The transaminase-ω-amidase pathway senses oxidative stress to control glutamine metabolism and α-ketoglutarate levels in endothelial cells
Oxidative stress 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 characterized changes in the endothelial cell metabolome in response to acute oxidative challenges and ident...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
February 2026
|
| In: |
The EMBO journal
Year: 2026, Jahrgang: 45, Heft: 3, Pages: 820-855 |
| ISSN: | 1460-2075 |
| DOI: | 10.1038/s44318-025-00642-7 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s44318-025-00642-7
|
| Verfasserangaben: | Niklas Herrle, Pedro F Malacarne, Timothy Warwick, Alfredo Cabrera-Orefice, Yiheng Chen, Maedeh Gheisari, Souradeep Chatterjee, Matthias S Leisegang, Tamim Sarakpi, Sarah Wionski, Melina Lopez, Carine Kader, Tom Teichmann, Maria-Kyriaki Drekolia, Ina Koch, Marcus Keßler, Sabine Klein, Frank Erhard Uschner, Jonel Trebicka, Steffen Brunst, Ewgenij Proschak, Stefan Günther, Mónica Rosas-Lemus, Nina Baumgarten, Stephan Klatt, Thimoteus Speer, Sofia-Iris Bibli, Marta Segarra, Amparo Acker-Palmer, Julian UG Wagner, Ilka Wittig, Stefanie Dimmeler, Marcel H Schulz, JB Richards, Ralf Gilsbach, Travis T Denton, Ingrid Fleming, Luciana Hannibal, Ralf P Brandes & Flávia Rezende |
MARC
| LEADER | 00000naa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1961771918 | ||
| 003 | DE-627 | ||
| 005 | 20260219105736.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 260219s2026 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s44318-025-00642-7 |2 doi | |
| 035 | |a (DE-627)1961771918 | ||
| 035 | |a (DE-599)KXP1961771918 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Herrle, Niklas |e VerfasserIn |0 (DE-588)1390716155 |0 (DE-627)196177335X |4 aut | |
| 245 | 1 | 4 | |a The transaminase-ω-amidase pathway senses oxidative stress to control glutamine metabolism and α-ketoglutarate levels in endothelial cells |c Niklas Herrle, Pedro F Malacarne, Timothy Warwick, Alfredo Cabrera-Orefice, Yiheng Chen, Maedeh Gheisari, Souradeep Chatterjee, Matthias S Leisegang, Tamim Sarakpi, Sarah Wionski, Melina Lopez, Carine Kader, Tom Teichmann, Maria-Kyriaki Drekolia, Ina Koch, Marcus Keßler, Sabine Klein, Frank Erhard Uschner, Jonel Trebicka, Steffen Brunst, Ewgenij Proschak, Stefan Günther, Mónica Rosas-Lemus, Nina Baumgarten, Stephan Klatt, Thimoteus Speer, Sofia-Iris Bibli, Marta Segarra, Amparo Acker-Palmer, Julian UG Wagner, Ilka Wittig, Stefanie Dimmeler, Marcel H Schulz, JB Richards, Ralf Gilsbach, Travis T Denton, Ingrid Fleming, Luciana Hannibal, Ralf P Brandes & Flávia Rezende |
| 246 | 3 | 3 | |a The transaminase-omega-amidase pathway senses oxidative stress to control glutamine metabolism and alpha-ketoglutarate levels in endothelial cells |
| 264 | 1 | |c February 2026 | |
| 300 | |b Illustrationen | ||
| 300 | |a 36 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Online veröffentlicht: 17. Dezember 2025 | ||
| 500 | |a Gesehen am 19.02.2026 | ||
| 520 | |a Oxidative stress 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 characterized 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 the 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 decreased expression in humans and was associated with increased plasma αKGM concentration. Endothelial-specific knockout of NIT2 in mice increased cellular αKGM levels and impaired angiogenesis. Further, NIT2 depletion impaired endothelial cell proliferation, sprouting, and induced senescence. In conclusion, we uncover NIT2 as a redox-sensitive enzyme of the glutamine transaminase-ω-amidase pathway that acts as a metabolic switch modulating endothelial glutamine metabolism in mice and humans. | ||
