{"id":"c70fcc37-2345-5b2b-8256-bfce03d87556","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-mate2k-metformin","predicate":"transports","statement":"MATE2-K transported metformin in a proton-gradient-dependent manner, with a Michaelis-Menten constant of 1.98 mM.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"58cd9ed3-a714-5f20-b645-df6b8e5d929b","mechanism_event_label":"A proton-driven pump moves the drug out of the cell into urine.","subject":{"id":"8542da6d-a425-5aef-9f1c-295282a663f1","slug":"slc47a2","display_name":"Human kidney-specific multidrug and toxin extrusion protein 2 / MATE2-K / SLC47A2","entity_type_key":"protein"},"object":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"evidence_count":1,"mechanism_event":{"id":"58cd9ed3-a714-5f20-b645-df6b8e5d929b","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-mate2k-metformin-event","event_type":"biochemical_relationship","label":"A proton-driven pump moves the drug out of the cell into urine.","description":"MATE2-K transported metformin in a proton-gradient-dependent manner, with a Michaelis-Menten constant of 1.98 mM.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"role":"transported_substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8542da6d-a425-5aef-9f1c-295282a663f1","slug":"slc47a2","display_name":"Human kidney-specific multidrug and toxin extrusion protein 2 / MATE2-K / SLC47A2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/metformin-research/17509534.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d2660dd67050133c958e8aa13cf2ac6b574bd56fcefa116d3a73c3db4a7cea44\", \"start_char\": 0, \"end_char\": 1841, \"text_sha256\": \"d2660dd67050133c958e8aa13cf2ac6b574bd56fcefa116d3a73c3db4a7cea44\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"MATE1 and MATE2-K cDNA transfection into HEK293 cells with kinetic analysis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Oppositely directed proton gradient; Michaelis-Menten constants for ten substrates","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Millimolar affinities in a transfected system. Substrate overlap describes a shared route, not a predicted clinical interaction.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake.","comparator":null,"unit":null,"notes":"","entity":{"slug":"metformin","display_name":"Metformin","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human transporters","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A proton-driven pump moves the drug out of the cell into urine.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[metformin-p17509534] Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. (2007). https://pubmed.ncbi.nlm.nih.gov/17509534/ DOI: 10.1016/j.bcp.2007.04.010","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Renal brush-border membrane transport","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"transport_effect","value_text":"depends","comparator":null,"unit":null,"notes":"Recorded as proton-gradient-dependent transport. MATE carriers run either way with the proton gradient, and the assay's pool and the extrusion role move opposite ways.","entity":null},{"dimension":"transport_pool","value_text":"the renal tubular cell interior","comparator":null,"unit":null,"notes":"Recorded as proton-gradient-dependent transport. MATE carriers run either way with the proton gradient, and the assay's pool and the extrusion role move opposite ways.","entity":null}],"evidence":[{"id":"a06bb5ee-deca-5698-906e-a40607556690","evidence_kind":"source_excerpt","locator":"Lines 216-227","start_line":216,"end_line":227,"excerpt":"### metformin-mate2k-metformin\nMATE2-K transported metformin in a proton-gradient-dependent manner, with a Michaelis-Menten constant of 1.98 mM.\nCondition category: normal\nnutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake.\nplain_language: A proton-driven pump moves the drug out of the cell into urine.\norganism: Human transporters\ntissue_or_cell_type: Renal brush-border membrane transport\nexperimental_model: MATE1 and MATE2-K cDNA transfection into HEK293 cells with kinetic analysis\nlimitations: Millimolar affinities in a transfected system. Substrate overlap describes a shared route, not a predicted clinical interaction.\nexposure: Oppositely directed proton gradient; Michaelis-Menten constants for ten substrates\nevidence_span: {\"source_cache\": \"artifacts/metformin-research/17509534.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d2660dd67050133c958e8aa13cf2ac6b574bd56fcefa116d3a73c3db4a7cea44\", \"start_char\": 0, \"end_char\": 1841, \"text_sha256\": \"d2660dd67050133c958e8aa13cf2ac6b574bd56fcefa116d3a73c3db4a7cea44\"}\n[metformin-p17509534] Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. (2007). https://pubmed.ncbi.nlm.nih.gov/17509534/ DOI: 10.1016/j.bcp.2007.04.010","model_system":"MATE1 and MATE2-K cDNA transfection into HEK293 cells with kinetic analysis","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [metformin-p17509534] Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. (2007). https://pubmed.ncbi.nlm.nih.gov/17509534/ DOI: 10.1016/j.bcp.2007.04.010","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"d0474bd9-7cfd-5695-a152-12f3633a6813","stable_key":"import-8b3cf083-ea9c-54f5-b42b-bf1fef5b2978","title":"Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. 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