{"id":"c0f72c7c-e57e-5f47-9cb9-3395744f3f8e","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:mcee-i53r-reduces-coupled-activity","predicate":"reduces","statement":"Human MCEE I53R lacked measured activity in the coupled patient-fibroblast assay with overexpressed MMUT and added adenosylcobalamin.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"d99cdb31-b005-5564-a4e1-a63d21f345d6","mechanism_event_label":"Adding activated B12 did not make this defective epimerase work in the human-cell assay.","subject":{"id":"47599dae-eb96-5326-9929-6b66df74d6f6","slug":"mcee-i53r","display_name":"Human MCEE p.Ile53Arg","entity_type_key":"protein_state"},"object":{"id":"2a710212-284b-5cf4-8554-5905f9eea1ce","slug":"human-mcee-coupled-pathway-activity","display_name":"Human MCEE-dependent coupled propionyl-CoA pathway activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"d99cdb31-b005-5564-a4e1-a63d21f345d6","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:mcee-i53r-reduces-coupled-activity-event","event_type":"biochemical_relationship","label":"Adding activated B12 did not make this defective epimerase work in the human-cell assay.","description":"Human MCEE I53R lacked measured activity in the coupled patient-fibroblast assay with overexpressed MMUT and added adenosylcobalamin.","status":"provisional","compartment":{"slug":"mitochondrial-matrix","display_name":"Mitochondrial matrix"},"participants":[{"entity":{"id":"8f690797-c976-5a5e-886e-dc49d1b17f5a","slug":"mmut","display_name":"Human methylmalonyl-CoA mutase / MMUT","entity_type_key":"protein"},"role":"coupled-enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"07657685-74aa-5d99-8625-0f6a3b521f07","slug":"adenosylcobalamin","display_name":"5'-Deoxyadenosylcobalamin","entity_type_key":"small_molecule"},"role":"added-cofactor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"47599dae-eb96-5326-9929-6b66df74d6f6","slug":"mcee-i53r","display_name":"Human MCEE p.Ile53Arg","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"2a710212-284b-5cf4-8554-5905f9eea1ce","slug":"human-mcee-coupled-pathway-activity","display_name":"Human MCEE-dependent coupled propionyl-CoA pathway activity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"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":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Full text Methods 2.6 and Results 3.6; Figure 5","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"MCEE-null human fibroblasts expressing MCEE I53R","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"I53R expression; MMUT coexpression; 50 micromolar AdoCbl","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Overexpression assay; not a clinical test of B12 treatment.","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":"Adding activated B12 did not make this defective epimerase work in the human-cell assay.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[heuberger-2019-mcee] Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/30682498/ DOI: 10.1016/j.bbadis.2019.01.021","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Fibroblasts","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":"37cd5bd3-6914-5431-91cc-c96603edd28a","evidence_kind":"source_excerpt","locator":"Lines 1188-1200","start_line":1188,"end_line":1200,"excerpt":"### mcee-i53r-reduces-coupled-activity\nHuman MCEE I53R lacked measured activity in the coupled patient-fibroblast assay with overexpressed MMUT and added adenosylcobalamin.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Adding activated B12 did not make this defective epimerase work in the human-cell assay.\norganism: Homo sapiens\ntissue_or_cell_type: Fibroblasts\nexperimental_model: MCEE-null human fibroblasts expressing MCEE I53R\nlimitations: Overexpression assay; not a clinical test of B12 treatment.\nexposure: I53R expression; MMUT coexpression; 50 micromolar AdoCbl\ncross_nutrient: false\nevidence_location: Full text Methods 2.6 and Results 3.6; Figure 5\n[heuberger-2019-mcee] Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/30682498/ DOI: 10.1016/j.bbadis.2019.01.021","model_system":"MCEE-null human fibroblasts expressing MCEE I53R","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [heuberger-2019-mcee] Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/30682498/ DOI: 10.1016/j.bbadis.2019.01.021","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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