| 650 | 4 | |a Endothelial Cells | |
| 650 | 4 | |a Glutamine Metabolism | |
| 650 | 4 | |a Oxidative Stress | |
| 650 | 4 | |a α-Ketoglutaramate | |
| 650 | 4 | |a α-Ketoglutarate | |
| 700 | 1 | |a Malacarne, Pedro F. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Warwick, Timothy |e VerfasserIn |4 aut | |
| 700 | 1 | |a Cabrera-Orefice, Alfredo |e VerfasserIn |4 aut | |
| 700 | 1 | |a Chen, Yiheng |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gheisari, Maedeh |e VerfasserIn |4 aut | |
| 700 | 1 | |a Chatterjee, Souradeep |e VerfasserIn |4 aut | |
| 700 | 1 | |a Leisegang, Matthias S. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sarakpi, Tamim |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wionski, Sarah |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lopez, Melina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kader, Carine |e VerfasserIn |4 aut | |
| 700 | 1 | |a Teichmann, Tom |e VerfasserIn |4 aut | |
| 700 | 1 | |a Drekolia, Maria-Kyriaki |d 1996- |e VerfasserIn |0 (DE-588)1341527697 |0 (DE-627)190225743X |4 aut | |
| 700 | 1 | |a Koch, Ina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Keßler, Marcus |e VerfasserIn |4 aut | |
| 700 | 1 | |a Klein, Sabine |e VerfasserIn |4 aut | |
| 700 | 1 | |a Erhard Uschner, Frank |e VerfasserIn |4 aut | |
| 700 | 1 | |a Trebicka, Jonel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Brunst, Steffen |e VerfasserIn |4 aut | |
| 700 | 1 | |a Proschak, Ewgenij |e VerfasserIn |4 aut | |
| 700 | 1 | |a Günther, Stefan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rosas-Lemus, Mónica |e VerfasserIn |4 aut | |
| 700 | 1 | |a Baumgarten, Nina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Klatt, Stephan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Speer, Thimoteus |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bibli, Sofia-Iris |e VerfasserIn |0 (DE-588)1341529843 |0 (DE-627)1902258363 |4 aut | |
| 700 | 1 | |a Segarra, Marta |e VerfasserIn |4 aut | |
| 700 | 1 | |a Acker-Palmer, Amparo |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wagner, Julian U. G. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wittig, Ilka |e VerfasserIn |4 aut | |
| 700 | 1 | |a Dimmeler, Stefanie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schulz, Marcel H. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Richards, J. B. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gilsbach, Ralf |d 1973- |e VerfasserIn |0 (DE-588)131641638 |0 (DE-627)512037701 |0 (DE-576)298644193 |4 aut | |
| 700 | 1 | |a Denton, Travis T. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Fleming, Ingrid |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hannibal, Luciana |e VerfasserIn |4 aut | |
| 700 | 1 | |a Brandes, Ralf P. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rezende, Flávia |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |a European Molecular Biology Organization |t The EMBO journal |d [London] : Nature Publishing Group UK, 1982 |g 45(2026), 3 vom: Feb., Seite 820-855 |h Online-Ressource |w (DE-627)266022529 |w (DE-600)1467419-1 |w (DE-576)075961377 |x 1460-2075 |7 nnas |
