{"id":"b8020fb8-c583-53a8-a5e1-9b9e9efba9c9","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-mmad-mito-target-methylcobalamin","predicate":"decreased-formation-of","statement":"In cblD-MMA/HC fibroblasts, an MMADHC construct with improved mitochondrial targeting decreased methylcobalamin formation relative to the targeting comparator.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"af1ad81f-adb1-5949-9456-b1d93bd1efd2","mechanism_event_label":"Redirecting MMADHC toward mitochondria decreased production of this B12 cofactor.","subject":{"id":"a0f0d59b-5625-5c6b-bac7-25ba065768e6","slug":"mmadhc-enhanced-mitochondrial-targeting","display_name":"MMADHC with enhanced mitochondrial targeting sequence","entity_type_key":"protein_state"},"object":{"id":"6563fbad-ebdc-5408-966a-d24f8b8cd854","slug":"methylcobalamin","display_name":"Methylcobalamin","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"af1ad81f-adb1-5949-9456-b1d93bd1efd2","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-mmad-mito-target-methylcobalamin-event","event_type":"biochemical_relationship","label":"Redirecting MMADHC toward mitochondria decreased production of this B12 cofactor.","description":"In cblD-MMA/HC fibroblasts, an MMADHC construct with improved mitochondrial targeting decreased methylcobalamin formation relative to the targeting comparator.","status":"provisional","compartment":{"slug":"cytosol","display_name":"Cytosol"},"participants":[{"entity":{"id":"c0fe6bd6-68d8-5ab4-a062-e9f4c70f94a3","slug":"mmadhc","display_name":"Human MMADHC / cobalamin-trafficking protein CblD","entity_type_key":"protein"},"role":"trafficking protein","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f5bd4edd-4298-5985-976f-897fd415c3d5","slug":"mitochondria","display_name":"Mitochondria","entity_type_key":"organelle"},"role":"target compartment","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a0f0d59b-5625-5c6b-bac7-25ba065768e6","slug":"mmadhc-enhanced-mitochondrial-targeting","display_name":"MMADHC with enhanced mitochondrial targeting sequence","entity_type_key":"protein_state"},"role":"subject","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":"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":"Abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human cblD-MMA/HC fibroblast transfection","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Engineered mitochondrial leader sequence","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Abstract-level construct experiment; effect in isolated cblD-MMA lines depended on mutation and endogenous expression.","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":"Redirecting MMADHC toward mitochondria decreased production of this B12 cofactor.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[stucki-2012-mmad-routing] Molecular mechanisms leading to three different phenotypes in the cblD defect of intracellular cobalamin metabolism (2012). https://pubmed.ncbi.nlm.nih.gov/22156578/ DOI: 10.1093/hmg/ddr579","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Patient 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":"e8b32543-f160-5bcd-8e94-0565f8dbb3fd","evidence_kind":"source_excerpt","locator":"Lines 837-849","start_line":837,"end_line":849,"excerpt":"### b12-mmad-mito-target-methylcobalamin\nIn cblD-MMA/HC fibroblasts, an MMADHC construct with improved mitochondrial targeting decreased methylcobalamin formation relative to the targeting comparator.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Redirecting MMADHC toward mitochondria decreased production of this B12 cofactor.\norganism: Homo sapiens\ntissue_or_cell_type: Patient fibroblasts\nexperimental_model: Human cblD-MMA/HC fibroblast transfection\nlimitations: Abstract-level construct experiment; effect in isolated cblD-MMA lines depended on mutation and endogenous expression.\nexposure: Engineered mitochondrial leader sequence\ncross_nutrient: false\nevidence_location: Abstract\n[stucki-2012-mmad-routing] Molecular mechanisms leading to three different phenotypes in the cblD defect of intracellular cobalamin metabolism (2012). https://pubmed.ncbi.nlm.nih.gov/22156578/ DOI: 10.1093/hmg/ddr579","model_system":"Human cblD-MMA/HC fibroblast transfection","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [stucki-2012-mmad-routing] Molecular mechanisms leading to three different phenotypes in the cblD defect of intracellular cobalamin metabolism (2012). https://pubmed.ncbi.nlm.nih.gov/22156578/ DOI: 10.1093/hmg/ddr579","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. Not publisher full text.","file_path":"","sha256":"ad5b3a51d36e856aa7fdfd1cc23f690b094689bad87d28e1a621a54675a01c92","revision_id":"118bd616-0c13-549f-bfeb-bc439715b89c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}