Component

NADPH-cytochrome P450 oxidoreductase / POR

Independent protein identity; organism and experimental state are specified on individual claims.

7 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. Crystallography and extracted-flavin analysis identified FAD bound to recombinant human POR.

    NADPH-cytochrome P450 oxidoreductase / POR → FAD source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    evidence_location
    Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC.
    experimental_model
    Human POR structure and flavin-content analysis
    exposure
    Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays.
    limitations
    The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record.
    nutrient
    Vitamin D2 and D3 · Vitamin D2 and D3
    nutrient_topic
    Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
    organism
    Homo sapiens protein
    plain_language
    POR carries a FAD cofactor derived from vitamin B2.
    primary_references
    [xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
    tissue_or_cell_type
    POR cofactor-binding domain

    Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 407–420

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human POR structure and flavin-content analysis · source_derived_draft · unverified_draft

    ### vd-act-por-fad Crystallography and extracted-flavin analysis identified FAD bound to recombinant human POR. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: POR carries a FAD cofactor derived from vitamin B2. organism: Homo sapiens protein tissue_or_cell_type: POR cofactor-binding domain experimental_model: Human POR structure and flavin-content analysis limitations: The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record. exposure: Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays. cross_nutrient: true evidence_location: Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC. nutrient: Vitamin D2 and D3 [xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
    Complete structured claim and evidence

  2. Crystallography and extracted-flavin analysis identified FMN bound to recombinant human POR.

    NADPH-cytochrome P450 oxidoreductase / POR → Flavin mononucleotide source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    evidence_location
    Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC.
    experimental_model
    Human POR structure and flavin-content analysis
    exposure
    Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays.
    limitations
    The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record.
    nutrient
    Vitamin D2 and D3 · Vitamin D2 and D3
    nutrient_topic
    Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
    organism
    Homo sapiens protein
    plain_language
    POR carries a FMN cofactor derived from vitamin B2.
    primary_references
    [xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
    tissue_or_cell_type
    POR cofactor-binding domain

    Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 422–435

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human POR structure and flavin-content analysis · source_derived_draft · unverified_draft

    ### vd-act-por-fmn Crystallography and extracted-flavin analysis identified FMN bound to recombinant human POR. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: POR carries a FMN cofactor derived from vitamin B2. organism: Homo sapiens protein tissue_or_cell_type: POR cofactor-binding domain experimental_model: Human POR structure and flavin-content analysis limitations: The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record. exposure: Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays. cross_nutrient: true evidence_location: Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC. nutrient: Vitamin D2 and D3 [xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
    Complete structured claim and evidence

  3. Human POR supported CYP2R1-mediated cholecalciferol 25-hydroxylation, with maximal measured activity near a 4:1 POR:CYP2R1 molar ratio.

    NADPH-cytochrome P450 oxidoreductase / POR → Human vitamin D 25-hydroxylase / CYP2R1 source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    evidence_location
    Primary Figure 2C; Methods 2.3 and reconstitution assays.
    experimental_model
    Purified enzyme and phospholipid-vesicle reconstitution
    exposure
    0.25 micromolar CYP2R1; varied POR; 30 min at 37 C; Figure 2C.
    limitations
    Assay optimum is not a tissue expression target or a vitamin dosing requirement.
    nutrient
    Vitamin D2 and D3 · Vitamin D2 and D3
    nutrient_topic
    Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
    organism
    Homo sapiens proteins
    plain_language
    CYP2R1 needs an electron-supplying partner.
    primary_references
    [cheng2018] Properties of purified CYP2R1 in a reconstituted membrane environment and its 25-hydroxylation of 20-hydroxyvitamin D3. (2018). https://pubmed.ncbi.nlm.nih.gov/28716760/ DOI: 10.1016/j.jsbmb.2017.07.011
    tissue_or_cell_type
    reconstituted membrane

    Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 392–405

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzyme and phospholipid-vesicle reconstitution · source_derived_draft · unverified_draft

    ### vd-act-por-support Human POR supported CYP2R1-mediated cholecalciferol 25-hydroxylation, with maximal measured activity near a 4:1 POR:CYP2R1 molar ratio. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP2R1 needs an electron-supplying partner. organism: Homo sapiens proteins tissue_or_cell_type: reconstituted membrane experimental_model: Purified enzyme and phospholipid-vesicle reconstitution limitations: Assay optimum is not a tissue expression target or a vitamin dosing requirement. exposure: 0.25 micromolar CYP2R1; varied POR; 30 min at 37 C; Figure 2C. cross_nutrient: true evidence_location: Primary Figure 2C; Methods 2.3 and reconstitution assays. nutrient: Vitamin D2 and D3 [cheng2018] Properties of purified CYP2R1 in a reconstituted membrane environment and its 25-hydroxylation of 20-hydroxyvitamin D3. (2018). https://pubmed.ncbi.nlm.nih.gov/28716760/ DOI: 10.1016/j.jsbmb.2017.07.011
    Complete structured claim and evidence

