ArticleBiochimica et biophysica acta. Molecular basis of disease2019
Multi-omics studies in cellular models of methylmalonic acidemia and propionic acidemia reveal dysregulation of serine metabolism.
Article in Biochimica et biophysica acta. Molecular basis of disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 33 citations in OpenAlex.
- Exploration of Metabolic Alterations in Methylmalonic Acidemia across Distinct Genetic Backgrounds.ACS omega · 2026Article
- Serum Lipidome as a Predictor of Significant Liver Fibrosis in Patients with Severe Obesity Undergoing Bariatric Surgery.Obesity surgery · 2026Article
- Too Early to Tell? Balancing Diagnostic Accuracy of Newborn Screening for Propionic Acidemia Versus a Timely Referral.International journal of neonatal screening · 2025Article
- Renal phenotyping in a hypomorphic murine model of propionic aciduria reveals common pathomechanisms in organic acidurias.Scientific reports · 2024Article
- Propionic Acidemia, Methylmalonic Acidemia, and Cobalamin C Deficiency: Comparison of Untargeted Metabolomic Profiles.Metabolites · 2024Article
- Methylmalonic acidemia triggers lysosomal-autophagy dysfunctions.Cell & bioscience · 2024Article
- Acyl-CoA dehydrogenase substrate promiscuity: Challenges and opportunities for development of substrate reduction therapy in disorders of valine and isoleucine metabolism.Journal of inherited metabolic disease · 2023Article
- Pathophysiological mechanisms of complications associated with propionic acidemia.Pharmacology & therapeutics · 2023Review
- Plasma Metabolomic Profiling after Feeding Dried Distiller's Grains with Solubles in Different Cattle Breeds.International journal of molecular sciences · 2023Article
- A narrative review of metabolomics in the era of "-omics": integration into clinical practice for inborn errors of metabolism.Translational pediatrics · 2022Review
- SMAD4 Controls Cancer Cell Metabolism by Regulating Methylmalonic Aciduria Cobalamin Deficiency (cbl) B Type.Molecules and cells · 2022Article
- Biomarkers for drug development in propionic and methylmalonic acidemias.Journal of inherited metabolic disease · 2022Review
- The potential and limitations of intrahepatic cholangiocyte organoids to study inborn errors of metabolism.Journal of inherited metabolic disease · 2022Article
- Mitochondrial disease, mitophagy, and cellular distress in methylmalonic acidemia.Cellular and molecular life sciences : CMLS · 2021Review
- Metabolomics analysis of serum in pediatric nephrotic syndrome based on targeted and non-targeted platforms.Metabolomics : Official journal of the Metabolomic Society · 2021Article
- Proteomics Reveals that Methylmalonyl-CoA Mutase Modulates Cell Architecture and Increases Susceptibility to Stress.International journal of molecular sciences · 2020Article
- Biochemical and anaplerotic applications of in vitro models of propionic acidemia and methylmalonic acidemia using patient-derived primary hepatocytes.Molecular genetics and metabolism · 2020Article
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundMethylmalonic acidemia (MMA) and propionic acidemia (PA) are related disorders of mitochondrial propionate metabolism, caused by defects in methylmalonyl-CoA mutase (MUT) and propionyl-CoA carboxylase (PCC), respectively. These biochemical defects lead to a complex cascade of downstream metabolic abnormalities, and identification of these abnormal pathways has important implications for understanding disease pathophysiology. Using a multi-omics approach in cellular models of MMA and PA, we identified serine and thiol metabolism as important areas of metabolic dysregulation.
methodsWe performed global proteomic analysis of fibroblasts and untargeted metabolomics analysis of plasma from individuals with MMA to identify novel pathways of dysfunction. We probed these novel pathways in CRISPR-edited, MUT and PCCA null HEK293 cell lines via targeted metabolomics, gene expression analysis, and flux metabolomics tracing utilization of
resultsProteomic analysis of fibroblasts identified upregulation of multiple proteins involved in serine synthesis and thiol metabolism including: phosphoserine amino transferase (PSAT1), cystathionine beta synthase (CBS), and mercaptopyruvate sulfurtransferase (MPST). Metabolomics analysis of plasma revealed significantly increased levels of cystathionine and glutathione, central metabolites in thiol metabolism. CRISPR-edited MUT and PCCA HEK293 cells recapitulate primary defects of MMA and PA and have upregulation of transcripts associated with serine and thiol metabolism including PSAT1.
conclusionWe identified abnormal serine metabolism as a novel area of cellular dysfunction in MMA and PA, thus introducing a potential new target for therapeutic investigation.
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