{"id":"4d6b3fe8-6c76-5425-85bc-0d68722fd6b7","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-hal-reaction","predicate":"forms","statement":"HAL initiates histidine degradation by converting L-histidine to trans-urocanate with ammonia release.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"44fea28d-0142-5943-882d-e97fedc12189","mechanism_event_label":"The first breakdown enzyme directs histidine toward urocanate.","subject":{"id":"1b502f98-4baa-530c-bc0f-31a38f740dd3","slug":"hal","display_name":"Human histidine ammonia-lyase / HAL","entity_type_key":"protein"},"object":{"id":"86f82ca3-8f80-5c1f-b724-27b78660c2a9","slug":"trans-urocanate","display_name":"trans-Urocanate","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"44fea28d-0142-5943-882d-e97fedc12189","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-hal-reaction-event","event_type":"observed_relationship","label":"The first breakdown enzyme directs histidine toward urocanate.","description":"HAL initiates histidine degradation by converting L-histidine to trans-urocanate with ammonia release.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"1b502f98-4baa-530c-bc0f-31a38f740dd3","slug":"hal","display_name":"Human histidine ammonia-lyase / HAL","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"86f82ca3-8f80-5c1f-b724-27b78660c2a9","slug":"trans-urocanate","display_name":"trans-Urocanate","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"44374451-3436-5136-a8ae-5dcc6d8c353b","slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text; pathway background","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Established reaction in the pathway map of a primary human cancer-cell study; genetic perturbation and metabolomics investigate pathway flux rather than purified kinetics of every individual enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Reaction background is distinguished from the study-specific CRISPR findings below. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"The first breakdown enzyme directs histidine toward urocanate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Histidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"fb4f8f94-cbc9-5a4a-a0fd-63dbb39e0b0c","evidence_kind":"source_excerpt","locator":"Lines 106-112","start_line":106,"end_line":112,"excerpt":"## histidine-hal-reaction\nThe first breakdown enzyme directs histidine toward urocanate.\nHAL initiates histidine degradation by converting L-histidine to trans-urocanate with ammonia release.\nModel: Established reaction in the pathway map of a primary human cancer-cell study; genetic perturbation and metabolomics investigate pathway flux rather than purified kinetics of every individual enzyme.\nLimitations: Reaction background is distinguished from the study-specific CRISPR findings below. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2\nEvidence access: Primary full text; pathway background\nHistidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7","model_system":"Established reaction in the pathway map of a primary human cancer-cell study; genetic perturbation and metabolomics investigate pathway flux rather than purified kinetics of every individual enzyme.","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":"ce59e6c9-1213-523b-9d0b-400b7a81cd1c","stable_key":"import-911fb3c7-8cc3-5667-b677-5682fab67648","title":"L-Histidine: supply, catabolism, histamine, receptors 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":"cb672530ec8b4a4542d0f3957e80ca76bb0449e9f988845b0f7681f623c4ec9b","revision_id":"19a7f26c-d9a1-5411-a81d-025f3d98a452","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}