| 773 | 1 | 8 | |g volume:45 |g year:2026 |g number:3 |g month:02 |g pages:820-855 |g extent:36 |a The transaminase-ω-amidase pathway senses oxidative stress to control glutamine metabolism and α-ketoglutarate levels in endothelial cells |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s44318-025-00642-7 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |7 0 |
| 951 | |a AR | ||
| 992 | |a 20260219 | ||
| 993 | |a Article | ||
| 994 | |a 2026 | ||
| 998 | |g 131641638 |a Gilsbach, Ralf |m 131641638:Gilsbach, Ralf |d 910000 |d 910100 |e 910000PG131641638 |e 910100PG131641638 |k 0/910000/ |k 1/910000/910100/ |p 35 | ||
| 998 | |g 1341529843 |a Bibli, Sofia-Iris |m 1341529843:Bibli, Sofia-Iris |d 60000 |d 65000 |e 60000PB1341529843 |e 65000PB1341529843 |k 0/60000/ |k 1/60000/65000/ |p 27 | ||
| 998 | |g 1341527697 |a Drekolia, Maria-Kyriaki |m 1341527697:Drekolia, Maria-Kyriaki |d 60000 |e 60000PD1341527697 |k 0/60000/ |p 14 | ||
| 999 | |a KXP-PPN1961771918 |e 4920238819 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"type":{"bibl":"article-journal","media":"Online-Ressource"},"language":["eng"],"titleAlt":[{"title":"The transaminase-omega-amidase pathway senses oxidative stress to control glutamine metabolism and alpha-ketoglutarate levels in endothelial cells"}],"physDesc":[{"extent":"36 S.","noteIll":"Illustrationen"}],"origin":[{"dateIssuedDisp":"February 2026","dateIssuedKey":"2026"}],"note":["Online veröffentlicht: 17. Dezember 2025","Gesehen am 19.02.2026"],"title":[{"title_sort":"transaminase-ω-amidase pathway senses oxidative stress to control glutamine metabolism and α-ketoglutarate levels in endothelial cells","title":"The transaminase-ω-amidase pathway senses oxidative stress to control glutamine metabolism and α-ketoglutarate levels in endothelial cells"}],"person":[{"role":"aut","given":"Niklas","family":"Herrle","display":"Herrle, Niklas"},{"given":"Pedro F.","role":"aut","family":"Malacarne","display":"Malacarne, Pedro F."},{"family":"Warwick","given":"Timothy","role":"aut","display":"Warwick, Timothy"},{"display":"Cabrera-Orefice, Alfredo","given":"Alfredo","role":"aut","family":"Cabrera-Orefice"},{"given":"Yiheng","role":"aut","family":"Chen","display":"Chen, Yiheng"},{"family":"Gheisari","given":"Maedeh","role":"aut","display":"Gheisari, Maedeh"},{"display":"Chatterjee, Souradeep","family":"Chatterjee","role":"aut","given":"Souradeep"},{"family":"Leisegang","role":"aut","given":"Matthias S.","display":"Leisegang, Matthias S."},{"display":"Sarakpi, Tamim","role":"aut","given":"Tamim","family":"Sarakpi"},{"role":"aut","given":"Sarah","family":"Wionski","display":"Wionski, Sarah"},{"display":"Lopez, Melina","family":"Lopez","given":"Melina","role":"aut"},{"family":"Kader","role":"aut","given":"Carine","display":"Kader, Carine"},{"display":"Teichmann, Tom","role":"aut","given":"Tom","family":"Teichmann"},{"display":"Drekolia, Maria-Kyriaki","role":"aut","given":"Maria-Kyriaki","family":"Drekolia"},{"display":"Koch, Ina","role":"aut","given":"Ina","family":"Koch"},{"role":"aut","given":"Marcus","family":"Keßler","display":"Keßler, Marcus"},{"display":"Klein, Sabine","given":"Sabine","role":"aut","family":"Klein"},{"family":"Erhard Uschner","role":"aut","given":"Frank","display":"Erhard