{"id":"167cd16c-76b3-5932-8e9b-fa56dc7b2d61","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-qprt-dosage","predicate":"gene_dosage_reduction_increases","statement":"Qprt-heterozygous mice had higher quinolinate, lower NAD and greater acute kidney injury susceptibility.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"217f6704-7ac3-5828-9398-980c79538b4f","mechanism_event_label":"Less conversion machinery increased vulnerability despite accumulated precursor.","subject":{"id":"0d90b4b2-8b33-5127-9d33-bceadab0af03","slug":"mouse-qprt","display_name":"Mouse quinolinate phosphoribosyltransferase / Qprt","entity_type_key":"protein"},"object":{"id":"0b59d40f-c328-57e3-9843-6f50657c2aab","slug":"mouse-acute-kidney-injury","display_name":"Mouse acute kidney injury susceptibility","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"217f6704-7ac3-5828-9398-980c79538b4f","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-qprt-dosage-event","event_type":"observed_relationship","label":"Less conversion machinery increased vulnerability despite accumulated precursor.","description":"Qprt-heterozygous mice had higher quinolinate, lower NAD and greater acute kidney injury susceptibility.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"0d90b4b2-8b33-5127-9d33-bceadab0af03","slug":"mouse-qprt","display_name":"Mouse quinolinate phosphoribosyltransferase / Qprt","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0b59d40f-c328-57e3-9843-6f50657c2aab","slug":"mouse-acute-kidney-injury","display_name":"Mouse acute kidney injury susceptibility","entity_type_key":"cellular_process"},"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":"e87b8b33-00ba-5e66-88cc-d287deec1d9a","slug":"mouse-renal-nad","display_name":"Mouse renal NAD abundance","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"ab444b3c-c8ec-5ada-8450-36ac9934d6b6","slug":"quinolinic-acid","display_name":"Quinolinic acid","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse Qprt heterozygous deletion.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"No inference that more tryptophan fixes the blocked step.","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":"Less conversion machinery increased vulnerability despite accumulated precursor.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"De novo NAD+ biosynthetic impairment in acute kidney injury in humans. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30127395/ · DOI 10.1038/s41591-018-0138-z","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":"3ce9ae2f-cb02-54fa-b689-7d475574361a","evidence_kind":"source_excerpt","locator":"Lines 250-256","start_line":250,"end_line":256,"excerpt":"## tryptophan-qprt-dosage\nLess conversion machinery increased vulnerability despite accumulated precursor.\nQprt-heterozygous mice had higher quinolinate, lower NAD and greater acute kidney injury susceptibility.\nModel: Mouse Qprt heterozygous deletion.\nLimitations: No inference that more tryptophan fixes the blocked step.\nEvidence access: Primary abstract\nDe novo NAD+ biosynthetic impairment in acute kidney injury in humans. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30127395/ · DOI 10.1038/s41591-018-0138-z","model_system":"Mouse Qprt heterozygous deletion.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"73f9d3e7-fdc9-5418-8f3c-f4ef145f6efa","stable_key":"import-584c58f5-ab9f-53f3-97a9-55783db943b0","title":"Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary-abstract references and experimental limitations individually identified. 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