ArticleThe Journal of biological chemistry2010
Glutamine synthetase in muscle is required for glutamine production during fasting and extrahepatic ammonia detoxification.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 82 citations in OpenAlex.
- Metabolic Brain Disorders: Prodromes, Symptoms, and Syndromes.International journal of molecular sciences · 2026Review
- Carbamoyl phosphate synthetase 1 deficiency manifested in an adult treated with prednisone for polymyositis, and cured by live-donor liver transplantation.Molecular genetics and metabolism reports · 2025Article
- Ablation of LAT2 Transporter Causes Intramuscular Glutamine Accumulation and Inhibition of Fasting-Induced Proteolysis.Journal of cachexia, sarcopenia and muscle · 2025Article
- Long-term leucine supplementation increases body weight in goats by controlling appetite and muscle protein synthesis under protein-restricted conditions.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- DELE1 maintains muscle proteostasis to promote growth and survival in mitochondrial myopathy.The EMBO journal · 2024Article
- Ammonia-induced stress response in liver disease progression and hepatic encephalopathy.Nature reviews. Gastroenterology & hepatology · 2024Review
- Myokines: metabolic regulation in obesity and type 2 diabetes.Life metabolism · 2024Review
- DELE1 promotes translation-associated homeostasis, growth, and survival in mitochondrial myopathy.bioRxiv : the preprint server for biology · 2024Article
- Role of glutamine metabolism in tuberculosis pathogenesis: a mini review.Frontiers in tuberculosis · 2024Review
- Baf155 regulates skeletal muscle metabolism via HIF-1a signaling.PLoS biology · 2023Article
- Glutamine synthetase: a tumor suppressor in hepatocellular carcinoma?Journal of molecular cell biology · 2023Article
- Tumour catabolism independent of malnutrition and inflammation in upper GI cancer patients revealed by longitudinal metabolomics.Journal of cachexia, sarcopenia and muscle · 2023Article
- Glutamine synthetase limits β-catenin-mutated liver cancer growth by maintaining nitrogen homeostasis and suppressing mTORC1.The Journal of clinical investigation · 2022Article
- Reproductive colonization of land by frogs: Embryos and larvae excrete urea to avoid ammonia toxicity.Ecology and evolution · 2022Article
- Impact of L-ornithine L-aspartate on non-alcoholic steatohepatitis-associated hyperammonemia and muscle alterations.Frontiers in nutrition · 2022Article
- Aerial ammonia exposure induces the perturbation of the interorgan ammonia disposal and branched-chain amino acid catabolism in growing pigs.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2021Article
- AMP deamination is sufficient to replicate an atrophy-like metabolic phenotype in skeletal muscle.Metabolism: clinical and experimental · 2021Article
- Sarcopenic metabolomic profile reflected a sarcopenic phenotype associated with amino acid and essential fatty acid changes.Metabolomics : Official journal of the Metabolomic Society · 2021Article
- KRAS, A Prime Mediator in Pancreatic Lipid Synthesis through Extra Mitochondrial Glutamine and Citrate Metabolism.International journal of molecular sciences · 2021Review
- Histone methyltransferase MLL4 controls myofiber identity and muscle performance through MEF2 interaction.The Journal of clinical investigation · 2020Article
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The main endogenous source of glutamine is de novo synthesis in striated muscle via the enzyme glutamine synthetase (GS). The mice in which GS is selectively but completely eliminated from striated muscle with the Cre-loxP strategy (GS-KO/M mice) are, nevertheless, healthy and fertile. Compared with controls, the circulating concentration and net production of glutamine across the hindquarter were not different in fed GS-KO/M mice. Only a approximately 3-fold higher escape of ammonia revealed the absence of GS in muscle. However, after 20 h of fasting, GS-KO/M mice were not able to mount the approximately 4-fold increase in glutamine production across the hindquarter that was observed in control mice. Instead, muscle ammonia production was approximately 5-fold higher than in control mice. The fasting-induced metabolic changes were transient and had returned to fed levels at 36 h of fasting. Glucose consumption and lactate and ketone-body production were similar in GS-KO/M and control mice. Challenging GS-KO/M and control mice with intravenous ammonia in stepwise increments revealed that normal muscle can detoxify approximately 2.5 micromol ammonia/g muscle.h in a muscle GS-dependent manner, with simultaneous accumulation of urea, whereas GS-KO/M mice responded with accumulation of glutamine and other amino acids but not urea. These findings demonstrate that GS in muscle is dispensable in fed mice but plays a key role in mounting the adaptive response to fasting by transiently facilitating the production of glutamine. Furthermore, muscle GS contributes to ammonia detoxification and urea synthesis. These functions are apparently not vital as long as other organs function normally.
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