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
Editorial
. 2013 Jul 1;12(13):1987-8.
doi: 10.4161/cc.25307. Epub 2013 Jun 10.

Pancreatic cancers rely on a novel glutamine metabolism pathway to maintain redox balance

Costas A Lyssiotis, Jaekyoung Son, Lewis C Cantley, Alec C Kimmelman
Editorial

Pancreatic cancers rely on a novel glutamine metabolism pathway to maintain redox balance

Costas A Lyssiotis et al. Cell Cycle. .
No abstract available

Keywords: NADPH; aspartate aminotransferase; cancer metabolism; glutamate dehydrogenase; malic enzyme.

PubMed Disclaimer

Figures

None
Figure 1. Gln metabolism is rewired in pancreatic cancer to facilitate NADPH production. (A) Canonical anabolic Gln metabolism. Gln-derived Glu is processed into αKG through mitochondrial GLUD1, which is used for anaplerotic filling of the TCA cycle (green circle). The TCA cycle is coupled to the malate-aspartate shuttle (blue circle), which is used to bring reducing equivalents derived from glycolysis into the mitochondria for oxidative phosphorylation. (B) In pancreatic cancer, Gln metabolism is reprogrammed through the mutant Kras-mediated activation of GOT1 expression and repression of GLUD1. Repression of GLUD1 promotes the mitochondrial aspartate aminotransferase (GOT2)-mediated generation of Asp in the mitochondria. This Asp is released into the cytosol and converted through a series of reactions into pyruvate and reducing potential in the form of NADPH. This series of reactions decouples TCA cycle activity from the malate-aspartate shuttle. Enzymes that facilitate this pathway are presented in upper-case letters. Metabolites are presented in lower-case letters. Cit, citrate; Fum, fumarate; Pyr, pyruvate; Iso, isocitrate; Suc, succinate.
See this image and copyright information in PMC

Comment on

  • Son J, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M, et al. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature. 2013;496:101–5. doi: 10.1038/nature12040.

References

    1. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324:1029–33. doi: 10.1126/science.1160809. - DOI - PMC - PubMed
    1. Lunt SY, Vander Heiden MG. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol. 2011;27:441–64. doi: 10.1146/annurev-cellbio-092910-154237. - DOI - PubMed
    1. Ying H, Kimmelman AC, Lyssiotis CA, Hua S, Chu GC, Fletcher-Sananikone E, et al. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell. 2012;149:656–70. doi: 10.1016/j.cell.2012.01.058. - DOI - PMC - PubMed
    1. Son J, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M, et al. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature. 2013;496:101–5. doi: 10.1038/nature12040. - DOI - PMC - PubMed
    1. Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK, et al. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci U S A. 2008;105:18782–7. doi: 10.1073/pnas.0810199105. - DOI - PMC - PubMed

Publication types