O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis
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...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
Published: |
Nature Portfolio
2022-09-01
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Series: | Nature Communications |
Online Access: | https://doi.org/10.1038/s41467-022-32904-x |
Summary: | 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. |
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ISSN: | 2041-1723 |