Component

Human methenyltetrahydrofolate synthetase / MTHFS

Human ATP-dependent 5-formyltetrahydrofolate cyclo-ligase.

3 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

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. Purified human liver MTHFS converts 5-formyl-THF into 5,10-methenyl-THF.

    Experimental context and source evidence
    experimental_model
    Purified liver enzyme
    exposure
    Purified human liver enzyme and folate substrates; initial-velocity measurements.
    limitations
    An enzyme assay does not establish clinical benefit from folinic acid.
    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 enzyme moves folinic acid into the methenyl-folate pool.
    primary_references
    [bertrand-1987] Human liver methenyltetrahydrofolate synthetase: improved purification and increased affinity for folate polyglutamate substrates (1987). https://pubmed.ncbi.nlm.nih.gov/3801490/ DOI: 10.1016/0167-4838(87)90004-5
    tissue_or_cell_type
    Liver-derived, cell-free

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1243–1253

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

    ### mthfs-folinic-acid-conversion Purified human liver MTHFS converts 5-formyl-THF into 5,10-methenyl-THF. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: This enzyme moves folinic acid into the methenyl-folate pool. organism: Homo sapiens tissue_or_cell_type: Liver-derived, cell-free experimental_model: Purified liver enzyme limitations: An enzyme assay does not establish clinical benefit from folinic acid. exposure: Purified human liver enzyme and folate substrates; initial-velocity measurements. [bertrand-1987] Human liver methenyltetrahydrofolate synthetase: improved purification and increased affinity for folate polyglutamate substrates (1987). https://pubmed.ncbi.nlm.nih.gov/3801490/ DOI: 10.1016/0167-4838(87)90004-5
    Complete structured claim and evidence

What acts on it

  1. The purified human liver MTHFS reaction requires ATP and Mg2+ and is an ADP-forming cyclo-ligase reaction.

    Experimental context and source evidence
    cross_nutrient
    Magnesium and ATP support folate interconversion.
    experimental_model
    Purified liver enzyme
    exposure
    Controlled enzyme assay with ATP and magnesium.
    limitations
    Cofactor dependence does not establish a dietary magnesium threshold.
    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
    ATP supplies energy for this magnesium-dependent folate conversion.
    primary_references
    [bertrand-1987] Human liver methenyltetrahydrofolate synthetase: improved purification and increased affinity for folate polyglutamate substrates (1987). https://pubmed.ncbi.nlm.nih.gov/3801490/ DOI: 10.1016/0167-4838(87)90004-5
    tissue_or_cell_type
    Liver-derived, cell-free

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1255–1266

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

    ### mthfs-atp-magnesium-dependence The purified human liver MTHFS reaction requires ATP and Mg2+ and is an ADP-forming cyclo-ligase reaction. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP supplies energy for this magnesium-dependent folate conversion. organism: Homo sapiens tissue_or_cell_type: Liver-derived, cell-free experimental_model: Purified liver enzyme limitations: Cofactor dependence does not establish a dietary magnesium threshold. exposure: Controlled enzyme assay with ATP and magnesium. cross_nutrient: Magnesium and ATP support folate interconversion. [bertrand-1987] Human liver methenyltetrahydrofolate synthetase: improved purification and increased affinity for folate polyglutamate substrates (1987). https://pubmed.ncbi.nlm.nih.gov/3801490/ DOI: 10.1016/0167-4838(87)90004-5
    Complete structured claim and evidence
  2. Patient 1 fibroblast lysate had no detectable MTHFS activity in the reported product-formation assay.

    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_location
    Results 3.3 and Figure 4.
    experimental_model
    Fibroblast lysate enzyme assay
    exposure
    Lysate enzyme assay versus control; Figure 4.
    limitations
    Assay-specific nondetection does not prove zero activity in every tissue or separate the two alleles.
    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
    These patient cells could not measurably perform the tested folate conversion.
    primary_references
    [rodan-2018] 5,10-methenyltetrahydrofolate synthetase deficiency causes a neurometabolic disorder associated with microcephaly, epilepsy, and cerebral hypomyelination (2018). https://pubmed.ncbi.nlm.nih.gov/30031689/ DOI: 10.1016/j.ymgme.2018.06.006
    tissue_or_cell_type
    Patient 1 skin fibroblasts
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1268–1279

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fibroblast lysate enzyme assay · source_derived_draft · unverified_draft

    ### mthfs-patient1-enzyme-activity Patient 1 fibroblast lysate had no detectable MTHFS activity in the reported product-formation assay. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: These patient cells could not measurably perform the tested folate conversion. organism: Homo sapiens tissue_or_cell_type: Patient 1 skin fibroblasts experimental_model: Fibroblast lysate enzyme assay limitations: Assay-specific nondetection does not prove zero activity in every tissue or separate the two alleles. exposure: Lysate enzyme assay versus control; Figure 4. evidence_location: Results 3.3 and Figure 4. [rodan-2018] 5,10-methenyltetrahydrofolate synthetase deficiency causes a neurometabolic disorder associated with microcephaly, epilepsy, and cerebral hypomyelination (2018). https://pubmed.ncbi.nlm.nih.gov/30031689/ DOI: 10.1016/j.ymgme.2018.06.006
    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