ArticleScientific reports2019
The ability to utilise ammonia as nitrogen source is cell type specific and intricately linked to GDH, AMPK and mTORC1.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Metabolites beyond metabolism: Exploring their atypical roles in protein modification and signaling transduction.Chinese medical journal · 2026Review
- FOXO1 links KRAS G12D and G12V alleles to glutamine and nitrogen metabolism in colorectal cancer.EMBO reports · 2026Article
- Ammonia metabolic reprogramming in the tumor microenvironment: emergence of an immunosuppressive niche.Frontiers in cell and developmental biology · 2026Review
- Effects of aging and anti-aging dietary restriction on regulators of the [NADPH]/[NADPFree radical biology & medicine · 2025Review
- Novel roles of ammonia in physiology and cancer.Journal of molecular cell biology · 2025Review
- High-ammonia microenvironment promotes stemness and metastatic potential in hepatocellular carcinoma through metabolic reprogramming.Discover oncology · 2025Article
- A narrative review about cognitive impairment in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Another matter to face through a holistic approach.Journal of advanced research · 2025Review
- Ammonia-induced stress response in liver disease progression and hepatic encephalopathy.Nature reviews. Gastroenterology & hepatology · 2024Review
- Enhancing Antibody-Specific Productivity: Unraveling the Impact of XBP1s Overexpression and Glutamine Availability in SP2/0 Cells.Bioengineering (Basel, Switzerland) · 2024Article
- Construction of a novel kinetic model for the production process of a CVA6 VLP vaccine in CHO cells.Cytotechnology · 2024Article
- Cellular Distribution of Aquaporin 3, 7 and 9 in the Male Reproductive System: A Lesson from Bovine Study (International journal of molecular sciences · 2024Article
- Role of ammonia in NAFLD: An unusual suspect.JHEP reports : innovation in hepatology · 2023Review
- Non-ammoniagenic proliferation and differentiation media for cultivated adipose tissue.Frontiers in bioengineering and biotechnology · 2023Article
- NDRG2 inhibits pyruvate carboxylase-mediated anaplerosis and combines with glutamine blockade to inhibit the proliferation of glioma cells.American journal of cancer research · 2022Article
- Low nitrogen conditions accelerate flowering by modulating the phosphorylation state of FLOWERING BHLH 4 inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- A TOR (target of rapamycin) and nutritional phosphoproteome of fission yeast reveals novel targets in networks conserved in humans.Open biology · 2021Article
- Article
- Nitrogen Metabolism in Cancer and Immunity.Trends in cell biology · 2020Review
- Physiological Role of Glutamate Dehydrogenase in Cancer Cells.Frontiers in oncology · 2020Article
- Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Ammonia can be utilised as an alternative nitrogen source to glutamine to support cell proliferation. However, the underlying molecular mechanisms and whether all cells have this ability is not fully understood. We find that eleven cancer and non-cancerous cell lines have opposite abilities to tolerate and utilise ammonia to support proliferation in a glutamine-depleted environment. HEK293, Huh7, T47D and MCF7 cells can use ammonia, when starved of glutamine, to support proliferation to varying degrees. Glutamine depletion reduced mTORC1 activity, while additional ammonia supplementation diminished this mTORC1 inhibition. Depletion of glutamine promoted a rapid and transient activation of AMPK, whereas, additional ammonia supplementation blocked this starvation-induced AMPK activation. As expected, drug-induced AMPK activation reduced cell proliferation in glutamine-depleted cells supplemented with ammonia. Surprisingly, mTORC1 activity was largely unchanged despite the enhanced AMPK activity, suggesting that AMPK does not inhibit mTORC1 signalling under these conditions. Finally, glutamate dehydrogenase (GDH) inhibition, a key enzyme regulating ammonia assimilation, leads to AMPK activation, mTORC1 inhibition and reduced proliferation. Ammonia provides an alternative nitrogen source that aids certain cancer cells ability to thrive in nutrient-deprived environment. The ability of cells to utilise ammonia as a nitrogen source is intricately linked to AMPK, mTORC1 and GDH.
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