What acts on it

  1. CYP2A6 K476E had lower affinity for NADPH-P450 reductase, contributing to reduced catalytic activity.

    Human CYP2A6 K476E experimental variant → NADPH-cytochrome P450 oxidoreductase / POR source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/coumarin-research/16207711.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7", "start_char": 0, "end_char": 1740, "text_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7"}
    experimental_model
    Random mutagenesis of recombinant human CYP2A6
    exposure
    Wild-type enzyme and selected activity-reducing mutants
    limitations
    Engineered protein dysfunction is not nutrient deficiency; no rescue by nutritional supplementation was tested.
    nutrient_topic
    Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
    organism
    Human engineered protein
    plain_language
    A protein change weakened its connection to the electron donor.
    primary_references
    [coumarin-p16207711] Analysis of coumarin 7-hydroxylation activity of cytochrome P450 2A6 using random mutagenesis. (2005). https://pubmed.ncbi.nlm.nih.gov/16207711/ DOI: 10.1074/jbc.m508171200
    tissue_or_cell_type
    Reconstituted enzyme system
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 605–616

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Random mutagenesis of recombinant human CYP2A6 · source_derived_draft · unverified_draft

    ### coumarin-k476e-por CYP2A6 K476E had lower affinity for NADPH-P450 reductase, contributing to reduced catalytic activity. Condition category: machinery_impairment nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A protein change weakened its connection to the electron donor. organism: Human engineered protein tissue_or_cell_type: Reconstituted enzyme system experimental_model: Random mutagenesis of recombinant human CYP2A6 limitations: Engineered protein dysfunction is not nutrient deficiency; no rescue by nutritional supplementation was tested. exposure: Wild-type enzyme and selected activity-reducing mutants evidence_span: {"source_cache": "artifacts/coumarin-research/16207711.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7", "start_char": 0, "end_char": 1740, "text_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7"} [coumarin-p16207711] Analysis of coumarin 7-hydroxylation activity of cytochrome P450 2A6 using random mutagenesis. (2005). https://pubmed.ncbi.nlm.nih.gov/16207711/ DOI: 10.1074/jbc.m508171200
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Recombinant human CYP26A1 hydroxylated all-trans-retinoic acid to 4-hydroxy-retinoic acid.

    Cytochrome P450 26A1 / CYP26A1 → 4-Hydroxy-all-trans-retinoic acid source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    NADPH and heme-containing P450 machinery support retinoid oxidation; nutritional deficiency was not tested.
    evidence_location
    Abstract
    experimental_model
    Human CYP26A1/CYP26B1 expressed in insect cells; purified/reconstituted metabolism and tissue assays.
    exposure
    All-trans-retinoic-acid concentration series with P450 reductase and NADPH.
    limitations
    Assay kinetics are not whole-body clearance; hydroxylated products are not assumed biologically inert.
    nutrient_topic
    Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
    organism
    Homo sapiens recombinant protein in insect cells
    outcome
    Recombinant human CYP26A1 hydroxylated all-trans-retinoic acid to 4-hydroxy-retinoic acid.
    plain_language
    This P450 begins oxidative removal of the signaling retinoid.
    primary_references
    [va-topletz-2012] Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases (2012). https://pubmed.ncbi.nlm.nih.gov/22020119/ DOI: 10.1016/j.bcp.2011.10.007
    tissue_or_cell_type
    Reconstituted enzyme/microsomes

    Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 601–614

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CYP26A1/CYP26B1 expressed in insect cells; purified/reconstituted metabolism and tissue assays. · source_derived_draft · unverified_draft

    ### va-cyp26a1-primary-hydroxylation Recombinant human CYP26A1 hydroxylated all-trans-retinoic acid to 4-hydroxy-retinoic acid. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: This P450 begins oxidative removal of the signaling retinoid. organism: Homo sapiens recombinant protein in insect cells tissue_or_cell_type: Reconstituted enzyme/microsomes experimental_model: Human CYP26A1/CYP26B1 expressed in insect cells; purified/reconstituted metabolism and tissue assays. limitations: Assay kinetics are not whole-body clearance; hydroxylated products are not assumed biologically inert. exposure: All-trans-retinoic-acid concentration series with P450 reductase and NADPH. outcome: Recombinant human CYP26A1 hydroxylated all-trans-retinoic acid to 4-hydroxy-retinoic acid. evidence_location: Abstract cross_nutrient: NADPH and heme-containing P450 machinery support retinoid oxidation; nutritional deficiency was not tested. [va-topletz-2012] Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases (2012). https://pubmed.ncbi.nlm.nih.gov/22020119/ DOI: 10.1016/j.bcp.2011.10.007
    Complete structured claim and evidence

