Component

Imidazole propionate

Context-specific entity; species, compartment and exposure are stated on each claim.

12 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. In HEK293 experiments, imidazole propionate increased basal Akt phosphorylation; p38-gamma knockdown blocked the Akt and inhibitory AMPK phosphorylation responses.

    Imidazole propionate → AKT serine/threonine kinase family source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human HEK293 cells; time-dependent signaling, siRNA and recombinant-kinase validation.
    limitations
    Basal activation differs from insulin-stimulated activation. Recombinant assay construct species is not inferred from the human host cells.
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    A microbial product changed a kinase pathway, and removing one kinase interrupted the response.
    primary_references
    Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 322–328

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293 cells; time-dependent signaling, siRNA and recombinant-kinase validation. · source_derived_draft · unverified_draft

    ## histidine-imp-akt A microbial product changed a kinase pathway, and removing one kinase interrupted the response. In HEK293 experiments, imidazole propionate increased basal Akt phosphorylation; p38-gamma knockdown blocked the Akt and inhibitory AMPK phosphorylation responses. Model: Human HEK293 cells; time-dependent signaling, siRNA and recombinant-kinase validation. Limitations: Basal activation differs from insulin-stimulated activation. Recombinant assay construct species is not inferred from the human host cells. Evidence access: Primary full text Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012
    Complete structured claim and evidence

  2. In HEK293 cells, imidazole propionate suppressed metformin-induced AMPK activation; expression of the study-labeled AMPK S485A mutant prevented suppression of activating T172 phosphorylation.

    Imidazole propionate → Human AMP-activated protein kinase complexes source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    HEK293 expression and phosphorylation assays; the paper labels the construct site S485.
    limitations
    Construct site numbering is retained without silently mapping it to a human endogenous isoform. No universal AMPK inhibition across all tissues.
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    Changing the inhibitory phosphorylation site interrupted the measured drug interaction.
    primary_references
    Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 330–336

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · HEK293 expression and phosphorylation assays; the paper labels the construct site S485. · source_derived_draft · unverified_draft

    ## histidine-imp-ampk Changing the inhibitory phosphorylation site interrupted the measured drug interaction. In HEK293 cells, imidazole propionate suppressed metformin-induced AMPK activation; expression of the study-labeled AMPK S485A mutant prevented suppression of activating T172 phosphorylation. Model: HEK293 expression and phosphorylation assays; the paper labels the construct site S485. Limitations: Construct site numbering is retained without silently mapping it to a human endogenous isoform. No universal AMPK inhibition across all tissues. Evidence access: Primary full text Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012
    Complete structured claim and evidence

  3. Circulating imidazole propionate was higher in the studied people with type 2 diabetes than comparison participants.

    Imidazole propionate → Circulating imidazole propionate in type 2 diabetes source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human observational metabolomics.
    limitations
    Association alone does not establish direction, causality or an individual diagnostic threshold.
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    A histidine-derived microbial metabolite tracked a metabolic phenotype.
    primary_references
    Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30401435/ · DOI 10.1016/j.cell.2018.09.055

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 290–296

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human observational metabolomics. · source_derived_draft · unverified_draft

    ## histidine-imp-human-association A histidine-derived microbial metabolite tracked a metabolic phenotype. Circulating imidazole propionate was higher in the studied people with type 2 diabetes than comparison participants. Model: Human observational metabolomics. Limitations: Association alone does not establish direction, causality or an individual diagnostic threshold. Evidence access: Primary abstract Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30401435/ · DOI 10.1016/j.cell.2018.09.055
    Complete structured claim and evidence

  4. Metformin-treated participants with high blood glucose had higher circulating imidazole propionate in the observational comparison.

    Imidazole propionate → Poor glucose control among metformin-treated participants source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human type 2 diabetes plasma comparison.
    limitations
    Confounding and reverse causation remain possible; no randomized metabolite or histidine intervention.
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    The human association is consistent with a hypothesis but does not test the mechanism.
    primary_references
    Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 354–360

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human type 2 diabetes plasma comparison. · source_derived_draft · unverified_draft

    ## histidine-imp-human-metformin The human association is consistent with a hypothesis but does not test the mechanism. Metformin-treated participants with high blood glucose had higher circulating imidazole propionate in the observational comparison. Model: Human type 2 diabetes plasma comparison. Limitations: Confounding and reverse causation remain possible; no randomized metabolite or histidine intervention. Evidence access: Primary full text Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012
    Complete structured claim and evidence