Uschner, Frank"},{"display":"Trebicka, Jonel","family":"Trebicka","role":"aut","given":"Jonel"},{"role":"aut","given":"Steffen","family":"Brunst","display":"Brunst, Steffen"},{"role":"aut","given":"Ewgenij","family":"Proschak","display":"Proschak, Ewgenij"},{"given":"Stefan","role":"aut","family":"Günther","display":"Günther, Stefan"},{"display":"Rosas-Lemus, Mónica","family":"Rosas-Lemus","given":"Mónica","role":"aut"},{"display":"Baumgarten, Nina","role":"aut","given":"Nina","family":"Baumgarten"},{"display":"Klatt, Stephan","given":"Stephan","role":"aut","family":"Klatt"},{"family":"Speer","given":"Thimoteus","role":"aut","display":"Speer, Thimoteus"},{"display":"Bibli, Sofia-Iris","family":"Bibli","role":"aut","given":"Sofia-Iris"},{"display":"Segarra, Marta","role":"aut","given":"Marta","family":"Segarra"},{"display":"Acker-Palmer, Amparo","role":"aut","given":"Amparo","family":"Acker-Palmer"},{"display":"Wagner, Julian U. G.","family":"Wagner","role":"aut","given":"Julian U. G."},{"family":"Wittig","given":"Ilka","role":"aut","display":"Wittig, Ilka"},{"given":"Stefanie","role":"aut","family":"Dimmeler","display":"Dimmeler, Stefanie"},{"given":"Marcel H.","role":"aut","family":"Schulz","display":"Schulz, Marcel H."},{"display":"Richards, J. B.","family":"Richards","given":"J. B.","role":"aut"},{"role":"aut","given":"Ralf","family":"Gilsbach","display":"Gilsbach, Ralf"},{"display":"Denton, Travis T.","family":"Denton","given":"Travis T.","role":"aut"},{"display":"Fleming, Ingrid","family":"Fleming","given":"Ingrid","role":"aut"},{"given":"Luciana","role":"aut","family":"Hannibal","display":"Hannibal, Luciana"},{"display":"Brandes, Ralf P.","family":"Brandes","given":"Ralf P.","role":"aut"},{"family":"Rezende","role":"aut","given":"Flávia","display":"Rezende, Flávia"}],"relHost":[{"origin":[{"dateIssuedDisp":"1982-","publisher":"Nature Publishing Group UK ; EMBO Press ; Oxford Univ. Press ; Nature Publ. Group ; Wiley","publisherPlace":"[London] ; Heidelberg ; Oxford [u.a.] ; London [u.a.] ; Hoboken, NJ [u.a.]","dateIssuedKey":"1982"}],"disp":"European Molecular Biology OrganizationThe EMBO journal","note":["Gesehen am 18.02.2016","Fortsetzung der Druckausgabe"],"title":[{"title_sort":"EMBO journal","title":"The EMBO journal"}],"corporate":[{"role":"aut","display":"European Molecular Biology Organization"}],"language":["eng"],"titleAlt":[{"title":"The EMBO journal online"}],"type":{"bibl":"periodical","media":"Online-Ressource"},"physDesc":[{"extent":"Online-Ressource"}],"pubHistory":["1.1982 -"],"part":{"year":"2026","text":"45(2026), 3 vom: Feb., Seite 820-855","extent":"36","pages":"820-855","volume":"45","issue":"3"},"id":{"doi":["10.1002/(ISSN)1460-2075"],"issn":["1460-2075"],"eki":["266022529"],"zdb":["1467419-1"]},"recId":"266022529","name":{"displayForm":["publ. for the European Molecular Biology Organization"]}}],"recId":"1961771918","name":{"displayForm":["Niklas Herrle, Pedro F Malacarne, Timothy Warwick, Alfredo Cabrera-Orefice, Yiheng Chen, Maedeh Gheisari, Souradeep Chatterjee, Matthias S Leisegang, Tamim Sarakpi, Sarah Wionski, Melina Lopez, Carine Kader, Tom Teichmann, Maria-Kyriaki Drekolia, Ina Koch, Marcus Keßler, Sabine Klein, Frank Erhard Uschner, Jonel Trebicka, Steffen Brunst, Ewgenij Proschak, Stefan Günther, Mónica Rosas-Lemus, Nina Baumgarten, Stephan Klatt, Thimoteus Speer, Sofia-Iris Bibli, Marta Segarra, Amparo Acker-Palmer, Julian UG Wagner, Ilka Wittig, Stefanie Dimmeler, Marcel H Schulz, JB Richards, Ralf Gilsbach, Travis T Denton, Ingrid Fleming, Luciana Hannibal, Ralf P Brandes & Flávia Rezende"]},"id":{"doi":["10.1038/s44318-025-00642-7"],"eki":["1961771918"]}} | ||
| SRT | |a HERRLENIKLTRANSAMINA2026 | ||