{"id":"420e366f-fbb5-5b3a-b657-ad89aa5bb759","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:b3-pre-haao-human-activity","predicate":"supports-production-of","statement":"Human HAAO expressed in HEK-293 cells was enzymatically active toward 3-hydroxyanthranilate, with an apparent substrate Km near 2 micromolar in the study of the quinolinate-producing pathway step.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"30e765e5-900b-5b7d-a875-6676b0d4f9d1","mechanism_event_label":"Expressed human HAAO processed the product made by B6-dependent KYNU.","subject":{"id":"1c637210-ac90-55bd-9af1-8bf3634fa221","slug":"haao","display_name":"Human 3-hydroxyanthranilate 3,4-dioxygenase / HAAO","entity_type_key":"protein"},"object":{"id":"ab444b3c-c8ec-5ada-8450-36ac9934d6b6","slug":"quinolinic-acid","display_name":"Quinolinic acid","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"30e765e5-900b-5b7d-a875-6676b0d4f9d1","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:b3-pre-haao-human-activity-event","event_type":"biochemical_relationship","label":"Expressed human HAAO processed the product made by B6-dependent KYNU.","description":"Human HAAO expressed in HEK-293 cells was enzymatically active toward 3-hydroxyanthranilate, with an apparent substrate Km near 2 micromolar in the study of the quinolinate-producing pathway step.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"1c637210-ac90-55bd-9af1-8bf3634fa221","slug":"haao","display_name":"Human 3-hydroxyanthranilate 3,4-dioxygenase / HAAO","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f73f064a-cc62-5755-8563-41ef84e86df9","slug":"3-hydroxyanthranilate","display_name":"3-Hydroxyanthranilate","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"08f61dcc-fb1a-5a16-b20b-142b09f42406","slug":"2-amino-3-carboxymuconate-semialdehyde","display_name":"2-Amino-3-carboxymuconate 6-semialdehyde","entity_type_key":"small_molecule"},"role":"immediate intermediate before spontaneous cyclization; biochemical pathway context","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"ab444b3c-c8ec-5ada-8450-36ac9934d6b6","slug":"quinolinic-acid","display_name":"Quinolinic acid","entity_type_key":"small_molecule"},"role":"downstream product","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"59d6d1cd-df32-5b58-b950-3188bc7b95d6","slug":"iron-ii","display_name":"Ferrous iron","entity_type_key":"ion"},"role":"enzyme metal","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"This step follows the canonical PLP-dependent KYNU reaction and uses a nonheme iron enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/niacin-precursors-sources/haao1994.abstract.txt\", \"locator\": \"Indexed primary abstract\", \"start_char\": 0, \"end_char\": 1874, \"file_sha256\": \"a79697b138bcb2957b0eff9580266c7879a1c5853aba34898f891559b4e435f8\", \"text_sha256\": \"a79697b138bcb2957b0eff9580266c7879a1c5853aba34898f891559b4e435f8\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human HAAO cDNA from HepG2 library, expressed in HEK-293 cells and assayed biochemically","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Biochemical or structural assay; no dietary intervention","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The immediate HAAO product is ACMS, which cyclizes to quinolinate; the indexed abstract uses pathway-level quinolinate wording. This claim does not assert direct NAD+ synthesis.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Niacin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"niacin","display_name":"Niacin (vitamin B3)","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Expressed human HAAO processed the product made by B6-dependent KYNU.