Component

Human histidine ammonia-lyase / HAL

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

3 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. CRISPR depletion of HAL reduced methotrexate sensitivity in the tested human cancer cells.

    Human histidine ammonia-lyase / HAL → 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 hematopoietic cancer-cell CRISPR experiments.
    limitations
    Enzyme depletion is different from lowering dietary histidine. 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
    An upstream histidine-breakdown step also changed drug sensitivity.
    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 162–168

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human hematopoietic cancer-cell CRISPR experiments. · source_derived_draft · unverified_draft

    ## histidine-hal-loss-mtx An upstream histidine-breakdown step also changed drug sensitivity. CRISPR depletion of HAL reduced methotrexate sensitivity in the tested human cancer cells. Model: Human hematopoietic cancer-cell CRISPR experiments. Limitations: Enzyme depletion is different from lowering dietary histidine. 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. HAL initiates histidine degradation by converting L-histidine to trans-urocanate with ammonia release.

    Human histidine ammonia-lyase / HAL → trans-Urocanate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text; pathway background
    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
    Reaction background is distinguished from the study-specific CRISPR findings below. 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
    The first breakdown enzyme directs histidine toward urocanate.
    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 106–112

    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-hal-reaction The first breakdown enzyme directs histidine toward urocanate. HAL initiates histidine degradation by converting L-histidine to trans-urocanate with ammonia release. 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: Reaction background is distinguished from the study-specific CRISPR findings below. 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; pathway background 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. Long-term follow-up of screen-detected histidinemia found normal growth, no relation of plasma histidine to DQ/IQ and no apparent benefit from early low-histidine diet.

    Human histidinemia → Development and growth in screen-detected histidinemia source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    113 detected children, nine lost to follow-up; 47 historically treated before 1981, others untreated.
    limitations
    Observational and nonrandom treatment allocation; not a general high-dose supplement safety study.
    nutrient_topic
    L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
    plain_language
    Higher histidine from slow breakdown did not by itself predict developmental impairment in this cohort.
    primary_references
    Histidinaemia: a benign metabolic disorder. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8669938/ · DOI 10.1136/adc.74.4.343
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 202–208

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 113 detected children, nine lost to follow-up; 47 historically treated before 1981, others untreated. · source_derived_draft · unverified_draft

    ## histidine-histidinemia-followup Higher histidine from slow breakdown did not by itself predict developmental impairment in this cohort. Long-term follow-up of screen-detected histidinemia found normal growth, no relation of plasma histidine to DQ/IQ and no apparent benefit from early low-histidine diet. Model: 113 detected children, nine lost to follow-up; 47 historically treated before 1981, others untreated. Limitations: Observational and nonrandom treatment allocation; not a general high-dose supplement safety study. Evidence access: Primary abstract Histidinaemia: a benign metabolic disorder. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8669938/ · DOI 10.1136/adc.74.4.343
    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