Component

GLUD1

Mitochondrial enzyme linking glutamate metabolism with the tricarboxylic acid cycle.

8 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. The GLUD1 study identifies glutamate oxidation to 2-oxoglutarate as the enzyme reaction underlying its metabolic and regulatory investigation.

    GLUD1 → 2-Oxoglutarate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Established reaction described in a primary human GLUD1 genetic/functional study.
    limitations
    Reaction background is distinguished from the directly measured mutant regulation; this record does not quantify tissue flux.
    nutrient_topic
    L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
    plain_language
    Removing amino nitrogen connects glutamate with the central carbon cycle.
    primary_references
    Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904

    L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 162–168

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Established reaction described in a primary human GLUD1 genetic/functional study. · source_derived_draft · unverified_draft

    ## glutamate-gdh-oxidation Removing amino nitrogen connects glutamate with the central carbon cycle. The GLUD1 study identifies glutamate oxidation to 2-oxoglutarate as the enzyme reaction underlying its metabolic and regulatory investigation. Model: Established reaction described in a primary human GLUD1 genetic/functional study. Limitations: Reaction background is distinguished from the directly measured mutant regulation; this record does not quantify tissue flux. Evidence access: Primary abstract Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904
    Complete structured claim and evidence

What acts on it

  1. Potassium deprivation increased renal glutamate dehydrogenase expression in the studied rats.

    Potassium → GLUD1 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    cross_nutrient
    Potassium deprivation changes glutamine nitrogen metabolism and sodium-coupled glutamine transport; these experiments did not manipulate dietary protein adequacy.
    endpoint
    Potassium deprivation increased renal glutamate dehydrogenase expression in the studied rats.
    experimental-exposure
    Rats on control or potassium-deficient diets for up to 6 days; NH4Cl co-loading and NRK52E/LLC-PK1 cell experiments.
    experimental_model
    Rats on control or potassium-deficient diets for up to 6 days; NH4Cl co-loading and NRK52E/LLC-PK1 cell experiments.
    limitations
    Dietary deprivation precedes detectable hypokalemia here; protein expression does not independently establish transport flux or quantify net bicarbonate generation.
    nutrient_topic
    Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
    organism
    Rattus norvegicus
    plain_language
    A second ammonia-producing enzyme increased; this connects glutamate nitrogen to ammonium and its carbon skeleton to 2-oxoglutarate.
    primary_references
    [hossain-2011-k-ammoniagenesis] Cellular and molecular basis of increased ammoniagenesis in potassium deprivation (2011). https://journals.physiology.org/doi/full/10.1152/ajprenal.00010.2011 DOI: 10.1152/ajprenal.00010.2011
    tissue_or_cell_type
    renal proximal tubule and whole-kidney excretion
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1000–1012

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats on control or potassium-deficient diets for up to 6 days; NH4Cl co-loading and NRK52E/LLC-PK1 cell experiments. · source_derived_draft · unverified_draft

    ### k-deprivation-glud1 Potassium deprivation increased renal glutamate dehydrogenase expression in the studied rats. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second ammonia-producing enzyme increased; this connects glutamate nitrogen to ammonium and its carbon skeleton to 2-oxoglutarate. organism: Rattus norvegicus tissue_or_cell_type: renal proximal tubule and whole-kidney excretion experimental_model: Rats on control or potassium-deficient diets for up to 6 days; NH4Cl co-loading and NRK52E/LLC-PK1 cell experiments. limitations: Dietary deprivation precedes detectable hypokalemia here; protein expression does not independently establish transport flux or quantify net bicarbonate generation. cross_nutrient: Potassium deprivation changes glutamine nitrogen metabolism and sodium-coupled glutamine transport; these experiments did not manipulate dietary protein adequacy. experimental-exposure: Rats on control or potassium-deficient diets for up to 6 days; NH4Cl co-loading and NRK52E/LLC-PK1 cell experiments. endpoint: Potassium deprivation increased renal glutamate dehydrogenase expression in the studied rats. [hossain-2011-k-ammoniagenesis] Cellular and molecular basis of increased ammoniagenesis in potassium deprivation (2011). https://journals.physiology.org/doi/full/10.1152/ajprenal.00010.2011 DOI: 10.1152/ajprenal.00010.2011
    Complete structured claim and evidence

  2. Human GLUD1 activity was inhibited by GTP; patient-derived regulatory variants showed reduced sensitivity to that inhibition.

    Guanosine triphosphate → GLUD1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human lymphoblast enzyme assays from eight unrelated affected children and controls.
    limitations
    GTP regulation is not evidence that dietary purines or glutamate normalize the disease.
    nutrient_topic
    L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
    plain_language
    An energy-related nucleotide restrains glutamate oxidation.
    primary_references
    Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904

    L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 170–176

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human lymphoblast enzyme assays from eight unrelated affected children and controls. · source_derived_draft · unverified_draft

    ## glutamate-gdh-gtp-control An energy-related nucleotide restrains glutamate oxidation. Human GLUD1 activity was inhibited by GTP; patient-derived regulatory variants showed reduced sensitivity to that inhibition. Model: Human lymphoblast enzyme assays from eight unrelated affected children and controls. Limitations: GTP regulation is not evidence that dietary purines or glutamate normalize the disease. Evidence access: Primary abstract Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904
    Complete structured claim and evidence

  3. Leucine activation of lymphoblast GDH varied among twelve patients with hyperinsulinism/hyperammonemia; reduced leucine sensitivity tracked failure of leucine restriction to improve glucose in four patients.

