ArticleThe journal of histochemistry and cytochemistry : official journal of the Histochemistry Society2014
Determination of phosphate-activated glutaminase activity and its kinetics in mouse tissues using metabolic mapping (quantitative enzyme histochemistry).
Article in The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
- Illuminating spatial dynamics of glutamine metabolism with a sensitive genetically encoded biosensor.RSC chemical biology · 2026Article
- Illuminating spatial dynamics of glutamine metabolism with a sensitive genetically encoded biosensor.bioRxiv : the preprint server for biology · 2026Article
- Glutaminase Reprogramming in Hepatocellular Carcinoma: Implications for Diagnosis, Prognosis, and Potential as a Novel Therapeutic Target.International journal of molecular sciences · 2025Article
- siRNA micelleplexes-mediated glutamine metabolism re-engineering for vascular normalization-boosted photo-immunotherapy.Acta pharmaceutica Sinica. B · 2025Article
- Exploring the relationship between anastasis and mitochondrial ROS-mediated ferroptosis in metastatic chemoresistant cancers: a call for investigation.Frontiers in immunology · 2024Review
- Review
- Yarrowia lipolytica biomass-a potential additive to boost metabolic and physiological responses of Nile tilapia.Fish physiology and biochemistry · 2023Article
- Glial Glutamine Homeostasis in Health and Disease.Neurochemical research · 2023Review
- Learning and memory disorders related to hippocampal inflammation following exposure to air pollution.Journal of environmental health science & engineering · 2021Article
- Disturbance of the Glutamate-Glutamine Cycle, Secondary to Hepatic Damage, Compromises Memory Function.Frontiers in neuroscience · 2021Review
- Inhibition of the MYC-Regulated Glutaminase Metabolic Axis Is an Effective Synthetic Lethal Approach for Treating Chemoresistant Ovarian Cancers.Cancer research · 2020Article
- A powerful drug combination strategy targeting glutamine addiction for the treatment of human liver cancer.eLife · 2020Article
- Review
- Dysregulation of metabolic enzymes in tumor and stromal cells: Role in oncogenesis and therapeutic opportunities.Cancer letters · 2020Review
- Targeting Glutamine Addiction in Gliomas.Cancers · 2020Review
- Increased Glutaminolysis Marks Active Scarring in Nonalcoholic Steatohepatitis Progression.Cellular and molecular gastroenterology and hepatology · 2020Article
- Glutaminase 1 Regulates Neuroinflammation After Cerebral Ischemia Through Enhancing Microglial Activation and Pro-Inflammatory Exosome Release.Frontiers in immunology · 2020Article
- Altered Glutaminase 1 Activity During Neurulation and Its Potential Implications in Neural Tube Defects.Frontiers in pharmacology · 2020Article
- High Levels of Glutaminase II Pathway Enzymes in Normal and Cancerous Prostate Suggest a Role in 'Glutamine Addiction'.Biomolecules · 2019Article
- Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphate-activated glutaminase (PAG) converts glutamine to glutamate as part of the glutaminolysis pathway in mitochondria. Two genes, GLS1 and GLS2, which encode for kidney-type PAG and liver-type PAG, respectively, differ in their tissue-specific activities and kinetics. Tissue-specific PAG activity and its kinetics were determined by metabolic mapping using a tetrazolium salt and glutamate dehydrogenase as an auxiliary enzyme in the presence of various glutamine concentrations. In kidney and brain, PAG showed Michaelis-Menten kinetics with a K(m) of 0.6 mM glutamine and a V(max) of 1.1 µmol/mL/min when using 5 mM glutamine. PAG activity was high in the kidney cortex and inner medulla but low in the outer medulla, papillary tip, glomeruli and the lis of Henle. In brain tissue sections, PAG was active in the grey matter and inactive in myelin-rich regions. Liver PAG showed allosteric regulation with a K(m) of 11.6 mM glutamine and a V(max) of 0.5 µmol/mL/min when using 20 mM glutamine. The specificity of the method was shown after incubation of brain tissue sections with the PAG inhibitor 6-diazo-5-oxo-L-norleucine. PAG activity was decreased to 22% in the presence of 2 mM 6-diazo-5-oxo-L-norleucine. At low glutamine concentrations, PAG activity was higher in periportal regions, indicating a lower K(m) for periportal PAG. When compared with liver, kidney and brain, other tissues showed 3-fold to 6-fold less PAG activity. In conclusion, PAG is mainly active in mouse kidney, brain and liver, and shows different kinetics depending on which type of PAG is expressed.
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