Component

Human GLUD1 hyperinsulinism/hyperammonemia

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

4 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

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

  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

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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