{"id":"2b639209-d324-5de1-88e9-9951f781cefe","stable_key":"cfa4bd86-d88d-555a-975c-68877bf00e0f:lutein-srbi-mutant","predicate":"abolishes_enhancement_of","statement":"SR-BI C384Y abolished the preferential lutein/zeaxanthin uptake effect observed with wild-type receptor.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"879b01f2-47c5-54f1-8d15-ebf2c0153fa0","mechanism_event_label":"An altered transport tunnel disrupted the effect.","subject":{"id":"d55282b7-9013-5db3-9559-51ce37bc246b","slug":"scarb1-c384y","display_name":"Human SR-BI C384Y tunnel-blocking variant","entity_type_key":"protein_state"},"object":{"id":"0991b9e6-6d8a-5cf2-8b8f-b04948da294c","slug":"hek293-lutein-uptake","display_name":"Lutein uptake by engineered human HEK293 cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"879b01f2-47c5-54f1-8d15-ebf2c0153fa0","stable_key":"cfa4bd86-d88d-555a-975c-68877bf00e0f:lutein-srbi-mutant-event","event_type":"biochemical_relationship","label":"An altered transport tunnel disrupted the effect.","description":"SR-BI C384Y abolished the preferential lutein/zeaxanthin uptake effect observed with wild-type receptor.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"5dd84367-3f8e-5a3f-b952-a96174ea51fa","slug":"lutein","display_name":"Lutein","entity_type_key":"small_molecule"},"role":"cargo","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d55282b7-9013-5db3-9559-51ce37bc246b","slug":"scarb1-c384y","display_name":"Human SR-BI C384Y tunnel-blocking variant","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"0991b9e6-6d8a-5cf2-8b8f-b04948da294c","slug":"hek293-lutein-uptake","display_name":"Lutein uptake by engineered human HEK293 cells","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/lutein-research/36863431.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"530dd42d442890be2e5cd11c18bf95c0bd850d8f67ad6682d12360dfc7f8aec0\", \"start_char\": 0, \"end_char\": 1551, \"text_sha256\": \"530dd42d442890be2e5cd11c18bf95c0bd850d8f67ad6682d12360dfc7f8aec0\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"SR-BI expression, tunnel mutation, binding and lipoprotein-partner assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Wild-type or C384Y SR-BI; HDL and hepatic lipase additions","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Engineered-cell mechanisms, not a clinical HDL-raising recommendation; no selective direct binding to lutein demonstrated.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Lutein research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"lutein","display_name":"Lutein","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human HEK293 cell system","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"An altered transport tunnel disrupted the effect.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[lutein-p36863431] Mechanism for the selective uptake of macular carotenoids mediated by the HDL cholesterol receptor SR-BI. (2023). https://pubmed.ncbi.nlm.nih.gov/36863431/ DOI: 10.1016/j.exer.2023.109429","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Engineered cells without endogenous SR-BI","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":"a4f16c8f-e547-58bb-846e-6f9d4a2585c1","evidence_kind":"source_excerpt","locator":"Lines 710-721","start_line":710,"end_line":721,"excerpt":"### lutein-srbi-mutant\nSR-BI C384Y abolished the preferential lutein/zeaxanthin uptake effect observed with wild-type receptor.\nCondition category: machinery_impairment\nnutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: An altered transport tunnel disrupted the effect.\norganism: Human HEK293 cell system\ntissue_or_cell_type: Engineered cells without endogenous SR-BI\nexperimental_model: SR-BI expression, tunnel mutation, binding and lipoprotein-partner assays\nlimitations: Engineered-cell mechanisms, not a clinical HDL-raising recommendation; no selective direct binding to lutein demonstrated.\nexposure: Wild-type or C384Y SR-BI; HDL and hepatic lipase additions\nevidence_span: {\"source_cache\": \"artifacts/lutein-research/36863431.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"530dd42d442890be2e5cd11c18bf95c0bd850d8f67ad6682d12360dfc7f8aec0\", \"start_char\": 0, \"end_char\": 1551, \"text_sha256\": \"530dd42d442890be2e5cd11c18bf95c0bd850d8f67ad6682d12360dfc7f8aec0\"}\n[lutein-p36863431] Mechanism for the selective uptake of macular carotenoids mediated by the HDL cholesterol receptor SR-BI. 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