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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http://dx.doi.org/10.1007/s11011-013-9439-6 | DOI Listing |
Int J Mol Sci
December 2024
Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Sadat City 32897, Egypt.
Cancer cells undergo metabolic rewiring to support rapid proliferation and survival in challenging environments. Glutamine is a preferred resource for cancer metabolism, as it provides both carbon and nitrogen for cellular biogenesis. Recent studies suggest the potential anticancer activity of amino acid analogs.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138.
C-Terminal cyclic imides are posttranslational modifications that can arise from spontaneous intramolecular cleavage of asparagine or glutamine residues resulting in a form of irreversible protein damage. These protein damage events are recognized and removed by the E3 ligase substrate adapter cereblon (CRBN), indicating that these aging-related modifications may require cellular quality control mechanisms to prevent deleterious effects. However, the factors that determine protein or peptide susceptibility to C-terminal cyclic imide formation or their effect on protein stability have not been explored in detail.
View Article and Find Full Text PDFJ Agric Food Chem
January 2025
College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing, Jiangsu Province 210095, China.
Legumes are well-known for symbiotic nitrogen fixation, whereas associative nitrogen fixation for nonlegume plants needs more attention. Most associative nitrogen-fixing bacteria are applied in their original plant species and need further study for broad adaptation. Additionally, if isolated nitrogen-fixing bacteria could function under fertilizer conditions, it is often ignored.
View Article and Find Full Text PDFPlant Cell Environ
January 2025
The Robert H. Smith Institute of Plant Sciences and Genetics in Agriculture, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
Nitrate reduction requires reducing equivalents produced by the photosynthetic electron transport chain. Therefore, it has been suggested that nitrate assimilation provides a sink for electrons under high light conditions. We tested this hypothesis by monitoring photosynthetic efficiency and the chloroplastic glutathione redox potential (chl-E) of plant lines with mutated glutamine synthetase 2 (GS2) and ferredoxin-dependent glutamate synthase 1 (GOGAT1).
View Article and Find Full Text PDFFront Plant Sci
December 2024
School of Hydraulic Engineering, Zhejiang University of Water Resources and Electric Power, Hangzhou, China.
Water-saving irrigation and the mixed application of controlled-release nitrogen fertilizer (CRNF) and common urea (CU; with a higher nitrogen release rate) have shown promise in improving rice yield with high resource use efficiency. However, the physiological mechanism underlying this effect remains largely unknown. This study involved a field experiment on rice in Jingzhou City, Central China, in 2020 and 2021.
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