Amino Acids Rather than Glucose Account for the Majority of Cell Mass in Proliferating Mammalian Cells.
Amino Acids Rather than Glucose Account for the Majority of Cell Mass in Proliferating Mammalian Cells.
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DOI：
10.1016/j.devcel.2016.02.012
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发表时间：
2016-03-07
影响因子：
11.8
通讯作者：
Vander Heiden MG
中科院分区：
文献类型：
--
作者：
Hosios AM;Hecht VC;Danai LV;Johnson MO;Rathmell JC;Steinhauser ML;Manalis SR;Vander Heiden MG
细胞必须复制它们的质量才能增殖。葡萄糖和谷氨酰胺是增殖的哺乳动物细胞消耗的主要营养物质，但这些和其他营养物质对细胞质量的贡献程度尚不清楚。我们量化了来自不同营养素的细胞质量分数，发现细胞中的大部分碳质量来自其他氨基酸，这些氨基酸的消耗率比葡萄糖和谷氨酰胺低得多。虽然葡萄糖碳具有不同的命运，但谷氨酰胺对蛋白质的贡献最大，这表明谷氨酰胺补充TCA循环中间体（回补）的能力主要用于氨基酸生物合成。这些发现表明，营养消耗率与质量积累间接相关，并表明高速率的葡萄糖和谷氨酰胺消耗支持快速细胞增殖，而不仅仅是为生物合成提供碳。
Cells must duplicate their mass in order to proliferate. Glucose and glutamine are the major nutrients consumed by proliferating mammalian cells, but the extent to which these and other nutrients contribute to cell mass is unknown. We quantified the fraction of cell mass derived from different nutrients and find that the majority of carbon mass in cells is derived from other amino acids, which are consumed at much lower rates than glucose and glutamine. While glucose carbon has diverse fates, glutamine contributes most to protein, and this suggests that glutamine’s ability to replenish TCA cycle intermediates (anaplerosis) is primarily used for amino acid biosynthesis. These findings demonstrate that rates of nutrient consumption are indirectly associated with mass accumulation and suggest that high rates of glucose and glutamine consumption support rapid cell proliferation beyond providing carbon for biosynthesis.