{"id":"fc84cd36-4eed-5f8a-83b4-fe8d1844545b","stable_key":"97957230-601f-5dec-8524-0812be8fadbf:l-threonine-acsf3-threonine-addition","predicate":"increases","statement":"Threonine in drinking water increased serum methylmalonic acid in Acsf3-null mice on a ketogenic diet, but not significantly in controls.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"4d882e97-2295-5ac3-96f5-c1a123e4cbf4","mechanism_event_label":"More substrate affected a blocked metabolic setting differently from controls.","subject":{"id":"fcef4dc2-a7b6-5812-bc33-c8af3d83f4d0","slug":"l-threonine","display_name":"L-Threonine","entity_type_key":"small_molecule"},"object":{"id":"039a1d21-ade2-5310-b47f-57865db39451","slug":"mouse-acsf3-null-serum-mma","display_name":"Serum methylmalonic acid in Acsf3-null mice","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"4d882e97-2295-5ac3-96f5-c1a123e4cbf4","stable_key":"97957230-601f-5dec-8524-0812be8fadbf:l-threonine-acsf3-threonine-addition-event","event_type":"observed_relationship","label":"More substrate affected a blocked metabolic setting differently from controls.","description":"Threonine in drinking water increased serum methylmalonic acid in Acsf3-null mice on a ketogenic diet, but not significantly in controls.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"fcef4dc2-a7b6-5812-bc33-c8af3d83f4d0","slug":"l-threonine","display_name":"L-Threonine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"039a1d21-ade2-5310-b47f-57865db39451","slug":"mouse-acsf3-null-serum-mma","display_name":"Serum methylmalonic acid in Acsf3-null mice","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a5610904-d941-5bd4-85bb-10417b4fe401","slug":"mouse-acsf3","display_name":"Mouse acyl-CoA synthetase family member 3 / Acsf3","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"a2fda496-9308-54c5-b478-bc0b0c175570","slug":"methylmalonic-acid","display_name":"Methylmalonic acid","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary full-text Figure 3 results excerpt","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse genotype-by-diet experiment; ketogenic diet with amino-acid supplementation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Not a human supplementation trial or evidence that serum MMA exclusively reports B12 status.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-threonine","display_name":"L-Threonine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"More substrate affected a blocked metabolic setting differently from controls.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"An ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40403731/ · DOI 10.1016/j.xgen.2025.100855","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"1d22bd3f-ca49-5ea1-a676-d6cba6c4fd7c","evidence_kind":"source_excerpt","locator":"Lines 410-416","start_line":410,"end_line":416,"excerpt":"## l-threonine-acsf3-threonine-addition\nMore substrate affected a blocked metabolic setting differently from controls.\nThreonine in drinking water increased serum methylmalonic acid in Acsf3-null mice on a ketogenic diet, but not significantly in controls.\nModel: Mouse genotype-by-diet experiment; ketogenic diet with amino-acid supplementation.\nLimitations: Not a human supplementation trial or evidence that serum MMA exclusively reports B12 status.\nEvidence access: Primary full-text Figure 3 results excerpt\nAn ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40403731/ · DOI 10.1016/j.xgen.2025.100855","model_system":"Mouse genotype-by-diet experiment; ketogenic diet with amino-acid supplementation.","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":"35396730-235a-537e-8a05-c6ef2960c509","stable_key":"import-97957230-601f-5dec-8524-0812be8fadbf","title":"L-Threonine: translation, intestinal barrier, metabolism 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":"3365aed939d9f567bd098449c7d67c7c00fb6c9ba163dcf34dc7cf6081f324fb","revision_id":"10a7b648-8dd7-5d4e-b618-c560a6e2d3c7","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}