Component

Human vitamin D 25-hydroxylase / CYP2R1

Microsomal P450 that hydroxylates D2 and D3 at C25 and accepts reducing equivalents through POR.

5 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. Recombinant human CYP2R1 hydroxylated ergocalciferol at C25 to form 25-hydroxyvitamin D2.

    Human vitamin D 25-hydroxylase / CYP2R1 → 25-Hydroxyvitamin D2 source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Primary abstract, substrate product positions and kinetic comparison.
    experimental_model
    Recombinant human enzyme product identification
    exposure
    D2 substrate incubations; detailed concentration/time not available in abstract.
    limitations
    A shared enzyme does not by itself prove equal long-term serum responses to all D2 and D3 dosing regimens.
    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
    The same first-step enzyme also activates D2.
    primary_references
    [shinkyo2004] Metabolism of vitamin D by human microsomal CYP2R1. (2004). https://pubmed.ncbi.nlm.nih.gov/15465040/ DOI: 10.1016/j.bbrc.2004.09.073
    tissue_or_cell_type
    microsomal enzyme preparation

    Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 302–315

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human enzyme product identification · source_derived_draft · unverified_draft

    ### vd-act-cyp2r1-d2 Recombinant human CYP2R1 hydroxylated ergocalciferol at C25 to form 25-hydroxyvitamin D2. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same first-step enzyme also activates D2. organism: Homo sapiens protein tissue_or_cell_type: microsomal enzyme preparation experimental_model: Recombinant human enzyme product identification limitations: A shared enzyme does not by itself prove equal long-term serum responses to all D2 and D3 dosing regimens. exposure: D2 substrate incubations; detailed concentration/time not available in abstract. cross_nutrient: false evidence_location: Primary abstract, substrate product positions and kinetic comparison. nutrient: Vitamin D2 and D3 [shinkyo2004] Metabolism of vitamin D by human microsomal CYP2R1. (2004). https://pubmed.ncbi.nlm.nih.gov/15465040/ DOI: 10.1016/j.bbrc.2004.09.073
    Complete structured claim and evidence

  2. Recombinant human CYP2R1 hydroxylated cholecalciferol at C25 to produce calcifediol.

    Human vitamin D 25-hydroxylase / CYP2R1 → Calcifediol / 25-hydroxyvitamin D3 source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Primary abstract, substrate product positions and kinetic comparison.
    experimental_model
    Recombinant human enzyme metabolism
    exposure
    D3 substrate series; reported Km 0.45 micromolar and kcat 0.97 per minute.
    limitations
    In-vitro kinetics depend on assay setup and are not serum cutoffs.
    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
    CYP2R1 performs the first activation step for D3.
    primary_references
    [shinkyo2004] Metabolism of vitamin D by human microsomal CYP2R1. (2004). https://pubmed.ncbi.nlm.nih.gov/15465040/ DOI: 10.1016/j.bbrc.2004.09.073
    tissue_or_cell_type
    microsomal enzyme preparation

    Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 287–300

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human enzyme metabolism · source_derived_draft · unverified_draft

    ### vd-act-cyp2r1-d3 Recombinant human CYP2R1 hydroxylated cholecalciferol at C25 to produce calcifediol. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP2R1 performs the first activation step for D3. organism: Homo sapiens protein tissue_or_cell_type: microsomal enzyme preparation experimental_model: Recombinant human enzyme metabolism limitations: In-vitro kinetics depend on assay setup and are not serum cutoffs. exposure: D3 substrate series; reported Km 0.45 micromolar and kcat 0.97 per minute. cross_nutrient: false evidence_location: Primary abstract, substrate product positions and kinetic comparison. nutrient: Vitamin D2 and D3 [shinkyo2004] Metabolism of vitamin D by human microsomal CYP2R1. (2004). https://pubmed.ncbi.nlm.nih.gov/15465040/ DOI: 10.1016/j.bbrc.2004.09.073
    Complete structured claim and evidence

  3. The human CYP2R1-D3 structure contained heme, with the vitamin D3 side chain directed toward this catalytic prosthetic group.

    Human vitamin D 25-hydroxylase / CYP2R1 → Heme source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    evidence_location
    Primary abstract and structure PDB 3C6G.
    experimental_model
    Purified human enzyme crystallography
    exposure
    CYP2R1-D3 crystal complex; PDB 3C6G.
    limitations
    A structural iron requirement is not evidence that iron supplements increase vitamin D activation in iron-replete people.
    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
    D3 activation uses an iron-containing heme enzyme.
    primary_references
    [strushkevich2008] Structural analysis of CYP2R1 in complex with vitamin D3. (2008). https://pubmed.ncbi.nlm.nih.gov/18511070/ DOI: 10.1016/j.jmb.2008.03.065
    tissue_or_cell_type
    CYP2R1 active site

    Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 377–390

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

    ### vd-act-cyp2r1-heme The human CYP2R1-D3 structure contained heme, with the vitamin D3 side chain directed toward this catalytic prosthetic group. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: D3 activation uses an iron-containing heme enzyme. organism: Homo sapiens protein tissue_or_cell_type: CYP2R1 active site experimental_model: Purified human enzyme crystallography limitations: A structural iron requirement is not evidence that iron supplements increase vitamin D activation in iron-replete people. exposure: CYP2R1-D3 crystal complex; PDB 3C6G. cross_nutrient: true evidence_location: Primary abstract and structure PDB 3C6G. nutrient: Vitamin D2 and D3 [strushkevich2008] Structural analysis of CYP2R1 in complex with vitamin D3. (2008). https://pubmed.ncbi.nlm.nih.gov/18511070/ DOI: 10.1016/j.jmb.2008.03.065
    Complete structured claim and evidence

What acts on it

  1. 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

Where it participates (unsigned role)

  1. The patient-derived human CYP2R1 Leu99Pro variant lost detectable D3 25-hydroxylase activity in the expression assays.

    Human CYP2R1 L99P variant → Calcifediol / 25-hydroxyvitamin D3 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    evidence_location
    Results, Figures 3-5 and primary abstract.
    experimental_model
    Patient-derived allele expressed in cells
    exposure
    L99P versus wild-type CYP2R1; D3 biochemical/reporting assays.
    limitations
    The patient had residual circulating metabolites and responded to D2 treatment; this does not prove zero whole-body activation or zero residual D2 activity.
    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
    A CYP2R1 mutation can break the first D3 activation step.
    primary_references
    [cheng2004] Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. (2004). https://pubmed.ncbi.nlm.nih.gov/15128933/ DOI: 10.1073/pnas.0402490101
    tissue_or_cell_type
    heterologous expression model
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 362–375

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient-derived allele expressed in cells · source_derived_draft · unverified_draft

    ### vd-act-cyp2r1-l99p The patient-derived human CYP2R1 Leu99Pro variant lost detectable D3 25-hydroxylase activity in the expression assays. Condition category: machinery_impairment nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A CYP2R1 mutation can break the first D3 activation step. organism: Homo sapiens protein tissue_or_cell_type: heterologous expression model experimental_model: Patient-derived allele expressed in cells limitations: The patient had residual circulating metabolites and responded to D2 treatment; this does not prove zero whole-body activation or zero residual D2 activity. exposure: L99P versus wild-type CYP2R1; D3 biochemical/reporting assays. cross_nutrient: false evidence_location: Results, Figures 3-5 and primary abstract. nutrient: Vitamin D2 and D3 [cheng2004] Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. (2004). https://pubmed.ncbi.nlm.nih.gov/15128933/ DOI: 10.1073/pnas.0402490101
    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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