Component

Mevalonate

Context-specific entity; species, compartment and exposure are stated on each 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. Activation of the cholesterol synthesis pathway but not the synthesis of cholesterol itself is essential for training of myeloid cells, rather the metabolite mevalonate is the mediator of training via activation of IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways, statins which block mevalonate generation prevent trained immunity induction, and monocytes of patients with hyper immunoglobulin D syndrome who are mevalonate kinase deficient and accumulate mevalonate have a constitutive trained immunity phenotype at both immunological and epigenetic levels.

    Mevalonate → Trained immunity, an altered response to a later challenge after the first has ended source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/glucan-research/29328908.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c7d8052926f6be1dad87fedf0023f60ac5441b04f9b8e180c4b1e07edc83eb03", "start_char": 0, "end_char": 1173, "text_sha256": "c7d8052926f6be1dad87fedf0023f60ac5441b04f9b8e180c4b1e07edc83eb03"}
    experimental_model
    Pharmacological and genetic dissection of the cholesterol synthesis pathway, with monocytes from patients accumulating mevalonate
    exposure
    Training of myeloid cells with statins to block mevalonate generation, and monocytes from mevalonate kinase deficient patients
    limitations
    The patient arm is a natural experiment in the opposite direction, which is what makes the mevalonate assignment convincing. The statin result is inhibition of an induced laboratory response.
    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
    plain_language
    It is the intermediate and not the cholesterol that does the training, and people who cannot clear that intermediate are permanently trained.
    primary_references
    [bg-p29328908] Metabolic Induction of Trained Immunity through the Mevalonate Pathway. (2018). https://pubmed.ncbi.nlm.nih.gov/29328908/ DOI: 10.1016/j.cell.2017.11.025
    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 463–474

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pharmacological and genetic dissection of the cholesterol synthesis pathway, with monocytes from patients accumulating mevalonate · source_derived_draft · unverified_draft

    ### bg-mevalonate-not-cholesterol-trains Activation of the cholesterol synthesis pathway but not the synthesis of cholesterol itself is essential for training of myeloid cells, rather the metabolite mevalonate is the mediator of training via activation of IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways, statins which block mevalonate generation prevent trained immunity induction, and monocytes of patients with hyper immunoglobulin D syndrome who are mevalonate kinase deficient and accumulate mevalonate have a constitutive trained immunity phenotype at both immunological and epigenetic levels. 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: It is the intermediate and not the cholesterol that does the training, and people who cannot clear that intermediate are permanently trained. organism: Human tissue_or_cell_type: Monocyte experimental_model: Pharmacological and genetic dissection of the cholesterol synthesis pathway, with monocytes from patients accumulating mevalonate limitations: The patient arm is a natural experiment in the opposite direction, which is what makes the mevalonate assignment convincing. The statin result is inhibition of an induced laboratory response. exposure: Training of myeloid cells with statins to block mevalonate generation, and monocytes from mevalonate kinase deficient patients evidence_span: {"source_cache": "artifacts/glucan-research/29328908.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c7d8052926f6be1dad87fedf0023f60ac5441b04f9b8e180c4b1e07edc83eb03", "start_char": 0, "end_char": 1173, "text_sha256": "c7d8052926f6be1dad87fedf0023f60ac5441b04f9b8e180c4b1e07edc83eb03"} [bg-p29328908] Metabolic Induction of Trained Immunity through the Mevalonate Pathway. (2018). https://pubmed.ncbi.nlm.nih.gov/29328908/ DOI: 10.1016/j.cell.2017.11.025
    Complete structured claim and evidence

  2. The mevalonate pathway produces isoprenoids required for functions ranging from cholesterol synthesis to growth control, under feedback regulation that also governs low-density-lipoprotein receptors.

