{"id":"c78dd43f-e0ae-5c9d-99bb-a3237958219f","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:mthfd1-formate-nuclear-carbon","predicate":"supplies","statement":"Nuclear MTHFD1 supplies formate-derived one-carbon units for thymidylate synthesis through its folate-interconversion activities.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"5104097d-40d4-52eb-a8a7-efe7880a7701","mechanism_event_label":"Formate can feed DNA-base production inside the nucleus.","subject":{"id":"ae1cf62b-2ef9-52d7-bbf6-6817abb50d98","slug":"mthfd1","display_name":"Human MTHFD1","entity_type_key":"protein"},"object":{"id":"0413b195-325e-5757-a72b-f445d65c17bc","slug":"5-10-methylenetetrahydrofolate","display_name":"5,10-Methylenetetrahydrofolate","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"5104097d-40d4-52eb-a8a7-efe7880a7701","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:mthfd1-formate-nuclear-carbon-event","event_type":"biochemical_relationship","label":"Formate can feed DNA-base production inside the nucleus.","description":"Nuclear MTHFD1 supplies formate-derived one-carbon units for thymidylate synthesis through its folate-interconversion activities.","status":"provisional","compartment":{"slug":"nucleus","display_name":"Nucleus"},"participants":[{"entity":{"id":"1fc1fa42-fcb5-5983-9a31-114703dc64c4","slug":"formate","display_name":"Formate","entity_type_key":"small_molecule"},"role":"carbon source","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d2b23343-c688-5fc3-9f42-bfac0050552b","slug":"tetrahydrofolate","display_name":"Tetrahydrofolate","entity_type_key":"small_molecule"},"role":"carbon acceptor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"58b974f1-d389-5bf6-81cd-889c44442c42","slug":"atp","display_name":"ATP","entity_type_key":"small_molecule"},"role":"energy substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"4aba2a5e-8d06-5304-bb01-c0402b225a94","slug":"nadph","display_name":"NADPH","entity_type_key":"small_molecule"},"role":"reducing cofactor","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"62cc6e56-d93e-54f5-9883-bd8ec32a9174","slug":"nuclear-dtmp-synthesis","display_name":"Nuclear de novo thymidylate synthesis","entity_type_key":"cellular_process"},"role":"downstream process","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"ae1cf62b-2ef9-52d7-bbf6-6817abb50d98","slug":"mthfd1","display_name":"Human MTHFD1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"0413b195-325e-5757-a72b-f445d65c17bc","slug":"5-10-methylenetetrahydrofolate","display_name":"5,10-Methylenetetrahydrofolate","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"ATP and NADPH support folate-mediated carbon use.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Localization and folate-pathway experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Assay conditions described in the linked primary study.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Compartmental flux varies with cell cycle.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"folate","display_name":"Folate (vitamin B9)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Formate can feed DNA-base production inside the nucleus.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[field-2014] Nuclear enrichment of folate cofactors and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) protect de novo thymidylate biosynthesis during folate deficiency (2014). https://pubmed.ncbi.nlm.nih.gov/25213861/ DOI: 10.1074/jbc.m114.599589","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HeLa and MCF7 cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"f571e205-1810-5906-90c1-d2dd8a7c8490","evidence_kind":"source_excerpt","locator":"Lines 936-947","start_line":936,"end_line":947,"excerpt":"### mthfd1-formate-nuclear-carbon\nNuclear MTHFD1 supplies formate-derived one-carbon units for thymidylate synthesis through its folate-interconversion activities.\nCondition category: normal\nnutrient_topic: Folate and folic acid research collection; 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Study references: [field-2014] Nuclear enrichment of folate cofactors and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) protect de novo thymidylate biosynthesis during folate deficiency (2014). https://pubmed.ncbi.nlm.nih.gov/25213861/ DOI: 10.1074/jbc.m114.599589","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"f4ce1a62-9582-5f7a-84f5-a23d0e1bfc68","stable_key":"import-ec174d5a-4903-5745-8646-df0e9d4265e8","title":"Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"e564d43989ece1006c95cd0748e9af6fe369074599a2eebba0a99ebff864b0dd","revision_id":"76674a33-b2a1-5e41-b71b-44399038ff7c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}