Component

Human 3-hydroxyanthranilate 3,4-dioxygenase / HAAO

Human nonheme iron-containing enzyme of the kynurenine pathway; 3HAO. Human 3-hydroxyanthranilate 3,4-dioxygenase / HAAO. The model and exposure of each linked claim define its scope.

3 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. 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.

    Human 3-hydroxyanthranilate 3,4-dioxygenase / HAAO → Quinolinic acid source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    This step follows the canonical PLP-dependent KYNU reaction and uses a nonheme iron enzyme.
    evidence_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"}
    experimental_model
    Human HAAO cDNA from HepG2 library, expressed in HEK-293 cells and assayed biochemically
    exposure
    Biochemical or structural assay; no dietary intervention
    limitations
    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.
    nutrient_topic
    Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
    organism
    Homo sapiens
    plain_language
    Expressed human HAAO processed the product made by B6-dependent KYNU.
    primary_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
    supporting_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"}]
    tissue_or_cell_type
    HEK-293 cells expressing human HAAO; biochemical activity assay

    Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 521–535

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HAAO cDNA from HepG2 library, expressed in HEK-293 cells and assayed biochemically · source_derived_draft · unverified_draft

    ### b3-pre-haao-human-activity 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. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Expressed human HAAO processed the product made by B6-dependent KYNU. organism: Homo sapiens tissue_or_cell_type: HEK-293 cells expressing human HAAO; biochemical activity assay experimental_model: Human HAAO cDNA from HepG2 library, expressed in HEK-293 cells and assayed biochemically limitations: 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. exposure: Biochemical or structural assay; no dietary intervention cross_nutrient: This step follows the canonical PLP-dependent KYNU reaction and uses a nonheme iron enzyme. evidence_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"} supporting_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"}] [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
    Complete structured claim and evidence

What acts on it

  1. Crystallography and metal characterization identified iron in the active site of human HAAO, with spectroscopic behavior consistent with the ferrous preparation before air oxidation.

    Ferrous iron → Human 3-hydroxyanthranilate 3,4-dioxygenase / HAAO source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Nonheme iron participates in a downstream tryptophan/niacin pathway enzyme; nutritional iron restriction was not tested.
    evidence_span
    {"source_cache": "artifacts/niacin-precursors-sources/haao2017.paragraphs.txt", "locator": "Normalized full-text paragraphs 33–33 (0-based)", "start_char": 22514, "end_char": 24337, "file_sha256": "d02386a59595104ccae2e62943e69030930da86ec005769b469f2001e31a6eb5", "text_sha256": "4c47aa3f5cdc1fd3c776752c345f1d60e4833d0e3b7e8227c574ae086c3b1783"}
    experimental_model
    Purified human HAAO metal-containing crystal structures and ICP-MS/XRF/EPR characterization
    exposure
    Biochemical or structural assay; no dietary intervention
    limitations
    Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.
    nutrient_topic
    Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
    organism
    Homo sapiens
    plain_language
    A second iron-containing enzyme acts farther along the tryptophan route.
    primary_references
    [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
    tissue_or_cell_type
    Purified recombinant protein; no intact tissue

    Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 507–519

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human HAAO metal-containing crystal structures and ICP-MS/XRF/EPR characterization · source_derived_draft · unverified_draft

    ### b3-pre-haao-iron Crystallography and metal characterization identified iron in the active site of human HAAO, with spectroscopic behavior consistent with the ferrous preparation before air oxidation. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second iron-containing enzyme acts farther along the tryptophan route. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human HAAO metal-containing crystal structures and ICP-MS/XRF/EPR characterization limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention cross_nutrient: Nonheme iron participates in a downstream tryptophan/niacin pathway enzyme; nutritional iron restriction was not tested. evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/haao2017.paragraphs.txt", "locator": "Normalized full-text paragraphs 33–33 (0-based)", "start_char": 22514, "end_char": 24337, "file_sha256": "d02386a59595104ccae2e62943e69030930da86ec005769b469f2001e31a6eb5", "text_sha256": "4c47aa3f5cdc1fd3c776752c345f1d60e4833d0e3b7e8227c574ae086c3b1783"} [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
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Two patients with homozygous HAAO truncating variants p.D162* or p.W186* belonged to the reported congenital-malformation cohort with reduced circulating NAD.

    Biallelic HAAO loss-of-function genotype → Circulating NAD content source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    Human 3-hydroxyanthranilate 3,4-dioxygenase / HAAO (affected_enzyme); L-Tryptophan (upstream_precursor); Nicotinamide adenine dinucleotide, oxidized (measured_coenzyme)
    evidence_span
    {"source_cache": "artifacts/niacin-clinical-sources/shi2017.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2c5dcc72d338ac41bd47e4363a149abc503859e2760398fed030f02d5891e2bb", "start_char": 0, "end_char": 1874, "text_sha256": "2c5dcc72d338ac41bd47e4363a149abc503859e2760398fed030f02d5891e2bb"}
    experimental_model
    Four patients from unrelated families; sequencing and circulating metabolites, with parallel enzyme and mouse experiments
    exposure
    Biallelic HAAO or KYNU loss-of-function variants
    limitations
    Rare inherited synthesis impairment is distinct from dietary shortage. Prevention with gestational niacin was demonstrated in mice, not as an established prenatal treatment in humans.
    nutrient_topic
    Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
    organism
    Homo sapiens
    plain_language
    An inherited break in the tryptophan pathway can leave NAD low even when the problem is not simply food intake.
    primary_references
    [nia-clin-shi2017] NAD Deficiency, Congenital Malformations, and Niacin Supplementation. (2017). https://pubmed.ncbi.nlm.nih.gov/28792876/ DOI: 10.1056/nejmoa1616361
    tissue_or_cell_type
    Circulation and congenital organ development
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1235–1247

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four patients from unrelated families; sequencing and circulating metabolites, with parallel enzyme and mouse experiments · source_derived_draft · unverified_draft

    ### nia-clin-haao-human-low-nad Two patients with homozygous HAAO truncating variants p.D162* or p.W186* belonged to the reported congenital-malformation cohort with reduced circulating NAD. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An inherited break in the tryptophan pathway can leave NAD low even when the problem is not simply food intake. organism: Homo sapiens tissue_or_cell_type: Circulation and congenital organ development experimental_model: Four patients from unrelated families; sequencing and circulating metabolites, with parallel enzyme and mouse experiments limitations: Rare inherited synthesis impairment is distinct from dietary shortage. Prevention with gestational niacin was demonstrated in mice, not as an established prenatal treatment in humans. exposure: Biallelic HAAO or KYNU loss-of-function variants cross_nutrient: Human 3-hydroxyanthranilate 3,4-dioxygenase / HAAO (affected_enzyme); L-Tryptophan (upstream_precursor); Nicotinamide adenine dinucleotide, oxidized (measured_coenzyme) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/shi2017.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2c5dcc72d338ac41bd47e4363a149abc503859e2760398fed030f02d5891e2bb", "start_char": 0, "end_char": 1874, "text_sha256": "2c5dcc72d338ac41bd47e4363a149abc503859e2760398fed030f02d5891e2bb"} [nia-clin-shi2017] NAD Deficiency, Congenital Malformations, and Niacin Supplementation. (2017). https://pubmed.ncbi.nlm.nih.gov/28792876/ DOI: 10.1056/nejmoa1616361
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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