Component

SDHA

Catalytic subunit of mitochondrial respiratory complex II.

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. Cryo-EM of active human complex II resolved FAD within SDHA and located the succinate-fumarate active site between its FAD-binding and capping domains.

    SDHA → FAD source_derived_draftungraded
    Experimental context and source evidence
    evidence_spans
    [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 3, "char_start": 0, "char_end": 2164, "evidence_access": "full-text"}]
    experimental_model
    Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays.
    exposure
    No nutrient intervention; structural or biochemical characterization.
    limitations
    Structure establishes location, not nutritional sensitivity.
    nutrient_topic
    Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
    organism
    Homo sapiens
    plain_language
    The B2-derived cofactor sits in the catalytic SDHA part of complex II.
    primary_references
    [du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120
    tissue_or_cell_type
    HEK293F-derived purified complex II

    Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 636–647

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. · source_derived_draft · unverified_draft

    ### b2-met-human-sdha-fad Cryo-EM of active human complex II resolved FAD within SDHA and located the succinate-fumarate active site between its FAD-binding and capping domains. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The B2-derived cofactor sits in the catalytic SDHA part of complex II. organism: Homo sapiens tissue_or_cell_type: HEK293F-derived purified complex II experimental_model: Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. limitations: Structure establishes location, not nutritional sensitivity. exposure: No nutrient intervention; structural or biochemical characterization. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 3, "char_start": 0, "char_end": 2164, "evidence_access": "full-text"}] [du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120
    Complete structured claim and evidence

What acts on it

  1. SDHAF2 knockout and independent siRNA knockdown in MDA-MB-231 cells retained SDHA flavination; knockout cells also retained measurable SDH and succinate-quinone reductase activity.

    Human SDHAF2 knockout state → SDHA source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_spans
    [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC5076811", "locator": "HTML article p", "paragraph_index": 20, "char_start": 0, "char_end": 1274, "evidence_access": "full-text"}]
    experimental_model
    Human MDA-MB-231 breast cancer cells with CRISPR SDHAF2 disruption and independent siRNA knockdown.
    exposure
    CRISPR knockout, two independent siRNAs; FAD fluorescence/antibody and enzyme activity.
    limitations
    Cell-line-specific redundancy is not proof that SDHAF2 is dispensable in every tissue; contextual boundary to yeast and tumor findings.
    nutrient_topic
    Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
    organism
    Homo sapiens
    plain_language
    This breast cancer cell model assembled active, flavinated complex II without SDHAF2.
    primary_references
    [bezawork-geleta-2016-sdhaf2] The Assembly Factor SDHAF2 Is Dispensable for Flavination of the Catalytic Subunit of Mitochondrial Complex II in Breast Cancer Cells (2016). https://pubmed.ncbi.nlm.nih.gov/27587393/ DOI: 10.1074/jbc.c116.755017
    tissue_or_cell_type
    MDA-MB-231 breast cancer cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 715–726

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MDA-MB-231 breast cancer cells with CRISPR SDHAF2 disruption and independent siRNA knockdown. · source_derived_draft · unverified_draft

    ### b2-met-sdhaf2-knockout-context-boundary SDHAF2 knockout and independent siRNA knockdown in MDA-MB-231 cells retained SDHA flavination; knockout cells also retained measurable SDH and succinate-quinone reductase activity. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This breast cancer cell model assembled active, flavinated complex II without SDHAF2. organism: Homo sapiens tissue_or_cell_type: MDA-MB-231 breast cancer cells experimental_model: Human MDA-MB-231 breast cancer cells with CRISPR SDHAF2 disruption and independent siRNA knockdown. limitations: Cell-line-specific redundancy is not proof that SDHAF2 is dispensable in every tissue; contextual boundary to yeast and tumor findings. exposure: CRISPR knockout, two independent siRNAs; FAD fluorescence/antibody and enzyme activity. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC5076811", "locator": "HTML article p", "paragraph_index": 20, "char_start": 0, "char_end": 1274, "evidence_access": "full-text"}] [bezawork-geleta-2016-sdhaf2] The Assembly Factor SDHAF2 Is Dispensable for Flavination of the Catalytic Subunit of Mitochondrial Complex II in Breast Cancer Cells (2016). https://pubmed.ncbi.nlm.nih.gov/27587393/ DOI: 10.1074/jbc.c116.755017
    Complete structured claim and evidence

