Component

Human dihydroorotate dehydrogenase / DHODH

Human dihydroorotate dehydrogenase / DHODH. Species, exposure and limitations are retained in each linked claim.

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. DHODH inactivation increased mitochondrial lipid peroxidation and ferroptosis in the reported GPX4-dependent experimental contexts.

    Human dihydroorotate dehydrogenase / DHODH → Mitochondrial membrane lipid peroxidation source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/coq10-research/33981038.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1af5a97412b5ebf797083a069385c4ed98258e68845692732448bfe061a453b", "start_char": 0, "end_char": 1716, "text_sha256": "b1af5a97412b5ebf797083a069385c4ed98258e68845692732448bfe061a453b"}
    experimental_model
    Genetic and pharmacological cancer-cell studies
    exposure
    DHODH loss or brequinar, with GPX4 inhibition
    limitations
    Pharmacological attribution and relative DHODH contribution were directly challenged in 2023; preserve the dispute rather than generalizing to dietary CoQ effects.
    nutrient_topic
    Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system
    organism
    Human cancer-cell and tumor models
    plain_language
    The effect depended on which other defense route remained available.
    primary_references
    [coq10-p33981038] DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. (2021). https://pubmed.ncbi.nlm.nih.gov/33981038/ DOI: 10.1038/s41586-021-03539-7
    tissue_or_cell_type
    Mitochondrial ferroptosis defense
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 827–838

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic and pharmacological cancer-cell studies · source_derived_draft · unverified_draft

    ### coq10-dhodh-loss DHODH inactivation increased mitochondrial lipid peroxidation and ferroptosis in the reported GPX4-dependent experimental contexts. Condition category: machinery_impairment nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The effect depended on which other defense route remained available. organism: Human cancer-cell and tumor models tissue_or_cell_type: Mitochondrial ferroptosis defense experimental_model: Genetic and pharmacological cancer-cell studies limitations: Pharmacological attribution and relative DHODH contribution were directly challenged in 2023; preserve the dispute rather than generalizing to dietary CoQ effects. exposure: DHODH loss or brequinar, with GPX4 inhibition evidence_span: {"source_cache": "artifacts/coq10-research/33981038.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1af5a97412b5ebf797083a069385c4ed98258e68845692732448bfe061a453b", "start_char": 0, "end_char": 1716, "text_sha256": "b1af5a97412b5ebf797083a069385c4ed98258e68845692732448bfe061a453b"} [coq10-p33981038] DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. (2021). https://pubmed.ncbi.nlm.nih.gov/33981038/ DOI: 10.1038/s41586-021-03539-7
    Complete structured claim and evidence

  2. Truncated human DHODH penetrated the outer lipid leaflet toward membrane-embedded Q10.

    Human dihydroorotate dehydrogenase / DHODH → Ubiquinone-10 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/coq10-research/35269583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bf7a62576c30f509f5b4fbcf701cdf1cb6058de5c75d71e4a5f000394254e29a", "start_char": 0, "end_char": 1389, "text_sha256": "bf7a62576c30f509f5b4fbcf701cdf1cb6058de5c75d71e4a5f000394254e29a"}
    experimental_model
    Neutron reflectometry in supported lipid membranes
    exposure
    Membrane composition and Q10 placement
    limitations
    Truncated human enzyme and synthetic bilayers, not complete mitochondrial nucleotide flux.
    nutrient_topic
    Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system
    organism
    Truncated human DHODH and E. coli DHODH
    plain_language
    The enzyme that helps make pyrimidines must reach its electron acceptor in the membrane.
    primary_references
    [coq10-p35269583] New Insights into the Interaction of Class II Dihydroorotate Dehydrogenases with Ubiquinone in Lipid Bilayers as a Function of Lipid Composition. (2022). https://pubmed.ncbi.nlm.nih.gov/35269583/ DOI: 10.3390/ijms23052437
    tissue_or_cell_type
    Ubiquinone-containing bilayers

    Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 450–461

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Neutron reflectometry in supported lipid membranes · source_derived_draft · unverified_draft

