GPNA inhibits the sodium-independent transport system l for neutral amino acids
Abstract
L-γ-Glutamyl-p-nitroanilide (GPNA) is widely used to inhibit the glutamine transporter ASCT2, although it is known that it also inhibits other sodium-dependent amino acid transporters. In a panel of human cancer cell lines, which express the system L transporters LAT1 and LAT2, GPNA inhibits the sodium-independent influx of leucine and glutamine. The kinetics of the effect suggests that GPNA is a low affinity, competitive inhibitor of system L transporters. In Hs683 human oligodendroglioma cells, the incubation in the presence of GPNA, but not ASCT2 silencing, lowers the cell content of leucine. Under the same conditions the activity of mTORC1 is inhibited. Decreased cell content of branched chain amino acids and mTORC1 inhibition are observed in most of the other cell lines upon incubation with GPNA. It is concluded that GPNA hinders the uptake of essential amino acids through system L transporters and lowers their cell content.
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GPNA also inhibits other glutamine transporters such as SLC38A1, and V-9302 is effective even in SLC1A5 knockout models.
“However, other researchers have argued that controversial issues exist because GPNA also inhibits other glutamine transporters, such as SLC38A1, and V-9302 is effective even in SLC1A5 knockout models206,207.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [207]
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References 27 · Cited by 77
- Authors
- Chiu, M., Sabino, C., Taurino, G., Bianchi, M. G., Andreoli, R., Giuliani, N., & Bussolati, O.
- Affiliations
- University of Parma (IT)
- Corresponding author
- Bussolati, Ovidio
- ORCID
- Venue
- Amino Acids
- Published
- 2017-05-17
- Volume
- 49
- Issue
- 8
- Pages
- 1365-1372
- ISSN
- 0939-4451 (ISSN-L)
- 1438-2199
- OpenAlex
- W2614615914
- Cited by
- 77
- References
- 27
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 12 · 2023: 8 · 2022: 9 · 2021: 9 · 2020: 6 · 2019: 13 · 2018: 7
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Amino Acids (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- system L amino acid transporter, LAT1, LAT2, ASCT2, glutamine uptake, leucine uptake, competitive inhibition, mTORC1 inhibition, branched-chain amino acids, oligodendroglioma, cancer cell lines
- MeSH terms
- Dipeptides, Humans, Neoplasms, Tumor Cells, Cultured, Amino Acids, Neutral, Large Neutral Amino Acid-Transporter 1, Adaptor Proteins, Signal Transducing, Cell Proliferation
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