ArticleNature communications2022
O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 21 citations in OpenAlex.
- CPS1: a multipurpose mitochondrial enzyme, bile protein, acute liver injury biomarker, and cytokine.Gut · 2026Review
- Urea cycle dysregulation and arginine pathways in the pathogenesis of NAFLD and NASH (Review).International journal of molecular medicine · 2026Review
- Genetic ablation ofiScience · 2026Article
- Vascularized Liver-on-a-Microsphere Reveals Alanine-Glucose Metabolism-Driven Regulation of Liver Function and Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Role of Urea Cycle Functional Studies in Preclinical Research.Journal of inherited metabolic disease · 2026Review
- B cell TET2 recruits OGT for nuclear TET2 and H2B O-GlcNAcylation to drive AID and BLIMP-1 expression and maturation of the antibody response.Cell reports · 2026Article
- It's a Gas: Bioconjugation With Vapor-Phase Reagents.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Review
- Targeting CPS1 attenuates lung cancer metastasis by regulating EMT through an epigenetic mechanism.Theranostics · 2026Article
- Targeting UAP1 with rabeprazole: a novel repurposed therapeutic strategy for multiple myeloma.Frontiers in pharmacology · 2026Article
- O-GlcNAc as ammonia-induced glycosylation during the development of hyperammonemia.Journal of molecular histology · 2025Article
- Zscan4 as a Candidate Conveyor of Early Developmental Defects in O-GlcNAc Transferase Intellectual Disability.Molecular & cellular proteomics : MCP · 2025Article
- Real-Time Tracking of ASCT2-Mediated Glutamine Uptake in Living Tumors With a Bioorthogonal Bioluminescent Probe.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Short-term Physical Activity Reduces Metabolic-associated Steatohepatitis by Promoting the Degradation of Branched-chain Amino Acids in Skeletal Muscle.Journal of clinical and translational hepatology · 2025Article
- Establishment and Validation of a Risk Prediction Model for Sepsis-Associated Liver Injury in ICU Patients: A Retrospective Cohort Study.Infection and drug resistance · 2025Article
- ASS1 metabolically contributes to the nuclear and cytosolic p53-mediated DNA damage response.Nature metabolism · 2024Article
- Gasdermin-E-Dependent Non-Canonical Pyroptosis Promotes Drug-Induced Liver Failure by Promoting CPS1 deISGylation and Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Metabolomics and transcriptomics of embryonic livers reveal hypoxia adaptation of Tibetan chickens.BMC genomics · 2024Article
- Fructose overconsumption impairs hepatic manganese homeostasis and ammonia disposal.Nature communications · 2023Article
- Extracellular arginine availability modulates eIF2α O-GlcNAcylation and heme oxygenase 1 translation for cellular homeostasis.Journal of biomedical science · 2023Article
- Emerging Role of Protein O-GlcNAcylation in Liver Metabolism: Implications for Diabetes and NAFLD.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 5 countries.
Funding
Abstract
Life-threatening hyperammonemia occurs in both inherited and acquired liver diseases affecting ureagenesis, the main pathway for detoxification of neurotoxic ammonia in mammals. Protein O-GlcNAcylation is a reversible and nutrient-sensitive post-translational modification using as substrate UDP-GlcNAc, the end-product of hexosamine biosynthesis pathway. Here we show that increased liver UDP-GlcNAc during hyperammonemia increases protein O-GlcNAcylation and enhances ureagenesis. Mechanistically, O-GlcNAcylation on specific threonine residues increased the catalytic efficiency for ammonia of carbamoyl phosphate synthetase 1 (CPS1), the rate-limiting enzyme in ureagenesis. Pharmacological inhibition of O-GlcNAcase, the enzyme removing O-GlcNAc from proteins, resulted in clinically relevant reductions of systemic ammonia in both genetic (hypomorphic mouse model of propionic acidemia) and acquired (thioacetamide-induced acute liver failure) mouse models of liver diseases. In conclusion, by fine-tuned control of ammonia entry into ureagenesis, hepatic O-GlcNAcylation of CPS1 increases ammonia detoxification and is a novel target for therapy of hyperammonemia in both genetic and acquired diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.