GLS and GLS2 Glutaminase Isoenzymes in the Antioxidant System of Cancer Cells

A pathway frequently altered in cancer is glutaminolysis, whereby glutaminase (GA) catalyzes the main step as follows: the deamidation of glutamine to form glutamate and ammonium. There are two types of GA isozymes, named GLS and GLS2, which differ considerably in their expression patterns and can e...

Full description

Saved in:
Bibliographic Details
Published in:Antioxidants 2024-06, Vol.13 (6), p.745
Main Authors: De Los Santos-Jiménez, Juan, Campos-Sandoval, José A, Alonso, Francisco J, Márquez, Javier, Matés, José M
Format: Article
Language:English
Subjects:
Adenosine triphosphate
Amino acids
Antioxidants
Biosynthesis
Breast cancer
Cancer
Carboxylation
Cell activation
Cell proliferation
Cervical cancer
Dehydrogenases
Enzymes
Ferroptosis
Glutaminase
glutaminolysis
Glutathione
Homeostasis
Isoenzymes
Medical prognosis
Metabolic rate
metabolic reprogramming
Metabolism
Metabolites
Neuroblastoma
Oxidants
Oxidation
Polyamines
Review
Tumor suppressor genes
Tumors
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A pathway frequently altered in cancer is glutaminolysis, whereby glutaminase (GA) catalyzes the main step as follows: the deamidation of glutamine to form glutamate and ammonium. There are two types of GA isozymes, named GLS and GLS2, which differ considerably in their expression patterns and can even perform opposing roles in cancer. GLS correlates with tumor growth and proliferation, while GLS2 can function as a context-dependent tumor suppressor. However, both isoenzymes have been described as essential molecules handling oxidant stress because of their involvement in glutathione production. We reviewed the literature to highlight the critical roles of GLS and GLS2 in restraining ROS and regulating both cellular signaling and metabolic stress due to their function as indirect antioxidant enzymes, as well as by modulating both reductive carboxylation and ferroptosis. Blocking GA activity appears to be a potential strategy in the dual activation of ferroptosis and inhibition of cancer cell growth in a ROS-mediated mechanism.
ISSN:2076-3921
2076-3921
DOI:10.3390/antiox13060745