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Nitrogen anabolism underlies the importance of glutaminolysis in proliferating cells
Journal article   Open access   Peer reviewed

Nitrogen anabolism underlies the importance of glutaminolysis in proliferating cells

Meng Meng, Shuyang Chen, Taotao Lao, Dongming Liang and Nianli Sang
Cell cycle (Georgetown, Tex.), v 9(19), pp 3921-3932
01 Oct 2010
PMID: 20935507
url
https://doi.org/10.4161/cc.9.19.13139View
Published, Version of Record (VoR)Open Access (License Unspecified) Open

Abstract

cancer glutaminolysis glycolysis hypoxia Report transamination Warburg effect
Glutaminolysis and the Warburg effect are the two most noticeable metabolic features of tumor cells, whereas their biological significance in cell proliferation remains elusive. A widely accepted current hypothesis is that tumor cells use glutamine as a preferred carbon source for energy and reducing power, which has been used to explain both glutaminolysis and the Warburg effect. Here we provide evidence to show that supplying nitrogen, not the carbon skeleton, underlies the major biological importance of glutaminolysis for proliferating cells. We show that alternative nitrogen supplying mechanisms rescue cell proliferation in glutamine-free media. Particularly, we show that ammonia is sufficient to maintain a long-term survival and proliferation of Hep3B in glutamine-free media. We also observed that nitrogen source restriction repressed carbon metabolic pathways, including glucose utilization. Based on these new observations and metabolic pathways well-established in published literature, we propose an alternative model that cellular demand for glutamate is a key molecule in nitrogen anabolism, which is the driving force of glutaminolysis in proliferating cells. Our model suggests that the Warburg effect may be a metabolic consequence secondary to the nitrogen anabolism.

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Cell Biology
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