{"id":"aa11fcad-14b9-5a80-8dc8-5f35e60d15f7","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:mthfd2-nadp-polyglutamate","predicate":"reduces","statement":"Human MTHFD2 also uses NADP+ with methylene-THF pentaglutamate; NADP-linked activity increases relative to the monoglutamate assay.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"7787555d-475c-5666-b552-d6ffa94677af","mechanism_event_label":"The folate tail affects which electron carrier the enzyme uses.","subject":{"id":"7eb553fe-bf57-5b72-a56f-4fef4bee90d0","slug":"mthfd2","display_name":"Human MTHFD2","entity_type_key":"protein"},"object":{"id":"be6e4670-953f-5a4e-97da-1e536a54e0e4","slug":"nadp-plus","display_name":"NADP+","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"7787555d-475c-5666-b552-d6ffa94677af","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:mthfd2-nadp-polyglutamate-event","event_type":"biochemical_relationship","label":"The folate tail affects which electron carrier the enzyme uses.","description":"Human MTHFD2 also uses NADP+ with methylene-THF pentaglutamate; NADP-linked activity increases relative to the monoglutamate assay.","status":"provisional","compartment":{"slug":"mitochondrial-matrix","display_name":"Mitochondrial matrix"},"participants":[{"entity":{"id":"4aba2a5e-8d06-5304-bb01-c0402b225a94","slug":"nadph","display_name":"NADPH","entity_type_key":"small_molecule"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0413b195-325e-5757-a72b-f445d65c17bc","slug":"5-10-methylenetetrahydrofolate","display_name":"5,10-Methylenetetrahydrofolate","entity_type_key":"small_molecule"},"role":"substrate family","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7eb553fe-bf57-5b72-a56f-4fef4bee90d0","slug":"mthfd2","display_name":"Human MTHFD2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"be6e4670-953f-5a4e-97da-1e536a54e0e4","slug":"nadp-plus","display_name":"NADP+","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Folate polyglutamylation changes nicotinamide-cofactor use.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified recombinant enzyme","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Mono- versus pentaglutamate folate substrates; controlled NAD(P)+ assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Kinetics do not establish dominant in vivo NADPH production.","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":"The folate tail affects which electron carrier the enzyme uses.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[shin-2017] Human mitochondrial MTHFD2 is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase (2017). https://pubmed.ncbi.nlm.nih.gov/29225823/ DOI: 10.1186/s40170-017-0173-0","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cell-free","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"267a0be8-4fa3-50bd-9176-bccaaeb665d7","evidence_kind":"source_excerpt","locator":"Lines 825-836","start_line":825,"end_line":836,"excerpt":"### mthfd2-nadp-polyglutamate\nHuman MTHFD2 also uses NADP+ with methylene-THF pentaglutamate; NADP-linked activity increases relative to the monoglutamate assay.\nCondition category: normal\nnutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The folate tail affects which electron carrier the enzyme uses.\norganism: Homo sapiens\ntissue_or_cell_type: Cell-free\nexperimental_model: Purified recombinant enzyme\nlimitations: Kinetics do not establish dominant in vivo NADPH production.\nexposure: Mono- versus pentaglutamate folate substrates; controlled NAD(P)+ assays.\ncross_nutrient: Folate polyglutamylation changes nicotinamide-cofactor use.\n[shin-2017] Human mitochondrial MTHFD2 is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase (2017). https://pubmed.ncbi.nlm.nih.gov/29225823/ DOI: 10.1186/s40170-017-0173-0","model_system":"Purified recombinant enzyme","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [shin-2017] Human mitochondrial MTHFD2 is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase (2017). https://pubmed.ncbi.nlm.nih.gov/29225823/ DOI: 10.1186/s40170-017-0173-0","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}