GLS Gene — Glutaminase <table class="infobox infobox-gene">Symbol </td>Full Name </td>Chromosomal Location </td>NCBI Gene ID </td>OMIM ID </td>Ensembl ID </td>UniProt ID </td>Protein Size </td>Molecular Weight </td>BPTES </td>CB-839 </td>Compound 968 </td>DON (6-Diazo-5-oxo-L-norleucine) </td>
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GLS Gene — Glutaminase <table class="infobox infobox-gene">Symbol </td>Full Name </td>Chromosomal Location </td>NCBI Gene ID </td>OMIM ID </td>Ensembl ID </td>UniProt ID </td>Protein Size </td>Molecular Weight </td>BPTES </td>CB-839 </td>Compound 968 </td>DON (6-Diazo-5-oxo-L-norleucine) </td>
Introduction
Mermaid diagram (expand to render)
The GLS gene (Glutaminase) encodes the enzyme glutaminase, which catalyzes the hydrolysis of glutamine to glutamate. This reaction is crucial for brain metabolism, neurotransmitter synthesis, and cellular energy production. GLS is implicated in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS)[@curthoys1995].
Protein Structure GLS is a homotetrameric enzyme:
N-terminal Domain : Glutamine bindingCatalytic Domain : Hydrolysis reaction centerC-terminal Domain : Regulatory interactionsNAD+ Binding Site : Allosteric regulationKGA (Kidney-type Glutaminase) : Full-length, widely expressedGAC (Glutaminase C) : Truncated, highly expressed in brainLGA : Liver isoformNormal Function
Glutamine Hydrolysis : GLS converts glutamine to glutamateTricarboxylic Acid Cycle : Provides anaplerotic substrateGlutamate Pool Maintenance : Maintains neurotransmitter glutamateNeurotransmission
Glutamate Synthesis : Produces neurotransmitter glutamateGABA Synthesis : Glutamate is precursor for GABAAmmonia Detoxification : Part of nitrogen metabolismAnaplerosis : Supplies intermediates for TCA cycleAstrocyte Function : Critical for astrocyte metabolismNeuronal Support : Supports neuronal energy needsExpression Pattern GLS is expressed throughout the brain:
Astrocytes (highest expression)Neurons (moderate expression)Oligodendrocytes Brain regions : Cortex, hippocampus, basal ganglia, cerebellumExpression is cell-type specific and regulated by metabolic demand.
Disease Associations
Alzheimer's Disease
Glutamate Dysregulation : Altered glutaminase activity in AD brainExcitotoxicity : Contributes to glutamate-mediated toxicityEnergy Metabolism : Impaired brain glucose metabolismTherapeutic Target : GLS inhibitors being investigatedParkinson's Disease
Dopaminergic Neurons : Altered glutamate metabolism in SNcExcitotoxicity : Contributes to neuron deathMitochondrial Dysfunction : Links to energy deficitsAmyotrophic Lateral Sclerosis (ALS)
Motor Neuron Vulnerability : Elevated GLS in motor neuronsExcitotoxicity : Excess glutamate contributes to toxicityTherapeutic Potential : GLS inhibitors show promiseHuntington's Disease
Mutant Huntingtin : Alters glutaminase regulationMetabolic Dysfunction : Contributes to energy deficitsTherapeutic Targeting
Regulation GLS is regulated by:
Allosteric Activation : ADP, phosphate activateAllosteric Inhibition : Glutamate,product inhibitionTranscriptional Regulation : p53, c-MycPost-translational Modification : Phosphorylation, acetylationGLS connects multiple metabolic pathways:
Glutamine → Glutamate → TCA Cycle Glutamate → GABA (GABA shunt) Glutamine → Glutathione synthesis See Also
[Glutamate Signaling Pathway](/mechanisms/glutamate-signaling-pathway)
[Glutamate Receptor Signaling](/mechanisms/glutamate-receptor-signaling)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
[Energy Metabolism](/mechanisms/energy-metabolism)
[Excitotoxicity](/mechanisms/excitotoxicity)
External Links
[NCBI Gene: GLS](https://www.ncbi.nlm.nih.gov/gene/2744)
[UniProt: O94925](https://www.uniprot.org/uniprot/O94925)
[OMIM: 138280](https://www.omim.org/entry/138280)
[GeneCards: GLS](https://www.genecards.org/cgi-bin/carddisp.pl?gene=GLS)
References
[Curthoys NP, et al., Kidney-type glutaminase (1995) (1995)](https://pubmed.ncbi.nlm.nih.gov/7647979/)
[Yang C, et al., Glutaminase in neurodegenerative disease (2011) (2011)](https://pubmed.ncbi.nlm.nih.gov/21855433/)
[Thomas AG, et al., GLS inhibitors for therapeutic use (2014) (2014)](https://pubmed.ncbi.nlm.nih.gov/25010966/)
[Sattler R, et al., Glutaminase in ALS (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/29341231/)
Pathway Diagram The following diagram shows the key molecular relationships involving GLS - Glutaminase discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)
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