{"id":"0815c038-61a9-59b1-9466-c65d902b303a","stable_key":"63ce713e-6aea-59f6-9896-ca30e010b2ce:l-tyrosine-sa-alad","predicate":"inhibits","statement":"Succinylacetone competitively inhibited purified human erythrocyte ALAD; the study reported submicromolar inhibition constants across human and animal preparations.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"1c6a1414-2684-5f4a-aa91-769d8a977dde","mechanism_event_label":"A blocked tyrosine pathway can interfere with heme production.","subject":{"id":"8b701577-fe59-56c6-9dcf-eb2488694b92","slug":"succinylacetone","display_name":"Succinylacetone","entity_type_key":"small_molecule"},"object":{"id":"f0e596a6-9fa2-558a-91b3-43efac4c1015","slug":"alad","display_name":"Human delta-aminolevulinate dehydratase / ALAD","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"1c6a1414-2684-5f4a-aa91-769d8a977dde","stable_key":"63ce713e-6aea-59f6-9896-ca30e010b2ce:l-tyrosine-sa-alad-event","event_type":"observed_relationship","label":"A blocked tyrosine pathway can interfere with heme production.","description":"Succinylacetone competitively inhibited purified human erythrocyte ALAD; the study reported submicromolar inhibition constants across human and animal preparations.","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":"f0e596a6-9fa2-558a-91b3-43efac4c1015","slug":"alad","display_name":"Human delta-aminolevulinate dehydratase / ALAD","entity_type_key":"protein"},"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":"d980549c-531a-538d-9f53-bac1b051bc4b","slug":"5-aminolevulinate","display_name":"5-Aminolevulinate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"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":4,"notes":""},{"entity":{"id":"aa4c2d18-df13-59ea-9ff3-5f7f9c3e0510","slug":"fah","display_name":"Human fumarylacetoacetate hydrolase / FAH","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"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":"Purified human erythrocyte enzyme plus mouse/bovine preparations; four affected patients.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The metabolite is associated with FAH deficiency, not demonstrated as a consequence of ordinary tyrosine supplements.","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":"A blocked tyrosine pathway can interfere with heme production.","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":"6b553def-fa3a-5a87-aee5-ade70ff59489","evidence_kind":"source_excerpt","locator":"Lines 284-290","start_line":284,"end_line":290,"excerpt":"## l-tyrosine-sa-alad\nA blocked tyrosine pathway can interfere with heme production.\nSuccinylacetone competitively inhibited purified human erythrocyte ALAD; the study reported submicromolar inhibition constants across human and animal preparations.\nModel: Purified human erythrocyte enzyme plus mouse/bovine preparations; four affected patients.\nLimitations: The metabolite is associated with FAH deficiency, not demonstrated as a consequence of ordinary tyrosine supplements.\nEvidence access: Primary abstract\nHereditary tyrosinemia and the heme biosynthetic pathway. 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