{"id":"f93e673b-5784-5fa0-8e8a-91e766b99aee","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-oct1-pdh","predicate":"deletion_reduces","statement":"Oct1 deletion reduced hepatic thiamine-dependent enzyme activity, including pyruvate dehydrogenase, in mice.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"a9dda588-d744-5b5c-aa1f-adb7fe0c6521","mechanism_event_label":"A transporter can affect how the liver uses a vitamin-dependent fuel pathway.","subject":{"id":"5b7e7ec2-0310-53bc-b1dd-ad3bac9803cf","slug":"mouse-slc22a1","display_name":"Mouse organic cation transporter 1 / Oct1","entity_type_key":"protein"},"object":{"id":"6abaf4ea-a890-5ee7-91f7-ef9f39546d1f","slug":"mouse-pdh-activity","display_name":"Mouse hepatic pyruvate dehydrogenase activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"a9dda588-d744-5b5c-aa1f-adb7fe0c6521","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-oct1-pdh-event","event_type":"biochemical_relationship","label":"A transporter can affect how the liver uses a vitamin-dependent fuel pathway.","description":"Oct1 deletion reduced hepatic thiamine-dependent enzyme activity, including pyruvate dehydrogenase, in mice.","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":"dependent_nutrient","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"5b7e7ec2-0310-53bc-b1dd-ad3bac9803cf","slug":"mouse-slc22a1","display_name":"Mouse organic cation transporter 1 / Oct1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6abaf4ea-a890-5ee7-91f7-ef9f39546d1f","slug":"mouse-pdh-activity","display_name":"Mouse hepatic pyruvate dehydrogenase activity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/berberine-research/29659562.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"10efb675e4e0cf5cea9c8607b6b2a5e3ad77c383f8b0a55efff5ed6d163be558\", \"start_char\": 0, \"end_char\": 1652, \"text_sha256\": \"10efb675e4e0cf5cea9c8607b6b2a5e3ad77c383f8b0a55efff5ed6d163be558\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse gene deletion and dietary depletion, with human genetic associations","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Oct1 deletion or a thiamine-deficient diet","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Mouse Oct1 deletion is not pharmacological berberine inhibition; human genetic associations do not establish berberine-induced thiamine depletion.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Berberine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Mice for causal thiamine and PDH experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A transporter can affect how the liver uses a vitamin-dependent fuel pathway.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[berberine-p29659562] Organic cation transporter 1 (OCT1) modulates multiple cardiometabolic traits through effects on hepatic thiamine content. (2018). https://pubmed.ncbi.nlm.nih.gov/29659562/ DOI: 10.1371/journal.pbio.2002907","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Hepatic thiamine-dependent metabolism","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":"58d72b31-4a8b-5536-a615-89a96df6a7e7","evidence_kind":"source_excerpt","locator":"Lines 311-322","start_line":311,"end_line":322,"excerpt":"### berberine-oct1-pdh\nOct1 deletion reduced hepatic thiamine-dependent enzyme activity, including pyruvate dehydrogenase, in mice.\nCondition category: machinery_impairment\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A transporter can affect how the liver uses a vitamin-dependent fuel pathway.\norganism: Mice for causal thiamine and PDH experiments\ntissue_or_cell_type: Hepatic thiamine-dependent metabolism\nexperimental_model: Mouse gene deletion and dietary depletion, with human genetic associations\nlimitations: Mouse Oct1 deletion is not pharmacological berberine inhibition; human genetic associations do not establish berberine-induced thiamine depletion.\nexposure: Oct1 deletion or a thiamine-deficient diet\nevidence_span: {\"source_cache\": \"artifacts/berberine-research/29659562.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"10efb675e4e0cf5cea9c8607b6b2a5e3ad77c383f8b0a55efff5ed6d163be558\", \"start_char\": 0, \"end_char\": 1652, \"text_sha256\": \"10efb675e4e0cf5cea9c8607b6b2a5e3ad77c383f8b0a55efff5ed6d163be558\"}\n[berberine-p29659562] Organic cation transporter 1 (OCT1) modulates multiple cardiometabolic traits through effects on hepatic thiamine content. 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