ArticleCell metabolism2024
Serine synthesis via reversed SHMT2 activity drives glycine depletion and acetaminophen hepatotoxicity in MASLD.
Article in Cell metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 52 citations in OpenAlex.
- [Role of glutathione in regulating ferroptosis and cuproptosis in metabolic dysfunction-associated steatotic liver disease].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Evaluation of the Health Status of Largemouth Bass (Animals : an open access journal from MDPI · 2026Article
- Covalent Inhibition of SHMT2 by Gambogic Acid Induces Ferroptosis Through Mitochondrial Collapse in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hepatic p38γ exacerbates acetaminophen‑induced acute liver injury via PI3K/Akt‑dependent mechanisms.International journal of molecular medicine · 2026Article
- Glycine: The missing link between carbohydrate and xenobiotic metabolism in the maturing human hepatocyte.iScience · 2026Article
- CD59 drives diet-induced obesity and glucose intolerance, insulin resistance, and metabolic dysfunction-associated steatotic liver disease.npj metabolic health and disease · 2026Article
- Age-related GSS promoter methylation in BMSCs drives osteoporosis and the reversal by targeted GSH delivery.Bioactive materials · 2026Article
- Chronic Low-Dose Unsymmetrical Dimethylhydrazine Exposure in Rats: Multiorgan Mechanisms and Biomarker Identification.Journal of applied toxicology : JAT · 2026Article
- Western diet-induced MASH in PWK/PhJ mice identifies disruptions in amino acid and sphingolipid metabolism contributing to cardiac dysfunction.Nature communications · 2026Article
- Metabolic Pathways Linking Atherosclerotic Cardiovascular Disease With Metabolic Dysfunction-Associated Steatotic Liver Disease.Current atherosclerosis reports · 2026Review
- Blood Focused-Metabolomics and Transcriptomics Uncover Non-Linear Risk Association of Inadequate Dietary Choline Intake-Linked Metabolic Stress with MASLD Through Amino Acid Biomarkers,International journal of molecular sciences · 2026Article
- Novel Insights Into the Association Between Parkinson's Disease and Constipation: Role of SHMT2 as a Promising Biomarker.CNS neuroscience & therapeutics · 2026Article
- SHMT2 deficiency disrupts transcriptional regulation through homocysteine-mediated suppression of histone lactylation in Huntington's disease models.The Journal of clinical investigation · 2026Article
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- P5CS-coupled proline metabolism manipulates metabolic dysfunction-associated steatotic liver disease.Life metabolism · 2026Article
- Genetic variations interact with polybrominated diphenyl ether exposure to alter lipid homeostasis.Nature communications · 2026Article
- Sex-based multiomics analysis uncovers metabolic and molecular mediators linking MASH and atherosclerosis.JHEP reports : innovation in hepatology · 2026Article
- A step-by-step guide to performing cancer metabolism research using custom-made media.Life science alliance · 2026Article
- ACSL4-Mediated Ferroptosis and its Biological Functions and Potential Therapeutic Significance in Liver Diseases.Current pharmaceutical design · 2026Review
- Article
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Authors and funding
23 authors at 5 institutions in 2 countries.
Funding
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one-third of the global population. Understanding the metabolic pathways involved can provide insights into disease progression and treatment. Untargeted metabolomics of livers from mice with early-stage steatosis uncovered decreased methylated metabolites, suggesting altered one-carbon metabolism. The levels of glycine, a central component of one-carbon metabolism, were lower in mice with hepatic steatosis, consistent with clinical evidence. Stable-isotope tracing demonstrated that increased serine synthesis from glycine via reverse serine hydroxymethyltransferase (SHMT) is the underlying cause for decreased glycine in steatotic livers. Consequently, limited glycine availability in steatotic livers impaired glutathione synthesis under acetaminophen-induced oxidative stress, enhancing acute hepatotoxicity. Glycine supplementation or hepatocyte-specific ablation of the mitochondrial SHMT2 isoform in mice with hepatic steatosis mitigated acetaminophen-induced hepatotoxicity by supporting de novo glutathione synthesis. Thus, early metabolic changes in MASLD that limit glycine availability sensitize mice to xenobiotics even at the reversible stage of this disease.
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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.