{"doi":"10.1126/science.abp9201","title":"Formaldehyde regulates <i>S</i> -adenosylmethionine biosynthesis and one-carbon metabolism","abstract":"One-carbon metabolism is an essential branch of cellular metabolism that intersects with epigenetic regulation. In this work, we show how formaldehyde (FA), a one-carbon unit derived from both endogenous sources and environmental exposure, regulates one-carbon metabolism by inhibiting the biosynthesis of S -adenosylmethionine (SAM), the major methyl donor in cells. FA reacts with privileged, hyperreactive cysteine sites in the proteome, including Cys120 in S-adenosylmethionine synthase isoform type-1 (MAT1A). FA exposure inhibited MAT1A activity and decreased SAM production with MAT-isoform specificity. A genetic mouse model of chronic FA overload showed a decrease n SAM and in methylation on selected histones and genes. Epigenetic and transcriptional regulation of Mat1a and related genes function as compensatory mechanisms for FA-dependent SAM depletion, revealing a biochemical feedback cycle between FA and SAM one-carbon units.","journal":"Science","year":2023,"id":317344,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":80,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9593,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":562106,"name":"Kevin J. Bruemmer","orcid":"0000-0003-3416-5615","position":1,"is_corresponding":false},{"id":562104,"name":"Joel D. W. Toh","orcid":"0000-0003-0253-2169","position":2,"is_corresponding":false},{"id":315412,"name":"Eva J. Ge","orcid":"0000-0002-9238-1466","position":3,"is_corresponding":false},{"id":1022684,"name":"Logan Tenney","orcid":"0000-0001-5723-0876","position":4,"is_corresponding":false},{"id":354119,"name":"Carl C. Ward","orcid":"0000-0002-1188-4839","position":5,"is_corresponding":false},{"id":417457,"name":"Felix A. Dingler","orcid":"0000-0002-6297-2986","position":6,"is_corresponding":false},{"id":1022685,"name":"Christopher L. Millington","orcid":"0009-0007-9219-0946","position":7,"is_corresponding":false},{"id":501340,"name":"Carlos A. García‐Prieto","orcid":"0000-0001-5021-6916","position":8,"is_corresponding":false},{"id":1023479,"name":"Mia C. Pulos-Holmes","orcid":null,"position":9,"is_corresponding":false},{"id":92026,"name":"Nicholas T. Ingolia","orcid":"0000-0002-3395-1545","position":10,"is_corresponding":false},{"id":1022686,"name":"Lucas B. Pontel","orcid":"0000-0001-8384-3422","position":11,"is_corresponding":false},{"id":279361,"name":"Manel Esteller","orcid":"0000-0003-4490-6093","position":12,"is_corresponding":false},{"id":1022687,"name":"Ketan J. Patel","orcid":"0000-0001-8641-5802","position":13,"is_corresponding":false},{"id":34058,"name":"Daniel K. Nomura","orcid":"0000-0003-1614-8360","position":14,"is_corresponding":false},{"id":240330,"name":"Christopher J. Chang","orcid":"0000-0001-5732-9497","position":15,"is_corresponding":false},{"id":1022683,"name":"Vanha N. Pham","orcid":"0000-0003-2200-9332","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T01:06:50.336418Z","pmid":"37917677","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}