Component

Human cytochrome P450 3A5

Human cytochrome P450 3A5. Species, exposure and limitations are retained in each linked claim.

6 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. CYP3A5 did not form AM1 from cyclosporine in the same comparison in which CYP3A4 did.

    Human cytochrome P450 3A5 → Cyclosporine metabolite AM1 source_derived_draftungraded
    Experimental context and source evidence
    duration
    Not stated here
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    Heterologously expressed human CYP3A4 and CYP3A5
    exposure
    Cyclosporin A
    limitations
    A measured absence in one recombinant system, not a statement that the reaction is impossible in tissue.
    organism
    Heterologously expressed human CYP3A4 and CYP3A5
    plain_language
    CYP3A5 did not form AM1 from cyclosporine in the same comparison in which CYP3A4 did.
    primary_references
    In vitro metabolism of cyclosporine A by human kidney CYP3A5. (2004). https://pubmed.ncbi.nlm.nih.gov/15450954/ DOI: 10.1016/j.bcp.2004.07.012
    route
    In vitro
    tissue
    Oxidative drug metabolism

    Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 201–201

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Heterologously expressed human CYP3A4 and CYP3A5 · source_derived_draft · unverified_draft

    CYP3A5 did not form AM1 from cyclosporine in the same comparison in which CYP3A4 did.
    Complete structured claim and evidence

  2. CYP3A5 formed only AM9 from cyclosporine, not AM1 or AM4N, with substrate inhibition and an apparent Km of 11.3 micromolar.

    Human cytochrome P450 3A5 → Cyclosporine metabolite AM9 source_derived_draftungraded
    Experimental context and source evidence
    duration
    Not stated here
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    Heterologously expressed human CYP3A5
    exposure
    Cyclosporin A
    limitations
    A narrower product range than CYP3A4 in the same comparison. Recorded as the enzyme raising one named metabolite, with the two metabolites it did not form recorded as a null in the companion claim.
    organism
    Heterologously expressed human CYP3A5
    plain_language
    CYP3A5 formed only AM9 from cyclosporine, not AM1 or AM4N, with substrate inhibition and an apparent Km of 11.3 micromolar.
    primary_references
    In vitro metabolism of cyclosporine A by human kidney CYP3A5. (2004). https://pubmed.ncbi.nlm.nih.gov/15450954/ DOI: 10.1016/j.bcp.2004.07.012
    route
    In vitro
    tissue
    Oxidative drug metabolism

    Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 190–190

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Heterologously expressed human CYP3A5 · source_derived_draft · unverified_draft

    CYP3A5 formed only AM9 from cyclosporine, not AM1 or AM4N, with substrate inhibition and an apparent Km of 11.3 micromolar.
    Complete structured claim and evidence

  3. Human CYP3A5 demethylated diosmetin more readily than chrysoeriol in vitro.

    Human cytochrome P450 3A5 → Diosmetin / 4′-O-methylluteolin source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Recombinant human CYP comparison.
    limitations
    Explains a candidate source of urinary bias; not proof of drug induction.
    nutrient_topic
    Luteolin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Luteolin / 3′,4′,5,7-tetrahydroxyflavone
    plain_language
    Downstream removal can reverse the apparent product preference.
    primary_references
    Luteolin is a rare substrate of human catechol-O-methyltransferase favoring a para-methylation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23386290/ · DOI 10.1002/mnfr.201200584

    Luteolin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 116–122

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human CYP comparison. · source_derived_draft · unverified_draft

    ## luteolin-cyp3a5-demethylation Downstream removal can reverse the apparent product preference. Human CYP3A5 demethylated diosmetin more readily than chrysoeriol in vitro. Model: Recombinant human CYP comparison. Limitations: Explains a candidate source of urinary bias; not proof of drug induction. Evidence access: Primary abstract Luteolin is a rare substrate of human catechol-O-methyltransferase favoring a para-methylation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23386290/ · DOI 10.1002/mnfr.201200584
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. CYP3A4/5 catalyzed formation of N-desmethyltamoxifen, the quantitatively major initial pathway.

    Human cytochrome P450 3A4 → Tamoxifen source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/dim-research/15159443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081", "start_char": 0, "end_char": 1544, "text_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081"}
    experimental_model
    Kinetic, inhibition and recombinant-enzyme pathway mapping
    exposure
    Therapeutically relevant substrate concentrations
    limitations
    Biochemical pathway identity; does not attribute the observed DIM interaction to any single CYP or prove clinical cancer outcomes.
    nutrient_topic
    Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
    organism
    Human liver microsomes and expressed CYPs
    plain_language
    The route to active metabolites begins with several linked transformations.
    primary_references
    [dim-p15159443] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. (2004). https://pubmed.ncbi.nlm.nih.gov/15159443/ DOI: 10.1124/jpet.104.065607
    tissue_or_cell_type
    Sequential tamoxifen metabolism

    Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 987–998

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetic, inhibition and recombinant-enzyme pathway mapping · source_derived_draft · unverified_draft

