructosediphosphatase,Hexosediphosphatase,D-Fructose-1,6-Bisphosphate 1-Phosphohydrolase,FDPase,Fructose-1,6-Biphosphatase,1-Phosphohydrolase, D-Fructose-1,6-Bisphosphate,D Fructose 1,6 Bisphosphate 1 Phosphohydrolase,Fructose 1,6 Biphosphatase,Fructose 1,6 Bisphosphatase,Fructose 1,6 Diphosphatase,Fructose Bisphosphatase
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured

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