Component

Mouse dihydrofolate reductase / Dhfr

Mouse dihydrofolate reductase / Dhfr. Species, exposure and limitations are retained in each linked claim.

2 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

Where it participates (unsigned role)

  1. DHFR knockdown decreased intracellular BH4 and increased BH2 in the cell systems.

    Mouse endothelial Dhfr knockdown → Endothelial BH4-to-BH2 ratio, model specified source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/citrulline-research/19666465.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1ef76ebbd312932011edd1b0f9f428026a4e4cdd53301bd66f99eaf543e77af", "start_char": 0, "end_char": 1716, "text_sha256": "b1ef76ebbd312932011edd1b0f9f428026a4e4cdd53301bd66f99eaf543e77af"}
    experimental_model
    DHFR knockdown/inhibition and controlled GTPCH-expression cell experiments
    exposure
    Methotrexate or RNA interference; comparison with GTPCH knockdown
    limitations
    Mouse models; DHFR also handles folate, but this study does not make folate and BH4 interchangeable.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Mouse endothelial and NIH-3T3-based experimental cell systems
    plain_language
    Recycling quality matters, not just the total amount of pterin.
    primary_references
    [citrulline-p19666465] Critical role for tetrahydrobiopterin recycling by dihydrofolate reductase in regulation of endothelial nitric-oxide synthase coupling: relative importance of the de novo biopterin synthesis versus salvage pathways. (2009). https://pubmed.ncbi.nlm.nih.gov/19666465/ DOI: 10.1074/jbc.m109.041483
    tissue_or_cell_type
    BH4/BH2 balance and NOS coupling
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 775–786

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · DHFR knockdown/inhibition and controlled GTPCH-expression cell experiments · source_derived_draft · unverified_draft

    ### citrulline-dhfr-ratio DHFR knockdown decreased intracellular BH4 and increased BH2 in the cell systems. Condition category: machinery_impairment nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Recycling quality matters, not just the total amount of pterin. organism: Mouse endothelial and NIH-3T3-based experimental cell systems tissue_or_cell_type: BH4/BH2 balance and NOS coupling experimental_model: DHFR knockdown/inhibition and controlled GTPCH-expression cell experiments limitations: Mouse models; DHFR also handles folate, but this study does not make folate and BH4 interchangeable. exposure: Methotrexate or RNA interference; comparison with GTPCH knockdown evidence_span: {"source_cache": "artifacts/citrulline-research/19666465.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1ef76ebbd312932011edd1b0f9f428026a4e4cdd53301bd66f99eaf543e77af", "start_char": 0, "end_char": 1716, "text_sha256": "b1ef76ebbd312932011edd1b0f9f428026a4e4cdd53301bd66f99eaf543e77af"} [citrulline-p19666465] Critical role for tetrahydrobiopterin recycling by dihydrofolate reductase in regulation of endothelial nitric-oxide synthase coupling: relative importance of the de novo biopterin synthesis versus salvage pathways. (2009). https://pubmed.ncbi.nlm.nih.gov/19666465/ DOI: 10.1074/jbc.m109.041483
    Complete structured claim and evidence

  2. DHFR loss increased eNOS-dependent superoxide while reducing NO production.

    Mouse endothelial Dhfr knockdown → Endothelial nitric oxide synthase uncoupling, model specified source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/citrulline-research/19666465.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1ef76ebbd312932011edd1b0f9f428026a4e4cdd53301bd66f99eaf543e77af", "start_char": 0, "end_char": 1716, "text_sha256": "b1ef76ebbd312932011edd1b0f9f428026a4e4cdd53301bd66f99eaf543e77af"}
    experimental_model
    DHFR knockdown/inhibition and controlled GTPCH-expression cell experiments
    exposure
    Methotrexate or RNA interference; comparison with GTPCH knockdown
    limitations
    Mouse models; DHFR also handles folate, but this study does not make folate and BH4 interchangeable.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Mouse endothelial and NIH-3T3-based experimental cell systems
    plain_language
    A damaged cofactor balance can change the enzyme output.
    primary_references
    [citrulline-p19666465] Critical role for tetrahydrobiopterin recycling by dihydrofolate reductase in regulation of endothelial nitric-oxide synthase coupling: relative importance of the de novo biopterin synthesis versus salvage pathways. (2009). https://pubmed.ncbi.nlm.nih.gov/19666465/ DOI: 10.1074/jbc.m109.041483
    tissue_or_cell_type
    BH4/BH2 balance and NOS coupling
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 788–799

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · DHFR knockdown/inhibition and controlled GTPCH-expression cell experiments · source_derived_draft · unverified_draft

    ### citrulline-dhfr-uncoupling DHFR loss increased eNOS-dependent superoxide while reducing NO production. Condition category: machinery_impairment nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A damaged cofactor balance can change the enzyme output. organism: Mouse endothelial and NIH-3T3-based experimental cell systems tissue_or_cell_type: BH4/BH2 balance and NOS coupling experimental_model: DHFR knockdown/inhibition and controlled GTPCH-expression cell experiments limitations: Mouse models; DHFR also handles folate, but this study does not make folate and BH4 interchangeable. exposure: Methotrexate or RNA interference; comparison with GTPCH knockdown evidence_span: {"source_cache": "artifacts/citrulline-research/19666465.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1ef76ebbd312932011edd1b0f9f428026a4e4cdd53301bd66f99eaf543e77af", "start_char": 0, "end_char": 1716, "text_sha256": "b1ef76ebbd312932011edd1b0f9f428026a4e4cdd53301bd66f99eaf543e77af"} [citrulline-p19666465] Critical role for tetrahydrobiopterin recycling by dihydrofolate reductase in regulation of endothelial nitric-oxide synthase coupling: relative importance of the de novo biopterin synthesis versus salvage pathways. (2009). https://pubmed.ncbi.nlm.nih.gov/19666465/ DOI: 10.1074/jbc.m109.041483
    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