ArticleMetabolic brain disease2014
Inhibition of human glutamine synthetase by L-methionine-S,R-sulfoximine-relevance to the treatment of neurological diseases.
Article in Metabolic brain disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Methionine Sulfoximine as a Tool for Studying Temporal Lobe Epilepsy: Initiator, Developer, Attenuator.Neurochemical research · 2025Review
- Clustered de novo start-loss variants in GLUL result in a developmental and epileptic encephalopathy via stabilization of glutamine synthetase.American journal of human genetics · 2024Article
- Ammonium chloride reduces excitatory synaptic transmission onto CA1 pyramidal neurons of mouse organotypic slice cultures.Frontiers in cellular neuroscience · 2024Article
- Distinct evolution of type I glutamine synthetase in Plasmodium and its species-specific requirement.Nature communications · 2023Article
- Neuroinflammation, Energy and Sphingolipid Metabolism Biomarkers Are Revealed by Metabolic Modeling of Autistic Brains.Biomedicines · 2023Article
- Glutaminase 2 knockdown reduces hyperammonemia and associated lethality of urea cycle disorder mouse model.Journal of inherited metabolic disease · 2022Article
- Inhibition of Glutamate Release, but Not of Glutamine Recycling to Glutamate, Is Involved in Delaying the Onset of Initial Lithium-Pilocarpine-Induced Seizures in Young Rats by a Non-Convulsive MSO Dose.International journal of molecular sciences · 2021Article
- An integrated approach to biomarker discovery reveals gene signatures highly predictive of cancer progression.Scientific reports · 2020Article
- Glufosinate constrains synchronous and metachronous metastasis by promoting anti-tumor macrophages.EMBO molecular medicine · 2020Article
- Article
- Phosphorylation of Glutamine Synthetase on Threonine 301 Contributes to Its Inactivation During Epilepsy.Frontiers in molecular neuroscience · 2019Article
- Mechanistic Basis for ATP-Dependent Inhibition of Glutamine Synthetase by Tabtoxinine-β-lactam.Biochemistry · 2018Article
- In vitro suppression of inflammatory cytokine response by methionine sulfoximine.Journal of inflammation (London, England) · 2018Article
- The glutamine synthetase of Trypanosoma cruzi is required for its resistance to ammonium accumulation and evasion of the parasitophorous vacuole during host-cell infection.PLoS neglected tropical diseases · 2018Article
- 1,25-Dihydroxyvitamin D Regulation of Glutamine Synthetase and Glutamine Metabolism in Human Mammary Epithelial Cells.Endocrinology · 2017Article
- The Enzymology of 2-Hydroxyglutarate, 2-Hydroxyglutaramate and 2-Hydroxysuccinamate and Their Relationship to Oncometabolites.Biology · 2017Article
- Fluorination at the 4 position alters the substrate behavior of L-glutamine and L-glutamate: Implications for positron emission tomography of neoplasias.Journal of fluorine chemistry · 2016Article
- Critical Evaluation of the Changes in Glutamine Synthetase Activity in Models of Cerebral Stroke.Neurochemical research · 2015Review
- Inhibition of glutamine synthetase: a potential drug target in Mycobacterium tuberculosis.Molecules (Basel, Switzerland) · 2014Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
At high concentrations, the glutamine synthetase inhibitor L-methionine-S,R-sulfoximine (MSO) is a convulsant, especially in dogs. Nevertheless, sub-convulsive doses of MSO are neuroprotective in rodent models of hyperammonemia, acute liver disease, and amyotrophic lateral sclerosis and suggest MSO may be clinically useful. Previous work has also shown that much lower doses of MSO are required to produce convulsions in dogs than in primates. Evidence from the mid-20th century suggests that humans are also less sensitive. In the present work, the inhibition of recombinant human glutamine synthetase by MSO is shown to be biphasic-an initial reversible competitive inhibition (K i 1.19 mM) is followed by rapid irreversible inactivation. This K i value for the human enzyme accounts, in part, for relative insensitivity of primates to MSO and suggests that this inhibitor could be used to safely inhibit glutamine synthetase activity in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.