{"id":"acf35be0-4107-5abb-a6f7-5e5501a19f32","stable_key":"3238e4f0-8d45-5c72-8624-6e9a8b20527c:ibu-equilibrium-favours-r","predicate":"modulates","statement":"The purified 2-arylpropionyl-CoA epimerases from rat liver cytosol and mitochondria are monomeric 42 kilodalton proteins distinct from methylmalonyl-CoA epimerase, show no bound cofactors and are unaffected by EDTA or metal ions except copper, and for 2-(4-isobutylphenyl)propionyl-CoA the equilibrium constant was estimated at 1.5 in favour of the R isomer, with evidence that proton exchange is mediated by a two-base mechanism and that an active-site carboxylic residue serves as a general base for proton abstraction.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"2ef69135-48f2-5783-b620-a0b29a96175d","mechanism_event_label":"Left to itself the enzyme slightly prefers the R form, which is the opposite of what happens in the body.","subject":{"id":"a5996d63-8ef0-5fbf-8357-b7cef59264c5","slug":"arylpropionyl-coa-epimerase","display_name":"2-arylpropionyl-CoA epimerase","entity_type_key":"protein"},"object":{"id":"69dce1aa-1cfe-5ce3-90f5-7332776d8904","slug":"chiral-inversion","display_name":"Metabolic chiral inversion of a 2-arylpropionic acid","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"2ef69135-48f2-5783-b620-a0b29a96175d","stable_key":"3238e4f0-8d45-5c72-8624-6e9a8b20527c:ibu-equilibrium-favours-r-event","event_type":"biochemical_relationship","label":"Left to itself the enzyme slightly prefers the R form, which is the opposite of what happens in the body.","description":"The purified 2-arylpropionyl-CoA epimerases from rat liver cytosol and mitochondria are monomeric 42 kilodalton proteins distinct from methylmalonyl-CoA epimerase, show no bound cofactors and are unaffected by EDTA or metal ions except copper, and for 2-(4-isobutylphenyl)propionyl-CoA the equilibrium constant was estimated at 1.5 in favour of the R isomer, with evidence that proton exchange is mediated by a two-base mechanism and that an active-site carboxylic residue serves as a general base for proton abstraction.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6b0d6dde-d70a-5bf4-b1a3-a606e219a68c","slug":"methylmalonyl-coa-epimerase","display_name":"Methylmalonyl-CoA epimerase","entity_type_key":"protein"},"role":"distinguished_enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c6720319-7f02-56a6-a435-abbc1b24c4ef","slug":"r-ibuprofenoyl-coa","display_name":"R-ibuprofenoyl-coenzyme A thioester","entity_type_key":"small_molecule"},"role":"favoured_at_equilibrium","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a5996d63-8ef0-5fbf-8357-b7cef59264c5","slug":"arylpropionyl-coa-epimerase","display_name":"2-arylpropionyl-CoA epimerase","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"69dce1aa-1cfe-5ce3-90f5-7332776d8904","slug":"chiral-inversion","display_name":"Metabolic chiral inversion of a 2-arylpropionic acid","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/ibuprofen-research/8381432.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9fab6c9ed036c30f7dbfa01fd8499243d7066dfb510489f189a07ac4811c8ff6\", \"start_char\": 0, \"end_char\": 1149, \"text_sha256\": \"9fab6c9ed036c30f7dbfa01fd8499243d7066dfb510489f189a07ac4811c8ff6\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purification and kinetic characterisation of 2-arylpropionyl-CoA epimerase from rat liver cytosol and mitochondria","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"2-(4-isobutylphenyl)propionyl-CoA and related thioesters","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Characterises the enzyme as a distinct protein and measures the equilibrium. Purified enzyme, so the equilibrium constant is a property of the epimerase and not of the intact animal.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers.","comparator":null,"unit":null,"notes":"","entity":{"slug":"ibuprofen","display_name":"Ibuprofen","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Rat","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Left to itself the enzyme slightly prefers the R form, which is the opposite of what happens in the body.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ibu-p8381432] Purification and characterization of novel \"2-arylpropionyl-CoA epimerases\" from rat liver cytosol and mitochondria. (1993). https://pubmed.ncbi.nlm.nih.gov/8381432/ DOI: 10.1016/s0021-9258(18)53720-0","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Liver cytosol and mitochondria","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"7d6519d2-4268-59f8-a757-acb3d0c90f30","evidence_kind":"source_excerpt","locator":"Lines 136-147","start_line":136,"end_line":147,"excerpt":"### ibu-equilibrium-favours-r\nThe purified 2-arylpropionyl-CoA epimerases from rat liver cytosol and mitochondria are monomeric 42 kilodalton proteins distinct from methylmalonyl-CoA epimerase, show no bound cofactors and are unaffected by EDTA or metal ions except copper, and for 2-(4-isobutylphenyl)propionyl-CoA the equilibrium constant was estimated at 1.5 in favour of the R isomer, with evidence that proton exchange is mediated by a two-base mechanism and that an active-site carboxylic residue serves as a general base for proton abstraction.\nCondition category: normal\nnutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers.\nplain_language: Left to itself the enzyme slightly prefers the R form, which is the opposite of what happens in the body.\norganism: Rat\ntissue_or_cell_type: Liver cytosol and mitochondria\nexperimental_model: Purification and kinetic characterisation of 2-arylpropionyl-CoA epimerase from rat liver cytosol and mitochondria\nlimitations: Characterises the enzyme as a distinct protein and measures the equilibrium. Purified enzyme, so the equilibrium constant is a property of the epimerase and not of the intact animal.\nexposure: 2-(4-isobutylphenyl)propionyl-CoA and related thioesters\nevidence_span: {\"source_cache\": \"artifacts/ibuprofen-research/8381432.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9fab6c9ed036c30f7dbfa01fd8499243d7066dfb510489f189a07ac4811c8ff6\", \"start_char\": 0, \"end_char\": 1149, \"text_sha256\": \"9fab6c9ed036c30f7dbfa01fd8499243d7066dfb510489f189a07ac4811c8ff6\"}\n[ibu-p8381432] Purification and characterization of novel \"2-arylpropionyl-CoA epimerases\" from rat liver cytosol and mitochondria. (1993). https://pubmed.ncbi.nlm.nih.gov/8381432/ DOI: 10.1016/s0021-9258(18)53720-0","model_system":"Purification and kinetic characterisation of 2-arylpropionyl-CoA epimerase from rat liver cytosol and mitochondria","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ibu-p8381432] Purification and characterization of novel \"2-arylpropionyl-CoA epimerases\" from rat liver cytosol and mitochondria. (1993). https://pubmed.ncbi.nlm.nih.gov/8381432/ DOI: 10.1016/s0021-9258(18)53720-0","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"31c4939d-f520-55c0-973b-224743caf245","stable_key":"import-3238e4f0-8d45-5c72-8624-6e9a8b20527c","title":"Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22)","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":"cc2b388178f97f5906b66ecbe441fc5c86d51fd645947c5260fb0b4bdb4bcd21","revision_id":"0b4e5c65-05d3-5430-a4cd-8d6a03647dcb","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}