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b3-pre-haao1994] Molecular cloning and functional expression of human 3-hydroxyanthranilic-acid dioxygenase. (1994). https://pubmed.ncbi.nlm.nih.gov/7514594/ DOI: 10.1016/s0021-9258(17)36717-0\n[b3-pre-haao2017] Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site. (2017). https://pubmed.ncbi.nlm.nih.gov/28375145/ DOI: 10.1107/s2059798317002029","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"supporting_evidence_spans","value_text":"[{\"source_cache\": \"artifacts/niacin-precursors-sources/haao2017.paragraphs.txt\", \"locator\": \"Normalized full-text paragraphs 14–14 (0-based)\", \"start_char\": 4395, \"end_char\": 7197, \"file_sha256\": \"d02386a59595104ccae2e62943e69030930da86ec005769b469f2001e31a6eb5\", \"text_sha256\": \"3b52b56d1b671c24721b47204cd30d19cd004f8a461fecd4875e94d3f491dbf6\"}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HEK-293 cells expressing human HAAO; biochemical activity assay","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"bfa65054-842b-5173-9840-86f949b689e1","evidence_kind":"source_excerpt","locator":"Lines 521-535","start_line":521,"end_line":535,"excerpt":"### b3-pre-haao-human-activity\nHuman HAAO expressed in HEK-293 cells was enzymatically active toward 3-hydroxyanthranilate, with an apparent substrate Km near 2 micromolar in the study of the quinolinate-producing pathway step.\nCondition category: normal\nnutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Expressed human HAAO processed the product made by B6-dependent KYNU.\norganism: Homo sapiens\ntissue_or_cell_type: HEK-293 cells expressing human HAAO; biochemical activity assay\nexperimental_model: Human HAAO cDNA from HepG2 library, expressed in HEK-293 cells and assayed biochemically\nlimitations: The immediate HAAO product is ACMS, which cyclizes to quinolinate; the indexed abstract uses pathway-level quinolinate wording. This claim does not assert direct NAD+ synthesis.\nexposure: Biochemical or structural assay; no dietary intervention\ncross_nutrient: This step follows the canonical PLP-dependent KYNU reaction and uses a nonheme iron enzyme.\nevidence_span: {\"source_cache\": \"artifacts/niacin-precursors-sources/haao1994.abstract.txt\", \"locator\": \"Indexed primary abstract\", \"start_char\": 0, \"end_char\": 1874, \"file_sha256\": \"a79697b138bcb2957b0eff9580266c7879a1c5853aba34898f891559b4e435f8\", \"text_sha256\": \"a79697b138bcb2957b0eff9580266c7879a1c5853aba34898f891559b4e435f8\"}\nsupporting_evidence_spans: [{\"source_cache\": \"artifacts/niacin-precursors-sources/haao2017.paragraphs.txt\", \"locator\": \"Normalized full-text paragraphs 14–14 (0-based)\", \"start_char\": 4395, \"end_char\": 7197, \"file_sha256\": \"d02386a59595104ccae2e62943e69030930da86ec005769b469f2001e31a6eb5\", \"text_sha256\": \"3b52b56d1b671c24721b47204cd30d19cd004f8a461fecd4875e94d3f491dbf6\"}]\n[b3-pre-haao1994] Molecular cloning and functional expression of human 3-hydroxyanthranilic-acid dioxygenase. (1994). https://pubmed.ncbi.nlm.nih.gov/7514594/ DOI: 10.1016/s0021-9258(17)36717-0\n[b3-pre-haao2017] Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site. (2017). https://pubmed.ncbi.nlm.nih.gov/28375145/ DOI: 10.1107/s2059798317002029","model_system":"Human HAAO cDNA from HepG2 library, expressed in HEK-293 cells and assayed biochemically","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b3-pre-haao1994] Molecular cloning and functional expression of human 3-hydroxyanthranilic-acid dioxygenase. (1994). https://pubmed.ncbi.nlm.nih.gov/7514594/ DOI: 10.1016/s0021-9258(17)36717-0; [b3-pre-haao2017] Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site. (2017). https://pubmed.ncbi.nlm.nih.gov/28375145/ DOI: 10.1107/s2059798317002029","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"a62b7b5b-786a-57e9-85e9-67c6912a5054","stable_key":"import-a9dd23c6-978a-5755-8bd8-f29bd1fe0cda","title":"Niacin: NAD metabolism, 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":"a8cac59639322f74812ce12eef338c2f6c385c04cc4af6ab511fc7c972f0c2e6","revision_id":"bec8fc45-12e7-5f75-a814-5d72ed015d01","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}