{"id":"bb240da2-b0bb-5adf-954c-586ef5b5a670","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:pcc-carboxylation-upstream-b12","predicate":"carboxylates","statement":"Human PCC supplies (S)-methylmalonyl-CoA by propionyl-CoA carboxylation upstream of the MCEE-MMUT sequence examined in fibroblast assays.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"e43d3fab-dde2-58cf-aba1-b66e14bf841e","mechanism_event_label":"Biotin-dependent PCC makes the precursor that must be rearranged before human MMUT can use B12 on it.","subject":{"id":"54eb0f2f-091c-54cd-b4a1-a528b994560a","slug":"human-propionyl-coa-carboxylase","display_name":"Human propionyl-CoA carboxylase / PCC","entity_type_key":"protein_complex"},"object":{"id":"69ac0570-94d8-59d8-85ef-7f67cf302d16","slug":"propionyl-coa","display_name":"Propionyl-CoA","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"e43d3fab-dde2-58cf-aba1-b66e14bf841e","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:pcc-carboxylation-upstream-b12-event","event_type":"biochemical_relationship","label":"Biotin-dependent PCC makes the precursor that must be rearranged before human MMUT can use B12 on it.","description":"Human PCC supplies (S)-methylmalonyl-CoA by propionyl-CoA carboxylation upstream of the MCEE-MMUT sequence examined in fibroblast assays.","status":"provisional","compartment":{"slug":"mitochondrial-matrix","display_name":"Mitochondrial matrix"},"participants":[{"entity":{"id":"37a8e96b-f95b-5ba7-a0bc-8ed3cfaf5fd8","slug":"biotin","display_name":"Biotin","entity_type_key":"small_molecule"},"role":"cofactor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"a70f19d8-f2d2-5951-9f48-7961317a14ea","slug":"s-methylmalonyl-coa","display_name":"(S)-Methylmalonyl-CoA","entity_type_key":"small_molecule"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"bfe643d7-840b-530f-81f1-e18fad48e79a","slug":"mcee","display_name":"Human methylmalonyl-CoA epimerase / MCEE","entity_type_key":"protein"},"role":"downstream-enzyme","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"8f690797-c976-5a5e-886e-dc49d1b17f5a","slug":"mmut","display_name":"Human methylmalonyl-CoA mutase / MMUT","entity_type_key":"protein"},"role":"downstream-enzyme","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"58b974f1-d389-5bf6-81cd-889c44442c42","slug":"atp","display_name":"ATP","entity_type_key":"small_molecule"},"role":"energy-substrate","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"54eb0f2f-091c-54cd-b4a1-a528b994560a","slug":"human-propionyl-coa-carboxylase","display_name":"Human propionyl-CoA carboxylase / PCC","entity_type_key":"protein_complex"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"69ac0570-94d8-59d8-85ef-7f67cf302d16","slug":"propionyl-coa","display_name":"Propionyl-CoA","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Indexed primary abstract; Full text Methods 2.6 and Results 3.6; Figure 5","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human fibroblast PCC and coupled-pathway assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Propionyl-CoA, ATP and bicarbonate in enzyme pathway","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Pathway assignment combines human PCC characterization with coupled assays; it is not a simultaneous dietary biotin/B12 intervention.","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":"Biotin-dependent PCC makes the precursor that must be rearranged before human MMUT can use B12 on it.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[hsia-1979-pcc] Human propionyl CoA carboxylase: some properties of the partially purified enzyme in fibroblasts from controls and patients with propionic acidemia. (1979). https://pubmed.ncbi.nlm.nih.gov/481943/ DOI: 10.1203/00006450-197906000-00005\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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Fibroblasts","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"4861192f-ac71-5ca7-8af3-67089cc1831b","evidence_kind":"source_excerpt","locator":"Lines 1159-1172","start_line":1159,"end_line":1172,"excerpt":"### pcc-carboxylation-upstream-b12\nHuman PCC supplies (S)-methylmalonyl-CoA by propionyl-CoA carboxylation upstream of the MCEE-MMUT sequence examined in fibroblast assays.\nCondition category: normal\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Biotin-dependent PCC makes the precursor that must be rearranged before human MMUT can use B12 on it.\norganism: Homo sapiens\ntissue_or_cell_type: Fibroblasts\nexperimental_model: Human fibroblast PCC and coupled-pathway assays\nlimitations: Pathway assignment combines human PCC characterization with coupled assays; it is not a simultaneous dietary biotin/B12 intervention.\nexposure: Propionyl-CoA, ATP and bicarbonate in enzyme pathway\ncross_nutrient: true\nevidence_location: Indexed primary abstract; Full text Methods 2.6 and Results 3.6; Figure 5\n[hsia-1979-pcc] Human propionyl CoA carboxylase: some properties of the partially purified enzyme in fibroblasts from controls and patients with propionic acidemia. (1979). https://pubmed.ncbi.nlm.nih.gov/481943/ DOI: 10.1203/00006450-197906000-00005\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":"Human fibroblast PCC and coupled-pathway assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [hsia-1979-pcc] Human propionyl CoA carboxylase: some properties of the partially purified enzyme in fibroblasts from controls and patients with propionic acidemia. (1979). https://pubmed.ncbi.nlm.nih.gov/481943/ DOI: 10.1203/00006450-197906000-00005; [heuberger-2019-mcee] Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency. 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