Component

Human cytosolic isoleucyl-tRNA synthetase / IARS1

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

6 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. Human IARS1 aminoacylates tRNA-Ile with isoleucine for cytosolic translation; purified-protein aminoacylation assays were used to study this reaction.

    Human cytosolic isoleucyl-tRNA synthetase / IARS1 → Human cytosolic isoleucyl-tRNA source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human IARS1/tRNA assays and primary human fibroblasts.
    limitations
    Reaction role is distinct from the study-specific shortage substitution experiments.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    A charging enzyme links free isoleucine to protein synthesis.
    primary_references
    Isoleucine-to-valine substitutions support cellular physiology during isoleucine deprivation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39657787/ · DOI 10.1093/nar/gkae1184

    L-Isoleucine: transport, translation, catabolism 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 · Human IARS1/tRNA assays and primary human fibroblasts. · source_derived_draft · unverified_draft

    ## isoleucine-iars-charging A charging enzyme links free isoleucine to protein synthesis. Human IARS1 aminoacylates tRNA-Ile with isoleucine for cytosolic translation; purified-protein aminoacylation assays were used to study this reaction. Model: Human IARS1/tRNA assays and primary human fibroblasts. Limitations: Reaction role is distinct from the study-specific shortage substitution experiments. Evidence access: Primary full text Isoleucine-to-valine substitutions support cellular physiology during isoleucine deprivation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39657787/ · DOI 10.1093/nar/gkae1184
    Complete structured claim and evidence

  2. IARS-deficient patient fibroblasts had reduced residual aminoacylation activity and greater growth sensitivity to low isoleucine.

    Human cytosolic isoleucyl-tRNA synthetase / IARS1 → Growth of IARS1-deficient human fibroblasts source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Patient-derived human fibroblasts tested across isoleucine concentrations.
    limitations
    Do not assign the study temperature sensitivity in LARS/FARSB to IARS without evidence.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Low substrate can expose the limited reserve of a faulty enzyme.
    primary_references
    Treatment of ARS deficiencies with specific amino acids. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34194004/ · DOI 10.1038/s41436-021-01249-z
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism 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 · Patient-derived human fibroblasts tested across isoleucine concentrations. · source_derived_draft · unverified_draft

    ## isoleucine-iars-low-substrate Low substrate can expose the limited reserve of a faulty enzyme. IARS-deficient patient fibroblasts had reduced residual aminoacylation activity and greater growth sensitivity to low isoleucine. Model: Patient-derived human fibroblasts tested across isoleucine concentrations. Limitations: Do not assign the study temperature sensitivity in LARS/FARSB to IARS without evidence. Evidence access: Primary abstract Treatment of ARS deficiencies with specific amino acids. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34194004/ · DOI 10.1038/s41436-021-01249-z
    Complete structured claim and evidence

  3. Under isoleucine restriction, healthy human fibroblasts incorporated valine at isoleucine codons; biochemical assays implicated IARS1-mediated valine misacylation.

    Human cytosolic isoleucyl-tRNA synthetase / IARS1 → Isoleucine-to-valine protein substitution in human fibroblasts source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Primary human fibroblasts, mass spectrometry and tRNA charging assays.
    limitations
    Amino-acid substitution is not proof of normal function for every affected protein or nutritional interchangeability.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Some cells preserve translation by sacrificing amino-acid accuracy.
    primary_references
    Isoleucine-to-valine substitutions support cellular physiology during isoleucine deprivation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39657787/ · DOI 10.1093/nar/gkae1184
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 114–120

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary human fibroblasts, mass spectrometry and tRNA charging assays. · source_derived_draft · unverified_draft

    ## isoleucine-valine-substitution Some cells preserve translation by sacrificing amino-acid accuracy. Under isoleucine restriction, healthy human fibroblasts incorporated valine at isoleucine codons; biochemical assays implicated IARS1-mediated valine misacylation. Model: Primary human fibroblasts, mass spectrometry and tRNA charging assays. Limitations: Amino-acid substitution is not proof of normal function for every affected protein or nutritional interchangeability. Evidence access: Primary full text Isoleucine-to-valine substitutions support cellular physiology during isoleucine deprivation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39657787/ · DOI 10.1093/nar/gkae1184
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. The IARS patients within a small personalized ARS-treatment series received cognate amino-acid supplementation and showed reported clinical benefit during follow-up.