    ### dim-tamoxifen-3a4 CYP3A4/5 catalyzed formation of N-desmethyltamoxifen, the quantitatively major initial pathway. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The route to active metabolites begins with several linked transformations. organism: Human liver microsomes and expressed CYPs tissue_or_cell_type: Sequential tamoxifen metabolism experimental_model: Kinetic, inhibition and recombinant-enzyme pathway mapping limitations: Biochemical pathway identity; does not attribute the observed DIM interaction to any single CYP or prove clinical cancer outcomes. exposure: Therapeutically relevant substrate concentrations evidence_span: {"source_cache": "artifacts/dim-research/15159443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081", "start_char": 0, "end_char": 1544, "text_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081"} [dim-p15159443] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. (2004). https://pubmed.ncbi.nlm.nih.gov/15159443/ DOI: 10.1124/jpet.104.065607
    Complete structured claim and evidence

  2. Clarithromycin was given with atorvastatin to test its effect on atorvastatin pharmacokinetics in healthy volunteers genotyped for CYP3A5.

    Clarithromycin → Plasma atorvastatin exposure source_derived_draftungraded
    Experimental context and source evidence
    duration
    Two phases separated by at least 14 days
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    23 healthy volunteers, 10 CYP3A5*1 expressors and 13 nonexpressors
    exposure
    Single oral atorvastatin 20 mg, with and without clarithromycin 500 mg twice daily for 5 days
    limitations
    A single-dose interaction study in healthy volunteers, and the abstract does not state the size of the exposure change here.
    organism
    23 healthy volunteers, 10 CYP3A5*1 expressors and 13 nonexpressors
    plain_language
    Clarithromycin was given with atorvastatin to test its effect on atorvastatin pharmacokinetics in healthy volunteers genotyped for CYP3A5.
    primary_references
    Effect of cytochrome P450 3A5 genotype on atorvastatin pharmacokinetics and its interaction with clarithromycin. (2011). https://pubmed.ncbi.nlm.nih.gov/21950641/ DOI: 10.1592/phco.31.10.942
    route
    Oral
    tissue
    Plasma atorvastatin acid and atorvastatin lactone

    Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 155–164

    Original AI-assisted curation of twelve primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Findings obtained with mevastatin, simvastatin or the statin class are recorded against those subjects. Study-specific citations, doses, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## clarithromycin-raises-atorvastatin-exposure Clarithromycin was given with atorvastatin to test its effect on atorvastatin pharmacokinetics in healthy volunteers genotyped for CYP3A5. Model/species: 23 healthy volunteers, 10 CYP3A5*1 expressors and 13 nonexpressors Tissue/system: Plasma atorvastatin acid and atorvastatin lactone Exposure: Single oral atorvastatin 20 mg, with and without clarithromycin 500 mg twice daily for 5 days Route: Oral Duration: Two phases separated by at least 14 days Limits: A single-dose interaction study in healthy volunteers, and the abstract does not state the size of the exposure change here. Primary reference: Effect of cytochrome P450 3A5 genotype on atorvastatin pharmacokinetics and its interaction with clarithromycin. (2011). https://pubmed.ncbi.nlm.nih.gov/21950641/ DOI: 10.1592/phco.31.10.942 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  3. Atorvastatin is metabolised mainly by CYP3A4 to para- and ortho-hydroxyatorvastatin, with intrinsic clearance 2.4-fold and 5.0-fold that of CYP3A5.

    Human CYP3A4 activity, probe and compartment specified → Plasma atorvastatin exposure source_derived_draftungraded
    Experimental context and source evidence
    duration
    Not applicable
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    Human liver microsomes and human recombinant CYP3A enzymes
    exposure
    Atorvastatin, enzyme kinetics showing substrate inhibition
    limitations
    The authors conclude the CYP3A5 polymorphism is therefore unlikely to be an important source of between-person variation in atorvastatin disposition.
    organism
    Human liver microsomes and human recombinant CYP3A enzymes
    plain_language
    Atorvastatin is metabolised mainly by CYP3A4 to para- and ortho-hydroxyatorvastatin, with intrinsic clearance 2.4-fold and 5.0-fold that of CYP3A5.
    primary_references
    Contribution of cytochrome P450 3A4 and 3A5 to the metabolism of atorvastatin. (2008). https://pubmed.ncbi.nlm.nih.gov/18720283/ DOI: 10.1080/00498250802334391
    route
    In vitro
    tissue
    Hepatic oxidative metabolism

    Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 144–153

    Original AI-assisted curation of twelve primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Findings obtained with mevastatin, simvastatin or the statin class are recorded against those subjects. Study-specific citations, doses, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## cyp3a4-clears-atorvastatin Atorvastatin is metabolised mainly by CYP3A4 to para- and ortho-hydroxyatorvastatin, with intrinsic clearance 2.4-fold and 5.0-fold that of CYP3A5. Model/species: Human liver microsomes and human recombinant CYP3A enzymes Tissue/system: Hepatic oxidative metabolism Exposure: Atorvastatin, enzyme kinetics showing substrate inhibition Route: In vitro Duration: Not applicable Limits: The authors conclude the CYP3A5 polymorphism is therefore unlikely to be an important source of between-person variation in atorvastatin disposition. Primary reference: Contribution of cytochrome P450 3A4 and 3A5 to the metabolism of atorvastatin. (2008). https://pubmed.ncbi.nlm.nih.gov/18720283/ DOI: 10.1080/00498250802334391 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    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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