    Mevalonate → Geranylgeranyl diphosphate / GGPP source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    Review of mammalian mevalonate-pathway regulation
    exposure
    Not applicable
    limitations
    A review of regulatory architecture, not a measurement of any one statin's effect on any one isoprenoid pool.
    organism
    Review of mammalian mevalonate-pathway regulation
    plain_language
    The mevalonate pathway produces isoprenoids required for functions ranging from cholesterol synthesis to growth control, under feedback regulation that also governs low-density-lipoprotein receptors.
    primary_references
    Regulation of the mevalonate pathway. (1990). https://pubmed.ncbi.nlm.nih.gov/1967820/ DOI: 10.1038/343425a0
    route
    Not applicable
    tissue
    Isoprenoid and sterol end-products

    Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 24–32

    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

    ## mevalonate-supplies-isoprenoids The mevalonate pathway produces isoprenoids required for functions ranging from cholesterol synthesis to growth control, under feedback regulation that also governs low-density-lipoprotein receptors. Model/species: Review of mammalian mevalonate-pathway regulation Tissue/system: Isoprenoid and sterol end-products Exposure: Not applicable Route: Not applicable Limits: A review of regulatory architecture, not a measurement of any one statin's effect on any one isoprenoid pool. Primary reference: Regulation of the mevalonate pathway. (1990). https://pubmed.ncbi.nlm.nih.gov/1967820/ DOI: 10.1038/343425a0 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

What acts on it

  1. Human HMG-CoA reductase catalyzes mevalonate formation; substrate/cofactor-bound structures locate HMG-CoA and the nicotinamide cofactor in the catalytic domain.

    HMG-CoA reductase (HMGCR) → Mevalonate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human recombinant catalytic-domain crystallography and biochemical background.
    limitations
    Shared human machinery; the source is not an experiment administering red yeast rice.
    nutrient_topic
    Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice
    plain_language
    This enzyme supplies a shared precursor pathway.
    primary_references
    [10698924] Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10698924/ · DOI 10.1093/emboj/19.5.819

    Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 76–82

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant catalytic-domain crystallography and biochemical background. · source_derived_draft · unverified_draft

    ## red-yeast-rice-human-mevalonate-machinery This enzyme supplies a shared precursor pathway. Human HMG-CoA reductase catalyzes mevalonate formation; substrate/cofactor-bound structures locate HMG-CoA and the nicotinamide cofactor in the catalytic domain. Model: Human recombinant catalytic-domain crystallography and biochemical background. Limitations: Shared human machinery; the source is not an experiment administering red yeast rice. Evidence access: Primary abstract [10698924] Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10698924/ · DOI 10.1093/emboj/19.5.819
    Complete structured claim and evidence

  2. Monacolin K inhibited lipid labeling from acetate or HMG-CoA, but did not inhibit incorporation from supplied mevalonate at concentrations up to 10 mM.

    Lovastatin / monacolin K lactone → Mevalonate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary PDF, p335 visually inspected
    experimental_model
    Rat liver cell-free nonsaponifiable-lipid synthesis; lactone and acid preparations tested.
    limitations
    A biochemical bypass is not a clinical repletion strategy; the 10 mM figure applies to tested monacolin concentrations, not human exposure.
    nutrient_topic
    Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice
    plain_language
    Supplying the downstream intermediate bypassed the inhibited step in this assay.
    primary_references
    [7380744] Monacolin K, a new hypocholesterolemic agent that specifically inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase. · 1980 · https://pubmed.ncbi.nlm.nih.gov/7380744/ · DOI 10.7164/antibiotics.33.334

    Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 68–74

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat liver cell-free nonsaponifiable-lipid synthesis; lactone and acid preparations tested. · source_derived_draft · unverified_draft

    ## red-yeast-rice-mevalonate-bypass Supplying the downstream intermediate bypassed the inhibited step in this assay. Monacolin K inhibited lipid labeling from acetate or HMG-CoA, but did not inhibit incorporation from supplied mevalonate at concentrations up to 10 mM. Model: Rat liver cell-free nonsaponifiable-lipid synthesis; lactone and acid preparations tested. Limitations: A biochemical bypass is not a clinical repletion strategy; the 10 mM figure applies to tested monacolin concentrations, not human exposure. Evidence access: Primary PDF, p335 visually inspected [7380744] Monacolin K, a new hypocholesterolemic agent that specifically inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase. · 1980 · https://pubmed.ncbi.nlm.nih.gov/7380744/ · DOI 10.7164/antibiotics.33.334
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Statins occupy a portion of the HMG-CoA binding site of HMG-CoA reductase and block access of the substrate to the active site.

