Glutaminolysis Supplying carbon or nitrogen or both for cancer cells?
Glutaminolysis Supplying carbon or nitrogen or both for cancer cells?
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DOI：
10.4161/cc.9.19.13302
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发表时间：
2010-10-01
期刊：
影响因子：
4.3
通讯作者：
Dang, Chi V.
中科院分区：
文献类型：
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作者：
Dang, Chi V.
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Warburg效应被热切地运输和转化为乳酸，还需要谷氨酰胺作为主要底物。谷氨酰胺和蛋氨酸等必需氨基酸通过TCA循环以及氮、硫和碳骨架为癌细胞的生长和增殖提供能量。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构成。MYC癌基因同时诱导有氧糖酵解和谷氨酰胺分解，而激活的β-连环蛋白诱导肝细胞癌谷氨酰胺合成。谷氨酰胺合成酶升高的癌细胞可以利用谷氨酸和氨来合成谷氨酰胺，因此不会对谷氨酰胺上瘾。因此，癌细胞有许多自由度来重新编程细胞代谢，这将导致更好的理解将导致新的治疗方法。
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 beta-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.