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TAMOHA incorporates a highly nucleophilic hydroxylamine that reacts quickly with electrophilic species upon tissue lysis, trapping them as stable derivatives that feature a tetraalkylammonium moiety whose constitutive charge and characteristic MS2 fragmentation fingerprint enable their highly sensitive detection. Using TAMOHA to survey the electrophilomes of E. coli,\u00a0C. elegans, and mice revealed several thousand electrophilic metabolites, most of which have not been characterized. We then demonstrate trapping of electrophilic metabolites with TAMOHA in the context of specific biochemical pathways, confirming previously proposed functions of two fatty acid metabolism enzymes, detecting formaldehyde production in mice, and providing new insights into the biosynthesis of ascaroside pheromones in C. elegans. We anticipate that use of TAMOHA for the profiling of electrophilic species will help clarify enzyme function and uncover previously elusive biochemical mechanisms in a wide range of biological systems.<\/jats:p>","DOI":"10.1021\/acschembio.6c00711","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:01:38Z","timestamp":1790978498000},"page":"2787-2799","source":"Crossref","is-referenced-by-count":0,"title":["Omics-Scale Capture of Electrophilic Metabolites"],"prefix":"10.1021","volume":"21","author":[{"given":"Allen F.","family":"Schroeder","sequence":"first","affiliation":[{"name":"Cornell University , , , ,","place":["Ithaca, New York, United States, 14853"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yu","sequence":"additional","affiliation":[{"name":"Cornell University , , , ,","place":["Ithaca, New York, United States, 14853"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Turk","sequence":"additional","affiliation":[{"name":"Cornell University , , , ,","place":["Ithaca, New York, United States, 14853"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2942-2357","authenticated-orcid":true,"given":"Henry H.","family":"Le","sequence":"additional","affiliation":[{"name":"Cornell University , , , ,","place":["Ithaca, New York, United States, 14853"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"LeClair","sequence":"additional","affiliation":[{"name":"Cornell University , , , ,","place":["Ithaca, New York, United States, 14853"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa A.","family":"Fontaine","sequence":"additional","affiliation":[{"name":"Cornell University , , , ,","place":["Ithaca, New York, United States, 14853"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas W.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Cornell University , , , ,","place":["Ithaca, New York, United States, 14853"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeideh","family":"Azad","sequence":"additional","affiliation":[{"name":"Cornell University , , , ,","place":["Ithaca, New York, United States, 14853"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher N.","family":"Parkhurst","sequence":"additional","affiliation":[{"name":"Weill Cornell Medicine , , , ,","place":["New York, New York, United States, 10065"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Pan","sequence":"additional","affiliation":[{"name":"Cornell University , , , ,","place":["Ithaca, New York, United States, 14853"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Artis","sequence":"additional","affiliation":[{"name":"Weill Cornell Medicine , , , ,","place":["New York, New York, United States, 10065"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Wang","sequence":"additional","affiliation":[{"name":"Cornell University , , , ,","place":["Ithaca, New York, United States, 14853"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4420-0237","authenticated-orcid":true,"given":"Frank C.","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Cornell University , , , ,","place":["Ithaca, New York, United States, 14853"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"issue":"8","key":"2026101523065082100_cit1","doi-asserted-by":"publisher","first-page":"2841","DOI":"10.1021\/jacs.7b11811","article-title":"Metabolomic \u201cDark Matter\u201d Dependent on Peroxisomal \u03b2-Oxidation in Caenorhabditis elegans","volume":"140","author":"Artyukhin","year":"2018","journal-title":"J. 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