{"id":"ce5e023f-4e21-5db5-aff7-2a2f36a38fc4","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:b1-hacl2-thdp-dependent-coa-cleavage","predicate":"cleaves","statement":"Affinity-purified human HACL2 produced fatty aldehyde from 2-hydroxy-C18:0-CoA, but not the free acid, and activity depended on added ThDP.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"a63977f7-2754-56df-8168-a1f3fc26193c","mechanism_event_label":"B1 supports HACL2 cleavage only after the fatty acid has been activated onto CoA.","subject":{"id":"e0cf5450-5814-51ea-bd5d-36026a3922f8","slug":"hacl2","display_name":"Human 2-hydroxyacyl-CoA lyase 2 / HACL2","entity_type_key":"protein"},"object":{"id":"00193b5b-f346-5b01-bd7b-7f20cf37d039","slug":"2-hydroxystearoyl-coa","display_name":"2-Hydroxystearoyl-CoA","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"a63977f7-2754-56df-8168-a1f3fc26193c","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:b1-hacl2-thdp-dependent-coa-cleavage-event","event_type":"biochemical_relationship","label":"B1 supports HACL2 cleavage only after the fatty acid has been activated onto CoA.","description":"Affinity-purified human HACL2 produced fatty aldehyde from 2-hydroxy-C18:0-CoA, but not the free acid, and activity depended on added ThDP.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"187db168-8028-5ce6-9f8b-4bc61ebad1a0","slug":"thiamine-diphosphate","display_name":"Thiamine diphosphate","entity_type_key":"small_molecule"},"role":"required cofactor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b5b3829d-0866-5f62-b752-981dc8e8f47c","slug":"2-hydroxystearate","display_name":"2-Hydroxystearate","entity_type_key":"small_molecule"},"role":"inactive free-acid comparator","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8f7b3cb5-4ea9-5f54-99fb-c717d9e50646","slug":"heptadecanal","display_name":"Heptadecanal","entity_type_key":"small_molecule"},"role":"expected one-carbon-shortened aldehyde","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"bff427ab-35f9-59c2-bb24-fd5953bbaec2","slug":"magnesium-ion","display_name":"Mg2+","entity_type_key":"ion"},"role":"included in assay buffer","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"e0cf5450-5814-51ea-bd5d-36026a3922f8","slug":"hacl2","display_name":"Human 2-hydroxyacyl-CoA lyase 2 / HACL2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"00193b5b-f346-5b01-bd7b-7f20cf37d039","slug":"2-hydroxystearoyl-coa","display_name":"2-Hydroxystearoyl-CoA","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"B1-dependent cleavage uses a B5-derived CoA-ester substrate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence","value_text":"[{\"paper_key\": \"kitamura-2017-hacl2\", \"source_bundle\": \"artifacts/thiamine_metabolism_sources.json\", \"passage_ids\": [\"p-32\"], \"locator\": \"generated fatty aldehyde\", \"preservation\": \"Exact text retained in the source bundle; full source document retained when openly retrievable.\"}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human tagged HACL2 purified from HEK293T cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Aldehyde detected by TLC/Schiff staining; expected C17 identity is not a separate mass-spectrometric assignment. Mg omission was not this experiment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient","value_text":"Thiamine (vitamin B1)","comparator":null,"unit":null,"notes":"","entity":{"slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"}},{"dimension":"nutrient_topic","value_text":"Thiamine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"B1 supports HACL2 cleavage only after the fatty acid has been activated onto CoA.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[kitamura-2017-hacl2] Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum (2017). https://pubmed.ncbi.nlm.nih.gov/28289220/ DOI: 10.1073/pnas.1700138114","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified membrane-associated protein","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ec3dc437-596f-5de1-9018-fe08d5d0f1b6","evidence_kind":"source_excerpt","locator":"Lines 1017-1029","start_line":1017,"end_line":1029,"excerpt":"### b1-hacl2-thdp-dependent-coa-cleavage\nAffinity-purified human HACL2 produced fatty aldehyde from 2-hydroxy-C18:0-CoA, but not the free acid, and activity depended on added ThDP.\nCondition category: normal\nnutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: B1 supports HACL2 cleavage only after the fatty acid has been activated onto CoA.\norganism: Homo sapiens\ntissue_or_cell_type: Purified membrane-associated protein\nexperimental_model: Human tagged HACL2 purified from HEK293T cells.\nlimitations: Aldehyde detected by TLC/Schiff staining; expected C17 identity is not a separate mass-spectrometric assignment. Mg omission was not this experiment.\nevidence: [{\"paper_key\": \"kitamura-2017-hacl2\", \"source_bundle\": \"artifacts/thiamine_metabolism_sources.json\", \"passage_ids\": [\"p-32\"], \"locator\": \"generated fatty aldehyde\", \"preservation\": \"Exact text retained in the source bundle; full source document retained when openly retrievable.\"}]\ncross_nutrient: B1-dependent cleavage uses a B5-derived CoA-ester substrate.\nnutrient: Thiamine (vitamin B1)\n[kitamura-2017-hacl2] Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum (2017). https://pubmed.ncbi.nlm.nih.gov/28289220/ DOI: 10.1073/pnas.1700138114","model_system":"Human tagged HACL2 purified from HEK293T cells.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [kitamura-2017-hacl2] Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum (2017). https://pubmed.ncbi.nlm.nih.gov/28289220/ DOI: 10.1073/pnas.1700138114","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"158d2c03-ac8c-589f-8270-c468165ae346","stable_key":"import-46d15d9e-d3b5-544d-ba01-b785aa3e4f42","title":"Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"f376512fb3310141315548015b387833e3af45146e73fb73cd02cee20e4ddb9c","revision_id":"53bc5eda-dec8-58cc-a56f-a9eb4ab036ef","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}