    Atorvastatin → HMG-CoA reductase (HMGCR) 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
    Catalytic portion of human HMG-CoA reductase, X-ray structures with six statins
    exposure
    Statin-enzyme complexes, inhibition constants in the nanomolar range
    limitations
    The abstract reports structures with six statins without naming them, so this is a class binding mode rather than an atorvastatin-specific structure. Several catalytically relevant residues near the carboxyl terminus are disordered in the complexes.
    organism
    Catalytic portion of human HMG-CoA reductase, X-ray structures with six statins
    plain_language
    Statins occupy a portion of the HMG-CoA binding site of HMG-CoA reductase and block access of the substrate to the active site.
    primary_references
    Structural mechanism for statin inhibition of HMG-CoA reductase. (2001). https://pubmed.ncbi.nlm.nih.gov/11349148/ DOI: 10.1126/science.1059344
    route
    Structural
    tissue
    Enzyme active-site occupancy

    Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 13–22

    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

    ## atorvastatin-hmgcr-occupancy Statins occupy a portion of the HMG-CoA binding site of HMG-CoA reductase and block access of the substrate to the active site. Model/species: Catalytic portion of human HMG-CoA reductase, X-ray structures with six statins Tissue/system: Enzyme active-site occupancy Exposure: Statin-enzyme complexes, inhibition constants in the nanomolar range Route: Structural Duration: Not applicable Limits: The abstract reports structures with six statins without naming them, so this is a class binding mode rather than an atorvastatin-specific structure. Several catalytically relevant residues near the carboxyl terminus are disordered in the complexes. Primary reference: Structural mechanism for statin inhibition of HMG-CoA reductase. (2001). https://pubmed.ncbi.nlm.nih.gov/11349148/ DOI: 10.1126/science.1059344 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  2. Monacolin K acid sodium salt competitively inhibited rat liver HMG-CoA reductase with respect to HMG-CoA; the reported Ki was 0.49 nM.

    Monacolin K hydroxy-acid sodium salt → Rat HMG-CoA reductase / Hmgcr source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary PDF, p335 and Figure 3 visually inspected
    experimental_model
    Partially purified rat liver microsomal reductase; radiolabeled product assay.
    limitations
    Assay-specific inhibition constant, not a human plasma threshold or potency of an entire rice product.
    nutrient_topic
    Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice
    plain_language
    The active preparation competed with the enzyme substrate.
    primary_references
    [7380744] Monacolin K, a new hypocholesterolemic agent that specifically inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase. · 1980 · https://pubmed.ncbi.nlm.nih.gov/7380744/ · DOI 10.7164/antibiotics.33.334

    Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 52–58

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Partially purified rat liver microsomal reductase; radiolabeled product assay. · source_derived_draft · unverified_draft

    ## red-yeast-rice-hmgcr-binding The active preparation competed with the enzyme substrate. Monacolin K acid sodium salt competitively inhibited rat liver HMG-CoA reductase with respect to HMG-CoA; the reported Ki was 0.49 nM. Model: Partially purified rat liver microsomal reductase; radiolabeled product assay. Limitations: Assay-specific inhibition constant, not a human plasma threshold or potency of an entire rice product. Evidence access: Primary PDF, p335 and Figure 3 visually inspected [7380744] Monacolin K, a new hypocholesterolemic agent that specifically inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase. · 1980 · https://pubmed.ncbi.nlm.nih.gov/7380744/ · DOI 10.7164/antibiotics.33.334
    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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