Component

Fumarate

Four-carbon dicarboxylate formed by succinate oxidation.

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. Network-level integration of transcriptomics and metabolomics data identifies glycolysis, glutaminolysis and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by beta-glucan in monocytes, accumulation of fumarate due to glutamine replenishment of the TCA cycle integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases, fumarate itself induced an epigenetic program similar to beta-glucan-induced trained immunity, and inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by beta-glucan.

    Fumarate → KDM5 histone demethylases source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/glucan-research/27866838.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c67ca385f9dd5e9e97432aa9141a594b7121acca8eea6eba3d0738fed75deba8", "start_char": 0, "end_char": 1031, "text_sha256": "c67ca385f9dd5e9e97432aa9141a594b7121acca8eea6eba3d0738fed75deba8"}
    experimental_model
    Network integration of transcriptomics and metabolomics with pathway inhibition in monocytes and in mice
    exposure
    Beta-glucan training with inhibition of glutaminolysis and cholesterol synthesis, and fumarate given alone
    limitations
    Fumarate reproducing the epigenetic programme on its own is the strongest part. The link runs through inhibition of a demethylase, which is not the same modification as an acetylation mark.
    nutrient_topic
    Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan
    organism
    Human cells and mouse
    plain_language
    A metabolite piles up and jams the enzyme that would strip the marks off, so the marks stay.
    primary_references
    [bg-p27866838] Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity. (2016). https://pubmed.ncbi.nlm.nih.gov/27866838/ DOI: 10.1016/j.cmet.2016.10.008
    tissue_or_cell_type
    Monocyte

    Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 450–461

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Network integration of transcriptomics and metabolomics with pathway inhibition in monocytes and in mice · source_derived_draft · unverified_draft

    ### bg-fumarate-blocks-a-demethylase Network-level integration of transcriptomics and metabolomics data identifies glycolysis, glutaminolysis and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by beta-glucan in monocytes, accumulation of fumarate due to glutamine replenishment of the TCA cycle integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases, fumarate itself induced an epigenetic program similar to beta-glucan-induced trained immunity, and inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by beta-glucan. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: A metabolite piles up and jams the enzyme that would strip the marks off, so the marks stay. organism: Human cells and mouse tissue_or_cell_type: Monocyte experimental_model: Network integration of transcriptomics and metabolomics with pathway inhibition in monocytes and in mice limitations: Fumarate reproducing the epigenetic programme on its own is the strongest part. The link runs through inhibition of a demethylase, which is not the same modification as an acetylation mark. exposure: Beta-glucan training with inhibition of glutaminolysis and cholesterol synthesis, and fumarate given alone evidence_span: {"source_cache": "artifacts/glucan-research/27866838.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c67ca385f9dd5e9e97432aa9141a594b7121acca8eea6eba3d0738fed75deba8", "start_char": 0, "end_char": 1031, "text_sha256": "c67ca385f9dd5e9e97432aa9141a594b7121acca8eea6eba3d0738fed75deba8"} [bg-p27866838] Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity. (2016). https://pubmed.ncbi.nlm.nih.gov/27866838/ DOI: 10.1016/j.cmet.2016.10.008
    Complete structured claim and evidence

What acts on it

  1. Fumarate is the other product of the ASL-catalyzed argininosuccinate cleavage reaction.

    Human argininosuccinate lyase / ASL → Fumarate source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/11747433.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d57b633c558211169c38f4dc40cceeeb373c63d291c80d2523c8e48b54427b1", "start_char": 0, "end_char": 1617, "text_sha256": "1d57b633c558211169c38f4dc40cceeeb373c63d291c80d2523c8e48b54427b1"}
    experimental_model
    Recombinant human enzyme complementation and stability experiments
    exposure
    Wild type and Q286R, D87G, M360T or A398D variants
    limitations
    Reaction identity and complementation are established in enzyme systems; these variants do not describe all ASL deficiencies.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Human ASL expressed experimentally
    plain_language
    This reaction connects amino-acid nitrogen handling with a carbon-metabolism intermediate.
    primary_references
    [citrulline-p11747433] Mechanisms for intragenic complementation at the human argininosuccinate lyase locus. (2001). https://pubmed.ncbi.nlm.nih.gov/11747433/ DOI: 10.1021/bi011526e
    tissue_or_cell_type
    Argininosuccinate cleavage

