Glutamine synthetase and hepatocellular carcinoma

Clin Res Hepatol Gastroenterol. 2023 Dec;47(10):102248. doi: 10.1016/j.clinre.2023.102248. Epub 2023 Nov 16.


Glutamine synthetase (GS) is an enzyme that converts ammonia and glutamate to glutamine using adenosine triphosphate. GS is expressed in the brain, kidney, and liver tissues under normal physiological conditions. GS is involved in abnormal lipid metabolism of the liver by catalyzing de novo synthesis of glutamine, thereby inducing liver inflammation. Metabolic dysfunction-associated steatotic liver diseases (MASLD), such as Metabolic Associated Fatty Liver Disease and Metabolic Associated Steato Hepatitis, are considered risk factors for HCC. GS may also be involved in the development and progression of hepatocellular carcinoma (HCC) through other signaling pathways, including the rapamycin (mTOR) and Wnt/β-catenin signaling pathways. Furthermore, the correct combination of HSP70, GPC3, and GS can improve the accuracy and precision of HCC diagnosis. However, the prognostic value of GS in different HCC populations remains controversial. The expression of GS affects the sensitivity of HCC cells to radiotherapy and chemotherapy. In addition, immunotherapy has been approved for the treatment of advanced HCC. This article delves into the development and application of GS in HCC, laying a theoretical foundation for the subsequent exploration of GS as a potential target for treating HCC.

Keywords: Biomarkers; Glutamine; Glutamine synthetase; Primary hepatocellular carcinoma.

MeSH terms

  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / metabolism
  • Glutamate-Ammonia Ligase* / metabolism
  • Glutamine / metabolism
  • Glutamine / therapeutic use
  • Glypicans / metabolism
  • Glypicans / therapeutic use
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / metabolism
  • Wnt Signaling Pathway


  • Glutamate-Ammonia Ligase
  • Glutamine
  • Glypicans
  • GPC3 protein, human