Component

10-Formyltetrahydrofolate

Chemically distinct folate-pathway or nucleotide intermediate; shared across species.

10 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. Phosphopantetheinylation restored recombinant ALDH1L2 folate dehydrogenase activity with NADPH formation.

    Human ALDH1L2 phosphopantetheinylated at Ser375 → 10-Formyltetrahydrofolate source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    CoA maturation enables the folate-to-NADPH reaction.
    experimental_model
    Recombinant enzyme activation assay
    exposure
    Assay conditions described in the linked primary study.
    limitations
    Figure 5 used stable dideazafolate analogue rather than physiological folate.
    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 installed arm enables oxidation of folate-bound carbon.
    primary_references
    [strickland-2011] Enzymatic properties of ALDH1L2, a mitochondrial 10-formyltetrahydrofolate dehydrogenase (2011). https://pubmed.ncbi.nlm.nih.gov/21238436/ DOI: 10.1016/j.cbi.2011.01.008
    tissue_or_cell_type
    Cell-free

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1059–1070

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

    ### aldh1l2-activation-folate-oxidation Phosphopantetheinylation restored recombinant ALDH1L2 folate dehydrogenase activity with NADPH formation. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The installed arm enables oxidation of folate-bound carbon. organism: Homo sapiens tissue_or_cell_type: Cell-free experimental_model: Recombinant enzyme activation assay limitations: Figure 5 used stable dideazafolate analogue rather than physiological folate. exposure: Assay conditions described in the linked primary study. cross_nutrient: CoA maturation enables the folate-to-NADPH reaction. [strickland-2011] Enzymatic properties of ALDH1L2, a mitochondrial 10-formyltetrahydrofolate dehydrogenase (2011). https://pubmed.ncbi.nlm.nih.gov/21238436/ DOI: 10.1016/j.cbi.2011.01.008
    Complete structured claim and evidence

  2. Rat MTHFD2L also has methenyl-THF cyclohydrolase activity, linking methenyl-THF to 10-formyl-THF.

    Rat mitochondrial MTHFD2L → 10-Formyltetrahydrofolate source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Purified recombinant rat protein
    exposure
    Assay conditions described in the linked primary study.
    limitations
    Reaction direction depends on chemical conditions.
    nutrient_topic
    Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
    organism
    Rattus norvegicus
    plain_language
    The same protein performs the next folate conversion.
    primary_references
    [shin-2014] Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and embryonic tissues (2014). https://pubmed.ncbi.nlm.nih.gov/24733394/ DOI: 10.1074/jbc.m114.555573
    tissue_or_cell_type
    Cell-free

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 850–860

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

    ### rat-mthfd2l-cyclohydrolase Rat MTHFD2L also has methenyl-THF cyclohydrolase activity, linking methenyl-THF to 10-formyl-THF. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same protein performs the next folate conversion. organism: Rattus norvegicus tissue_or_cell_type: Cell-free experimental_model: Purified recombinant rat protein limitations: Reaction direction depends on chemical conditions. exposure: Assay conditions described in the linked primary study. [shin-2014] Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and embryonic tissues (2014). https://pubmed.ncbi.nlm.nih.gov/24733394/ DOI: 10.1074/jbc.m114.555573
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Ectopic ALDH1L1 expression in HuH-7 cells increased ZMP/AICAR ribotide, consistent with reduced formyl-donor availability for ATIC.