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 190–201

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

    ### citrulline-asl-fumarate Fumarate is the other product of the ASL-catalyzed argininosuccinate cleavage reaction. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This reaction connects amino-acid nitrogen handling with a carbon-metabolism intermediate. organism: Human ASL expressed experimentally tissue_or_cell_type: Argininosuccinate cleavage experimental_model: Recombinant human enzyme complementation and stability experiments limitations: Reaction identity and complementation are established in enzyme systems; these variants do not describe all ASL deficiencies. exposure: Wild type and Q286R, D87G, M360T or A398D variants evidence_span: {"source_cache": "artifacts/citrulline-research/11747433.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d57b633c558211169c38f4dc40cceeeb373c63d291c80d2523c8e48b54427b1", "start_char": 0, "end_char": 1617, "text_sha256": "1d57b633c558211169c38f4dc40cceeeb373c63d291c80d2523c8e48b54427b1"} [citrulline-p11747433] Mechanisms for intragenic complementation at the human argininosuccinate lyase locus. (2001). https://pubmed.ncbi.nlm.nih.gov/11747433/ DOI: 10.1021/bi011526e
    Complete structured claim and evidence

Where it participates (unsigned role)

  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

  2. Mouse FAH structural and biochemical studies support cleavage of fumarylacetoacetate into fumarate and acetoacetate.

    Mouse fumarylacetoacetate hydrolase / Fah → Fumarylacetoacetate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Mouse enzyme structure and physiological-product complexes.
    limitations
    The product-bound structure is mouse evidence; the separate human FAH gene/disease record is retained.
    nutrient_topic
    L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
    plain_language
    The pathway connects the amino-acid carbon skeleton to central metabolism.
    primary_references
    Crystal structure and mechanism of a carbon-carbon bond hydrolase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10508789/ · DOI 10.1016/s0969-2126(99)80170-1

    L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 260–266

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse enzyme structure and physiological-product complexes. · source_derived_draft · unverified_draft

    ## l-tyrosine-fah-products The pathway connects the amino-acid carbon skeleton to central metabolism. Mouse FAH structural and biochemical studies support cleavage of fumarylacetoacetate into fumarate and acetoacetate. Model: Mouse enzyme structure and physiological-product complexes. Limitations: The product-bound structure is mouse evidence; the separate human FAH gene/disease record is retained. Evidence access: Primary abstract Crystal structure and mechanism of a carbon-carbon bond hydrolase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10508789/ · DOI 10.1016/s0969-2126(99)80170-1
    Complete structured claim and evidence

  3. Human ASL catalyzes reversible cleavage of argininosuccinate to arginine and fumarate.

    Human argininosuccinate lyase / ASL → L-Arginine source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/11747433.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d57b633c558211169c38f4dc40cceeeb373c63d291c80d2523c8e48b54427b1", "start_char": 0, "end_char": 1617, "text_sha256": "1d57b633c558211169c38f4dc40cceeeb373c63d291c80d2523c8e48b54427b1"}
    experimental_model
    Recombinant human enzyme complementation and stability experiments
    exposure
    Wild type and Q286R, D87G, M360T or A398D variants
    limitations
    Reaction identity and complementation are established in enzyme systems; these variants do not describe all ASL deficiencies.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Human ASL expressed experimentally
    plain_language
    The second enzyme releases arginine from the intermediate.
    primary_references
    [citrulline-p11747433] Mechanisms for intragenic complementation at the human argininosuccinate lyase locus. (2001). https://pubmed.ncbi.nlm.nih.gov/11747433/ DOI: 10.1021/bi011526e
    tissue_or_cell_type
    Argininosuccinate cleavage

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 177–188

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

    ### citrulline-asl-arginine Human ASL catalyzes reversible cleavage of argininosuccinate to arginine and fumarate. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The second enzyme releases arginine from the intermediate. organism: Human ASL expressed experimentally tissue_or_cell_type: Argininosuccinate cleavage experimental_model: Recombinant human enzyme complementation and stability experiments limitations: Reaction identity and complementation are established in enzyme systems; these variants do not describe all ASL deficiencies. exposure: Wild type and Q286R, D87G, M360T or A398D variants evidence_span: {"source_cache": "artifacts/citrulline-research/11747433.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d57b633c558211169c38f4dc40cceeeb373c63d291c80d2523c8e48b54427b1", "start_char": 0, "end_char": 1617, "text_sha256": "1d57b633c558211169c38f4dc40cceeeb373c63d291c80d2523c8e48b54427b1"} [citrulline-p11747433] Mechanisms for intragenic complementation at the human argininosuccinate lyase locus. (2001). https://pubmed.ncbi.nlm.nih.gov/11747433/ DOI: 10.1021/bi011526e
    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