{"id":"379c576f-d9c8-5579-8ad7-656ba1cf9bd4","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:mcee-epimerizes-methylmalonyl-coa","predicate":"interconverts","statement":"Human MCEE interconverts methylmalonyl-CoA epimers, supplying the (R) form for MMUT; MCEE expression increased coupled succinate production.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"d1f31c0c-05f5-563c-827c-f099a5ad3341","mechanism_event_label":"Human fibroblast assays showed why the epimerase step matters before the B12 enzyme.","subject":{"id":"bfe643d7-840b-530f-81f1-e18fad48e79a","slug":"mcee","display_name":"Human methylmalonyl-CoA epimerase / MCEE","entity_type_key":"protein"},"object":{"id":"a70f19d8-f2d2-5951-9f48-7961317a14ea","slug":"s-methylmalonyl-coa","display_name":"(S)-Methylmalonyl-CoA","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"d1f31c0c-05f5-563c-827c-f099a5ad3341","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:mcee-epimerizes-methylmalonyl-coa-event","event_type":"biochemical_relationship","label":"Human fibroblast assays showed why the epimerase step matters before the B12 enzyme.","description":"Human MCEE interconverts methylmalonyl-CoA epimers, supplying the (R) form for MMUT; MCEE expression increased coupled succinate production.","status":"provisional","compartment":{"slug":"mitochondrial-matrix","display_name":"Mitochondrial matrix"},"participants":[{"entity":{"id":"3a142dbd-fc69-58b9-bcc7-4fa1ffe14374","slug":"r-methylmalonyl-coa","display_name":"(R)-Methylmalonyl-CoA","entity_type_key":"small_molecule"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":0,"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":1,"notes":""},{"entity":{"id":"07657685-74aa-5d99-8625-0f6a3b521f07","slug":"adenosylcobalamin","display_name":"5'-Deoxyadenosylcobalamin","entity_type_key":"small_molecule"},"role":"mmut-cofactor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"1b7ace51-f2c3-583b-89ed-196fa96d2b0a","slug":"succinyl-coa","display_name":"Succinyl-CoA","entity_type_key":"small_molecule"},"role":"downstream-product","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"bfe643d7-840b-530f-81f1-e18fad48e79a","slug":"mcee","display_name":"Human methylmalonyl-CoA epimerase / MCEE","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"a70f19d8-f2d2-5951-9f48-7961317a14ea","slug":"s-methylmalonyl-coa","display_name":"(S)-Methylmalonyl-CoA","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"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":"Human fibroblast lysates overexpressing MCEE and/or MMUT","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Radiolabeled propionyl-CoA; MCEE/MMUT expression and AdoCbl","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Coupled labeled hydrolysis-product assay; MCEE being limiting here is not a universal in-vivo rate limitation.","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":"Human fibroblast assays showed why the epimerase step matters before the B12 enzyme.","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}],"evidence":[{"id":"3a583d59-6805-53fb-9287-338ac2aac2f7","evidence_kind":"source_excerpt","locator":"Lines 1174-1186","start_line":1174,"end_line":1186,"excerpt":"### mcee-epimerizes-methylmalonyl-coa\nHuman MCEE interconverts methylmalonyl-CoA epimers, supplying the (R) form for MMUT; MCEE expression increased coupled succinate production.\nCondition category: normal\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Human fibroblast assays showed why the epimerase step matters before the B12 enzyme.\norganism: Homo sapiens\ntissue_or_cell_type: Fibroblasts\nexperimental_model: Human fibroblast lysates overexpressing MCEE and/or MMUT\nlimitations: Coupled labeled hydrolysis-product assay; MCEE being limiting here is not a universal in-vivo rate limitation.\nexposure: Radiolabeled propionyl-CoA; MCEE/MMUT expression and 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. 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