dc.contributor.author	Bayram, Șafak
dc.contributor.author	Razzaque, Yasmin Sophiya
dc.contributor.author	Geisberger, Sabrina
dc.contributor.author	Pietzke, Matthias
dc.contributor.author	Fürst, Susanne
dc.contributor.author	Vechiatto, Carolina
dc.contributor.author	Forbes, Martin
dc.contributor.author	Mastrobuoni, Guido
dc.contributor.author	Kempa, Stefan
dc.date.accessioned	2022-10-05T13:39:51Z
dc.date.available	2022-10-05T13:39:51Z
dc.date.issued	2022-08-12
dc.date.updated	2022-08-26T11:14:23Z
dc.description.abstract	Cellular glutamine synthesis is thought to be an important resistance factor in protecting cells from nutrient deprivation and may also contribute to drug resistance. The application of ‟targeted stable isotope resolved metabolomics” allowed to directly measure the activity of glutamine synthetase in the cell. With the help of this method, the fate of glutamine derived nitrogen within the biochemical network of the cells was traced. The application of stable isotope labelled substrates and analyses of isotope enrichment in metabolic intermediates allows the determination of metabolic activity and flux in biological systems. In our study we used stable isotope labelled substrates of glutamine synthetase to demonstrate its role in the starvation response of cancer cells. We applied 13C labelled glutamate and 15N labelled ammonium and determined the enrichment of both isotopes in glutamine and nucleotide species. Our results show that the metabolic compensatory pathways to overcome glutamine depletion depend on the ability to synthesise glutamine via glutamine synthetase. We demonstrate that the application of dual-isotope tracing can be used to address specific reactions within the biochemical network directly. Our study highlights the potential of concurrent isotope tracing methods in medical research.
dc.identifier.eissn	2296-889X
dc.identifier.uri	https://depositonce.tu-berlin.de/handle/11303/17551
dc.identifier.uri	https://doi.org/10.14279/depositonce-16332
dc.language.iso	en
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/
dc.subject.ddc	540 Chemie und zugeordnete Wissenschaften	de
dc.subject.other	targeted stable isotope resolved metabolomics
dc.subject.other	GLUL
dc.subject.other	nucleotide biosynthesis
dc.subject.other	glutamine addiction
dc.subject.other	cancer metabolism
dc.subject.other	glutamine synthetase
dc.title	Investigating the role of GLUL as a survival factor in cellular adaptation to glutamine depletion via targeted stable isotope resolved metabolomics
dc.type	Article
dc.type.version	publishedVersion
dcterms.bibliographicCitation.articlenumber	859787
dcterms.bibliographicCitation.doi	10.3389/fmolb.2022.859787
dcterms.bibliographicCitation.journaltitle	Frontiers in Molecular Biosciences
dcterms.bibliographicCitation.originalpublishername	Frontiers
dcterms.bibliographicCitation.originalpublisherplace	Lausanne
dcterms.bibliographicCitation.volume	9
tub.accessrights.dnb	free
tub.affiliation	Fak. 2 Mathematik und Naturwissenschaften::Inst. Chemie::FG Theoretische Chemie - Quantenchemie
tub.publisher.universityorinstitution	Technische Universität Berlin

Investigating the role of GLUL as a survival factor in cellular adaptation to glutamine depletion via targeted stable isotope resolved metabolomics

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