Component

5-Formyltetrahydrofolate

Reduced formyl folate; the 6S isomer was used in the human portal study.

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. After oral labeled 6S-5-formylTHF, portal folate was predominantly labeled 5-MTHF at 15 minutes; unchanged formylTHF was 4 ± 18%.

    5-Formyltetrahydrofolate → 5-Methyltetrahydrofolate source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Portal/peripheral isotope crossover in six TIPSS patients
    exposure
    500 nmol labeled 6S-5-formylTHF; four comparator participants
    limitations
    Does not show superiority for clinical outcomes.
    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 gut readily processed the reduced folate in this comparison.
    primary_references
    [patanwala2014] Folic acid handling by the human gut: implications for food fortification and supplementation (2014). https://pubmed.ncbi.nlm.nih.gov/24944062/ DOI: 10.3945/ajcn.113.080507
    tissue_or_cell_type
    Hepatic portal blood

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 399–409

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Portal/peripheral isotope crossover in six TIPSS patients · source_derived_draft · unverified_draft

    ### folate-portal-formyl-to-methyl-conversion After oral labeled 6S-5-formylTHF, portal folate was predominantly labeled 5-MTHF at 15 minutes; unchanged formylTHF was 4 ± 18%. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The gut readily processed the reduced folate in this comparison. organism: Homo sapiens tissue_or_cell_type: Hepatic portal blood experimental_model: Portal/peripheral isotope crossover in six TIPSS patients limitations: Does not show superiority for clinical outcomes. exposure: 500 nmol labeled 6S-5-formylTHF; four comparator participants [patanwala2014] Folic acid handling by the human gut: implications for food fortification and supplementation (2014). https://pubmed.ncbi.nlm.nih.gov/24944062/ DOI: 10.3945/ajcn.113.080507
    Complete structured claim and evidence

What acts on it

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

    Human methenyltetrahydrofolate synthetase / MTHFS → 5-Formyltetrahydrofolate source_derived_draftungraded
    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

  2. Patient 1 fibroblasts accumulated about 30-fold more 5-formyl-THF than control cells.

    Human MTHFS gene → 5-Formyltetrahydrofolate source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_location
    Results 3.4 and Figure 5.
    experimental_model
    Cellular folate mass spectrometry
    exposure
    Patient 1183-01 versus EC/BJ control fibroblasts; Figure 5.
    limitations
    Substrate accumulation does not establish that it causes the neurologic phenotype.
    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 substrate built up in cells with impaired MTHFS.
    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 1281–1292

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cellular folate mass spectrometry · source_derived_draft · unverified_draft

    ### mthfs-patient1-folinic-accumulation Patient 1 fibroblasts accumulated about 30-fold more 5-formyl-THF than control cells. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The substrate built up in cells with impaired MTHFS. organism: Homo sapiens tissue_or_cell_type: Patient 1 skin fibroblasts experimental_model: Cellular folate mass spectrometry limitations: Substrate accumulation does not establish that it causes the neurologic phenotype. exposure: Patient 1183-01 versus EC/BJ control fibroblasts; Figure 5. evidence_location: Results 3.4 and Figure 5. [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

Where it participates (unsigned role)

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

    ATP → Human methenyltetrahydrofolate synthetase / MTHFS source_derived_draftungraded
    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

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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