    L-Leucine → GLUD1 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human patient series with enzyme allostery and dietary-response observations.
    limitations
    Observational genotype/phenotype evidence, not a controlled general-population dietary trial.
    nutrient_topic
    L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
    plain_language
    Another amino acid regulates how glutamate is processed, but the response varies by enzyme defect.
    primary_references
    Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11518822/ · DOI 10.1203/00006450-200109000-00010
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 186–192

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human patient series with enzyme allostery and dietary-response observations. · source_derived_draft · unverified_draft

    ## glutamate-gdh-leucine-context Another amino acid regulates how glutamate is processed, but the response varies by enzyme defect. Leucine activation of lymphoblast GDH varied among twelve patients with hyperinsulinism/hyperammonemia; reduced leucine sensitivity tracked failure of leucine restriction to improve glucose in four patients. Model: Human patient series with enzyme allostery and dietary-response observations. Limitations: Observational genotype/phenotype evidence, not a controlled general-population dietary trial. Evidence access: Primary abstract Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11518822/ · DOI 10.1203/00006450-200109000-00010
    Complete structured claim and evidence

  4. Expressing a patient GLUD1 mutant in COS7 cells reproduced reduced GTP inhibition observed in the patient lymphoblasts.

    Human GLUD1 regulatory mutations → GLUD1 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human disease variant expressed in nonhuman COS7 host cells; biochemical confirmation.
    limitations
    Host cell species and human protein identity are distinct; no intake intervention was tested.
    nutrient_topic
    L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
    plain_language
    Changing the enzyme altered its response to a brake.
    primary_references
    Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 178–184

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human disease variant expressed in nonhuman COS7 host cells; biochemical confirmation. · source_derived_draft · unverified_draft

    ## glutamate-gdh-regulatory-variants Changing the enzyme altered its response to a brake. Expressing a patient GLUD1 mutant in COS7 cells reproduced reduced GTP inhibition observed in the patient lymphoblasts. Model: Human disease variant expressed in nonhuman COS7 host cells; biochemical confirmation. Limitations: Host cell species and human protein identity are distinct; no intake intervention was tested. Evidence access: Primary abstract Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904
    Complete structured claim and evidence

  5. AMPylation decreased GLUD1 enzymatic activity in the tested assays.

    AMPylated GLUD1 → GLUD1 source_derived_draftliterature_reviewed:direct_experimental
    Experimental context and source evidence
    cell_type
    experimental assay
    experimental_model
    Modified-enzyme activity measurements
    limitations
    No human dietary response established.
    organism
    mammalian

    Selenium: literature corrections and mechanism additions · lines 498–508

    Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Modified-enzyme activity measurements · secondary_verified · secondary_verified

    ## glud1-ampylation-decreases-activity The AMP modification reduced GLUD1 activity in these experiments. AMPylation decreased GLUD1 enzymatic activity in the tested assays. Organism: mammalian Cell type: experimental assay Experimental model: Modified-enzyme activity measurements Limitations: No human dietary response established. Primary reference: [A repurposed AMP binding domain reveals mitochondrial protein AMPylation as a regulator of cellular metabolism](https://www.nature.com/articles/s41467-025-63014-z)
    Complete structured claim and evidence

  6. SELENOO catalyzes AMP attachment to GLUD1.

    SELENOO → GLUD1 source_derived_draftliterature_reviewed:direct_experimental
    Experimental context and source evidence
    cell_type
    experimental cells
    experimental_model
    Biochemical AMPylation assays
    limitations
    Substrate identification does not establish every tissue context.
    organism
    mammalian

    Selenium: literature corrections and mechanism additions · lines 486–496

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

    ## selenoo-ampylates-glud1 SELENOO can modify the metabolic enzyme GLUD1 with AMP. SELENOO catalyzes AMP attachment to GLUD1. Organism: mammalian Cell type: experimental cells Experimental model: Biochemical AMPylation assays Limitations: Substrate identification does not establish every tissue context. Primary reference: [A repurposed AMP binding domain reveals mitochondrial protein AMPylation as a regulator of cellular metabolism](https://www.nature.com/articles/s41467-025-63014-z)
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Hyperammonemia persisted despite protein/leucine restriction in the reported twelve-patient series.

    Protein/leucine restriction in the GLUD1 patient series → Persistent hyperammonemia in human GLUD1 disease source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human rare-disease clinical series.
    limitations
    This does not establish treatment futility across all regimens or justify dietary advice outside the study.
    nutrient_topic
    L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
    plain_language
    Changing a regulator or diet did not correct every downstream outcome.
    primary_references
    Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11518822/ · DOI 10.1203/00006450-200109000-00010
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 194–200

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

    ## glutamate-gdh-ammonia-limit Changing a regulator or diet did not correct every downstream outcome. Hyperammonemia persisted despite protein/leucine restriction in the reported twelve-patient series. Model: Human rare-disease clinical series. Limitations: This does not establish treatment futility across all regimens or justify dietary advice outside the study. Evidence access: Primary abstract Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11518822/ · DOI 10.1203/00006450-200109000-00010
    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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