Component

7,8-Dihydrofolate

Oxidized intermediate reduced by DHFR to tetrahydrofolate. Chemically distinct folate-pathway or nucleotide intermediate; shared across species.

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 acts on it

  1. Human liver DHFR converted 7,8-dihydrofolate to tetrahydrofolate in NADPH-containing assays.

    Human dihydrofolate reductase / DHFR → 7,8-Dihydrofolate source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Fresh human liver extracts from six donors and rat comparison
    exposure
    DHF substrate; THF quantified by HPLC
    limitations
    Assay chemistry, not an outcome study.
    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
    DHFR regenerates reduced folate from DHF.
    primary_references
    [bailey2009] The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake (2009). https://pubmed.ncbi.nlm.nih.gov/19706381/ DOI: 10.1073/pnas.0902072106
    tissue_or_cell_type
    Liver extracts

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 363–373

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fresh human liver extracts from six donors and rat comparison · source_derived_draft · unverified_draft

    ### folate-dhfr-dhf-recycling Human liver DHFR converted 7,8-dihydrofolate to tetrahydrofolate in NADPH-containing assays. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: DHFR regenerates reduced folate from DHF. organism: Homo sapiens tissue_or_cell_type: Liver extracts experimental_model: Fresh human liver extracts from six donors and rat comparison limitations: Assay chemistry, not an outcome study. exposure: DHF substrate; THF quantified by HPLC [bailey2009] The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake (2009). https://pubmed.ncbi.nlm.nih.gov/19706381/ DOI: 10.1073/pnas.0902072106
    Complete structured claim and evidence

  2. Dihydrofolate was also an effective substrate for purified human cytosolic FPGS.

    Human cytosolic FPGS isoform → 7,8-Dihydrofolate source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Purified human cytosolic FPGS expressed in bacteria
    exposure
    Comparative substrate enzyme assays
    limitations
    Does not establish net DHF pool size in human tissues.
    nutrient_topic
    Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
    organism
    Homo sapiens protein expressed in Escherichia coli
    plain_language
    Polyglutamate tails can be attached before DHF is reduced.
    primary_references
    [chen1996] Purification and properties of human cytosolic folylpoly-gamma-glutamate synthetase and organization, localization, and differential splicing of its gene (1996). https://pubmed.ncbi.nlm.nih.gov/8662720/ DOI: 10.1074/jbc.271.22.13077
    tissue_or_cell_type
    Purified enzyme

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 267–277

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human cytosolic FPGS expressed in bacteria · source_derived_draft · unverified_draft

    ### folate-fpgs-dhf-substrate Dihydrofolate was also an effective substrate for purified human cytosolic FPGS. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Polyglutamate tails can be attached before DHF is reduced. organism: Homo sapiens protein expressed in Escherichia coli tissue_or_cell_type: Purified enzyme experimental_model: Purified human cytosolic FPGS expressed in bacteria limitations: Does not establish net DHF pool size in human tissues. exposure: Comparative substrate enzyme assays [chen1996] Purification and properties of human cytosolic folylpoly-gamma-glutamate synthetase and organization, localization, and differential splicing of its gene (1996). https://pubmed.ncbi.nlm.nih.gov/8662720/ DOI: 10.1074/jbc.271.22.13077
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. DHFR reduces folic acid to dihydrofolate before further reduction to tetrahydrofolate.

    Human dihydrofolate reductase / DHFR → Folic acid source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Fresh human liver extracts from six donors and rat comparison
    exposure
    Folic acid substrate with NADPH
    limitations
    Reaction identity; liver rates cannot define a universal intake ceiling.
    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
    Folic acid needs a reduction step before it becomes usable folate.
    primary_references
    [bailey2009] The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake (2009). https://pubmed.ncbi.nlm.nih.gov/19706381/ DOI: 10.1073/pnas.0902072106
    tissue_or_cell_type
    Liver enzyme preparations

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 351–361

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fresh human liver extracts from six donors and rat comparison · source_derived_draft · unverified_draft

    ### folate-dhfr-folic-acid-first-reduction DHFR reduces folic acid to dihydrofolate before further reduction to tetrahydrofolate. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Folic acid needs a reduction step before it becomes usable folate. organism: Homo sapiens tissue_or_cell_type: Liver enzyme preparations experimental_model: Fresh human liver extracts from six donors and rat comparison limitations: Reaction identity; liver rates cannot define a universal intake ceiling. exposure: Folic acid substrate with NADPH [bailey2009] The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake (2009). https://pubmed.ncbi.nlm.nih.gov/19706381/ DOI: 10.1073/pnas.0902072106
    Complete structured claim and evidence

  2. Human TYMS uses 5,10-methylene-THF to convert dUMP to dTMP, producing dihydrofolate.

    Human thymidylate synthase / TYMS → Deoxyuridine monophosphate source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Purified human TYMS reaction assays
    exposure
    Assay conditions described in the linked primary study.
    limitations
    Purified-enzyme chemistry does not specify cellular flux.
    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
    Folate supplies the carbon and reducing power to make a DNA base.
    primary_references
    [islam-2018] Bacterial versus human thymidylate synthase: Kinetics and functionality (2018). https://pubmed.ncbi.nlm.nih.gov/29715278/ DOI: 10.1371/journal.pone.0196506
    tissue_or_cell_type
    Cell-free

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 973–983

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human TYMS reaction assays · source_derived_draft · unverified_draft

    ### tyms-dump-methylation Human TYMS uses 5,10-methylene-THF to convert dUMP to dTMP, producing dihydrofolate. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Folate supplies the carbon and reducing power to make a DNA base. organism: Homo sapiens tissue_or_cell_type: Cell-free experimental_model: Purified human TYMS reaction assays limitations: Purified-enzyme chemistry does not specify cellular flux. exposure: Assay conditions described in the linked primary study. [islam-2018] Bacterial versus human thymidylate synthase: Kinetics and functionality (2018). https://pubmed.ncbi.nlm.nih.gov/29715278/ DOI: 10.1371/journal.pone.0196506
    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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