{"id":"d38d06d3-0097-55f1-85d0-44033a91feee","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-indole-oxidation","predicate":"microsomally_oxidized_to","statement":"Rat liver microsomal induction/inhibition experiments implicated CYP2E1 as the major enzyme oxidizing indole to indoxyl with NADPH support.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"31ccd85d-5038-5468-a575-927bfc85655e","mechanism_event_label":"A gut-derived indole can enter a liver oxidation route.","subject":{"id":"456cd56f-01cb-5202-bb9d-86824e845498","slug":"indole","display_name":"Indole","entity_type_key":"small_molecule"},"object":{"id":"f53f8923-359a-5c38-b601-604497114e8c","slug":"indoxyl","display_name":"Indoxyl / 3-hydroxyindole","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"31ccd85d-5038-5468-a575-927bfc85655e","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-indole-oxidation-event","event_type":"observed_relationship","label":"A gut-derived indole can enter a liver oxidation route.","description":"Rat liver microsomal induction/inhibition experiments implicated CYP2E1 as the major enzyme oxidizing indole to indoxyl with NADPH support.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"456cd56f-01cb-5202-bb9d-86824e845498","slug":"indole","display_name":"Indole","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f53f8923-359a-5c38-b601-604497114e8c","slug":"indoxyl","display_name":"Indoxyl / 3-hydroxyindole","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"769339cb-213b-559e-acc0-07ed00368b94","slug":"l-tryptophan","display_name":"L-Tryptophan","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"c0e64c99-83d6-5619-89ba-40ab5a15d54f","slug":"rat-cyp2e1","display_name":"Rat cytochrome P450 2E1 / Cyp2e1","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"4aba2a5e-8d06-5304-bb01-c0402b225a94","slug":"nadph","display_name":"NADPH","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Rat liver microsomes with inducer/inhibitor profiling.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"CYP2E1 assignment is supported by convergent microsomal tests rather than exclusive purified-enzyme proof.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-tryptophan","display_name":"L-Tryptophan","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A gut-derived indole can enter a liver oxidation route.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Hepatic microsomal metabolism of indole to indoxyl, a precursor of indoxyl sulfate. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11808865/ · DOI 10.1007/BF03226377","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"2191f86b-03ec-5c74-82f5-f03ba9857beb","evidence_kind":"source_excerpt","locator":"Lines 586-592","start_line":586,"end_line":592,"excerpt":"## tryptophan-indole-oxidation\nA gut-derived indole can enter a liver oxidation route.\nRat liver microsomal induction/inhibition experiments implicated CYP2E1 as the major enzyme oxidizing indole to indoxyl with NADPH support.\nModel: Rat liver microsomes with inducer/inhibitor profiling.\nLimitations: CYP2E1 assignment is supported by convergent microsomal tests rather than exclusive purified-enzyme proof.\nEvidence access: Primary abstract\nHepatic microsomal metabolism of indole to indoxyl, a precursor of indoxyl sulfate. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11808865/ · DOI 10.1007/BF03226377","model_system":"Rat liver microsomes with inducer/inhibitor profiling.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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