  2. Wild-type human SDHAF2 coimmunoprecipitated SDHA from transfected HEK293 cells.

    Human succinate dehydrogenase assembly factor 2 / SDHAF2 → SDHA source_derived_draftungraded
    Experimental context and source evidence
    evidence_spans
    [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3881419", "locator": "HTML article p", "paragraph_index": 21, "char_start": 0, "char_end": 672, "evidence_access": "full-text"}]
    experimental_model
    Yeast genetics, recombinant coexpression, human HEK293 binding assays and familial paraganglioma tissue.
    exposure
    No nutrient intervention; structural or biochemical characterization.
    limitations
    Coimmunoprecipitation does not by itself establish the chemistry of FAD attachment.
    nutrient_topic
    Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
    organism
    Homo sapiens
    plain_language
    The human assembly factor physically associated with the flavin-bearing subunit.
    primary_references
    [hao-2009-sdh5] SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma (2009). https://pubmed.ncbi.nlm.nih.gov/19628817/ DOI: 10.1126/science.1175689
    tissue_or_cell_type
    HEK293 cells

    Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 676–687

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Yeast genetics, recombinant coexpression, human HEK293 binding assays and familial paraganglioma tissue. · source_derived_draft · unverified_draft

    ### b2-met-sdhaf2-sdha-binding Wild-type human SDHAF2 coimmunoprecipitated SDHA from transfected HEK293 cells. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The human assembly factor physically associated with the flavin-bearing subunit. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: Yeast genetics, recombinant coexpression, human HEK293 binding assays and familial paraganglioma tissue. limitations: Coimmunoprecipitation does not by itself establish the chemistry of FAD attachment. exposure: No nutrient intervention; structural or biochemical characterization. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3881419", "locator": "HTML article p", "paragraph_index": 21, "char_start": 0, "char_end": 672, "evidence_access": "full-text"}] [hao-2009-sdh5] SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma (2009). https://pubmed.ncbi.nlm.nih.gov/19628817/ DOI: 10.1126/science.1175689
    Complete structured claim and evidence

  3. SELENOO transfers AMP from ATP onto SDHA in the reported AMPylation experiments.

    SELENOO → SDHA source_derived_draftliterature_reviewed:direct_experimental
    Experimental context and source evidence
    cell_type
    melanoma-related assays
    experimental_model
    Biochemical substrate experiments
    limitations
    Keep this reaction separate from NAD hydrolysis.
    organism
    mammalian

    Selenium: literature corrections and mechanism additions · lines 462–472

    Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Biochemical substrate experiments · secondary_verified · secondary_verified

    ## selenoo-ampylates-sdha SELENOO can attach an AMP group to a respiratory enzyme. SELENOO transfers AMP from ATP onto SDHA in the reported AMPylation experiments. Organism: mammalian Cell type: melanoma-related assays Experimental model: Biochemical substrate experiments Limitations: Keep this reaction separate from NAD hydrolysis. Primary reference: [Selenoprotein O Promotes Melanoma Metastasis and Regulates Mitochondrial Complex II Activity](https://pubmed.ncbi.nlm.nih.gov/39700395/)
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Purified human complex II coupled succinate oxidation to ubiquinone reduction in a UQ1/DCIP assay, with reported kcat 0.67 +/- 0.02 per second.

