{"id":"d390b382-1868-567c-bb38-88c38d5ea8be","stable_key":"08ce9896-9d1c-5bbf-b705-5bfe771091d5:b7-leucine-challenge-3hia","predicate":"provokes_higher_deficiency_marker","statement":"Challenge-induced urinary 3-HIA rose more than twofold by day 14 in both biotin-depleted cohorts.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"0db9ca5b-9433-5e66-945e-e61efefbcff2","mechanism_event_label":"Extra leucine made the impaired pathway easier to observe.","subject":{"id":"f707c753-cc8c-5f06-90be-bb3d73c60a18","slug":"leucine","display_name":"L-Leucine","entity_type_key":"small_molecule"},"object":{"id":"ebbcb656-4274-5f50-a1be-9d69df5e3434","slug":"human-urinary-3hia","display_name":"Human urinary 3-hydroxyisovaleric acid excretion","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"0db9ca5b-9433-5e66-945e-e61efefbcff2","stable_key":"08ce9896-9d1c-5bbf-b705-5bfe771091d5:b7-leucine-challenge-3hia-event","event_type":"observed_intervention","label":"Extra leucine made the impaired pathway easier to observe.","description":"Challenge-induced urinary 3-HIA rose more than twofold by day 14 in both biotin-depleted cohorts.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"37a8e96b-f95b-5ba7-a0bc-8ed3cfaf5fd8","slug":"biotin","display_name":"Biotin","entity_type_key":"small_molecule"},"role":"restricted cofactor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"871496e9-19bf-5fd0-a2a2-82d1b0bff8b4","slug":"human-mcc","display_name":"Human 3-methylcrotonyl-CoA carboxylase complex","entity_type_key":"protein_complex"},"role":"pathway bottleneck","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"f707c753-cc8c-5f06-90be-bb3d73c60a18","slug":"leucine","display_name":"L-Leucine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"ebbcb656-4274-5f50-a1be-9d69df5e3434","slug":"human-urinary-3hia","display_name":"Human urinary 3-hydroxyisovaleric acid excretion","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/biotin-research/21918059.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"5cf1d7e25ae7bdfeb2ac3225cee8e4e660723d5197fc057f63327b3ad9eb3aaf\", \"start_char\": 0, \"end_char\": 1723, \"text_sha256\": \"5cf1d7e25ae7bdfeb2ac3225cee8e4e660723d5197fc057f63327b3ad9eb3aaf\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Leucine challenge during biotin depletion in two cohorts of 5 and 7 healthy adults","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"28-day egg-white depletion; weekly oral leucine challenge","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The challenge was sensitive but not diagnostically superior to 24-hour urine measurements; no validated universal threshold follows.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Biotin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"biotin","display_name":"Biotin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Extra leucine made the impaired pathway easier to observe.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b7-p21918059] Urinary excretion of 3-hydroxyisovaleric acid and 3-hydroxyisovaleryl carnitine increases in response to a leucine challenge in marginally biotin-deficient humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21918059/ DOI: 10.3945/jn.111.146126","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Urine","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"dc1e31cd-dbfc-5376-b552-5fc41f611aa4","evidence_kind":"source_excerpt","locator":"Lines 910-921","start_line":910,"end_line":921,"excerpt":"### b7-leucine-challenge-3hia\nChallenge-induced urinary 3-HIA rose more than twofold by day 14 in both biotin-depleted cohorts.\nCondition category: nutrient_deficiency\nnutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Extra leucine made the impaired pathway easier to observe.\norganism: Homo sapiens\ntissue_or_cell_type: Urine\nexperimental_model: Leucine challenge during biotin depletion in two cohorts of 5 and 7 healthy adults\nlimitations: The challenge was sensitive but not diagnostically superior to 24-hour urine measurements; no validated universal threshold follows.\nexposure: 28-day egg-white depletion; weekly oral leucine challenge\nevidence_span: {\"source_cache\": \"artifacts/biotin-research/21918059.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"5cf1d7e25ae7bdfeb2ac3225cee8e4e660723d5197fc057f63327b3ad9eb3aaf\", \"start_char\": 0, \"end_char\": 1723, \"text_sha256\": \"5cf1d7e25ae7bdfeb2ac3225cee8e4e660723d5197fc057f63327b3ad9eb3aaf\"}\n[b7-p21918059] Urinary excretion of 3-hydroxyisovaleric acid and 3-hydroxyisovaleryl carnitine increases in response to a leucine challenge in marginally biotin-deficient humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21918059/ DOI: 10.3945/jn.111.146126","model_system":"Leucine challenge during biotin depletion in two cohorts of 5 and 7 healthy adults","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b7-p21918059] Urinary excretion of 3-hydroxyisovaleric acid and 3-hydroxyisovaleryl carnitine increases in response to a leucine challenge in marginally biotin-deficient humans. 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