Component

Glutamine synthetase / GLUL

Enzyme assimilating ammonium and glutamate into glutamine.

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. Human glutamine synthetase catalyzes ATP-coupled ligation of glutamate and ammonia to make glutamine.

    Glutamine synthetase / GLUL → L-Glutamine source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Human GLUL ligand-complex crystal structures; canine apoenzyme comparison
    exposure
    ADP/phosphate/Mn and ADP/phosphorylated-inhibitor/Mn complexes
    limitations
    Reaction identity does not determine the predominant metal in living human brain.
    nutrient_topic
    Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
    organism
    Homo sapiens protein
    plain_language
    GLUL combines glutamate and ammonia using ATP.
    primary_references
    [mn-enz-18005987] Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design. (2008). https://pubmed.ncbi.nlm.nih.gov/18005987/ DOI: 10.1016/j.jmb.2007.10.029
    tissue_or_cell_type
    Purified GLUL

    Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 596–606

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GLUL ligand-complex crystal structures; canine apoenzyme comparison · source_derived_draft · unverified_draft

    ### mn-enz-glul-reaction Human glutamine synthetase catalyzes ATP-coupled ligation of glutamate and ammonia to make glutamine. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: GLUL combines glutamate and ammonia using ATP. organism: Homo sapiens protein tissue_or_cell_type: Purified GLUL experimental_model: Human GLUL ligand-complex crystal structures; canine apoenzyme comparison limitations: Reaction identity does not determine the predominant metal in living human brain. exposure: ADP/phosphate/Mn and ADP/phosphorylated-inhibitor/Mn complexes [mn-enz-18005987] Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design. (2008). https://pubmed.ncbi.nlm.nih.gov/18005987/ DOI: 10.1016/j.jmb.2007.10.029
    Complete structured claim and evidence

What acts on it

  1. The same hypokalemic diet increased glutamine synthetase expression in type A intercalated cells.

    Potassium → Glutamine synthetase / GLUL source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    endpoint
    The same hypokalemic diet increased glutamine synthetase expression in type A intercalated cells.
    experimental-exposure
    Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays.
    experimental_model
    Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays.
    limitations
    Cell-specific regulation is not a contradiction of the proximal-tubule result; neither establishes net flux in an intact human kidney.
    nutrient_topic
    Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
    organism
    Mus musculus
    plain_language
    Different kidney cells adjusted the same ammonia-recycling enzyme in opposite directions.
    primary_references
    [verlander-2013-gs] Expression of glutamine synthetase in the mouse kidney: localization in multiple epithelial cell types and differential regulation by hypokalemia (2013). https://pubmed.ncbi.nlm.nih.gov/23804452/ DOI: 10.1152/ajprenal.00030.2013
    tissue_or_cell_type
    type A intercalated cells of cortical and outer medullary collecting duct
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1055–1066

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays. · source_derived_draft · unverified_draft

    ### k-depletion-intercalated-glul The same hypokalemic diet increased glutamine synthetase expression in type A intercalated cells. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different kidney cells adjusted the same ammonia-recycling enzyme in opposite directions. organism: Mus musculus tissue_or_cell_type: type A intercalated cells of cortical and outer medullary collecting duct experimental_model: Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays. limitations: Cell-specific regulation is not a contradiction of the proximal-tubule result; neither establishes net flux in an intact human kidney. experimental-exposure: Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays. endpoint: The same hypokalemic diet increased glutamine synthetase expression in type A intercalated cells. [verlander-2013-gs] Expression of glutamine synthetase in the mouse kidney: localization in multiple epithelial cell types and differential regulation by hypokalemia (2013). https://pubmed.ncbi.nlm.nih.gov/23804452/ DOI: 10.1152/ajprenal.00030.2013
    Complete structured claim and evidence

  2. Diet-induced hypokalemia decreased glutamine synthetase expression throughout the mouse proximal tubule.

    Potassium → Glutamine synthetase / GLUL source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    endpoint
    Diet-induced hypokalemia decreased glutamine synthetase expression throughout the mouse proximal tubule.
    experimental-exposure
    Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays.
    experimental_model
    Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays.
    limitations
    Expression and localization were measured; the quantitative contribution of GLUL to total flux was not isolated.
    nutrient_topic
    Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
    organism
    Mus musculus
    plain_language
    Less ammonia-recycling enzyme was present in this compartment, potentially leaving more ammonia available for excretion.
    primary_references
    [verlander-2013-gs] Expression of glutamine synthetase in the mouse kidney: localization in multiple epithelial cell types and differential regulation by hypokalemia (2013). https://pubmed.ncbi.nlm.nih.gov/23804452/ DOI: 10.1152/ajprenal.00030.2013
    tissue_or_cell_type
    renal proximal tubule
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1028–1039

