{"id":"25d9a324-79f7-5ac2-83e8-162e517b5609","stable_key":"63ce713e-6aea-59f6-9896-ca30e010b2ce:l-tyrosine-sa-heme","predicate":"reduces","statement":"Adding succinylacetone to avian hepatocytes reduced cellular heme and cytochrome P450 content.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"a788b40e-137f-5b60-ac57-2d262f4c5131","mechanism_event_label":"One pathway blockage can reduce machinery used by other pathways.","subject":{"id":"8b701577-fe59-56c6-9dcf-eb2488694b92","slug":"succinylacetone","display_name":"Succinylacetone","entity_type_key":"small_molecule"},"object":{"id":"9a4f2d58-7ee3-5ff8-ab3e-e1fd8e670f02","slug":"avian-hepatocyte-heme-content","display_name":"Avian cultured-hepatocyte heme content","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"a788b40e-137f-5b60-ac57-2d262f4c5131","stable_key":"63ce713e-6aea-59f6-9896-ca30e010b2ce:l-tyrosine-sa-heme-event","event_type":"observed_relationship","label":"One pathway blockage can reduce machinery used by other pathways.","description":"Adding succinylacetone to avian hepatocytes reduced cellular heme and cytochrome P450 content.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"8b701577-fe59-56c6-9dcf-eb2488694b92","slug":"succinylacetone","display_name":"Succinylacetone","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9a4f2d58-7ee3-5ff8-ab3e-e1fd8e670f02","slug":"avian-hepatocyte-heme-content","display_name":"Avian cultured-hepatocyte heme content","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"bcfef85f-831d-5439-ba51-1aef4b090441","slug":"l-tyrosine","display_name":"L-Tyrosine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"2e1f7e0a-8b54-5ea3-9d34-01e7167f9097","slug":"heme","display_name":"Heme","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"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":"Cultured avian hepatocytes with direct metabolite exposure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The cellular effect is avian; the human ALAD inhibition is recorded separately.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-tyrosine","display_name":"L-Tyrosine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"One pathway blockage can reduce machinery used by other pathways.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Hereditary tyrosinemia and the heme biosynthetic pathway. Profound inhibition of delta-aminolevulinic acid dehydratase activity by succinylacetone. · 1983 · https://pubmed.ncbi.nlm.nih.gov/6826727/ · DOI 10.1172/jci110809","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":"baedf027-362f-56bf-b9d8-267320940e2a","evidence_kind":"source_excerpt","locator":"Lines 292-298","start_line":292,"end_line":298,"excerpt":"## l-tyrosine-sa-heme\nOne pathway blockage can reduce machinery used by other pathways.\nAdding succinylacetone to avian hepatocytes reduced cellular heme and cytochrome P450 content.\nModel: Cultured avian hepatocytes with direct metabolite exposure.\nLimitations: The cellular effect is avian; the human ALAD inhibition is recorded separately.\nEvidence access: Primary abstract\nHereditary tyrosinemia and the heme biosynthetic pathway. Profound inhibition of delta-aminolevulinic acid dehydratase activity by succinylacetone. · 1983 · https://pubmed.ncbi.nlm.nih.gov/6826727/ · DOI 10.1172/jci110809","model_system":"Cultured avian hepatocytes with direct metabolite exposure.","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":"12917df2-c6e0-5b61-850f-dbff6d4b4d30","stable_key":"import-63ce713e-6aea-59f6-9896-ca30e010b2ce","title":"L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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