{"id":"08224329-1558-537d-9213-cdf242cb8116","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-enz-ovine-glul-native-mn-interpretation","predicate":"proposed_native_cofactor","statement":"From ovine-brain GLUL binding and tissue-metal measurements, the 1982 authors proposed that the enzyme may be manganese-bound in vivo.","claim_class":"hypothesis_link","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"f87635f4-be4e-5808-aaa9-d8c318bb0e65","mechanism_event_label":"One primary study proposed manganese as the native sheep-brain GLUL metal.","subject":{"id":"a8082b11-c484-5792-bb81-48e8e699cbe4","slug":"manganese-ion","display_name":"Mn2+","entity_type_key":"ion"},"object":{"id":"8f613a27-6378-5cce-98c4-21b4e13c1708","slug":"ovine-glul","display_name":"Ovine glutamine synthetase / GLUL","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"f87635f4-be4e-5808-aaa9-d8c318bb0e65","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-enz-ovine-glul-native-mn-interpretation-event","event_type":"biochemical_relationship","label":"One primary study proposed manganese as the native sheep-brain GLUL metal.","description":"From ovine-brain GLUL binding and tissue-metal measurements, the 1982 authors proposed that the enzyme may be manganese-bound in vivo.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a8082b11-c484-5792-bb81-48e8e699cbe4","slug":"manganese-ion","display_name":"Mn2+","entity_type_key":"ion"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8f613a27-6378-5cce-98c4-21b4e13c1708","slug":"ovine-glul","display_name":"Ovine glutamine synthetase / GLUL","entity_type_key":"protein"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"bff427ab-35f9-59c2-bb24-fd5953bbaec2","slug":"magnesium-ion","display_name":"Mg2+","entity_type_key":"ion"},"role":"competing physiological metal","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Published inference about Mn versus Mg native occupancy; paired with the competing 1986 cofactor-trapping interpretation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Ovine brain glutamine synthetase steady-state kinetics and metal-binding measurements","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Mn(II) and Mg(II) titrations; binding and tissue metal measurements","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Author inference; not a universal human GLUL cofactor assignment. Contradicted by a later overlapping ovine/bovine study using endogenous-cofactor trapping.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Manganese research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"manganese","display_name":"Manganese","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Ovis aries","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"One primary study proposed manganese as the native sheep-brain GLUL metal.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mn-enz-6129892] Glutamine synthetase from ovine brain is a manganese(II) enzyme. (1982). https://pubmed.ncbi.nlm.nih.gov/6129892/ DOI: 10.1021/bi00268a011","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Brain-derived purified enzyme","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"fed17e6c-ad62-5648-b196-e747fab94ba7","evidence_kind":"source_excerpt","locator":"Lines 633-644","start_line":633,"end_line":644,"excerpt":"### mn-enz-ovine-glul-native-mn-interpretation\nFrom ovine-brain GLUL binding and tissue-metal measurements, the 1982 authors proposed that the enzyme may be manganese-bound in vivo.\nCondition category: normal\nnutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: One primary study proposed manganese as the native sheep-brain GLUL metal.\norganism: Ovis aries\ntissue_or_cell_type: Brain-derived purified enzyme\nexperimental_model: Ovine brain glutamine synthetase steady-state kinetics and metal-binding measurements\nlimitations: Author inference; not a universal human GLUL cofactor assignment. Contradicted by a later overlapping ovine/bovine study using endogenous-cofactor trapping.\nexposure: Mn(II) and Mg(II) titrations; binding and tissue metal measurements\ncross_nutrient: Published inference about Mn versus Mg native occupancy; paired with the competing 1986 cofactor-trapping interpretation.