{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T22:28:19Z","timestamp":1787783299632,"version":"build-2784847793"},"reference-count":58,"publisher":"SAGE Publications","issue":"13-15","license":[{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants & Redox Signaling"],"published-print":{"date-parts":[[2024,5]]},"abstract":"\n Aims:<\/jats:title>\n \n To determine the role of the kynurenine (KYN) pathway in rhodoquinone (RQ) and\n de novo<\/jats:italic>\n NAD\n +<\/jats:sup>\n biosynthesis and whether NAD\n +<\/jats:sup>\n rescue pathways are essential in parasitic worms (helminths).\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n We demonstrate that RQ, the key electron transporter used by helminths under hypoxia, derives from the tryptophan (Trp) catabolism even in the presence of a minimal KYN pathway. We show that of the KYN pathway genes only the kynureninase and tryptophan\/indoleamine dioxygenases are essential for RQ biosynthesis. Metabolic labeling with Trp revealed that the lack of the formamidase and kynurenine monooxygenase genes did not preclude RQ biosynthesis in the flatworm\n Mesocestoides corti<\/jats:italic>\n . In contrast, a minimal KYN pathway prevented\n de novo<\/jats:italic>\n NAD\n +<\/jats:sup>\n biosynthesis, as revealed by metabolic labeling in\n M. corti<\/jats:italic>\n , which also lacks the 3-hydroxyanthranilate 3,4-dioxygenase gene. Our results indicate that most helminths depend solely on NAD\n +<\/jats:sup>\n rescue pathways, and some lineages rely exclusively on the nicotinamide salvage pathway. Importantly, the inhibition of the NAD\n +<\/jats:sup>\n recycling enzyme nicotinamide phosphoribosyltransferase with FK866 led cultured\n M. corti<\/jats:italic>\n to death.\n <\/jats:p>\n <\/jats:sec>\n \n Innovation:<\/jats:title>\n \n We use comparative genomics of more than 100 hundred helminth genomes, metabolic labeling, HPLC-mass spectrometry targeted metabolomics, and enzyme inhibitors to define pathways that lead to RQ and NAD\n +<\/jats:sup>\n biosynthesis in helminths. We identified the essential enzymes of these pathways in helminth lineages, revealing new potential pharmacological targets for helminthiasis.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n \n Our results demonstrate that a minimal KYN pathway was evolutionary maintained for RQ and not for\n de novo<\/jats:italic>\n NAD\n +<\/jats:sup>\n biosynthesis in helminths and shed light on the essentiality of NAD\n +<\/jats:sup>\n rescue pathways in helminths.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1089\/ars.2023.0293","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T13:01:13Z","timestamp":1693227673000},"page":"737-750","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["A Minimal Kynurenine Pathway Was Preserved for Rhodoquinone but Not for\n De Novo<\/i>\n NAD\n +<\/sup>\n Biosynthesis in Parasitic Worms: The Essential Role of NAD\n +<\/sup>\n Rescue Pathways"],"prefix":"10.1177","volume":"40","author":[{"given":"Rosina","family":"Comas-Ghierra","sequence":"first","affiliation":[{"name":"Institut Pasteur de Montevideo, Montevideo, Uruguay."},{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Qu\u00edmica, Universidad de la Republica, Montevideo, Uruguay."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulkareem","family":"Alshaheeb","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Pennsylvania State University, Hershey, Pennsylvania, USA."},{"name":"The Pennsylvania State University-Huck Institutes of the Life Sciences, University Park, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie R.","family":"McReynolds","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Pennsylvania State University, Hershey, Pennsylvania, USA."},{"name":"The Pennsylvania State University-Huck Institutes of the Life Sciences, University Park, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer N.","family":"Shepherd","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Gonzaga University, Spokane, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3350-3002","authenticated-orcid":false,"given":"Gustavo","family":"Salinas","sequence":"additional","affiliation":[{"name":"Institut Pasteur de Montevideo, Montevideo, Uruguay."},{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Qu\u00edmica, Universidad de la Republica, Montevideo, Uruguay."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"key":"e_1_3_6_2_1","first-page":"339","volume-title":"Methods in Molecular Biology","author":"Adusumilli R","year":"2017","unstructured":"Adusumilli R, , Mallick P. 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