{"id":"c7cc5e9e-7342-530d-82fe-cfad9017497e","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:mmab-r186q-fdx-system-fails","predicate":"fails-to-support-detectable","statement":"R186Q human MMAB showed no detectable adenosylcobalamin synthesis with FDX1/FDXR/NADPH, although a strong chemical reductant supported activity.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"98504597-9146-571d-aa20-1f13ed06246d","mechanism_event_label":"This MMAB variant failed in the ferredoxin assay; the result depended on the electron donor.","subject":{"id":"5fdf7edb-4e32-5f94-a882-03da3cdca0fc","slug":"mmab-r186q","display_name":"Human MMAB p.Arg186Gln","entity_type_key":"protein_state"},"object":{"id":"638f0feb-8d47-55fe-a790-df7386061b39","slug":"mmab-adenosylcobalamin-synthesis","display_name":"Human MMAB adenosylcobalamin synthesis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"98504597-9146-571d-aa20-1f13ed06246d","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:mmab-r186q-fdx-system-fails-event","event_type":"biochemical_relationship","label":"This MMAB variant failed in the ferredoxin assay; the result depended on the electron donor.","description":"R186Q human MMAB showed no detectable adenosylcobalamin synthesis with FDX1/FDXR/NADPH, although a strong chemical reductant supported activity.","status":"provisional","compartment":{"slug":"mitochondrial-matrix","display_name":"Mitochondrial matrix"},"participants":[{"entity":{"id":"34590b7b-744d-5654-8b8c-8dc447c667bf","slug":"fdx1","display_name":"Human adrenodoxin / FDX1","entity_type_key":"protein"},"role":"electron-donor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"57304e14-8bdf-5490-a897-058461023f2e","slug":"fdxr","display_name":"Human ferredoxin reductase / FDXR","entity_type_key":"protein"},"role":"electron-transfer-partner","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"4aba2a5e-8d06-5304-bb01-c0402b225a94","slug":"nadph","display_name":"NADPH","entity_type_key":"small_molecule"},"role":"reducing-equivalent-source","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"07657685-74aa-5d99-8625-0f6a3b521f07","slug":"adenosylcobalamin","display_name":"5'-Deoxyadenosylcobalamin","entity_type_key":"small_molecule"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"5fdf7edb-4e32-5f94-a882-03da3cdca0fc","slug":"mmab-r186q","display_name":"Human MMAB p.Arg186Gln","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"638f0feb-8d47-55fe-a790-df7386061b39","slug":"mmab-adenosylcobalamin-synthesis","display_name":"Human MMAB adenosylcobalamin synthesis","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"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":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Abstract and indexed primary Results, Figure 3","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified human MMAB R186Q","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"R186Q variant; FDX1/FDXR/NADPH versus titanium(III)citrate","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Detection-limited in-vitro activity; not proof of zero activity in every tissue.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This MMAB variant failed in the ferredoxin assay; the result depended on the electron donor.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[gouda-2023-mmab-redox] Coordination Chemistry Controls Coenzyme B12 Synthesis by Human Adenosine Triphosphate:Cob(I)alamin Adenosyltransferase. (2023). https://pubmed.ncbi.nlm.nih.gov/37526260/ DOI: 10.1021/acs.inorgchem.3c02163","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified protein assay","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":"6b9349a4-487d-5488-9d04-96da61168eb4","evidence_kind":"source_excerpt","locator":"Lines 1019-1031","start_line":1019,"end_line":1031,"excerpt":"### mmab-r186q-fdx-system-fails\nR186Q human MMAB showed no detectable adenosylcobalamin synthesis with FDX1/FDXR/NADPH, although a strong chemical reductant supported activity.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This MMAB variant failed in the ferredoxin assay; the result depended on the electron donor.\norganism: Homo sapiens\ntissue_or_cell_type: Purified protein assay\nexperimental_model: Purified human MMAB R186Q\nlimitations: Detection-limited in-vitro activity; not proof of zero activity in every tissue.\nexposure: R186Q variant; FDX1/FDXR/NADPH versus titanium(III)citrate\ncross_nutrient: true\nevidence_location: Abstract and indexed primary Results, Figure 3\n[gouda-2023-mmab-redox] Coordination Chemistry Controls Coenzyme B12 Synthesis by Human Adenosine Triphosphate:Cob(I)alamin Adenosyltransferase. (2023). https://pubmed.ncbi.nlm.nih.gov/37526260/ DOI: 10.1021/acs.inorgchem.3c02163","model_system":"Purified human MMAB R186Q","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [gouda-2023-mmab-redox] Coordination Chemistry Controls Coenzyme B12 Synthesis by Human Adenosine Triphosphate:Cob(I)alamin Adenosyltransferase. (2023). https://pubmed.ncbi.nlm.nih.gov/37526260/ DOI: 10.1021/acs.inorgchem.3c02163","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"73145023-2982-5848-aff2-8d8875d6b9c5","stable_key":"import-7fc92b9e-9cbf-556e-8719-6b5244625250","title":"Vitamin B12: 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. 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