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Glutaminase kidney isoform (GLS1)
- Target
- GLS1
- Molecular classification
- Enzyme
01
Overview
GLS1 is a mitochondrial enzyme that catalyzes the conversion of glutamine to glutamate and ammonia. It plays a critical role in renal glutamine catabolism, acid-base homeostasis, neurotransmitter regulation, and cellular energy metabolism, particularly in cancer cells exhibiting "glutamine addiction." It has two main isoforms: KGA and GAC. GLS1 is upregulated in many cancers, making it a target for anti-cancer therapies. Inhibition impairs EC proliferation, migration and survival and increases sensitivity to oxidative stress. Selective inhibitors like CB-839 are being developed to block the enzyme's active site.
- Other names
- Kidney-type glutaminaseKGAGACMitochondrial glutaminase
02
Mechanism of action
Inhibition of glutamine conversion to glutamate
03
Biological functions
Renal catabolism of glutamineMaintenance of acid-base homeostasisRegulation of neurotransmitter levelsCellular energy metabolismCellular amino acid biosynthesisNitrogen compound metabolismGlutamate biosynthetic processGlutamine catabolic processNeurotransmitter secretionSynaptic transmissionGene expression regulationProtein homotetramerizationSmall molecule metabolismRespiratory gaseous exchange by neurological systemsSuckling behaviorTranscription initiation from RNA polymerase II promoter
04
Disease associations
CancerVascular diseasesAcidosisAbnormal angiogenesis disorders
05
Safety considerations
Potential for disrupting normal glutamine metabolismImpact on acid-base balance
06
Interacting drugs
CB-839
07
Biomarkers
Expression levels in certain cancers
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