Lipton P, Robacker K
Fed Proc. 1983 Sep;42(12):2875-80.
Glucose is essentially the sole energy substrate in the normally functioning brain. There are, however, situations in which other substrates can partially substitute for glucose and maintain an apparently normal brain function. However, in no case has it been possible to completely substitute other substrates for glucose and maintain normal brain function. Studies on insulin-induced hypoglycemia suggest that this glucose dependence does not result from its involvement in ATP generation. Two explantation that have been offered are that toxic catabolites arise if nonglucose substrates are oxidized or that glycolysis is necessary to maintain neurotransmitter metabolism. We consider a third basis for the glucose requirement: our past studies have shown that hippocampal slice protein synthesis is activated by small increases in extracellular [K+] ([K+]o), and that this results from activation of K+ uptake into brain cells. We find that this process specifically requires aerobic glycolysis. The basis for the requirement appears to be that [K+]o activation of the Na+-K+ pump is specifically dependent on glycolytically generated energy. Thus, it is possible that glucose is required to maintain normal K+ clearance from the extracellular space during neural activity. This could partially account for the dependence of brain function on glycolysis.
葡萄糖本质上是正常运转的大脑唯一的能量底物。然而，在某些情况下，其他底物可以部分替代葡萄糖并维持明显正常的脑功能。然而，在任何情况下都不可能完全用其他底物替代葡萄糖并维持正常的脑功能。对胰岛素诱导的低血糖的研究表明，这种对葡萄糖的依赖并非源于其参与三磷酸腺苷（ATP）的生成。提出的两种解释是，如果非葡萄糖底物被氧化会产生有毒的分解代谢产物，或者糖酵解对于维持神经递质代谢是必要的。我们考虑葡萄糖需求的第三个原因：我们过去的研究表明，细胞外[钾离子]（[K +] o）的小幅增加会激活海马切片蛋白质合成，这是由于钾离子摄取到脑细胞中被激活所致。我们发现这个过程特别需要有氧糖酵解。这种需求的基础似乎是[K +] o对钠钾泵的激活特别依赖于糖酵解产生的能量。因此，在神经活动期间，可能需要葡萄糖来维持细胞外空间正常的钾离子清除。这可能部分解释了脑功能对糖酵解的依赖性。