  2. Recombinant human CYP26B1 formed 4-hydroxy-retinoic acid from all-trans-retinoic acid.

    Cytochrome P450 26B1 / CYP26B1 → 4-Hydroxy-all-trans-retinoic acid source_derived_draftungraded
    Experimental context and source evidence
    evidence_location
    Abstract
    experimental_model
    Human CYP26A1/CYP26B1 expressed in insect cells; purified/reconstituted metabolism and tissue assays.
    exposure
    Substrate series with NADPH and P450 reductase.
    limitations
    Lower in vitro turnover than CYP26A1 does not mean lower importance in every tissue.
    nutrient_topic
    Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
    organism
    Homo sapiens recombinant protein in insect cells
    outcome
    Recombinant human CYP26B1 formed 4-hydroxy-retinoic acid from all-trans-retinoic acid.
    plain_language
    A second independent P450 enzyme also removes the signaling precursor.
    primary_references
    [va-topletz-2012] Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases (2012). https://pubmed.ncbi.nlm.nih.gov/22020119/ DOI: 10.1016/j.bcp.2011.10.007
    tissue_or_cell_type
    Reconstituted enzyme/microsomes

    Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 616–628

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CYP26A1/CYP26B1 expressed in insect cells; purified/reconstituted metabolism and tissue assays. · source_derived_draft · unverified_draft

    ### va-cyp26b1-primary-hydroxylation Recombinant human CYP26B1 formed 4-hydroxy-retinoic acid from all-trans-retinoic acid. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second independent P450 enzyme also removes the signaling precursor. organism: Homo sapiens recombinant protein in insect cells tissue_or_cell_type: Reconstituted enzyme/microsomes experimental_model: Human CYP26A1/CYP26B1 expressed in insect cells; purified/reconstituted metabolism and tissue assays. limitations: Lower in vitro turnover than CYP26A1 does not mean lower importance in every tissue. exposure: Substrate series with NADPH and P450 reductase. outcome: Recombinant human CYP26B1 formed 4-hydroxy-retinoic acid from all-trans-retinoic acid. evidence_location: Abstract [va-topletz-2012] Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases (2012). https://pubmed.ncbi.nlm.nih.gov/22020119/ DOI: 10.1016/j.bcp.2011.10.007
    Complete structured claim and evidence

  3. K476E reduced NADPH oxidation and ferric-enzyme reduction; excess reductase did not restore wild-type coumarin hydroxylation.

    Human CYP2A6 K476E experimental variant → Coumarin 7-hydroxylation source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/coumarin-research/16207711.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7", "start_char": 0, "end_char": 1740, "text_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7"}
    experimental_model
    Random mutagenesis of recombinant human CYP2A6
    exposure
    Wild-type enzyme and selected activity-reducing mutants
    limitations
    Engineered protein dysfunction is not nutrient deficiency; no rescue by nutritional supplementation was tested.
    nutrient_topic
    Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
    organism
    Human engineered protein
    plain_language
    Adding more partner enzyme did not fully repair this variant.
    primary_references
    [coumarin-p16207711] Analysis of coumarin 7-hydroxylation activity of cytochrome P450 2A6 using random mutagenesis. (2005). https://pubmed.ncbi.nlm.nih.gov/16207711/ DOI: 10.1074/jbc.m508171200
    tissue_or_cell_type
    Reconstituted enzyme system
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 618–629

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Random mutagenesis of recombinant human CYP2A6 · source_derived_draft · unverified_draft

    ### coumarin-k476e-hydroxylation K476E reduced NADPH oxidation and ferric-enzyme reduction; excess reductase did not restore wild-type coumarin hydroxylation. Condition category: machinery_impairment nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding more partner enzyme did not fully repair this variant. organism: Human engineered protein tissue_or_cell_type: Reconstituted enzyme system experimental_model: Random mutagenesis of recombinant human CYP2A6 limitations: Engineered protein dysfunction is not nutrient deficiency; no rescue by nutritional supplementation was tested. exposure: Wild-type enzyme and selected activity-reducing mutants evidence_span: {"source_cache": "artifacts/coumarin-research/16207711.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7", "start_char": 0, "end_char": 1740, "text_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7"} [coumarin-p16207711] Analysis of coumarin 7-hydroxylation activity of cytochrome P450 2A6 using random mutagenesis. (2005). https://pubmed.ncbi.nlm.nih.gov/16207711/ DOI: 10.1074/jbc.m508171200
    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.

    Evidence, AI assistance and curation standards