    Human ALDH1L1 → 5-Aminoimidazole-4-carboxamide ribonucleotide source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Stable expression and metabolomics
    exposure
    Engineered ALDH1L1 expression.
    limitations
    Overexpression in one cancer line; substrate competition is the study 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
    Disposing of folate-bound carbon can slow a purine-building step.
    primary_references
    [sasaki-2023] One-carbon metabolizing enzyme ALDH1L1 influences mitochondrial metabolism through 5-aminoimidazole-4-carboxamide ribonucleotide accumulation and serine depletion, contributing to tumor suppression (2023). https://pubmed.ncbi.nlm.nih.gov/37596270/ DOI: 10.1038/s41598-023-38142-5
    tissue_or_cell_type
    HuH-7 hepatocellular carcinoma cells

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1072–1082

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

    ### aldh1l1-aicar-accumulation Ectopic ALDH1L1 expression in HuH-7 cells increased ZMP/AICAR ribotide, consistent with reduced formyl-donor availability for ATIC. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Disposing of folate-bound carbon can slow a purine-building step. organism: Homo sapiens tissue_or_cell_type: HuH-7 hepatocellular carcinoma cells experimental_model: Stable expression and metabolomics limitations: Overexpression in one cancer line; substrate competition is the study interpretation. exposure: Engineered ALDH1L1 expression. [sasaki-2023] One-carbon metabolizing enzyme ALDH1L1 influences mitochondrial metabolism through 5-aminoimidazole-4-carboxamide ribonucleotide accumulation and serine depletion, contributing to tumor suppression (2023). https://pubmed.ncbi.nlm.nih.gov/37596270/ DOI: 10.1038/s41598-023-38142-5
    Complete structured claim and evidence

  2. Purified human ATIC uses 10-formyl-THF for its AICAR formyltransferase reaction, yielding FAICAR.

    Human bifunctional ATIC → 5-Aminoimidazole-4-carboxamide ribonucleotide source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Recombinant enzyme kinetics
    exposure
    Assay conditions described in the linked primary study.
    limitations
    Reported folate kinetics used a 6R/6S mixture.
    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
    A second folate donation helps finish the purine ring.
    primary_references
    [rayl-1996] The human purH gene product, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase. Cloning, sequencing, expression, purification, kinetic analysis, and domain mapping (1996). https://pubmed.ncbi.nlm.nih.gov/8567683/ DOI: 10.1074/jbc.271.4.2225
    tissue_or_cell_type
    Cell-free

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1010–1020

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

    ### atic-aicar-formylation Purified human ATIC uses 10-formyl-THF for its AICAR formyltransferase reaction, yielding FAICAR. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second folate donation helps finish the purine ring. organism: Homo sapiens tissue_or_cell_type: Cell-free experimental_model: Recombinant enzyme kinetics limitations: Reported folate kinetics used a 6R/6S mixture. exposure: Assay conditions described in the linked primary study. [rayl-1996] The human purH gene product, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase. Cloning, sequencing, expression, purification, kinetic analysis, and domain mapping (1996). https://pubmed.ncbi.nlm.nih.gov/8567683/ DOI: 10.1074/jbc.271.4.2225
    Complete structured claim and evidence

  3. Provided carbon-13 formate entered cytosolic 10-formyl-THF and ATP in wild-type HEK293T cells through the MTHFD1 assimilation route.

    Human MTHFD1 → Formate source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Formate rescue and metabolomics
    exposure
    Carbon-13 formate tracer in wild-type cells; Figure 2d.
    limitations
    Tracing supports pathway use but is not an isolated enzyme assay or dietary recommendation.
    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
    Cells incorporate formate carbon into purine nucleotides.
    primary_references
    [ducker-2016] Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway (2016). https://pubmed.ncbi.nlm.nih.gov/27211901/ DOI: 10.1016/j.cmet.2016.04.016
    tissue_or_cell_type
    HEK293T cells

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 911–921

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

    ### formate-mthfd1-assimilation Provided carbon-13 formate entered cytosolic 10-formyl-THF and ATP in wild-type HEK293T cells through the MTHFD1 assimilation route. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cells incorporate formate carbon into purine nucleotides. organism: Homo sapiens tissue_or_cell_type: HEK293T cells experimental_model: Formate rescue and metabolomics limitations: Tracing supports pathway use but is not an isolated enzyme assay or dietary recommendation. exposure: Carbon-13 formate tracer in wild-type cells; Figure 2d. [ducker-2016] Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway (2016). https://pubmed.ncbi.nlm.nih.gov/27211901/ DOI: 10.1016/j.cmet.2016.04.016
    Complete structured claim and evidence

  4. The human GART transformylase domain binds a folate formyl donor and GAR-site acceptor in a ternary complex supporting GAR formylation to FGAR.

