Hue L, Rousseau G G
Hormone and Metabolic Research Unit, University of Louvain Medical School, Brussels, Belgium.
Adv Enzyme Regul. 1993;33:97-110. doi: 10.1016/0065-2571(93)90011-2.
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.
肿瘤细胞和增殖细胞即使在有氧条件下也维持着较高的糖酵解速率。果糖2,6 -二磷酸作为糖酵解的一种强效刺激剂的发现，促使人们对这一现象进行重新研究。以受有丝分裂原刺激或被携带v-src癌基因的劳氏肉瘤病毒转化的大鼠肝癌细胞和成纤维细胞作为模型。结果表明，在已建立的肝癌细胞系中，参与果糖2,6 -二磷酸合成与降解的双功能酶PFK-2/FBPase-2的生化特性与正常肝脏中的该酶不同。此外，佛波酯和pp60v-src诱导的糖酵解刺激可通过果糖2,6 -二磷酸浓度的增加和PFK-2的激活来解释。刺激机制涉及一个基因的转录，该基因的产物激活PFK-2或为一种独特的PFK-2同工酶。最后，发现巯基嘌呤在体外以及在淋巴细胞和淋巴母细胞中可阻断果糖2,6 -二磷酸的合成。在这些细胞中，这导致了糖酵解的抑制。
