{"id":"0f8186cc-b016-539d-b20f-68f0b866fd9a","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-methylfolate-mthfr-retention","predicate":"stabilizes","statement":"Methyltetrahydrofolate slowed FAD loss from diluted Ala222Val MTHFR in the tested concentration series.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"7f8adba4-0fea-5929-9531-daab7a83830a","mechanism_event_label":"Folate product helped the variant retain FAD in vitro.","subject":{"id":"23f48782-478e-5f62-874a-31273c075fe7","slug":"5-methyltetrahydrofolate","display_name":"5-Methyltetrahydrofolate","entity_type_key":"small_molecule"},"object":{"id":"7dfc117d-3ae8-592f-b13f-d7b38798e043","slug":"mthfr-ala222val","display_name":"MTHFR Ala222Val protein","entity_type_key":"protein_state"},"evidence_count":1,"mechanism_event":{"id":"7f8adba4-0fea-5929-9531-daab7a83830a","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-methylfolate-mthfr-retention-event","event_type":"biochemical_relationship","label":"Folate product helped the variant retain FAD in vitro.","description":"Methyltetrahydrofolate slowed FAD loss from diluted Ala222Val MTHFR in the tested concentration series.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e2cd7179-f218-54e8-9ce9-7a836ae35fac","slug":"fad","display_name":"FAD","entity_type_key":"small_molecule"},"role":"retained cofactor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"7dfc117d-3ae8-592f-b13f-d7b38798e043","slug":"mthfr-ala222val","display_name":"MTHFR Ala222Val protein","entity_type_key":"protein_state"},"role":"tested enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"23f48782-478e-5f62-874a-31273c075fe7","slug":"5-methyltetrahydrofolate","display_name":"5-Methyltetrahydrofolate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"Folate binding can stabilize a B2-derived cofactor interaction.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Results: FAD loss; Figs 1-3","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Baculovirus-produced purified human wild-type, Ala222Val, Glu429Ala and double-mutant MTHFR; dilution/cofactor-release assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Purified-enzyme assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Protein-stability assay; clinical folate or riboflavin treatment effects were not tested here.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Riboflavin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"riboflavin","display_name":"Riboflavin (vitamin B2)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Folate product helped the variant retain FAD in vitro.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[yamada2001] Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. (2001). https://pubmed.ncbi.nlm.nih.gov/11742092/ DOI: 10.1073/pnas.261469998","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified recombinant enzyme; no intact tissue","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"2cce64df-236b-5a94-9582-63d3c4c21626","evidence_kind":"source_excerpt","locator":"Lines 1052-1064","start_line":1052,"end_line":1064,"excerpt":"### b2-methylfolate-mthfr-retention\nMethyltetrahydrofolate slowed FAD loss from diluted Ala222Val MTHFR in the tested concentration series.\nCondition category: machinery_impairment\nnutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Folate product helped the variant retain FAD in vitro.\norganism: Homo sapiens\ntissue_or_cell_type: Purified recombinant enzyme; no intact tissue\nexperimental_model: Baculovirus-produced purified human wild-type, Ala222Val, Glu429Ala and double-mutant MTHFR; dilution/cofactor-release assays.\nlimitations: Protein-stability assay; clinical folate or riboflavin treatment effects were not tested here.\nexposure: Purified-enzyme assay\ncross_nutrient: Folate binding can stabilize a B2-derived cofactor interaction.\nevidence_location: Results: FAD loss; Figs 1-3\n[yamada2001] Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. 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