{"id":"05aba141-8aa0-5ed7-90fe-a5d4a52d3dce","stable_key":"88eb7407-f147-558b-889b-0c89c4e0aa4a:spermidine-mitochondrial-target-mmut","predicate":"supports_expression","statement":"Hypusination disruption lowered expression of methylmalonyl-CoA mutase; its mitochondrial targeting sequence increased reporter dependence on eIF5A.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"4267073f-9a8d-529b-b9d3-608befb4d039","mechanism_event_label":"Making a cofactor-dependent enzyme is another potential bottleneck.","subject":{"id":"d220a16a-9534-52fd-a43c-cc577f7bc4aa","slug":"mouse-eif5a","display_name":"Mouse eIF5A translation factor","entity_type_key":"protein"},"object":{"id":"68ad0d67-6cb7-572f-b668-13da014d2fb2","slug":"mouse-mmut","display_name":"Mouse methylmalonyl-CoA mutase / MMUT","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"4267073f-9a8d-529b-b9d3-608befb4d039","stable_key":"88eb7407-f147-558b-889b-0c89c4e0aa4a:spermidine-mitochondrial-target-mmut-event","event_type":"observed_relationship","label":"Making a cofactor-dependent enzyme is another potential bottleneck.","description":"Hypusination disruption lowered expression of methylmalonyl-CoA mutase; its mitochondrial targeting sequence increased reporter dependence on eIF5A.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d220a16a-9534-52fd-a43c-cc577f7bc4aa","slug":"mouse-eif5a","display_name":"Mouse eIF5A translation factor","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"68ad0d67-6cb7-572f-b668-13da014d2fb2","slug":"mouse-mmut","display_name":"Mouse methylmalonyl-CoA mutase / MMUT","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7014993c-468f-5c6b-ab04-80c87f9dfd9f","slug":"spermidine","display_name":"Spermidine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse macrophage/MEF protein experiments and targeting-sequence reporters.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This is protein expression, not proof of riboflavin, CoA or B12 deficiency; the relevant cofactor requires separate evidence.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"spermidine","display_name":"Spermidine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Making a cofactor-dependent enzyme is another potential bottleneck.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31130465/ · DOI 10.1016/j.cmet.2019.05.003","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"24543bbb-849a-515f-867c-9d73e19ef8b6","evidence_kind":"source_excerpt","locator":"Lines 286-292","start_line":286,"end_line":292,"excerpt":"## spermidine-mitochondrial-target-mmut\nMaking a cofactor-dependent enzyme is another potential bottleneck.\nHypusination disruption lowered expression of methylmalonyl-CoA mutase; its mitochondrial targeting sequence increased reporter dependence on eIF5A.\nModel: Mouse macrophage/MEF protein experiments and targeting-sequence reporters.\nLimitations: This is protein expression, not proof of riboflavin, CoA or B12 deficiency; the relevant cofactor requires separate evidence.\nEvidence access: Primary full text\nPolyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31130465/ · DOI 10.1016/j.cmet.2019.05.003","model_system":"Mouse macrophage/MEF protein experiments and targeting-sequence reporters.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4348f3f8-0180-58a3-b61c-55d03bb322d2","stable_key":"import-88eb7407-f147-558b-889b-0c89c4e0aa4a","title":"Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"8eec8784bc2bd0384cfd53c6603c4ced8e53c227d9ab29ed85594c43e34c68ef","revision_id":"7c421a18-4526-59f6-b84e-4be533bc35ac","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}