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays. · source_derived_draft · unverified_draft

    ### k-depletion-proximal-glul Diet-induced hypokalemia decreased glutamine synthetase expression throughout the mouse proximal tubule. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less ammonia-recycling enzyme was present in this compartment, potentially leaving more ammonia available for excretion. organism: Mus musculus tissue_or_cell_type: renal proximal tubule experimental_model: Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays. limitations: Expression and localization were measured; the quantitative contribution of GLUL to total flux was not isolated. experimental-exposure: Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays. endpoint: Diet-induced hypokalemia decreased glutamine synthetase expression throughout the mouse proximal tubule. [verlander-2013-gs] Expression of glutamine synthetase in the mouse kidney: localization in multiple epithelial cell types and differential regulation by hypokalemia (2013). https://pubmed.ncbi.nlm.nih.gov/23804452/ DOI: 10.1152/ajprenal.00030.2013
    Complete structured claim and evidence

  3. Two infants with homozygous GLUL mutations had profoundly low glutamine and severe neonatal disease; variant expression assays showed reduced enzyme activity.

    Human GLUL R324C/R341C deficiency → Glutamine synthetase / GLUL source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Two unrelated newborns, patient lymphocytes and mutant expression in COS7 cells.
    limitations
    This is congenital glutamine-synthesis failure, not evidence of inadequate dietary glutamate.
    nutrient_topic
    L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
    plain_language
    A synthesis defect can prevent conversion of one available amino acid into another.
    primary_references
    Congenital glutamine deficiency with glutamine synthetase mutations. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16267323/ · DOI 10.1056/NEJMoa050456
    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 122–128

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Two unrelated newborns, patient lymphocytes and mutant expression in COS7 cells. · source_derived_draft · unverified_draft

    ## glutamate-glul-human-loss A synthesis defect can prevent conversion of one available amino acid into another. Two infants with homozygous GLUL mutations had profoundly low glutamine and severe neonatal disease; variant expression assays showed reduced enzyme activity. Model: Two unrelated newborns, patient lymphocytes and mutant expression in COS7 cells. Limitations: This is congenital glutamine-synthesis failure, not evidence of inadequate dietary glutamate. Evidence access: Primary abstract Congenital glutamine deficiency with glutamine synthetase mutations. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16267323/ · DOI 10.1056/NEJMoa050456
    Complete structured claim and evidence

  4. Human GLUL crystal structures contained Mn with ADP/phosphate or ADP/phosphorylated methionine-sulfoximine.

    Mn2+ → Glutamine synthetase / GLUL source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Human GLUL ligand-complex crystal structures; canine apoenzyme comparison
    exposure
    ADP/phosphate/Mn and ADP/phosphorylated-inhibitor/Mn complexes
    limitations
    Crystallographic Mn binding does not establish exclusive Mn dependence or endogenous human brain metal occupancy.
    nutrient_topic
    Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
    organism
    Homo sapiens protein
    plain_language
    Human GLUL can bind manganese in the reported structural complexes.
    primary_references
    [mn-enz-18005987] Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design. (2008). https://pubmed.ncbi.nlm.nih.gov/18005987/ DOI: 10.1016/j.jmb.2007.10.029
    tissue_or_cell_type
    Purified GLUL

    Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 608–618

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GLUL ligand-complex crystal structures; canine apoenzyme comparison · source_derived_draft · unverified_draft

    ### mn-enz-glul-mn-crystals Human GLUL crystal structures contained Mn with ADP/phosphate or ADP/phosphorylated methionine-sulfoximine. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human GLUL can bind manganese in the reported structural complexes. organism: Homo sapiens protein tissue_or_cell_type: Purified GLUL experimental_model: Human GLUL ligand-complex crystal structures; canine apoenzyme comparison limitations: Crystallographic Mn binding does not establish exclusive Mn dependence or endogenous human brain metal occupancy. exposure: ADP/phosphate/Mn and ADP/phosphorylated-inhibitor/Mn complexes [mn-enz-18005987] Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design. (2008). https://pubmed.ncbi.nlm.nih.gov/18005987/ DOI: 10.1016/j.jmb.2007.10.029
    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