Component

Phenylacetylglutamine / PAGln

Context-specific entity; species, compartment and exposure are stated on each 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. Seven days of broad-spectrum antibiotics in fifteen subjects markedly reduced circulating PAGln, with recovery after microbial repopulation.

    Phenylacetylglutamine / PAGln → Human PAGln response to microbiota suppression source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human antibiotic suppression and post-antibiotic recovery sampling at least three weeks later.
    limitations
    Antibiotics affect many microbes and metabolites; this does not isolate one bacterial enzyme or recommend antimicrobial use.
    nutrient_topic
    L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Phenylalanine
    plain_language
    The human circulating metabolite depends in part on gut microbial activity.
    primary_references
    A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32142679/ · DOI 10.1016/j.cell.2020.02.016

    L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 366–372

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human antibiotic suppression and post-antibiotic recovery sampling at least three weeks later. · source_derived_draft · unverified_draft

    ## l-phenylalanine-microbial-human-dependence The human circulating metabolite depends in part on gut microbial activity. Seven days of broad-spectrum antibiotics in fifteen subjects markedly reduced circulating PAGln, with recovery after microbial repopulation. Model: Human antibiotic suppression and post-antibiotic recovery sampling at least three weeks later. Limitations: Antibiotics affect many microbes and metabolites; this does not isolate one bacterial enzyme or recommend antimicrobial use. Evidence access: Primary full text A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32142679/ · DOI 10.1016/j.cell.2020.02.016
    Complete structured claim and evidence

  2. Knockdown and overexpression experiments implicated ADRA2A, ADRA2B and ADRB2 in PAGln-associated signaling, supporting an adrenergic-receptor-dependent route.

    Phenylacetylglutamine / PAGln → PAGln adrenergic-receptor-associated signaling source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human MEG-01 receptor knockdown and HEK293 receptor-expression experiments, with pharmacologic comparisons.
    limitations
    Functional dependence is not proof of a single orthosteric binding mode or a clinical drug interaction.
    nutrient_topic
    L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Phenylalanine
    plain_language
    The platelet-related signal connects to receptors used by other physiological pathways.
    primary_references
    A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32142679/ · DOI 10.1016/j.cell.2020.02.016

    L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 382–388

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human MEG-01 receptor knockdown and HEK293 receptor-expression experiments, with pharmacologic comparisons. · source_derived_draft · unverified_draft

    ## l-phenylalanine-pagln-adrenergic The platelet-related signal connects to receptors used by other physiological pathways. Knockdown and overexpression experiments implicated ADRA2A, ADRA2B and ADRB2 in PAGln-associated signaling, supporting an adrenergic-receptor-dependent route. Model: Human MEG-01 receptor knockdown and HEK293 receptor-expression experiments, with pharmacologic comparisons. Limitations: Functional dependence is not proof of a single orthosteric binding mode or a clinical drug interaction. Evidence access: Primary full text A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32142679/ · DOI 10.1016/j.cell.2020.02.016
    Complete structured claim and evidence

  3. Circulating PAGln was associated with cardiovascular disease and subsequent major adverse cardiovascular events in discovery and validation cohorts of 1162 and 4000 subjects.

    Phenylacetylglutamine / PAGln → Cardiovascular events associated with circulating PAGln source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human clinical cohorts; three-year event follow-up.
    limitations
    Residual confounding and renal clearance matter; no randomized dietary phenylalanine intervention establishes causation.
    nutrient_topic
    L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Phenylalanine
    plain_language
    A blood association identifies a research signal, not the cause by itself.
    primary_references
    A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32142679/ · DOI 10.1016/j.cell.2020.02.016

    L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 390–396

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human clinical cohorts; three-year event follow-up. · source_derived_draft · unverified_draft

    ## l-phenylalanine-pagln-outcomes A blood association identifies a research signal, not the cause by itself. Circulating PAGln was associated with cardiovascular disease and subsequent major adverse cardiovascular events in discovery and validation cohorts of 1162 and 4000 subjects. Model: Human clinical cohorts; three-year event follow-up. Limitations: Residual confounding and renal clearance matter; no randomized dietary phenylalanine intervention establishes causation. Evidence access: Primary full text A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32142679/ · DOI 10.1016/j.cell.2020.02.016
    Complete structured claim and evidence

  4. PAGln at 100 micromolar for 30 minutes enhanced agonist-induced human platelet responses, including calcium signaling.

    Phenylacetylglutamine / PAGln → Human platelet agonist responsiveness during PAGln exposure source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Isolated human platelets; agonist-challenge experiments.
    limitations
    Metabolite exposure is not phenylalanine exposure; this does not establish that dietary phenylalanine causes thrombosis.
    nutrient_topic
    L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Phenylalanine
    plain_language
    A downstream microbial-host metabolite can alter platelet responsiveness in an assay.
    primary_references
    A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32142679/ · DOI 10.1016/j.cell.2020.02.016

    L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 374–380

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated human platelets; agonist-challenge experiments. · source_derived_draft · unverified_draft

    ## l-phenylalanine-pagln-platelets A downstream microbial-host metabolite can alter platelet responsiveness in an assay. PAGln at 100 micromolar for 30 minutes enhanced agonist-induced human platelet responses, including calcium signaling. Model: Isolated human platelets; agonist-challenge experiments. Limitations: Metabolite exposure is not phenylalanine exposure; this does not establish that dietary phenylalanine causes thrombosis. Evidence access: Primary full text A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32142679/ · DOI 10.1016/j.cell.2020.02.016
    Complete structured claim and evidence

What acts on it

  1. Host conjugation of microbially derived phenylacetate with glutamine produces PAGln, the predominant human conjugate in the study; glycine conjugation produces PAGly, predominant in mice.

    Phenylacetic acid / phenylacetate → Phenylacetylglutamine / PAGln source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human/mouse metabolomics study; established conjugation route described in primary full text.
    limitations
    This is not a purified conjugating-enzyme kinetic experiment and does not show clinically meaningful glutamine or glycine depletion.
    nutrient_topic
    L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Phenylalanine
    plain_language
    Host amino acids help turn a bacterial product into circulating metabolites.
    primary_references
    A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32142679/ · DOI 10.1016/j.cell.2020.02.016

    L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 358–364

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human/mouse metabolomics study; established conjugation route described in primary full text. · source_derived_draft · unverified_draft

    ## l-phenylalanine-host-conjugation Host amino acids help turn a bacterial product into circulating metabolites. Host conjugation of microbially derived phenylacetate with glutamine produces PAGln, the predominant human conjugate in the study; glycine conjugation produces PAGly, predominant in mice. Model: Human/mouse metabolomics study; established conjugation route described in primary full text. Limitations: This is not a purified conjugating-enzyme kinetic experiment and does not show clinically meaningful glutamine or glycine depletion. Evidence access: Primary full text A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32142679/ · DOI 10.1016/j.cell.2020.02.016
    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