\n[mn-enz-6129892] Glutamine synthetase from ovine brain is a manganese(II) enzyme. (1982). https://pubmed.ncbi.nlm.nih.gov/6129892/ DOI: 10.1021/bi00268a011","model_system":"Ovine brain glutamine synthetase steady-state kinetics and metal-binding measurements","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [mn-enz-6129892] Glutamine synthetase from ovine brain is a manganese(II) enzyme. (1982). https://pubmed.ncbi.nlm.nih.gov/6129892/ DOI: 10.1021/bi00268a011","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"03224387-8a73-5b4f-906d-9f0be6625b7f","stable_key":"import-be889add-cec8-500b-be89-676431432a70","title":"Manganese: enzyme cofactors, glycosylation, transport 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":"f029ee5a1133a4f296047f06a6f0178deb9fd02e8d9707bc285bbe0f4e08fcb5","revision_id":"a77068c1-5a13-5aa9-bbac-d1cff6d34f15","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"4adf34e3-b9e8-5bc5-8344-e8c13d87da0e","title":"Native ovine brain GLUL: manganese or magnesium?","kind":"contradiction","status":"open","why":"Published competing interpretations concern the same native cofactor question in ovine brain GLUL. The 1982 binding/kinetic study proposed a manganoenzyme; the 1986 cofactor-trapping study recovered predominantly Mg and favored Mg in vivo. Overlapping ovine brain enzyme and endogenous cofactor interpretation; 1986 additionally studied bovine brain. Methods differ. The conflict records competing published interpretations, not proof that identical assay results disagree. Neither paper determines living human brain GLUL occupancy.","resolution":"The later cofactor-trapping study provides direct evidence favoring magnesium in the sampled native animal brain enzyme. Preserve both published interpretations and the different methods. Do not extend either interpretation to a universal human GLUL cofactor assignment.","created_at":"2026-09-17 15:32:53","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/4adf34e3-b9e8-5bc5-8344-e8c13d87da0e","sides":[{"conflict_id":"4adf34e3-b9e8-5bc5-8344-e8c13d87da0e","ordinal":0,"label":"One primary study proposed manganese as the native sheep-brain GLUL metal.","revision_id":"a77068c1-5a13-5aa9-bbac-d1cff6d34f15","start_line":633,"end_line":644,"quote":"### mn-enz-ovine-glul-native-mn-interpretation\nFrom ovine-brain GLUL binding and tissue-metal measurements, the 1982 authors proposed that the enzyme may be manganese-bound in vivo.\nCondition category: normal\nnutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: One primary study proposed manganese as the native sheep-brain GLUL metal.\norganism: Ovis aries\ntissue_or_cell_type: Brain-derived purified enzyme\nexperimental_model: Ovine brain glutamine synthetase steady-state kinetics and metal-binding measurements\nlimitations: Author inference; not a universal human GLUL cofactor assignment. Contradicted by a later overlapping ovine/bovine study using endogenous-cofactor trapping.\nexposure: Mn(II) and Mg(II) titrations; binding and tissue metal measurements\ncross_nutrient: Published inference about Mn versus Mg native occupancy; paired with the competing 1986 cofactor-trapping interpretation.\n[mn-enz-6129892] Glutamine synthetase from ovine brain is a manganese(II) enzyme. (1982). https://pubmed.ncbi.nlm.nih.gov/6129892/ DOI: 10.1021/bi00268a011","source_key":"import-be889add-cec8-500b-be89-676431432a70","source_title":"Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17)","claim_ids":["08224329-1558-537d-9213-cdf242cb8116"]},{"conflict_id":"4adf34e3-b9e8-5bc5-8344-e8c13d87da0e","ordinal":1,"label":"Another primary study supported magnesium as the native brain GLUL metal.","revision_id":"a77068c1-5a13-5aa9-bbac-d1cff6d34f15","start_line":659,"end_line":670,"quote":"### mn-enz-brain-glul-native-mg-interpretation\nThe 1986 cofactor-trapping study concluded that Mg, rather than Mn, appears to be bound to bovine/ovine brain GLUL in vivo, although either metal supports assays.\nCondition category: normal\nnutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Another primary study supported magnesium as the native brain GLUL metal.\norganism: Bos taurus; Ovis aries\ntissue_or_cell_type: Brain extracts and purified enzyme\nexperimental_model: Cofactor trapping and immunoprecipitation of bovine and ovine brain glutamine synthetase\nlimitations: Author interpretation of extracted enzyme; overlaps the ovine brain question in 1982, with different methods.\nexposure: Methionine sulfoximine phosphate/ADP cofactor trapping\ncross_nutrient: Competing primary interpretation of native GLUL Mn versus Mg identity.\n[mn-enz-2870682] Mg2+ is bound to glutamine synthetase extracted from bovine or ovine brain in the presence of L-methionine-S-sulfoximine phosphate. (1986). https://pubmed.ncbi.nlm.nih.gov/2870682/ DOI: 10.1016/0003-9861(86)90496-0","source_key":"import-be889add-cec8-500b-be89-676431432a70","source_title":"Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17)","claim_ids":["ddacded5-43a8-59d4-92ec-fe1c108e84b4"]}]}],"corrections":[],"research":null}