ArticleMolecules (Basel, Switzerland)2022
Exploratory Metabolomics Underscores the Folate Enzyme ALDH1L1 as a Regulator of Glycine and Methylation Reactions.
Article in Molecules (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- Tissue-Specific Transcriptomic Profiling of Vitamin-Dependent Mitochondrial Pathways in Female Buffalo.Cell biochemistry and biophysics · 2026Article
- ALDH1L1 suppresses the replication of porcine epidemic diarrhea virus by degrading viral nucleocapsid and envelope proteins.Journal of virology · 2026Article
- FLARE: Fine-grained Learning for Alignment of spectra-molecule REpresentation Enhances Metabolite Annotation.bioRxiv : the preprint server for biology · 2026Article
- Clinical implications of 10-formyltetrahydrofolate dehydrogenase expression in hormone receptor-positive breast cancer.Frontiers in oncology · 2026Article
- Polatuzumab vedotin and CD79B: A study of efficacy in R-CHOP-resistant diffuse large B-cell lymphoma.British journal of haematology · 2025Article
- Differential Expression of One-Carbon Pathway Enzyme ALDH1L1 Is Linked to Tumorigenicity of Low-Grade Bladder Cancer Cells Through Metabolic Reprogramming.Cancer medicine · 2025Article
- Probing the metabolic regulator and candidate tumor suppressor ALDH1L1 as a target for non-small cell lung cancer gene therapy.Molecular therapy. Oncology · 2025Article
- Untargeted Metabolomics Reveals Acylcarnitines as Major Metabolic Targets of Resveratrol in Breast Cancer Cells.Metabolites · 2025Article
- Disrupted mitochondrial morphology and function exacerbate inflammation in elderly-onset ulcerative colitis.Immunity & ageing : I & A · 2025Article
- An untargeted metabolomic analysis of acute AFB1 treatment in liver, breast, and lung cells.PloS one · 2025Article
- Untargeted Metabolomics Reveals Dysregulation of Glycine- and Serine-Coupled Metabolic Pathways in an ALDH1L1-Dependent Manner In Vivo.Metabolites · 2024Article
- Metabolomics Analysis Reveals Altered Metabolic Pathways and Response to Doxorubicin in Drug-Resistant Triple-Negative Breast Cancer Cells.Metabolites · 2023Article
- Metabolomics Analysis Reveals Novel Targets of Chemosensitizing Polyphenols and Omega-3 Polyunsaturated Fatty Acids in Triple Negative Breast Cancer Cells.International journal of molecular sciences · 2023Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Folate (vitamin B9) is involved in one-carbon transfer reactions and plays a significant role in nucleic acid synthesis and control of cellular proliferation, among other key cellular processes. It is now recognized that the role of folates in different stages of carcinogenesis is complex, and more research is needed to understand how folate reactions become dysregulated in cancers and the metabolic consequences that occur as a result. ALDH1L1 (cytosolic 10-formyltetrahydrofolate dehydrogenase), an enzyme of folate metabolism expressed in many tissues, is ubiquitously downregulated in cancers and is not expressed in cancer cell lines. The RT4 cell line (derived from papillary bladder cancer) which expresses high levels of ALDH1L1 represents an exception, providing an opportunity to explore the metabolic consequences of the loss of this enzyme. We have downregulated this protein in RT4 cells (shRNA driven knockdown or CRISPR driven knockout) and compared metabolomes of ALDH1L1-expressing and -deficient cells to determine if metabolic changes linked to the loss of this enzyme might provide proliferative and/or survival advantages for cancer cells. In this study, cell extracts were analyzed using Ultra High Performance Liquid Chromatography High Resolution Mass Spectrometry (UHPLC-HR-MS). A total of 13,339 signals were identified or annotated using an in-house library and public databases. Supervised and unsupervised multivariate analysis revealed metabolic differences between RT4 cells and ALDH1L1-deficient clones. Glycine (8-fold decrease) and metabolites derived from S-adenosylmethionine utilizing pathways were significantly decreased in the ALDH1L1-deficient clones, compared with RT4 cells. Other changes linked to ALDH1L1 downregulation include decreased levels of amino acids, Krebs cycle intermediates, and ribose-5-phosphate, and increased nicotinic acid. While the ALDH1L1-catalyzed reaction is directly linked to glycine biosynthesis and methyl group flux, its overall effect on cellular metabolism extends beyond immediate metabolic pathways controlled by this enzyme.
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