{"id":"4c6a1668-5deb-509f-9190-ebb554b82f92","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-imp-ampk","predicate":"inhibits_tested","statement":"In HEK293 cells, imidazole propionate suppressed metformin-induced AMPK activation; expression of the study-labeled AMPK S485A mutant prevented suppression of activating T172 phosphorylation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"4f7d6050-eef5-5378-b5d0-6c0256039269","mechanism_event_label":"Changing the inhibitory phosphorylation site interrupted the measured drug interaction.","subject":{"id":"06c093ed-025c-54bc-8016-6a3da64ffbf9","slug":"imidazole-propionate","display_name":"Imidazole propionate","entity_type_key":"small_molecule"},"object":{"id":"95bc303f-ad04-59ea-8e1e-32f9e8b72c56","slug":"human-ampk-complexes","display_name":"Human AMP-activated protein kinase complexes","entity_type_key":"protein_family"},"evidence_count":1,"mechanism_event":{"id":"4f7d6050-eef5-5378-b5d0-6c0256039269","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-imp-ampk-event","event_type":"observed_relationship","label":"Changing the inhibitory phosphorylation site interrupted the measured drug interaction.","description":"In HEK293 cells, imidazole propionate suppressed metformin-induced AMPK activation; expression of the study-labeled AMPK S485A mutant prevented suppression of activating T172 phosphorylation.","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":"95bc303f-ad04-59ea-8e1e-32f9e8b72c56","slug":"human-ampk-complexes","display_name":"Human AMP-activated protein kinase complexes","entity_type_key":"protein_family"},"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":"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":3,"notes":""},{"entity":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"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":5,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"HEK293 expression and phosphorylation assays; the paper labels the construct site S485.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Construct site numbering is retained without silently mapping it to a human endogenous isoform. No universal AMPK inhibition across all tissues.","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":"Changing the inhibitory phosphorylation site interrupted the measured drug interaction.","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":"216fa10f-abfc-5d34-b574-ba3de8be2955","evidence_kind":"source_excerpt","locator":"Lines 330-336","start_line":330,"end_line":336,"excerpt":"## histidine-imp-ampk\nChanging the inhibitory phosphorylation site interrupted the measured drug interaction.\nIn HEK293 cells, imidazole propionate suppressed metformin-induced AMPK activation; expression of the study-labeled AMPK S485A mutant prevented suppression of activating T172 phosphorylation.\nModel: HEK293 expression and phosphorylation assays; the paper labels the construct site S485.\nLimitations: Construct site numbering is retained without silently mapping it to a human endogenous isoform. No universal AMPK inhibition across all tissues.\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":"HEK293 expression and phosphorylation assays; the paper labels the construct site S485.","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}