    Respiratory complex II → Ubiquinone-1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_spans
    [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 2, "char_start": 0, "char_end": 1105, "evidence_access": "full-text"}]
    experimental_model
    Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays.
    exposure
    No nutrient intervention; structural or biochemical characterization.
    limitations
    UQ1/DCIP are assay reagents; the isolated turnover value is not whole-cell ATP production.
    nutrient_topic
    Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
    organism
    Homo sapiens
    plain_language
    The intact complex moves electrons from succinate into a quinone carrier.
    primary_references
    [du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120
    tissue_or_cell_type
    HEK293F-derived purified complex II

    Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 663–674

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. · source_derived_draft · unverified_draft

    ### b2-met-human-complex-ii-succinate-quinone Purified human complex II coupled succinate oxidation to ubiquinone reduction in a UQ1/DCIP assay, with reported kcat 0.67 +/- 0.02 per second. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The intact complex moves electrons from succinate into a quinone carrier. organism: Homo sapiens tissue_or_cell_type: HEK293F-derived purified complex II experimental_model: Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. limitations: UQ1/DCIP are assay reagents; the isolated turnover value is not whole-cell ATP production. exposure: No nutrient intervention; structural or biochemical characterization. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 2, "char_start": 0, "char_end": 1105, "evidence_access": "full-text"}] [du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120
    Complete structured claim and evidence

  2. Human complex II structure and EPR resolved SDHB-associated [2Fe-2S], [4Fe-4S] and [3Fe-4S] redox centers adjacent to its SDHA FAD system.

    Human succinate dehydrogenase iron-sulfur subunit / SDHB → [4Fe-4S] iron-sulfur cluster source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    B2-derived FAD and iron-containing redox centers cooperate within one respiratory complex.
    evidence_spans
    [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 2, "char_start": 0, "char_end": 1105, "evidence_access": "full-text"}]
    experimental_model
    Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays.
    exposure
    No nutrient intervention; structural or biochemical characterization.
    limitations
    Structural co-dependence does not show that B2 corrects iron deficiency or that iron supplementation improves this reaction.
    nutrient_topic
    Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
    organism
    Homo sapiens
    plain_language
    Complex II couples a B2-derived flavin with separate iron-sulfur centers.
    primary_references
    [du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120
    tissue_or_cell_type
    HEK293F-derived purified complex II

    Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 649–661

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. · source_derived_draft · unverified_draft

    ### b2-met-human-sdhb-iron-sulfur Human complex II structure and EPR resolved SDHB-associated [2Fe-2S], [4Fe-4S] and [3Fe-4S] redox centers adjacent to its SDHA FAD system. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Complex II couples a B2-derived flavin with separate iron-sulfur centers. organism: Homo sapiens tissue_or_cell_type: HEK293F-derived purified complex II experimental_model: Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. limitations: Structural co-dependence does not show that B2 corrects iron deficiency or that iron supplementation improves this reaction. exposure: No nutrient intervention; structural or biochemical characterization. cross_nutrient: B2-derived FAD and iron-containing redox centers cooperate within one respiratory complex. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 2, "char_start": 0, "char_end": 1105, "evidence_access": "full-text"}] [du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120
    Complete structured claim and evidence

  3. SELENOO deletion increased complex-II activity in the tested melanoma model.

    SELENOO → Respiratory complex II source_derived_draftliterature_reviewed:direct_experimental
    Experimental context and source evidence
    cell_type
    melanoma
    experimental_model
    Selenoo deletion
    limitations
    Does not isolate SDHA AMPylation as the sole cause.
    organism
    mouse

    Selenium: literature corrections and mechanism additions · lines 474–484

    Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Selenoo deletion · secondary_verified · secondary_verified

    ## selenoo-loss-increases-complex-ii-activity Removing SELENOO increased respiratory complex-II activity in this model. SELENOO deletion increased complex-II activity in the tested melanoma model. Organism: mouse Cell type: melanoma Experimental model: Selenoo deletion Limitations: Does not isolate SDHA AMPylation as the sole cause. Primary reference: [Selenoprotein O Promotes Melanoma Metastasis and Regulates Mitochondrial Complex II Activity](https://pubmed.ncbi.nlm.nih.gov/39700395/)
    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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