    Human trifunctional GART → Glycinamide ribonucleotide source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    X-ray crystallography
    exposure
    Assay conditions described in the linked primary study.
    limitations
    Structures used 10-formyl-dideazafolate and hydroxyacetamide ribonucleotide analogues.
    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 donates one carbon early in purine-base construction.
    primary_references
    [dahms-2005] The apo and ternary complex structures of a chemotherapeutic target: human glycinamide ribonucleotide transformylase (2005). https://pubmed.ncbi.nlm.nih.gov/16026156/ DOI: 10.1021/bi050307g
    tissue_or_cell_type
    Purified domain

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 998–1008

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

    ### gart-formyl-transfer The human GART transformylase domain binds a folate formyl donor and GAR-site acceptor in a ternary complex supporting GAR formylation to FGAR. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Folate donates one carbon early in purine-base construction. organism: Homo sapiens tissue_or_cell_type: Purified domain experimental_model: X-ray crystallography limitations: Structures used 10-formyl-dideazafolate and hydroxyacetamide ribonucleotide analogues. exposure: Assay conditions described in the linked primary study. [dahms-2005] The apo and ternary complex structures of a chemotherapeutic target: human glycinamide ribonucleotide transformylase (2005). https://pubmed.ncbi.nlm.nih.gov/16026156/ DOI: 10.1021/bi050307g
    Complete structured claim and evidence

  5. MTHFD2 deletion depleted formyl-folate availability and activated cytosolic serine-derived one-carbon production.

    Human MTHFD2 gene → Human MTHFD1 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    experimental_model
    CRISPR and isotope tracing
    exposure
    Assay conditions described in the linked primary study.
    limitations
    Compensation depends on nutrient availability.
    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
    Cells can reroute carbon production after losing the mitochondrial pathway.
    primary_references
    [ducker-2016] Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway (2016). https://pubmed.ncbi.nlm.nih.gov/27211901/ DOI: 10.1016/j.cmet.2016.04.016
    tissue_or_cell_type
    HEK293T cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 899–909

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

    ### mitochondrial-loss-cytosolic-reversal MTHFD2 deletion depleted formyl-folate availability and activated cytosolic serine-derived one-carbon production. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cells can reroute carbon production after losing the mitochondrial pathway. organism: Homo sapiens tissue_or_cell_type: HEK293T cells experimental_model: CRISPR and isotope tracing limitations: Compensation depends on nutrient availability. exposure: Assay conditions described in the linked primary study. [ducker-2016] Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway (2016). https://pubmed.ncbi.nlm.nih.gov/27211901/ DOI: 10.1016/j.cmet.2016.04.016
    Complete structured claim and evidence

  6. MTFMT uses mitochondrial 10-formyl-THF to generate formylmethionyl-tRNA needed for translation initiation.

    Human mitochondrial methionyl-tRNA formyltransferase / MTFMT → Mitochondrial methionyl-tRNA source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Genetic and tRNA-formylation experiments
    exposure
    Assay conditions described in the linked primary study.
    limitations
    Does not imply that plasma folate directly reports mitochondrial folate.
    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 small chemical tag used to start mitochondrial proteins.
    primary_references
    [minton-2018] Serine Catabolism by SHMT2 Is Required for Proper Mitochondrial Translation Initiation and Maintenance of Formylmethionyl-tRNAs (2018). https://pubmed.ncbi.nlm.nih.gov/29452640/ DOI: 10.1016/j.molcel.2018.01.024
    tissue_or_cell_type
    Jurkat cells

