{"id":"9020faab-91b0-52e5-8c32-fa62c2544897","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-ftcd-cyclodeamination","predicate":"forms","statement":"The cyclodeaminase domain of FTCD converts 5-formimino-THF to 5,10-methenyl-THF.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"84c295e9-1111-57c3-a0bc-1d69986d213a","mechanism_event_label":"A second activity of the same enzyme hands the group into one-carbon metabolism.","subject":{"id":"fe0cc4ee-60bc-5b41-a073-114f8e4107b6","slug":"ftcd","display_name":"Human formimidoyltransferase cyclodeaminase / FTCD","entity_type_key":"protein"},"object":{"id":"7978c99f-fb17-5d91-a9e4-178558bfa69f","slug":"5-10-methenyltetrahydrofolate","display_name":"5,10-Methenyltetrahydrofolate","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"84c295e9-1111-57c3-a0bc-1d69986d213a","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-ftcd-cyclodeamination-event","event_type":"observed_relationship","label":"A second activity of the same enzyme hands the group into one-carbon metabolism.","description":"The cyclodeaminase domain of FTCD converts 5-formimino-THF to 5,10-methenyl-THF.","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":"7978c99f-fb17-5d91-a9e4-178558bfa69f","slug":"5-10-methenyltetrahydrofolate","display_name":"5,10-Methenyltetrahydrofolate","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":"0770ecec-23d8-5681-8c71-c7899075d20e","slug":"5-formiminotetrahydrofolate","display_name":"5-Formiminotetrahydrofolate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","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":"Two catalytic activities are separately searchable; this does not establish folate depletion in a normally nourished person. 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":"A second activity of the same enzyme hands the group into one-carbon metabolism.","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":"b948b7f8-01a8-50d3-afd9-5ebbbccb43b6","evidence_kind":"source_excerpt","locator":"Lines 138-144","start_line":138,"end_line":144,"excerpt":"## histidine-ftcd-cyclodeamination\nA second activity of the same enzyme hands the group into one-carbon metabolism.\nThe cyclodeaminase domain of FTCD converts 5-formimino-THF to 5,10-methenyl-THF.\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: Two catalytic activities are separately searchable; this does not establish folate depletion in a normally nourished person. 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":"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}