Component

Human glutamate carboxypeptidase II / FOLH1

Human glutamate carboxypeptidase II / FOLH1; species and subcellular isoforms retained separately.

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

What it acts on

  1. Partially purified human jejunal brush-border folate hydrolase progressively removed glutamates, producing predominantly monoglutamate after 120 minutes.

    Human glutamate carboxypeptidase II / FOLH1 → Folate polyglutamates source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Partially purified human jejunal brush-border enzyme
    exposure
    Radiolabeled synthetic folate polyglutamates in enzyme incubations
    limitations
    Ex-vivo digestion, not a meal bioavailability measurement.
    nutrient_topic
    Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
    organism
    Homo sapiens
    plain_language
    Food folate tails are shortened before absorption.
    primary_references
    [reisenauer1981] Human jejunal brush border folate conjugase. Characteristics and inhibition by salicylazosulfapyridine (1981). https://pubmed.ncbi.nlm.nih.gov/6113848/ DOI: 10.1016/0005-2744(81)90271-0
    tissue_or_cell_type
    Jejunal brush border

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 82–92

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Partially purified human jejunal brush-border enzyme · source_derived_draft · unverified_draft

    ### folate-brush-border-deconjugation Partially purified human jejunal brush-border folate hydrolase progressively removed glutamates, producing predominantly monoglutamate after 120 minutes. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Food folate tails are shortened before absorption. organism: Homo sapiens tissue_or_cell_type: Jejunal brush border experimental_model: Partially purified human jejunal brush-border enzyme limitations: Ex-vivo digestion, not a meal bioavailability measurement. exposure: Radiolabeled synthetic folate polyglutamates in enzyme incubations [reisenauer1981] Human jejunal brush border folate conjugase. Characteristics and inhibition by salicylazosulfapyridine (1981). https://pubmed.ncbi.nlm.nih.gov/6113848/ DOI: 10.1016/0005-2744(81)90271-0
    Complete structured claim and evidence

  2. Human GCPII structures and mutagenesis identified an arene-binding site that recognizes the folate portion of polyglutamate substrates.

    Human glutamate carboxypeptidase II / FOLH1 → Folate polyglutamates source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Recombinant human GCPII structure and enzyme assays
    exposure
    Substrate complexes and arene-site mutants
    limitations
    Catalytically inactive structures require the accompanying kinetic experiments for functional interpretation.
    nutrient_topic
    Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
    organism
    Homo sapiens
    plain_language
    The enzyme recognizes more than the glutamate tail.
    primary_references
    [navratil2014] Structural and biochemical characterization of the folyl-poly-γ-l-glutamate hydrolyzing activity of human glutamate carboxypeptidase II (2014). https://pubmed.ncbi.nlm.nih.gov/24863754/ DOI: 10.1111/febs.12857
    tissue_or_cell_type
    Purified recombinant protein

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 106–116

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human GCPII structure and enzyme assays · source_derived_draft · unverified_draft

    ### folate-gcpii-arene-recognition Human GCPII structures and mutagenesis identified an arene-binding site that recognizes the folate portion of polyglutamate substrates. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme recognizes more than the glutamate tail. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein experimental_model: Recombinant human GCPII structure and enzyme assays limitations: Catalytically inactive structures require the accompanying kinetic experiments for functional interpretation. exposure: Substrate complexes and arene-site mutants [navratil2014] Structural and biochemical characterization of the folyl-poly-γ-l-glutamate hydrolyzing activity of human glutamate carboxypeptidase II (2014). https://pubmed.ncbi.nlm.nih.gov/24863754/ DOI: 10.1111/febs.12857
    Complete structured claim and evidence

What acts on it

  1. Human GCPII crystal structures resolved two zinc ions at the catalytic center, bridged by water or hydroxide and Asp387.

    Zinc(II) ion → Human glutamate carboxypeptidase II / FOLH1 source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Zinc-folate: molecular catalytic-site dependency; dietary zinc deficiency was not tested.
    experimental_model
    Recombinant human GCPII crystallography
    exposure
    Glutamate, phosphate and inhibitor-bound structures
    limitations
    Structural cofactor evidence does not establish zinc intake thresholds.
    nutrient_topic
    Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
    organism
    Homo sapiens
    plain_language
    The folate-processing enzyme contains a two-zinc catalytic site.
    primary_references
    [mesters2006] Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer (2006). https://pubmed.ncbi.nlm.nih.gov/16467855/ DOI: 10.1038/sj.emboj.7600969
    tissue_or_cell_type
    Purified recombinant protein

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 118–129

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human GCPII crystallography · source_derived_draft · unverified_draft

    ### folate-gcpii-zinc-catalytic-center Human GCPII crystal structures resolved two zinc ions at the catalytic center, bridged by water or hydroxide and Asp387. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The folate-processing enzyme contains a two-zinc catalytic site. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein experimental_model: Recombinant human GCPII crystallography limitations: Structural cofactor evidence does not establish zinc intake thresholds. exposure: Glutamate, phosphate and inhibitor-bound structures cross_nutrient: Zinc-folate: molecular catalytic-site dependency; dietary zinc deficiency was not tested. [mesters2006] Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer (2006). https://pubmed.ncbi.nlm.nih.gov/16467855/ DOI: 10.1038/sj.emboj.7600969
    Complete structured claim and evidence

  2. Sulfasalazine competitively inhibited human jejunal brush-border folate hydrolase, with reported Ki 0.13 mM.

    Sulfasalazine → Human glutamate carboxypeptidase II / FOLH1 source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Partially purified human jejunal brush-border enzyme
    exposure
    In-vitro inhibitor concentration series
    limitations
    Does not quantify clinical malabsorption or establish every drug mechanism.
    nutrient_topic
    Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
    organism
    Homo sapiens
    plain_language
    This drug can inhibit the folate digestion enzyme.
    primary_references
    [reisenauer1981] Human jejunal brush border folate conjugase. Characteristics and inhibition by salicylazosulfapyridine (1981). https://pubmed.ncbi.nlm.nih.gov/6113848/ DOI: 10.1016/0005-2744(81)90271-0
    tissue_or_cell_type
    Jejunal brush border

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 94–104

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Partially purified human jejunal brush-border enzyme · source_derived_draft · unverified_draft

    ### folate-sulfasalazine-conjugase-inhibition Sulfasalazine competitively inhibited human jejunal brush-border folate hydrolase, with reported Ki 0.13 mM. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: This drug can inhibit the folate digestion enzyme. organism: Homo sapiens tissue_or_cell_type: Jejunal brush border experimental_model: Partially purified human jejunal brush-border enzyme limitations: Does not quantify clinical malabsorption or establish every drug mechanism. exposure: In-vitro inhibitor concentration series [reisenauer1981] Human jejunal brush border folate conjugase. Characteristics and inhibition by salicylazosulfapyridine (1981). https://pubmed.ncbi.nlm.nih.gov/6113848/ DOI: 10.1016/0005-2744(81)90271-0
    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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