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1133–1143

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic and tRNA-formylation experiments · source_derived_draft · unverified_draft

    ### mtfmt-folate-formylation MTFMT uses mitochondrial 10-formyl-THF to generate formylmethionyl-tRNA needed for translation initiation. 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 small chemical tag used to start mitochondrial proteins. organism: Homo sapiens tissue_or_cell_type: Jurkat cells experimental_model: Genetic and tRNA-formylation experiments limitations: Does not imply that plasma folate directly reports mitochondrial folate. exposure: Assay conditions described in the linked primary study. [minton-2018] Serine Catabolism by SHMT2 Is Required for Proper Mitochondrial Translation Initiation and Maintenance of Formylmethionyl-tRNAs (2018). https://pubmed.ncbi.nlm.nih.gov/29452640/ DOI: 10.1016/j.molcel.2018.01.024
    Complete structured claim and evidence

  7. MTHFD1L knockdown lowered formate release in the tested human cells.

    Human MTHFD1L gene → Cellular formate release source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    experimental_model
    Knockdown and extracellular metabolite assay
    exposure
    Assay conditions described in the linked primary study.
    limitations
    Does not establish the transporter responsible for formate exchange.
    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
    Mitochondrial MTHFD1L helps release carbon as formate.
    primary_references
    [meiser-2016] Serine one-carbon catabolism with formate overflow (2016). https://pubmed.ncbi.nlm.nih.gov/27819051/ DOI: 10.1126/sciadv.1601273
    tissue_or_cell_type
    Cancer cell lines and IMR90 fibroblasts
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1218–1228

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

    ### mthfd1l-formate-release MTHFD1L knockdown lowered formate release in the tested human 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: Mitochondrial MTHFD1L helps release carbon as formate. organism: Homo sapiens tissue_or_cell_type: Cancer cell lines and IMR90 fibroblasts experimental_model: Knockdown and extracellular metabolite assay limitations: Does not establish the transporter responsible for formate exchange. exposure: Assay conditions described in the linked primary study. [meiser-2016] Serine one-carbon catabolism with formate overflow (2016). https://pubmed.ncbi.nlm.nih.gov/27819051/ DOI: 10.1126/sciadv.1601273
    Complete structured claim and evidence

  8. SHMT2-null Jurkat cells failed to maintain normal mitochondrial formylmethionyl-tRNA pools.

    Human SHMT2 gene → Mitochondrial formylmethionyl-tRNA source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    experimental_model
    CRISPR and tRNA assays
    exposure
    Assay conditions described in the linked primary study.
    limitations
    Several downstream mitochondrial consequences may coexist.
    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
    Mitochondrial serine breakdown helps prepare the tRNA that starts translation.
    primary_references
    [minton-2018] Serine Catabolism by SHMT2 Is Required for Proper Mitochondrial Translation Initiation and Maintenance of Formylmethionyl-tRNAs (2018). https://pubmed.ncbi.nlm.nih.gov/29452640/ DOI: 10.1016/j.molcel.2018.01.024
    tissue_or_cell_type
    Jurkat cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1109–1119

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

    ### shmt2-loss-formyltrna SHMT2-null Jurkat cells failed to maintain normal mitochondrial formylmethionyl-tRNA pools. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mitochondrial serine breakdown helps prepare the tRNA that starts translation. organism: Homo sapiens tissue_or_cell_type: Jurkat cells experimental_model: CRISPR and tRNA assays limitations: Several downstream mitochondrial consequences may coexist. exposure: Assay conditions described in the linked primary study. [minton-2018] Serine Catabolism by SHMT2 Is Required for Proper Mitochondrial Translation Initiation and Maintenance of Formylmethionyl-tRNAs (2018). https://pubmed.ncbi.nlm.nih.gov/29452640/ DOI: 10.1016/j.molcel.2018.01.024
    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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