{"id":"3cad1c85-cf7e-5b4a-ac7b-b35b3816a519","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-ftcd-thf-sparing","predicate":"consumes","statement":"Under methotrexate, FTCD depletion preserved THF and increased serine-derived labeling of IMP and TTP relative to controls.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"4ed2c93e-3962-578a-a8b1-00ed761dee14","mechanism_event_label":"Blocking histidine breakdown spared folate for nucleotide production in this drug-stressed setting.","subject":{"id":"fe0cc4ee-60bc-5b41-a073-114f8e4107b6","slug":"ftcd","display_name":"Human formimidoyltransferase cyclodeaminase / FTCD","entity_type_key":"protein"},"object":{"id":"d2b23343-c688-5fc3-9f42-bfac0050552b","slug":"tetrahydrofolate","display_name":"Tetrahydrofolate","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"4ed2c93e-3962-578a-a8b1-00ed761dee14","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-ftcd-thf-sparing-event","event_type":"observed_relationship","label":"Blocking histidine breakdown spared folate for nucleotide production in this drug-stressed setting.","description":"Under methotrexate, FTCD depletion preserved THF and increased serine-derived labeling of IMP and TTP relative to controls.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"fe0cc4ee-60bc-5b41-a073-114f8e4107b6","slug":"ftcd","display_name":"Human formimidoyltransferase cyclodeaminase / FTCD","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d2b23343-c688-5fc3-9f42-bfac0050552b","slug":"tetrahydrofolate","display_name":"Tetrahydrofolate","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":""},{"entity":{"id":"1f13ebf9-42c9-516e-b462-0e1b3952c2a2","slug":"methotrexate","display_name":"Methotrexate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"c882cd0b-9d83-5b07-bd1c-fe4d45657dcb","slug":"l-serine","display_name":"L-Serine","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 full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human cancer cells with FTCD depletion, metabolomics and U-13C-serine tracing.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Measured under methotrexate; do not generalize to normal folate demand or all tissues. 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":"Blocking histidine breakdown spared folate for nucleotide production in this drug-stressed setting.","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},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"9d6b2a69-ffe3-546a-93e4-976072a6172b","evidence_kind":"source_excerpt","locator":"Lines 154-160","start_line":154,"end_line":160,"excerpt":"## histidine-ftcd-thf-sparing\nBlocking histidine breakdown spared folate for nucleotide production in this drug-stressed setting.\nUnder methotrexate, FTCD depletion preserved THF and increased serine-derived labeling of IMP and TTP relative to controls.\nModel: Human cancer cells with FTCD depletion, metabolomics and U-13C-serine tracing.\nLimitations: Measured under methotrexate; do not generalize to normal folate demand or all tissues. 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\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":"Human cancer cells with FTCD depletion, metabolomics and U-13C-serine tracing.","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}