Redox control of glutamine utilization in cancer.
Redox control of glutamine utilization in cancer.
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DOI：
10.1038/cddis.2014.513
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发表时间：
2014-12-04
影响因子：
9
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中科院分区：
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谷氨酰胺的利用促进癌细胞的生长。我们提出了癌症代谢的新概念图，其中线粒体 NADH 和 NADPH 在电子传递链功能失调的情况下促进谷氨酰胺的还原羧化。我们还讨论了为什么体内需要烟酰胺核苷酸转氢酶（NNT）来通过还原羧化利用谷氨酰胺。此外，由戊糖磷酸途径和癌症特异性丝氨酸糖酵解转移产生的 NADPH 似乎可以维持谷氨酰胺对氨基酸合成、脂质合成和 ROS 猝灭的利用。 NAD+ 前体的供应降低了肿瘤的侵袭性，这一事实表明可以通过实验方法来阐明 NADH 驱动的氧化还原网络在癌症中的作用。
Glutamine utilization promotes enhanced growth of cancer cells. We propose a new concept map of cancer metabolism in which mitochondrial NADH and NADPH, in the presence of a dysfunctional electron transfer chain, promote reductive carboxylation from glutamine. We also discuss why nicotinamide nucleotide transhydrogenase (NNT) is required in vivo for glutamine utilization by reductive carboxylation. Moreover, NADPH, generated by both the pentose phosphate pathway and the cancer-specific serine glycolytic diversion, appears to sustain glutamine utilization for amino-acid synthesis, lipid synthesis, and for ROS quenching. The fact that the supply of NAD+ precursors reduces tumor aggressiveness suggests experimental approaches to clarify the role of the NADH-driven redox network in cancer.