Component

Human formimidoyltransferase cyclodeaminase / FTCD

Context-specific entity; species, compartment and exposure are stated on each claim.

5 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. The cyclodeaminase domain of FTCD converts 5-formimino-THF to 5,10-methenyl-THF.

    Human formimidoyltransferase cyclodeaminase / FTCD → 5,10-Methenyltetrahydrofolate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Established reaction in the pathway map of a primary human cancer-cell study; genetic perturbation and metabolomics investigate pathway flux rather than purified kinetics of every individual enzyme.
    limitations
    Two catalytic activities are separately searchable; this does not establish folate depletion in a normally nourished person. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    A second activity of the same enzyme hands the group into one-carbon metabolism.
    primary_references
    Histidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 138–144

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Established reaction in the pathway map of a primary human cancer-cell study; genetic perturbation and metabolomics investigate pathway flux rather than purified kinetics of every individual enzyme. · source_derived_draft · unverified_draft

    ## histidine-ftcd-cyclodeamination A second activity of the same enzyme hands the group into one-carbon metabolism. The cyclodeaminase domain of FTCD converts 5-formimino-THF to 5,10-methenyl-THF. Model: Established reaction in the pathway map of a primary human cancer-cell study; genetic perturbation and metabolomics investigate pathway flux rather than purified kinetics of every individual enzyme. Limitations: Two catalytic activities are separately searchable; this does not establish folate depletion in a normally nourished person. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2 Evidence access: Primary full text Histidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7
    Complete structured claim and evidence

  2. CRISPR depletion of FTCD reduced methotrexate sensitivity in HEL, Ramos and LAMA84 cells; an sgRNA-resistant murine Ftcd construct restored sensitivity in the rescue experiment.

    Human formimidoyltransferase cyclodeaminase / FTCD → Methotrexate sensitivity in human hematopoietic cancer cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human cancer lines, CRISPR/RNAi and mouse-cDNA rescue.
    limitations
    Drug-exposed culture and cross-species rescue; not evidence that histidine is universally harmful or beneficial. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    Removing this histidine-processing step made the tested cancer cells less sensitive to the drug.
    primary_references
    Histidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 146–152

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer lines, CRISPR/RNAi and mouse-cDNA rescue. · source_derived_draft · unverified_draft

    ## histidine-ftcd-loss-mtx Removing this histidine-processing step made the tested cancer cells less sensitive to the drug. CRISPR depletion of FTCD reduced methotrexate sensitivity in HEL, Ramos and LAMA84 cells; an sgRNA-resistant murine Ftcd construct restored sensitivity in the rescue experiment. Model: Human cancer lines, CRISPR/RNAi and mouse-cDNA rescue. Limitations: Drug-exposed culture and cross-species rescue; not evidence that histidine is universally harmful or beneficial. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2 Evidence access: Primary full text Histidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7
    Complete structured claim and evidence

  3. Under methotrexate, FTCD depletion preserved THF and increased serine-derived labeling of IMP and TTP relative to controls.

    Human formimidoyltransferase cyclodeaminase / FTCD → Tetrahydrofolate source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human cancer cells with FTCD depletion, metabolomics and U-13C-serine tracing.
    limitations
    Measured under methotrexate; do not generalize to normal folate demand or all tissues. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    Blocking histidine breakdown spared folate for nucleotide production in this drug-stressed setting.
    primary_references
    Histidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 154–160

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer cells with FTCD depletion, metabolomics and U-13C-serine tracing. · source_derived_draft · unverified_draft

    ## histidine-ftcd-thf-sparing Blocking histidine breakdown spared folate for nucleotide production in this drug-stressed setting. Under methotrexate, FTCD depletion preserved THF and increased serine-derived labeling of IMP and TTP relative to controls. Model: Human cancer cells with FTCD depletion, metabolomics and U-13C-serine tracing. Limitations: Measured under methotrexate; do not generalize to normal folate demand or all tissues. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2 Evidence access: Primary full text Histidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7
    Complete structured claim and evidence

  4. The formiminotransferase domain of FTCD transfers the formimino group from FIGLU to THF, producing 5-formimino-THF and glutamate.

    Human formimidoyltransferase cyclodeaminase / FTCD → 5-Formiminotetrahydrofolate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Established reaction in the pathway map of a primary human cancer-cell study; genetic perturbation and metabolomics investigate pathway flux rather than purified kinetics of every individual enzyme.
    limitations
    The existing rat FTCD biochemical claim remains a separate species-specific record. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    Folate accepts a group from a histidine-derived intermediate.
    primary_references
    Histidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 130–136

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Established reaction in the pathway map of a primary human cancer-cell study; genetic perturbation and metabolomics investigate pathway flux rather than purified kinetics of every individual enzyme. · source_derived_draft · unverified_draft

    ## histidine-ftcd-transfer Folate accepts a group from a histidine-derived intermediate. The formiminotransferase domain of FTCD transfers the formimino group from FIGLU to THF, producing 5-formimino-THF and glutamate. Model: Established reaction in the pathway map of a primary human cancer-cell study; genetic perturbation and metabolomics investigate pathway flux rather than purified kinetics of every individual enzyme. Limitations: The existing rat FTCD biochemical claim remains a separate species-specific record. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2 Evidence access: Primary full text Histidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Among 18 newborn-screen-detected FTCD-deficient patients, most were asymptomatic at mean 56-month follow-up; 3/18 had educationally significant developmental delay and 4/16 mild self-limited anemia.

    Human FTCD deficiency → N-Formimino-L-glutamate source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Retrospective two-center newborn-screen cohort.
    limitations
    Ascertainment differs from early severe case series; follow-up is limited and this does not exclude later or rare severe effects. Correction record: The 2019 publisher erratum corrects patient 4 genotypes to c.1366dupG (p.E456Gfs*56) and c.236A>C (p.Q79P). The imported cohort-outcome claim does not use the erroneous genotype labels. https://onlinelibrary.wiley.com/doi/10.1002/jimd.12145
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    A biochemical processing defect did not uniformly produce severe disease.
    primary_references
    Characteristics and outcomes of patients with formiminoglutamic aciduria detected through newborn screening. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30740726/ · DOI 10.1002/jimd.12035
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 194–200

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Retrospective two-center newborn-screen cohort. · source_derived_draft · unverified_draft

    ## histidine-ftcd-screening-spectrum A biochemical processing defect did not uniformly produce severe disease. Among 18 newborn-screen-detected FTCD-deficient patients, most were asymptomatic at mean 56-month follow-up; 3/18 had educationally significant developmental delay and 4/16 mild self-limited anemia. Model: Retrospective two-center newborn-screen cohort. Limitations: Ascertainment differs from early severe case series; follow-up is limited and this does not exclude later or rare severe effects. Correction record: The 2019 publisher erratum corrects patient 4 genotypes to c.1366dupG (p.E456Gfs*56) and c.236A>C (p.Q79P). The imported cohort-outcome claim does not use the erroneous genotype labels. https://onlinelibrary.wiley.com/doi/10.1002/jimd.12145 Evidence access: Primary abstract Characteristics and outcomes of patients with formiminoglutamic aciduria detected through newborn screening. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30740726/ · DOI 10.1002/jimd.12035
    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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