{"id":"4d8821a3-2edb-568e-9138-1e985d72b6f8","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-imp-mtor-boundary","predicate":"activates_tested","statement":"The study distinguished p38-gamma-dependent basal Akt activation from mTORC1-dependent IRS loss; direct mTORC2 activation was not detected in the tested kinase assay.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"632e356f-b5df-5917-8cde-5c15cb592a5d","mechanism_event_label":"Two routes from the same metabolite have different timing and intermediates.","subject":{"id":"06c093ed-025c-54bc-8016-6a3da64ffbf9","slug":"imidazole-propionate","display_name":"Imidazole propionate","entity_type_key":"small_molecule"},"object":{"id":"5a0170cf-cee5-505b-9315-902f80c60385","slug":"human-imp-basal-akt-route","display_name":"Imidazole-propionate-dependent basal Akt pathway","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"632e356f-b5df-5917-8cde-5c15cb592a5d","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-imp-mtor-boundary-event","event_type":"observed_relationship","label":"Two routes from the same metabolite have different timing and intermediates.","description":"The study distinguished p38-gamma-dependent basal Akt activation from mTORC1-dependent IRS loss; direct mTORC2 activation was not detected in the tested kinase assay.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"06c093ed-025c-54bc-8016-6a3da64ffbf9","slug":"imidazole-propionate","display_name":"Imidazole propionate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"5a0170cf-cee5-505b-9315-902f80c60385","slug":"human-imp-basal-akt-route","display_name":"Imidazole-propionate-dependent basal Akt pathway","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"44374451-3436-5136-a8ae-5dcc6d8c353b","slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"48fe76e5-ccdd-5eeb-8c82-4fe742c17a03","slug":"mapk12","display_name":"Human p38-gamma MAP kinase / MAPK12","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"a13cb592-c939-5f92-9206-d774248802fc","slug":"akt-proteins","display_name":"AKT serine/threonine kinase family","entity_type_key":"protein_family"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"9f025af3-f039-517f-908b-4af6fc65415e","slug":"mtorc1","display_name":"Mechanistic target of rapamycin complex 1","entity_type_key":"protein_complex"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human-cell signaling, kinase assays and inhibitor/knockdown experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Does not eliminate mTOR signaling from all imidazole-propionate effects; model and time point matter.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Two routes from the same metabolite have different timing and intermediates.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ddbf76b4-a8ad-52c1-b607-8f29828c0172","evidence_kind":"source_excerpt","locator":"Lines 338-344","start_line":338,"end_line":344,"excerpt":"## histidine-imp-mtor-boundary\nTwo routes from the same metabolite have different timing and intermediates.\nThe study distinguished p38-gamma-dependent basal Akt activation from mTORC1-dependent IRS loss; direct mTORC2 activation was not detected in the tested kinase assay.\nModel: Human-cell signaling, kinase assays and inhibitor/knockdown experiments.\nLimitations: Does not eliminate mTOR signaling from all imidazole-propionate effects; model and time point matter.\nEvidence access: Primary full text\nMicrobial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012","model_system":"Human-cell signaling, kinase assays and inhibitor/knockdown experiments.","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":"ce59e6c9-1213-523b-9d0b-400b7a81cd1c","stable_key":"import-911fb3c7-8cc3-5667-b677-5682fab67648","title":"L-Histidine: supply, catabolism, histamine, receptors 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":"cb672530ec8b4a4542d0f3957e80ca76bb0449e9f988845b0f7681f623c4ec9b","revision_id":"19a7f26c-d9a1-5411-a81d-025f3d98a452","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}