Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Mar;3(3):169-180.
doi: 10.1016/j.trecan.2017.01.005.

Glutamine Metabolism in Cancer: Understanding the Heterogeneity

Ahmad A Cluntun  1 , Michael J Lukey  2 , Richard A Cerione  3 , Jason W Locasale  4
Affiliations
Review

Glutamine Metabolism in Cancer: Understanding the Heterogeneity

Ahmad A Cluntun et al. Trends Cancer. 2017 Mar.

Abstract

Reliance on glutamine has long been considered a hallmark of cancer cell metabolism. However, some recent studies have challenged this notion in vivo, prompting a need for further clarifications on the role of glutamine metabolism in cancer. We find that there is ample evidence of an essential role for glutamine in tumors and that a variety of factors, including tissue type, the underlying cancer genetics, the tumor microenvironment and other variables such as diet and host physiology collectively influence the role of glutamine in cancer. Thus the requirements for glutamine in cancer are overall highly heterogeneous. In this review, we discuss the implications both for basic science and for targeting glutamine metabolism in cancer therapy.

Keywords: Cancer Metabolism; Glutaminase; Glutamine Metabolism; TCA Cycle Anaplerosis.

PubMed Disclaimer

Figures

Figure 1
Figure 1. The Glutamine Metabolic Footprint in Cancer
Glutamine has a five-carbon backbone and two nitrogen atoms (α and γ) to donate. Glutamine’s metabolic footprint goes well beyond TCA cycle anaplerosis. Gln: Glutamine, Glu: Glutamate, GSH: Glutathione, Asp: Aspartate, Ala: Alanine, Thr: Threonine, Gly: Glycine, Ser: Serine, Cys: Cysteine, Pro: Proline, Mal: Malate, Pyr: Pyruvate, Lac: Lactate, OAA: Oxaloacetate, Cit: Citrate, TCA: Citric acid cycle, α-KG: alpha-ketoglutarate.
Figure 2
Figure 2. TCA cycle anaplerotic fluxes affect glutaminase inhibition efficacy
There are two main anaplerotic fluxes that can feed the citric acid cycle, a glutamine flux via glutaminase (GLS and/or GLS2) and a glucose flux via pyruvate carboxylase (PC). Glutamine synthetase (GLUL) is also an important enzyme for this process as it can synthesize glutamine from glutamate and thus allow cells to survive in glutamine-depleted conditions. The expression levels of these enzymes vary according to tissue type and can greatly affect their sensitivity to glutaminase inhibition. GBM: Glioblastoma, NSCLC: non-small cell lung carcinoma, Pyr: Pyruvate, Lac: Lactate, Cit: Citrate, TCA: Citric acid cycle, α-KG: alpha-ketoglutarate.
See this image and copyright information in PMC

References

    1. Pavlova NN, Thompson CB. The Emerging Hallmarks of Cancer Metabolism. Cell Metab. 2016;23(1):27–47. - PMC - PubMed
    1. DeBerardinis RJ, Chandel NS. Fundamentals of cancer metabolism. Sci Adv. 2016;2(5):e1600200. - PMC - PubMed
    1. Boroughs LK, DeBerardinis RJ. Metabolic pathways promoting cancer cell survival and growth. Nat Cell Biol. 2015;17(4):351–9. - PMC - PubMed
    1. Nagarajan A, Malvi P, Wajapeyee N. Oncogene-directed alterations in cancer cell metabolism. Trends Cancer. 2016;2(7):365–377. - PMC - PubMed
    1. Liberti MV, Locasale JW. The Warburg Effect: How Does it Benefit Cancer Cells? Trends Biochem Sci. 2016;41(3):211–8. - PMC - PubMed

Publication types