{"id":"0e80db16-80c0-5dfc-a5ee-9f2c86174a44","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-oct1-species-thiamine","predicate":"differs_in_affinity_from","statement":"The affinity for thiamine was 9.5-fold lower in human than in mouse OCT1.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"18317a6e-da6e-5ccc-b494-0d7072f1a0bf","mechanism_event_label":"The same species gap applies to the vitamin the transporter carries.","subject":{"id":"3cced77c-b044-5d97-8c81-4ff9ed3dd169","slug":"slc22a1","display_name":"Human organic cation transporter 1 / OCT1 / SLC22A1","entity_type_key":"protein"},"object":{"id":"5b7e7ec2-0310-53bc-b1dd-ad3bac9803cf","slug":"mouse-slc22a1","display_name":"Mouse organic cation transporter 1 / Oct1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"18317a6e-da6e-5ccc-b494-0d7072f1a0bf","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-oct1-species-thiamine-event","event_type":"biochemical_relationship","label":"The same species gap applies to the vitamin the transporter carries.","description":"The affinity for thiamine was 9.5-fold lower in human than in mouse OCT1.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"36b7c3eb-068b-500f-af1c-078829df1ecc","slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"},"role":"transported_substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3cced77c-b044-5d97-8c81-4ff9ed3dd169","slug":"slc22a1","display_name":"Human organic cation transporter 1 / OCT1 / SLC22A1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5b7e7ec2-0310-53bc-b1dd-ad3bac9803cf","slug":"mouse-slc22a1","display_name":"Mouse organic cation transporter 1 / Oct1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/metformin-research/33037045.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67\", \"start_char\": 0, \"end_char\": 2296, \"text_sha256\": \"861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Stably transfected HEK293 cells comparing human and mouse OCT1, with human-mouse chimeras and homology modelling","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Metformin and thiamine uptake kinetics; transmembrane-helix substitutions","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A species comparison of transport affinity. 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(2020). https://pubmed.ncbi.nlm.nih.gov/33037045/ DOI: 10.1124/dmd.120.000170","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Hepatic uptake","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"87773dd6-6735-5d32-838b-dc6a67cd4601","evidence_kind":"source_excerpt","locator":"Lines 333-344","start_line":333,"end_line":344,"excerpt":"### metformin-oct1-species-thiamine\nThe affinity for thiamine was 9.5-fold lower in human than in mouse OCT1.\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: The same species gap applies to the vitamin the transporter carries.\norganism: Human and mouse orthologues side by side\ntissue_or_cell_type: Hepatic uptake\nexperimental_model: Stably transfected HEK293 cells comparing human and mouse OCT1, with human-mouse chimeras and homology modelling\nlimitations: A species comparison of transport affinity. It limits how far mouse OCT1 results can be read as human ones; it is not itself a human tissue measurement.\nexposure: Metformin and thiamine uptake kinetics; transmembrane-helix substitutions\nevidence_span: {\"source_cache\": \"artifacts/metformin-research/33037045.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67\", \"start_char\": 0, \"end_char\": 2296, \"text_sha256\": \"861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67\"}\n[metformin-p33037045] Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations. 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