    L-Isoleucine → Personalized isoleucine treatment in IARS deficiency source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Uncontrolled human case series with preclinical patient-cell testing; multiple different ARS disorders.
    limitations
    Do not attribute every pooled outcome to IARS or generalize to all IARS variants; not a randomized trial.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Some residual-function disorders may respond to carefully selected substrate support.
    primary_references
    Treatment of ARS deficiencies with specific amino acids. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34194004/ · DOI 10.1038/s41436-021-01249-z
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism 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 · Uncontrolled human case series with preclinical patient-cell testing; multiple different ARS disorders. · source_derived_draft · unverified_draft

    ## isoleucine-iars-clinical-supplement Some residual-function disorders may respond to carefully selected substrate support. The IARS patients within a small personalized ARS-treatment series received cognate amino-acid supplementation and showed reported clinical benefit during follow-up. Model: Uncontrolled human case series with preclinical patient-cell testing; multiple different ARS disorders. Limitations: Do not attribute every pooled outcome to IARS or generalize to all IARS variants; not a randomized trial. Evidence access: Primary abstract Treatment of ARS deficiencies with specific amino acids. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34194004/ · DOI 10.1038/s41436-021-01249-z
    Complete structured claim and evidence

  2. Three individuals with biallelic IARS variants had zinc deficiency; one showed improved growth with zinc supplementation.

    Biallelic human IARS1 variants → Zinc deficiency in reported IARS1 patients source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human family/variant study; yeast functional validation of variants.
    limitations
    An association and one treatment observation do not establish how IARS dysfunction caused low zinc or that all isoleucine shortages deplete zinc.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    A coexisting nutrient shortage was documented in this rare genetic disorder.
    primary_references
    Biallelic IARS Mutations Cause Growth Retardation with Prenatal Onset, Intellectual Disability, Muscular Hypotonia, and Infantile Hepatopathy. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27426735/ · DOI 10.1016/j.ajhg.2016.05.027
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism 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 family/variant study; yeast functional validation of variants. · source_derived_draft · unverified_draft

    ## isoleucine-iars-zinc-context A coexisting nutrient shortage was documented in this rare genetic disorder. Three individuals with biallelic IARS variants had zinc deficiency; one showed improved growth with zinc supplementation. Model: Human family/variant study; yeast functional validation of variants. Limitations: An association and one treatment observation do not establish how IARS dysfunction caused low zinc or that all isoleucine shortages deplete zinc. Evidence access: Primary abstract Biallelic IARS Mutations Cause Growth Retardation with Prenatal Onset, Intellectual Disability, Muscular Hypotonia, and Infantile Hepatopathy. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27426735/ · DOI 10.1016/j.ajhg.2016.05.027
    Complete structured claim and evidence

  3. Valine supplementation restored translation and proliferation during severe isoleucine deprivation in healthy fibroblasts but not in the tested IARS1-deficient fibroblasts.

    L-Valine → Protein translation in human fibroblasts source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human fibroblast experiments; representative low isoleucine 1.02 micromolar and high valine 2330 micromolar conditions.
    limitations
    Culture conditions are not a recommended dietary ratio; two patient lines shared the investigated variants.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    The rescue required functioning charging machinery.
    primary_references
    Isoleucine-to-valine substitutions support cellular physiology during isoleucine deprivation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39657787/ · DOI 10.1093/nar/gkae1184
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 122–128

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human fibroblast experiments; representative low isoleucine 1.02 micromolar and high valine 2330 micromolar conditions. · source_derived_draft · unverified_draft

    ## isoleucine-valine-translation-rescue The rescue required functioning charging machinery. Valine supplementation restored translation and proliferation during severe isoleucine deprivation in healthy fibroblasts but not in the tested IARS1-deficient fibroblasts. Model: Human fibroblast experiments; representative low isoleucine 1.02 micromolar and high valine 2330 micromolar conditions. Limitations: Culture conditions are not a recommended dietary ratio; two patient lines shared the investigated variants. Evidence access: Primary full text Isoleucine-to-valine substitutions support cellular physiology during isoleucine deprivation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39657787/ · DOI 10.1093/nar/gkae1184
    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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