Glutaminase is an important target that is often over expressed in neurodegenerative and lifestyle related diseases but few effective inhibitors of this enzyme have yet reached clinical trials. Ursolic acid (), betulinic acid () and oleanolic acid (), three pentacyclic triterpene acids, have been isolated from the leaves of L. Enzyme inhibition experiments demonstrated their inhibitory effects against glutaminase activity. Compound significantly inhibited the glutaminase activity with IC of 0.31 mM, stronger than the positive control 6-diazo-5-oxo-L-norleucine (DON) with IC of 0.57 mM. Compound may serve as a potential lead compound for the prevention and treatment of neurodegenerative diseases and lifestyle related diseases by targeting glutaminase. This is the first report on glutaminase inhibitory activities of - isolated from L.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1080/14786419.2021.1921766 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Controlling enzyme activity by mutagenesis and metal exchange to obtain crystal structures of stable substrate complexes of Class 3 l-asparaginase.
FEBS J
January 2025
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
Rhizobium etli is a nitrogen-fixing bacterium that encodes two l-asparaginases. The structure of the inducible R. etli asparaginase ReAV has been recently determined to reveal a protein with no similarity to known enzymes with l-asparaginase activity, but showing a curious resemblance to glutaminases and β-lactamases.
View Article and Find Full Text PDFInhibition of Glutamate-to-Glutathione Flux Promotes Tumor Antigen Presentation in Colorectal Cancer Cells.
Adv Sci (Weinh)
January 2025
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Colorectal cancer (CRC) cells display remarkable adaptability, orchestrating metabolic changes that confer growth advantages, pro-tumor microenvironment, and therapeutic resistance. One such metabolic change occurs in glutamine metabolism. Colorectal tumors with high glutaminase (GLS) expression exhibited reduced T cell infiltration and cytotoxicity, leading to poor clinical outcomes.
View Article and Find Full Text PDFDorsomedial Ventromedial Hypothalamic Nucleus Growth Hormone-Releasing Hormone Neuron Steroidogenic Factor-1 Gene Targets in Female Rat.
ASN Neuro
October 2024
School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA, USA.
The prospect that the ventromedial hypothalamic nucleus (VMN) transcription factor steroidogenic factor-1/NR5A1 (SF-1) may exert sex-dimorphic control of glucose counterregulation is unresolved. Recent studies in male rats show that SF-1 regulates transcription of co-expressed hypoglycemia-sensitive neurochemicals in dorsomedial VMN growth hormone-releasing hormone (Ghrh) neurons. Gene knockdown and laser-catapult-microdissection/single-cell multiplex qPCR techniques were used here in a female rat model to determine if SF-1 control of Ghrh neuron transmitter marker, energy sensor, and estrogen receptor (ER) variant mRNAs varies according to sex.
View Article and Find Full Text PDFRobustanic acid as a glutaminase and Na, K-ATPase inhibitor from leaves of .
Z Naturforsch C J Biosci
November 2024
Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Yasuda Women's University, Hiroshima 731-0153, Japan.
This study was to compare glutaminase and Na, K-ATPase inhibitory activities of 20 herbal extracts and investigate the isolation, structural elucidation and those inhibitory activities of three triterpenes from the selected extract of Labill. Three triterpenes, ursolic acid (), robustanic acid () and ursolic acid lactone (), were identified by analyzing their NMR and MS spectral data and comparison of these with reported data. The IC values of - and the control compound against glutaminase, 6-diazo-5-oxo-l-norleucine (DON), were 443 μM, 334 μM, 963 μM and 134 μM, respectively.
View Article and Find Full Text PDFSIRT4 Has an Anti-Cancer Role in Cervical Cancer by Inhibiting Glutamine Metabolism the MEK/ERK/C-Myc Axis.
Anticancer Res
July 2024
Women's Hospital, School of Medicine, Zhejiang University, Zhejiang, P.R. China
Background/aim: Glutamine metabolism is crucial in cell proliferation, aging, and apoptosis across various cancer types. Existing research indicates that Sirtuin 4 (SIRT4), primarily located in mitochondria, modulates this process. This study aimed to clarify the regulatory relationship between SIRT4 and glutamine metabolism in cervical cancer.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!