학술논문
O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis
Document Type
article
Author
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
Source
Nature Communications, Vol 13, Iss 1, Pp 1-14 (2022)
Subject
Language
English
ISSN
2041-1723
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.