{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:56:37Z","timestamp":1792788997127,"version":"4.5.0"},"reference-count":117,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:00:00Z","timestamp":1790985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:00:00Z","timestamp":1790985600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Extremadura","id":[{"id":"https:\/\/ror.org\/0174shg90","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/0174shg90","id-type":"ROR","asserted-by":"publisher"}]},{"name":"European Union structural funds","id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Junta de Extremadura, Spain","award":["GR24138"],"award-info":[{"award-number":["GR24138"]}],"id":[{"id":"https:\/\/ror.org\/01df4mv68","id-type":"ROR","asserted-by":"crossref"}]},{"award":["GR24138"],"award-info":[{"award-number":["GR24138"]}],"id":[{"id":"https:\/\/ror.org\/01df4mv68","id-type":"ROR","asserted-by":"publisher"}]},{"name":"European Regional Development Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Triokinase\/FMN cyclase (TKFC) is a bifunctional enzyme that catalyzes both ATP-dependent triose phosphorylation and the formation of riboflavin 4\u2032,5\u2032-cyclic phosphate (cFMN) from FAD, thereby linking fructose and flavin metabolism through a single protein. Structural modeling supports a model of TKFC as a conformationally dynamic homodimer in which interacting K and L domains cooperate through composite intersubunit active sites to support both kinase and cyclase reactions. Beyond its classical role in fructose metabolism, TKFC has emerged as a determinant of fructose-derived carbon partitioning and has been implicated in nutrient sensing, oxidative stress adaptation, innate immunity, ferroptosis and several inherited human disorders. Recent biochemical and analytical studies have renewed interest in cFMN as a bona fide metabolite and provide evidence consistent with cFMN synthesis and degradation, while its physiological turnover remains to be established. Here, we review the historical development, structural organization, catalytic mechanisms and expanding biological functions of TKFC, highlighting its links with intermediary metabolism, cellular stress adaptation and human disease.<\/jats:p>","DOI":"10.3390\/biology15191764","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:00:22Z","timestamp":1791187222000},"page":"1764","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Triokinase\/FMN Cyclase: A Bifunctional Enzyme Linking Metabolism, Stress Responses and Disease"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6548-1402","authenticated-orcid":false,"given":"Jo\u00e3o Meireles","family":"Ribeiro","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Gen\u00e9tica, Facultad de Medicina y Ciencias de la Salud, Universidad de Extremadura, 06006 Badajoz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Mart\u00edn-Ruiz","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Gen\u00e9tica, Facultad de Medicina y Ciencias de la Salud, Universidad de Extremadura, 06006 Badajoz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0005-081X","authenticated-orcid":false,"given":"Jos\u00e9 Carlos","family":"Cameselle","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Gen\u00e9tica, Facultad de Medicina y Ciencias de la Salud, Universidad de Extremadura, 06006 Badajoz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1042\/bj3300881","article-title":"Enzymic formation of riboflavin 4\u2032,5\u2032-cyclic phosphate from FAD: Evidence for a specific low-Km FMN cyclase in rat liver","volume":"330","author":"Fraiz","year":"1998","journal-title":"Biochem. 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