{"id":"04d35bd1-6881-56b4-8def-33373e55e017","stable_key":"63ce713e-6aea-59f6-9896-ca30e010b2ce:l-tyrosine-chloral-gstz","predicate":"impairs","statement":"Five days of 1 g/day chloral hydrate produced detectable dichloroacetate and urinary maleylacetone in healthy volunteers, consistent with inhibition of GSTZ1/MAAI-dependent tyrosine catabolism.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"55acff72-fce3-5e06-aeb7-22fbed28dcb2","mechanism_event_label":"A drug metabolite can interfere with an amino-acid disposal enzyme.","subject":{"id":"5929c0fc-205c-5250-9ca4-dc076f2e4df1","slug":"chloral-hydrate","display_name":"Chloral hydrate","entity_type_key":"drug"},"object":{"id":"098eb575-0232-50d0-8620-bfabc07eadea","slug":"gstz1","display_name":"Human maleylacetoacetate isomerase / GSTZ1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"55acff72-fce3-5e06-aeb7-22fbed28dcb2","stable_key":"63ce713e-6aea-59f6-9896-ca30e010b2ce:l-tyrosine-chloral-gstz-event","event_type":"observed_relationship","label":"A drug metabolite can interfere with an amino-acid disposal enzyme.","description":"Five days of 1 g/day chloral hydrate produced detectable dichloroacetate and urinary maleylacetone in healthy volunteers, consistent with inhibition of GSTZ1/MAAI-dependent tyrosine catabolism.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"5929c0fc-205c-5250-9ca4-dc076f2e4df1","slug":"chloral-hydrate","display_name":"Chloral hydrate","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"098eb575-0232-50d0-8620-bfabc07eadea","slug":"gstz1","display_name":"Human maleylacetoacetate isomerase / GSTZ1","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":"4c1b9a61-ba8b-5be4-9c98-4f82b1263911","slug":"dichloroacetate","display_name":"Dichloroacetate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"7d77ea69-5470-5532-a26b-0d3919da7dd3","slug":"maleylacetone","display_name":"Maleylacetone","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"b44c9e27-4bbb-52d3-a022-14cddded5073","slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"},"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":"Eight adults studied at clinical or environmental exposure levels; stable-isotope and metabolite assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Environmental-dose plasma DCA was undetectable; direct tissue-enzyme inhibition was inferred from metabolism, not biopsied. No low-dose equivalence is assumed.","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 drug metabolite can interfere with an amino-acid disposal enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Chloral hydrate, through biotransformation to dichloroacetate, inhibits maleylacetoacetate isomerase and tyrosine catabolism in humans. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25283137/ · DOI 10.1515/dmdi-2014-0015","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":"88b263c3-115a-5033-bd3b-7dd1dc06d4fd","evidence_kind":"source_excerpt","locator":"Lines 300-306","start_line":300,"end_line":306,"excerpt":"## l-tyrosine-chloral-gstz\nA drug metabolite can interfere with an amino-acid disposal enzyme.\nFive days of 1 g/day chloral hydrate produced detectable dichloroacetate and urinary maleylacetone in healthy volunteers, consistent with inhibition of GSTZ1/MAAI-dependent tyrosine catabolism.\nModel: Eight adults studied at clinical or environmental exposure levels; stable-isotope and metabolite assays.\nLimitations: Environmental-dose plasma DCA was undetectable; direct tissue-enzyme inhibition was inferred from metabolism, not biopsied. No low-dose equivalence is assumed.\nEvidence access: Primary abstract\nChloral hydrate, through biotransformation to dichloroacetate, inhibits maleylacetoacetate isomerase and tyrosine catabolism in humans. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25283137/ · DOI 10.1515/dmdi-2014-0015","model_system":"Eight adults studied at clinical or environmental exposure levels; stable-isotope and metabolite assays.","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. Not publisher full text.","file_path":"","sha256":"7777f4440a8bfb14a04ff73e73392ccc45d8ee89f7853ecbcc0027d6f563b8a0","revision_id":"e1206111-3a75-5809-b8e9-231ff809ff1e","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}