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Glutamine Synthetase (GS)
- Target
- GS
- Molecular classification
- Enzyme, Ligase
01
Overview
Glutamine synthetase (GS) is an ATP-dependent enzyme that catalyzes the synthesis of glutamine from glutamate and ammonia. This reaction is central to nitrogen metabolism, detoxifying ammonia and regulating glutamate levels. It is crucial for glutamine production, which is essential for various biosynthetic processes. GS activity is tightly regulated and also exhibits 'moonlighting' functions beyond its primary catalytic role. Dysregulation is implicated in neurological disorders and cancer.
- Other names
- Glutamate-ammonia ligaseGlutamate synthetase
02
Mechanism of action
Two-step mechanism involving ATP-dependent phosphorylation of glutamate followed by ammonia attack to form glutamine and inorganic phosphate.
03
Biological functions
Ammonia detoxificationGlutamine biosynthesisNitrogen metabolismRegulation of glutamate levelsProtein synthesisNucleotide biosynthesisCell migration (moonlighting function)Ribosomal biogenesis (moonlighting function)Ion channel modulation (moonlighting function)
04
Disease associations
Neurological disordersCancerHepatic encephalopathyRenal dysfunction
05
Safety considerations
Dysregulation can lead to ammonia toxicityContext-dependent effects in cancer (both pro- and anti-tumorigenic)
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