{"id":"8c1580c6-10be-5d4f-add0-69e7ab13f03b","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-mtrr-mtr-reactivation","predicate":"reactivates","statement":"Reconstituted assays showed human MTRR sufficient to support NADPH-dependent activity of cobalamin-dependent methionine synthase.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"6b0015d7-dbcf-5056-a34a-9acbb87abc63","mechanism_event_label":"The flavin reductase helps restore an enzyme that uses B12 and methylfolate.","subject":{"id":"a0be0dca-5f6e-54a8-b760-e59a0658207d","slug":"mtrr","display_name":"Methionine synthase reductase / MTRR","entity_type_key":"protein"},"object":{"id":"91aa077a-bfee-574d-9e5f-28da25239196","slug":"mtr","display_name":"Cobalamin-dependent methionine synthase / MTR","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"6b0015d7-dbcf-5056-a34a-9acbb87abc63","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-mtrr-mtr-reactivation-event","event_type":"biochemical_relationship","label":"The flavin reductase helps restore an enzyme that uses B12 and methylfolate.","description":"Reconstituted assays showed human MTRR sufficient to support NADPH-dependent activity of cobalamin-dependent methionine synthase.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"4aba2a5e-8d06-5304-bb01-c0402b225a94","slug":"nadph","display_name":"NADPH","entity_type_key":"small_molecule"},"role":"electron donor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e2cd7179-f218-54e8-9ce9-7a836ae35fac","slug":"fad","display_name":"FAD","entity_type_key":"small_molecule"},"role":"MTRR cofactor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"d3eacf85-1a35-546d-bd30-161474dd9691","slug":"fmn","display_name":"Flavin mononucleotide","entity_type_key":"small_molecule"},"role":"MTRR cofactor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"6563fbad-ebdc-5408-966a-d24f8b8cd854","slug":"methylcobalamin","display_name":"Methylcobalamin","entity_type_key":"small_molecule"},"role":"active MTR cofactor form","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"23f48782-478e-5f62-874a-31273c075fe7","slug":"5-methyltetrahydrofolate","display_name":"5-Methyltetrahydrofolate","entity_type_key":"small_molecule"},"role":"MTR methyl donor","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"5b635b42-bc0d-5c54-aa94-9cf76cd0ed47","slug":"homocysteine","display_name":"Homocysteine","entity_type_key":"small_molecule"},"role":"MTR substrate","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"9d39f561-740b-5f67-bba7-8a72ef612a99","slug":"methionine","display_name":"L-Methionine","entity_type_key":"small_molecule"},"role":"MTR product","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""},{"entity":{"id":"a0be0dca-5f6e-54a8-b760-e59a0658207d","slug":"mtrr","display_name":"Methionine synthase reductase / MTRR","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":7,"notes":""},{"entity":{"id":"91aa077a-bfee-574d-9e5f-28da25239196","slug":"mtr","display_name":"Cobalamin-dependent methionine synthase / MTR","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":8,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"B2 flavins support reactivation of B12-dependent folate/homocysteine metabolism.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution.","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":"Reconstituted biochemistry; the accessible abstract identifies human MTRR but not the target MTR species. No dietary B2/B12 synergy was tested.","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":"The flavin reductase helps restore an enzyme that uses B12 and methylfolate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200","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}],"evidence":[{"id":"bc866602-631d-5e93-88d1-0a3276dacf6a","evidence_kind":"source_excerpt","locator":"Lines 1122-1134","start_line":1122,"end_line":1134,"excerpt":"### b2-mtrr-mtr-reactivation\nReconstituted assays showed human MTRR sufficient to support NADPH-dependent activity of cobalamin-dependent methionine synthase.\nCondition category: normal\nnutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The flavin reductase helps restore an enzyme that uses B12 and methylfolate.\norganism: Homo sapiens\ntissue_or_cell_type: Purified recombinant enzyme; no intact tissue\nexperimental_model: Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution.\nlimitations: Reconstituted biochemistry; the accessible abstract identifies human MTRR but not the target MTR species. No dietary B2/B12 synergy was tested.\nexposure: Purified-enzyme assay\ncross_nutrient: B2 flavins support reactivation of B12-dependent folate/homocysteine metabolism.\nevidence_location: Abstract\n[olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200","model_system":"Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. 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