The transaminase-ω-amidase pathway senses oxidative stress to control glutamine metabolism and α-ketoglutarate levels in endothelial cells

ABSTRACT: Oxidative stress is is a major driver of cardiovascular disease, however the fast changes in cellular metabolism caused by short-lived reactive oxygen species (ROS) remain ill-defined. Here, we characterised changes in the endothelial cell metabolome in response to acute oxidative challenges and identified novel redox-sensitive metabolic enzymes. H2O2 selectively increased the amount of α-ketoglutaramate (αKGM), a largely uncharacterized metabolite produced by glutamine transamination and an unrecognized intermediate of endothelial glutamine catabolism. In addition, H2O2 impaired catalytic activity of nitrilase-like 2 ω-amidase (NIT2), the enzyme that converts αKGM to α-ketoglutarate (αKG), by the reversible oxidation of specific cysteine residues. Moreover, a NIT2 gene variant exhibited d

SUBMITTER: Niklas Herrle 

PROVIDER: S-SCDT-10_1038-S44318-025-00642-7 | biostudies-other |

REPOSITORIES: biostudies-other