{"doi":"10.1002/anie.202005915","title":"Unexpected Acetylation of Endogenous Aliphatic Amines by Arylamine <i>N</i>‐Acetyltransferase NAT2","abstract":"<jats:title>Abstract</jats:title><jats:p><jats:italic>N</jats:italic>‐Acetyltransferases play critical roles in the deactivation and clearance of xenobiotics, including clinical drugs. NAT2 has been classified as an arylamine <jats:italic>N</jats:italic>‐acetyltransferase that mainly converts aromatic amines, hydroxylamines, and hydrazines. Herein, we demonstrate that the human arylamine <jats:italic>N</jats:italic>‐acetyltransferase NAT2 also acetylates aliphatic endogenous amines. Metabolomic analysis and chemical synthesis revealed increased intracellular concentrations of mono‐ and diacetylated spermidine in human cell lines expressing the rapid compared to the slow acetylator NAT2 phenotype. The regioselective <jats:italic>N</jats:italic><jats:sup>8</jats:sup>‐acetylation of monoacetylated spermidine by NAT2 answers the long‐standing question of the source of diacetylspermidine. We also identified selective acetylation of structurally diverse alkylamine‐containing drugs by NAT2, which may contribute to variations in patient responses. The results demonstrate a previously unknown functionality and potential regulatory role for NAT2, and we suggest that this enzyme should be considered for re‐classification.</jats:p>","journal":"Angewandte Chemie International Edition","year":2020,"id":14597,"datarank":1.3355466234255804,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"self_citation_contribution":0.519860385419959,"citation_network_contribution":0.8156862380056212,"self_endowment_contribution":0.519860385419959,"citer_contribution":0.8156862380056212,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":23,"citers_with_citation_signal":21,"citers_with_endowment":21,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":114616,"name":"Veronica Rendo","orcid":"0000-0002-2983-4020","position":1,"is_corresponding":false},{"id":114617,"name":"Mário S. P. Correia","orcid":"0000-0003-2125-4184","position":2,"is_corresponding":false},{"id":114618,"name":"Ingvar A. Bergdahl","orcid":"0000-0003-1227-6859","position":3,"is_corresponding":false},{"id":2229,"name":"Tobias Sjöblom","orcid":"0000-0001-6668-4140","position":4,"is_corresponding":false},{"id":114619,"name":"Daniel Globisch","orcid":"0000-0002-4526-5788","position":5,"is_corresponding":false},{"id":114615,"name":"Louis P. Conway","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32497306","pmcid":"PMC7497018","openalex_id":"https://openalex.org/W3033025794","authors":[],"funders":[{"funder_name":"Science for Life Laboratory","grant_id":"Start-up Grant","title":null},{"funder_name":"Vetenskapsrådet","grant_id":"2016-04423","title":null},{"funder_name":"Vetenskapsrådet","grant_id":"VR 2017-00650","title":null},{"funder_name":"Vetenskapsrådet","grant_id":"VR 2016-01890","title":null},{"funder_name":"Carl Tryggers Stiftelse för Vetenskaplig Forskning","grant_id":"CTS 2016:155","title":null},{"funder_name":"Carl Tryggers Stiftelse för Vetenskaplig Forskning","grant_id":"CTS 2018:820","title":null},{"funder_name":"Cancerfonden","grant_id":"CAN 2018/772","title":null},{"funder_name":"Swedish Research Council","grant_id":"unidentified","title":"unidentified"}],"total_grants":8,"fwci":1.5003,"citation_percentile":0.8223961,"influential_citations":1,"citation_trend":[{"year":2020,"count":3},{"year":2021,"count":7},{"year":2022,"count":5},{"year":2023,"count":3},{"year":2024,"count":5},{"year":2025,"count":4},{"year":2026,"count":4}],"oa_status":"hybrid","license":"cc-by-nc","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/anie.202005915","host_type":"journal"},{"url":"https://umu.diva-portal.org/smash/get/diva2:1455418/FULLTEXT02","host_type":"GREEN"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/anie.202005915","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fanie.202005915","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.202005915","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/anie.202005915","host_type":"publisher"},{"url":"https://doi.org/10.1002/anie.202005915","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32497306","host_type":"repository"},{"url":"http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-173696","host_type":"repository"},{"url":"http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-439944","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7497018","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7497018","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7497018?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1002/ange.202005915","host_type":""},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ange.202005915","host_type":""},{"url":"http://dx.doi.org/10.1002/anie.202005915","host_type":""},{"url":"https://dx.doi.org/10.1002/anie.202005915","host_type":""},{"url":"https://publications-affiliated.scilifelab.se/publication/9b558221d00b4b45ad6db03f6f58941a","host_type":""}],"fields_of_study":["Polyamine Metabolism and Applications","Epigenetics and DNA Methylation","Cannabis and Cannabinoid Research","Chemistry","Medicine","Acetylation","Amines","Arylamine N-Acetyltransferase","Cell Line, Tumor","Chromatography, Liquid","Genotype","Humans","Kinetics","Mass Spectrometry"],"mesh_terms":["Acetylation","Amines","Arylamine N-Acetyltransferase","Chromatography, Liquid","Genotype","Humans","Kinetics","Mass Spectrometry","Cell Line, Tumor"],"keywords":["Acetylation","Acetyltransferases","Acetyltransferase","Arylamine N-acetyltransferase","Spermidine","Endogeny","Biochemistry","Xenobiotic","Chemistry","Regioselectivity","Enzyme","Gene","Polyamines","Mass spectrometry","Drug metabolism","Metabolomics","N-acetyltransferases","Molekylärbiologi","Medicinska och farmaceutiska grundvetenskaper","Genotype","Biochemistry and Molecular Biology","Basic Medicine","Communications","Kinetics","Cell Line, Tumor","Humans","Amines","Biokemi","Molecular Biology","Biokemi och molekylärbiologi","Chromatography, Liquid"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-01T12:47:29.089566Z","pmid":null,"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":[]}