ArticleJournal of inherited metabolic disease2019
Hepatic glutamine synthetase augmentation enhances ammonia detoxification.
Article in Journal of inherited metabolic disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Umbilical cord-derived mitochondrial transplantation restores tendon structure and function in a preclinical model of achilles tendinopathy.Journal of translational medicine · 2026Article
- Review
- Mesenchymal stromal cells ameliorate hyperammonemia in acute hepatic failure via inhibiting glutaminolysis.Chinese medical journal · 2026Article
- Integrated multi‑omics analysis of liver metabolic dysregulation in ACE2 knockout mice.International journal of molecular medicine · 2025Article
- Not 'Inactive' After All: Cardiotoxic Mechanisms of Catecholamine Metabolism by Monoamine Oxidase.Cardiovascular toxicology · 2025Review
- Activation of glutamine synthetase (GS) as a new strategy for the treatment of major depressive disorder and other GS-related diseases.Acta pharmacologica Sinica · 2025Article
- Glutamine Synthetase: Diverse Regulation and Functions of an Ancient Enzyme.Biochemistry · 2025Review
- Dynamics of glutamine synthetase expression in hepatic ischemia-reperfusion injury: Implications for therapeutic interventions.World journal of hepatology · 2024Article
- Glutamine synthetase limits β-catenin-mutated liver cancer growth by maintaining nitrogen homeostasis and suppressing mTORC1.The Journal of clinical investigation · 2022Article
- Lactulose: A treatment for hyperammonemia in a lysinuric protein-intolerant patient with dynamic blood amino acid concentrations.Molecular genetics and metabolism reports · 2022Article
- Metabolic Diffusion in Neuropathologies: The Relevance of Brain-Liver Axis.Frontiers in physiology · 2022Review
- Hyperammonemia Post Lung Transplantation: A Review.Clinical medicine insights. Circulatory, respiratory and pulmonary medicine · 2020Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The urea cycle and glutamine synthetase (GS) are the two main pathways for waste nitrogen removal and their deficiency results in hyperammonemia. Here, we investigated the efficacy of liver-specific GS overexpression for therapy of hyperammonemia. To achieve hepatic GS overexpression, we generated a helper-dependent adenoviral (HDAd) vector expressing the murine GS under the control of a liver-specific expression cassette (HDAd-GS). Compared to mice injected with a control vector expressing an unrelated reporter gene (HDAd-alpha-fetoprotein), wild-type mice with increased hepatic GS showed reduced blood ammonia levels and a concomitant increase of blood glutamine after intraperitoneal injections of ammonium chloride, whereas blood urea was unaffected. Moreover, injection of HDAd-GS reduced blood ammonia levels at baseline and protected against acute hyperammonemia following ammonia challenge in a mouse model with conditional hepatic deficiency of carbamoyl phosphate synthetase 1 (Cps1), the initial and rate-limiting step of ureagenesis. In summary, we found that upregulation of hepatic GS reduced hyperammonemia in wild-type and Cps1-deficient mice, thus confirming a key role of GS in ammonia detoxification. These results suggest that hepatic GS augmentation therapy has potential for treatment of both primary and secondary forms of hyperammonemia.
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Registered trials
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