    ### coq10-dhodh-q-access Truncated human DHODH penetrated the outer lipid leaflet toward membrane-embedded Q10. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme that helps make pyrimidines must reach its electron acceptor in the membrane. organism: Truncated human DHODH and E. coli DHODH tissue_or_cell_type: Ubiquinone-containing bilayers experimental_model: Neutron reflectometry in supported lipid membranes limitations: Truncated human enzyme and synthetic bilayers, not complete mitochondrial nucleotide flux. exposure: Membrane composition and Q10 placement evidence_span: {"source_cache": "artifacts/coq10-research/35269583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bf7a62576c30f509f5b4fbcf701cdf1cb6058de5c75d71e4a5f000394254e29a", "start_char": 0, "end_char": 1389, "text_sha256": "bf7a62576c30f509f5b4fbcf701cdf1cb6058de5c75d71e4a5f000394254e29a"} [coq10-p35269583] New Insights into the Interaction of Class II Dihydroorotate Dehydrogenases with Ubiquinone in Lipid Bilayers as a Function of Lipid Composition. (2022). https://pubmed.ncbi.nlm.nih.gov/35269583/ DOI: 10.3390/ijms23052437
    Complete structured claim and evidence

  3. The study reported DHODH-dependent ubiquinol generation as a mitochondrial ferroptosis-defense pathway.

    Human dihydroorotate dehydrogenase / DHODH → Ubiquinone source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/coq10-research/33981038.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1af5a97412b5ebf797083a069385c4ed98258e68845692732448bfe061a453b", "start_char": 0, "end_char": 1716, "text_sha256": "b1af5a97412b5ebf797083a069385c4ed98258e68845692732448bfe061a453b"}
    experimental_model
    Genetic and pharmacological cancer-cell studies
    exposure
    DHODH loss or brequinar, with GPX4 inhibition
    limitations
    Pharmacological attribution and relative DHODH contribution were directly challenged in 2023; preserve the dispute rather than generalizing to dietary CoQ effects.
    nutrient_topic
    Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system
    organism
    Human cancer-cell and tumor models
    plain_language
    A pyrimidine-synthesis enzyme can also contribute reduced CoQ in the studied system.
    primary_references
    [coq10-p33981038] DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. (2021). https://pubmed.ncbi.nlm.nih.gov/33981038/ DOI: 10.1038/s41586-021-03539-7
    tissue_or_cell_type
    Mitochondrial ferroptosis defense

    Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 814–825

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic and pharmacological cancer-cell studies · source_derived_draft · unverified_draft

    ### coq10-dhodh-quinol The study reported DHODH-dependent ubiquinol generation as a mitochondrial ferroptosis-defense pathway. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A pyrimidine-synthesis enzyme can also contribute reduced CoQ in the studied system. organism: Human cancer-cell and tumor models tissue_or_cell_type: Mitochondrial ferroptosis defense experimental_model: Genetic and pharmacological cancer-cell studies limitations: Pharmacological attribution and relative DHODH contribution were directly challenged in 2023; preserve the dispute rather than generalizing to dietary CoQ effects. exposure: DHODH loss or brequinar, with GPX4 inhibition evidence_span: {"source_cache": "artifacts/coq10-research/33981038.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1af5a97412b5ebf797083a069385c4ed98258e68845692732448bfe061a453b", "start_char": 0, "end_char": 1716, "text_sha256": "b1af5a97412b5ebf797083a069385c4ed98258e68845692732448bfe061a453b"} [coq10-p33981038] DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. (2021). https://pubmed.ncbi.nlm.nih.gov/33981038/ DOI: 10.1038/s41586-021-03539-7
    Complete structured claim and evidence

  4. DHODH did not support vitamin K-dependent carboxylation in the tested reporter system despite its separate ubiquinone-associated ferroptosis role.

