{"id":"88272e59-ea55-5981-8cf9-edf688747943","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-met-alas1-fxr","predicate":"increases-activity-of","statement":"Chenodeoxycholic acid increased ALAS1 mRNA and enzyme activity in primary human hepatocytes and liver slices through an FXR-linked regulatory mechanism.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"1f1828d2-a621-5610-bbca-362d7d0446d5","mechanism_event_label":"The liver heme pathway has its own regulation in addition to its cofactor needs.","subject":{"id":"e5471bad-9b2f-50cb-ad36-c2ce4518ec85","slug":"chenodeoxycholic-acid","display_name":"Chenodeoxycholic acid","entity_type_key":"small_molecule"},"object":{"id":"d06ccced-50c3-5201-896f-479363f6445d","slug":"alas1","display_name":"Human aminolevulinate synthase 1 / ALAS1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"1f1828d2-a621-5610-bbca-362d7d0446d5","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-met-alas1-fxr-event","event_type":"biochemical_relationship","label":"The liver heme pathway has its own regulation in addition to its cofactor needs.","description":"Chenodeoxycholic acid increased ALAS1 mRNA and enzyme activity in primary human hepatocytes and liver slices through an FXR-linked regulatory mechanism.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e5471bad-9b2f-50cb-ad36-c2ce4518ec85","slug":"chenodeoxycholic-acid","display_name":"Chenodeoxycholic acid","entity_type_key":"small_molecule"},"role":"exposure","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"fcb53473-c0bd-5e70-891f-ab3b48353d25","slug":"nr1h4","display_name":"Human farnesoid X receptor / NR1H4","entity_type_key":"protein"},"role":"regulatory receptor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"d06ccced-50c3-5201-896f-479363f6445d","slug":"alas1","display_name":"Human aminolevulinate synthase 1 / ALAS1","entity_type_key":"protein"},"role":"regulated enzyme","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Hepatic heme synthesis; ALAS1 is distinct from erythroid ALAS2.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Primary human hepatocytes and human liver slices; reporter assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Experimental bile-acid or FXR-agonist treatment","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"No B6 manipulation; this is regulation of the pathway, not proof of a B6 rescue effect.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-b6","display_name":"Vitamin B6","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The liver heme pathway has its own regulation in addition to its cofactor needs.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b6-alas1-2007] Regulation of human liver delta-aminolevulinic acid synthase by bile acids. (2007). https://pubmed.ncbi.nlm.nih.gov/17975826/ DOI: 10.1002/hep.21879","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Primary human hepatocytes and human liver slices","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"8171c91e-9f2f-5819-bba7-14d337b7c9e1","evidence_kind":"source_excerpt","locator":"Lines 835-846","start_line":835,"end_line":846,"excerpt":"### b6-met-alas1-fxr\nChenodeoxycholic acid increased ALAS1 mRNA and enzyme activity in primary human hepatocytes and liver slices through an FXR-linked regulatory mechanism.\nCondition category: normal\nnutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The liver heme pathway has its own regulation in addition to its cofactor needs.\norganism: Homo sapiens\ntissue_or_cell_type: Primary human hepatocytes and human liver slices\nexperimental_model: Primary human hepatocytes and human liver slices; reporter assays\nlimitations: No B6 manipulation; this is regulation of the pathway, not proof of a B6 rescue effect.\ncross_nutrient: Hepatic heme synthesis; ALAS1 is distinct from erythroid ALAS2.\nexposure: Experimental bile-acid or FXR-agonist treatment\n[b6-alas1-2007] Regulation of human liver delta-aminolevulinic acid synthase by bile acids. (2007). https://pubmed.ncbi.nlm.nih.gov/17975826/ DOI: 10.1002/hep.21879","model_system":"Primary human hepatocytes and human liver slices; reporter assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b6-alas1-2007] Regulation of human liver delta-aminolevulinic acid synthase by bile acids. (2007). https://pubmed.ncbi.nlm.nih.gov/17975826/ DOI: 10.1002/hep.21879","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"251773bb-16f5-5903-b135-db4a61d9dec4","stable_key":"import-1310afbd-6010-586e-805d-551d846da421","title":"Vitamin B6: 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":"ef0019b344b2219220f801a84d0d138ff6880c1be1a59540d9034bfa4334f61e","revision_id":"cac3555f-48af-5c52-a84e-add4482c87fb","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}