Departamento de Bioquimica y Biologia Molecular, Instituto de Neurociencias de Castilla y Leon, Universidad de Salamanca, Salamanca, Spain.
Trends Biochem Sci. 2010 Mar;35(3):145-9. doi: 10.1016/j.tibs.2009.10.006. Epub 2009 Dec 16.
Following inhibition of mitochondrial respiration neurons die rapidly, whereas astrocytes utilize glycolytically-generated ATP to increase their mitochondrial membrane potential, thus becoming more resistant to pro-apoptotic stimuli. Neurons are unable to increase glycolysis due to the lack of activity of the glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase, isoform 3 (PFKFB3). In neurons, PFKFB3 is degraded constantly via the E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C)- CDH1. Glucose metabolism in neurons is directed mainly to the pentose phosphate pathway, leading to regeneration of reduced glutathione. In addition to their relevance to brain physiology and pathophysiology, these observations suggest that APC/C-CDH1 might link activation of glycolysis and cell proliferation as it is also involved in the regulation of cell cycle proteins.
抑制线粒体呼吸后神经元会迅速死亡，而星形胶质细胞利用糖酵解产生的 ATP 来增加其线粒体膜电位，从而对促凋亡刺激更具抵抗力。由于缺乏促进糖酵解的酶 6-磷酸果糖-2-激酶/果糖 2,6-二磷酸酶，同工型 3（PFKFB3）的活性，神经元无法增加糖酵解。在神经元中，PFKFB3 通过有丝分裂后期促进复合物/环体（APC/C）-CDH1 不断降解。神经元中的葡萄糖代谢主要定向于戊糖磷酸途径，导致还原型谷胱甘肽的再生。除了与大脑生理学和病理生理学相关外，这些观察结果表明 APC/C-CDH1 可能将糖酵解和细胞增殖的激活联系起来，因为它也参与细胞周期蛋白的调节。