  5. Imidazole-propionate pretreatment prevented the measured glucose-lowering response to metformin in mice.

    Imidazole propionate → Glucose-lowering response to metformin in mice source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Mouse pretreatment and metformin experiments; separate from observational human plasma data.
    limitations
    Not evidence that histidine supplementation causes metformin failure in humans.
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    A microbial metabolite changed a drug response in an animal model.
    primary_references
    Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 346–352

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse pretreatment and metformin experiments; separate from observational human plasma data. · source_derived_draft · unverified_draft

    ## histidine-imp-mouse-metformin A microbial metabolite changed a drug response in an animal model. Imidazole-propionate pretreatment prevented the measured glucose-lowering response to metformin in mice. Model: Mouse pretreatment and metformin experiments; separate from observational human plasma data. Limitations: Not evidence that histidine supplementation causes metformin failure in humans. Evidence access: Primary full text Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012
    Complete structured claim and evidence

  6. Administering imidazole propionate impaired glucose tolerance in the reported mouse experiments.

    Imidazole propionate → Glucose tolerance after imidazole-propionate administration in mice source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Mouse metabolite-administration study; dose details not extracted from accessed primary abstract.
    limitations
    Not a dietary-histidine intervention or a demonstrated human clinical effect.
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    Giving the microbial product affected glucose control in an animal experiment.
    primary_references
    Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30401435/ · DOI 10.1016/j.cell.2018.09.055

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 298–304

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse metabolite-administration study; dose details not extracted from accessed primary abstract. · source_derived_draft · unverified_draft

    ## histidine-imp-mouse-tolerance Giving the microbial product affected glucose control in an animal experiment. Administering imidazole propionate impaired glucose tolerance in the reported mouse experiments. Model: Mouse metabolite-administration study; dose details not extracted from accessed primary abstract. Limitations: Not a dietary-histidine intervention or a demonstrated human clinical effect. Evidence access: Primary abstract Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30401435/ · DOI 10.1016/j.cell.2018.09.055
    Complete structured claim and evidence

  7. The study distinguished p38-gamma-dependent basal Akt activation from mTORC1-dependent IRS loss; direct mTORC2 activation was not detected in the tested kinase assay.

    Imidazole propionate → Imidazole-propionate-dependent basal Akt pathway source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human-cell signaling, kinase assays and inhibitor/knockdown experiments.
    limitations
    Does not eliminate mTOR signaling from all imidazole-propionate effects; model and time point matter.
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    Two routes from the same metabolite have different timing and intermediates.
    primary_references
    Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 338–344

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human-cell signaling, kinase assays and inhibitor/knockdown experiments. · source_derived_draft · unverified_draft

    ## histidine-imp-mtor-boundary Two routes from the same metabolite have different timing and intermediates. The study distinguished p38-gamma-dependent basal Akt activation from mTORC1-dependent IRS loss; direct mTORC2 activation was not detected in the tested kinase assay. Model: Human-cell signaling, kinase assays and inhibitor/knockdown experiments. Limitations: Does not eliminate mTOR signaling from all imidazole-propionate effects; model and time point matter. Evidence access: Primary full text Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012
    Complete structured claim and evidence

What acts on it

  1. Fecal microbiota from donors with type 2 diabetes generated more imidazole propionate from histidine in the gut simulator than microbiota from donors without diabetes.

    L-Histidine → Imidazole propionate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human-donor fecal communities in a gut simulator.
    limitations
    Ex-vivo community behavior is not a controlled human histidine-feeding outcome.
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    The same substrate produced different output with different microbial communities.
    primary_references
    Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30401435/ · DOI 10.1016/j.cell.2018.09.055

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 282–288

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human-donor fecal communities in a gut simulator. · source_derived_draft · unverified_draft

    ## histidine-microbial-imp-generation The same substrate produced different output with different microbial communities. Fecal microbiota from donors with type 2 diabetes generated more imidazole propionate from histidine in the gut simulator than microbiota from donors without diabetes. Model: Human-donor fecal communities in a gut simulator. Limitations: Ex-vivo community behavior is not a controlled human histidine-feeding outcome. Evidence access: Primary abstract Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30401435/ · DOI 10.1016/j.cell.2018.09.055
    Complete structured claim and evidence

  2. Full-length and two-domain S. oneidensis UrdA converted urocanate to imidazole propionate and did not show the tested fumarate-reductase activity.

