Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Cell Cycle. 2010 Oct 1;9(19):3884-6. doi: 10.4161/cc.9.19.13302. Epub 2010 Oct 9.
A cancer cell comprising largely of carbon, hydrogen, oxygen, phosphorus, nitrogen and sulfur requires not only glucose, which is avidly transported and converted to lactate by aerobic glycolysis or the Warburg effect, but also glutamine as a major substrate. Glutamine and essential amino acids, such as methionine, provide energy through the TCA cycle as well as nitrogen, sulfur and carbon skeletons for growing and proliferating cancer cells. The interplay between utilization of glutamine and glucose is likely to depend on the genetic make-up of a cancer cell. While the MYC oncogene induces both aerobic glycolysis and glutaminolysis, activated β-catenin induces glutamine synthesis in hepatocellular carcinoma. Cancer cells that have elevated glutamine synthetase can use glutamate and ammonia to synthesize glutamine and are hence not addicted to glutamine. As such, cancer cells have many degrees of freedom for re-programming cell metabolism, which with better understanding will result in novel therapeutic approaches.
一个主要由碳、氢、氧、磷、氮和硫组成的癌细胞不仅需要葡萄糖，葡萄糖通过有氧糖酵解或瓦博格效应被积极转运并转化为乳酸，还需要谷氨酰胺作为主要底物。谷氨酰胺和必需氨基酸，如蛋氨酸，通过 TCA 循环提供能量，以及氮、硫和碳骨架，以支持生长和增殖的癌细胞。谷氨酰胺和葡萄糖的利用之间的相互作用可能取决于癌细胞的基因组成。虽然 MYC 癌基因诱导有氧糖酵解和谷氨酰胺分解，但激活的 β-连环蛋白在肝细胞癌中诱导谷氨酰胺合成。具有高谷氨酸合成酶的癌细胞可以利用谷氨酸和氨合成谷氨酰胺，因此不依赖于谷氨酰胺。因此，癌细胞在重新编程细胞代谢方面有许多自由度，随着更好的理解，将产生新的治疗方法。
