Nature Communications (Sep 2022)
O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis
- Leandro R. Soria,
- Georgios Makris,
- Alfonso M. D’Alessio,
- Angela De Angelis,
- Iolanda Boffa,
- Veronica M. Pravata,
- Véronique Rüfenacht,
- Sergio Attanasio,
- Edoardo Nusco,
- Paola Arena,
- Andrew T. Ferenbach,
- Debora Paris,
- Paola Cuomo,
- Andrea Motta,
- Matthew Nitzahn,
- Gerald S. Lipshutz,
- Ainhoa Martínez-Pizarro,
- Eva Richard,
- Lourdes R. Desviat,
- Johannes Häberle,
- Daan M. F. van Aalten,
- Nicola Brunetti-Pierri
Affiliations
- Leandro R. Soria
- Telethon Institute of Genetics and Medicine
- Georgios Makris
- Division of Metabolism and Children’s Research Center, University Children’s Hospital
- Alfonso M. D’Alessio
- Telethon Institute of Genetics and Medicine
- Angela De Angelis
- Telethon Institute of Genetics and Medicine
- Iolanda Boffa
- Telethon Institute of Genetics and Medicine
- Veronica M. Pravata
- School of Life Sciences, University of Dundee
- Véronique Rüfenacht
- Division of Metabolism and Children’s Research Center, University Children’s Hospital
- Sergio Attanasio
- Telethon Institute of Genetics and Medicine
- Edoardo Nusco
- Telethon Institute of Genetics and Medicine
- Paola Arena
- Telethon Institute of Genetics and Medicine
- Andrew T. Ferenbach
- School of Life Sciences, University of Dundee
- Debora Paris
- Institute of Biomolecular Chemistry, National Research Council
- Paola Cuomo
- Institute of Biomolecular Chemistry, National Research Council
- Andrea Motta
- Institute of Biomolecular Chemistry, National Research Council
- Matthew Nitzahn
- Molecular Biology Institute, David Geffen School of Medicine at UCLA
- Gerald S. Lipshutz
- Molecular Biology Institute, David Geffen School of Medicine at UCLA
- Ainhoa Martínez-Pizarro
- Centro de Biología Molecular Severo Ochoa UAM-CSIC, CIBERER, IdiPaz, Universidad Autónoma
- Eva Richard
- Centro de Biología Molecular Severo Ochoa UAM-CSIC, CIBERER, IdiPaz, Universidad Autónoma
- Lourdes R. Desviat
- Centro de Biología Molecular Severo Ochoa UAM-CSIC, CIBERER, IdiPaz, Universidad Autónoma
- Johannes Häberle
- Division of Metabolism and Children’s Research Center, University Children’s Hospital
- Daan M. F. van Aalten
- School of Life Sciences, University of Dundee
- Nicola Brunetti-Pierri
- Telethon Institute of Genetics and Medicine
- DOI
- https://doi.org/10.1038/s41467-022-32904-x
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 14
Abstract
Hyperammonemia occurs in liver diseases affecting ureagenesis, and is life-threatening. Here, the authors show that liver UDP-GlcNAc is increased during hyperammonemia, leading to O-GlcNAcylation of the rate-limiting ureagenesis enzyme CPS1, that enhanced ureagenesis and ammonia detoxification. They also showed that pharmacological increase of protein O-GlcNAcylation reduces hyperammonemia in mouse models of liver disease.