    Shewanella oneidensis MR-1 urocanate reductase / UrdA → Imidazole propionate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Purified bacterial full-length/truncated proteins, activity assays and ligand-bound crystal structures.
    limitations
    This species is a structural model; abundance or flux in an individual human microbiome is not measured.
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    A bacterial enzyme sends a histidine-derived intermediate down a different branch.
    primary_references
    Structural characterization of the microbial enzyme urocanate reductase mediating imidazole propionate production. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33649331/ · DOI 10.1038/s41467-021-21548-y

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 266–272

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified bacterial full-length/truncated proteins, activity assays and ligand-bound crystal structures. · source_derived_draft · unverified_draft

    ## histidine-urda-product A bacterial enzyme sends a histidine-derived intermediate down a different branch. Full-length and two-domain S. oneidensis UrdA converted urocanate to imidazole propionate and did not show the tested fumarate-reductase activity. Model: Purified bacterial full-length/truncated proteins, activity assays and ligand-bound crystal structures. Limitations: This species is a structural model; abundance or flux in an individual human microbiome is not measured. Evidence access: Primary full text Structural characterization of the microbial enzyme urocanate reductase mediating imidazole propionate production. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33649331/ · DOI 10.1038/s41467-021-21548-y
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. The 2018 study linked imidazole-propionate-activated p38-gamma to p62 phosphorylation.

    p38-gamma assay protein in the 2018 ImP study; species unresolved in accessed abstract → p62 assay protein in the 2018 ImP study; species unresolved in accessed abstract source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Biochemical/cellular experiments summarized in the primary abstract; study also contains mouse intervention and human observations.
    limitations
    The abstract does not resolve species and construct for each biochemical step; assay proteins are not silently assigned human identity.
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    A kinase relays the microbial-metabolite signal to an adaptor protein.
    primary_references
    Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30401435/ · DOI 10.1016/j.cell.2018.09.055

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 306–312

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Biochemical/cellular experiments summarized in the primary abstract; study also contains mouse intervention and human observations. · source_derived_draft · unverified_draft

    ## histidine-imp-p38-p62 A kinase relays the microbial-metabolite signal to an adaptor protein. The 2018 study linked imidazole-propionate-activated p38-gamma to p62 phosphorylation. Model: Biochemical/cellular experiments summarized in the primary abstract; study also contains mouse intervention and human observations. Limitations: The abstract does not resolve species and construct for each biochemical step; assay proteins are not silently assigned human identity. Evidence access: Primary abstract Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30401435/ · DOI 10.1016/j.cell.2018.09.055
    Complete structured claim and evidence

  2. The study connected p62 phosphorylation to mTORC1 activation and impaired signaling at insulin receptor substrate.

    p62 assay protein in the 2018 ImP study; species unresolved in accessed abstract → Mechanistic target of rapamycin complex 1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Primary abstract-level biochemical/cellular pathway report.
    limitations
    Complete construct, dose and cell-specific mapping remains a follow-up; this route is distinct from ordinary dietary histidine intake.
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    The adaptor connects this branch to nutrient-sensitive signaling and insulin response.
    primary_references
    Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30401435/ · DOI 10.1016/j.cell.2018.09.055

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 314–320

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary abstract-level biochemical/cellular pathway report. · source_derived_draft · unverified_draft

    ## histidine-imp-p62-mtor The adaptor connects this branch to nutrient-sensitive signaling and insulin response. The study connected p62 phosphorylation to mTORC1 activation and impaired signaling at insulin receptor substrate. Model: Primary abstract-level biochemical/cellular pathway report. Limitations: Complete construct, dose and cell-specific mapping remains a follow-up; this route is distinct from ordinary dietary histidine intake. Evidence access: Primary abstract Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30401435/ · DOI 10.1016/j.cell.2018.09.055
    Complete structured claim and evidence

  3. The UrdA catalytic-domain structures contained FAD alongside substrate or product, and assays supported flavin-associated urocanate reduction.

    FAD → Shewanella oneidensis MR-1 urocanate reductase / UrdA source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Bacterial structural enzymology; FAD-supplemented enzyme assays.
    limitations
    Does not show that human riboflavin intake limits or increases microbial imidazole-propionate production.
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    This microbial reaction uses a riboflavin-derived chemical tool.
    primary_references
    Structural characterization of the microbial enzyme urocanate reductase mediating imidazole propionate production. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33649331/ · DOI 10.1038/s41467-021-21548-y

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 274–280

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Bacterial structural enzymology; FAD-supplemented enzyme assays. · source_derived_draft · unverified_draft

    ## histidine-urda-flavin This microbial reaction uses a riboflavin-derived chemical tool. The UrdA catalytic-domain structures contained FAD alongside substrate or product, and assays supported flavin-associated urocanate reduction. Model: Bacterial structural enzymology; FAD-supplemented enzyme assays. Limitations: Does not show that human riboflavin intake limits or increases microbial imidazole-propionate production. Evidence access: Primary full text Structural characterization of the microbial enzyme urocanate reductase mediating imidazole propionate production. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33649331/ · DOI 10.1038/s41467-021-21548-y
    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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