PXD055885-1

PXD055885 is an original dataset announced via ProteomeXchange.

Title	The transaminase-ω-amidase pathway is a redox switch in glutamine metabolism that generates α-ketoglutarate
Description	Oxidative stress is caused by short-lived molecules and metabolic changes belong to the fastest cellular responses. Here we studied how the endothelial cell metabolome reacts to acute oxidative challenges (menadione or H2O2) to identify redox-sensitive metabolic enzymes. H2O2 selectively increased α-ketoglutaramate (αKGM), a largely uncharacterized metabolite produced by glutamine transamination and a yet unrecognized intermediate of endothelial glutamine catabolism. The enzyme nitrilase-like 2 ω-amidase (NIT2) converts αKGM to α-ketoglutarate (αKG). Reversible oxidation of specific cysteine in NIT2 by H2O2 inhibited its catalytic activity. Furthermore, a variant in the NIT2 gene that decreases its expression is associated with high plasma αKGM level in humans. Endothelial-specific knockout mice of NIT2 exhibited increased levels of αKGM and impaired angiogenesis. Knockout of NIT2 impaired endothelial cell proliferation and sprouting and induced senescence. In conclusion, we show that the glutamine transaminase-ω-amidase pathway is a metabolic switch in which NIT2 is the redox-sensitive enzyme. The pathway is modulated in humans and functionally important for endothelial glutamine metabolism.
HostingRepository	PRIDE
AnnounceDate	2025-09-22
AnnouncementXML	Submission_2025-09-22_15:22:51.057.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alfredo Cabrera-Orefice
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	N-ethylmaleimide derivatized cysteine; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-16 02:29:57	ID requested
⏵ 1	2025-09-22 15:22:51	announced

Dataset with its publication pending

submitter keyword: Glutamine metabolism

oxidative stress

ω-amidase

reactive oxygen species

endothelial cells

α-ketoglutarate

α-ketoglutaramate

salvage pathway

kynurenine aminotransferases

nitrilase

Flávia Rezende
contact affiliation	Junior Group leader Vascular Research Centre, Medicine Faculty Goethe-Universität, Theodor-Stern-Kai 7 60590 Frankfurt am Main, Germany
contact email	rezende@vrc.uni-franfurt.de
lab head
Alfredo Cabrera-Orefice
contact affiliation	Goethe University Frankfurt
contact email	alfredbiomed@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055885
     1. Label: PRIDE project
     2. Name: The transaminase-ω-amidase pathway is a redox switch in glutamine metabolism that generates α-ketoglutarate