    Human dihydroorotate dehydrogenase / DHODH → Vitamin K-dependent protein gamma-carboxylation source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/k2-research/36788244.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93", "start_char": 0, "end_char": 1359, "text_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93"}
    experimental_model
    Genome-wide CRISPR screen and reporter biochemistry
    exposure
    FSP1 knockout/inhibition and DHODH comparison
    limitations
    Supports cycle biochemistry; a different ferroptosis defense enzyme need not share the same vitamin K function.
    nutrient_topic
    Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
    organism
    Human vitamin K-dependent reporter cells
    plain_language
    Similar antioxidant roles do not make two enzymes interchangeable.
    primary_references
    [k2-p36788244] A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase. (2023). https://pubmed.ncbi.nlm.nih.gov/36788244/ DOI: 10.1038/s41467-023-36446-8
    tissue_or_cell_type
    Warfarin-resistant quinone reduction

    Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 838–849

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genome-wide CRISPR screen and reporter biochemistry · source_derived_draft · unverified_draft

    ### k2-dhodh-not-k-reductase DHODH did not support vitamin K-dependent carboxylation in the tested reporter system despite its separate ubiquinone-associated ferroptosis role. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Similar antioxidant roles do not make two enzymes interchangeable. organism: Human vitamin K-dependent reporter cells tissue_or_cell_type: Warfarin-resistant quinone reduction experimental_model: Genome-wide CRISPR screen and reporter biochemistry limitations: Supports cycle biochemistry; a different ferroptosis defense enzyme need not share the same vitamin K function. exposure: FSP1 knockout/inhibition and DHODH comparison evidence_span: {"source_cache": "artifacts/k2-research/36788244.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93", "start_char": 0, "end_char": 1359, "text_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93"} [k2-p36788244] A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase. (2023). https://pubmed.ncbi.nlm.nih.gov/36788244/ DOI: 10.1038/s41467-023-36446-8
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. The 2023 study attributed strong ferroptosis sensitization by high concentrations of DHODH inhibitors to concurrent FSP1 inhibition.

    Brequinar → FSP1 / AIFM2 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/coq10-research/37407687.publisher-preview.txt", "locator": "Primary public publisher preview, reference superscripts removed; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dd04682c5ac5215eff4a195cf2fcff7c5f6cf59eb659cc5710e6a2ecd09b0529", "start_char": 0, "end_char": 477, "text_sha256": "dd04682c5ac5215eff4a195cf2fcff7c5f6cf59eb659cc5710e6a2ecd09b0529"}
    experimental_model
    Primary experimental Matters Arising; public publisher preview
    exposure
    DHODH inhibitors at different concentrations
    limitations
    Public preview only; exact dose-response tables not extracted. Do not deny all DHODH effects or invent a universal concentration cutoff.
    nutrient_topic
    Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system
    organism
    Cancer-cell inhibitor and genetic comparisons
    plain_language
    A drug can affect a second enzyme, changing the explanation of its result.
    primary_references
    [coq10-p37407687] DHODH inhibitors sensitize to ferroptosis by FSP1 inhibition. (2023). https://pubmed.ncbi.nlm.nih.gov/37407687/ DOI: 10.1038/s41586-023-06269-0
    tissue_or_cell_type
    DHODH versus FSP1 attribution

    Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 840–851

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary experimental Matters Arising; public publisher preview · source_derived_draft · unverified_draft

    ### coq10-dhodh-offtarget The 2023 study attributed strong ferroptosis sensitization by high concentrations of DHODH inhibitors to concurrent FSP1 inhibition. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A drug can affect a second enzyme, changing the explanation of its result. organism: Cancer-cell inhibitor and genetic comparisons tissue_or_cell_type: DHODH versus FSP1 attribution experimental_model: Primary experimental Matters Arising; public publisher preview limitations: Public preview only; exact dose-response tables not extracted. Do not deny all DHODH effects or invent a universal concentration cutoff. exposure: DHODH inhibitors at different concentrations evidence_span: {"source_cache": "artifacts/coq10-research/37407687.publisher-preview.txt", "locator": "Primary public publisher preview, reference superscripts removed; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dd04682c5ac5215eff4a195cf2fcff7c5f6cf59eb659cc5710e6a2ecd09b0529", "start_char": 0, "end_char": 477, "text_sha256": "dd04682c5ac5215eff4a195cf2fcff7c5f6cf59eb659cc5710e6a2ecd09b0529"} [coq10-p37407687] DHODH inhibitors sensitize to ferroptosis by FSP1 inhibition. (2023). https://pubmed.ncbi.nlm.nih.gov/37407687/ DOI: 10.1038/s41586-023-06269-0
    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