Component

Factor inhibiting HIF / FIH asparaginyl hydroxylase

Factor inhibiting HIF / FIH asparaginyl hydroxylase. Species, exposure and limitations are retained in each linked 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

Where it participates (unsigned role)

  1. The findings suggest that ascorbate acts primarily to stabilise and reduce the iron atom in the hydroxylase active site, and that the asparagine hydroxylase controlling HIF-1 transcriptional activity is particularly susceptible to fluctuations in intracellular ascorbate.

    L-Ascorbate → Ferrous iron / Fe(II) source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/hbot-research/24495550.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a", "start_char": 0, "end_char": 1497, "text_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a"}
    experimental_model
    Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors
    exposure
    Intracellular ascorbate loading with CoCl2, NiCl2, desferrioxamine, dimethyloxalylglycine or hypoxia
    limitations
    Establishes an effect of intracellular ascorbate on the HIF response. The iron-competing inhibitors are the conditions where ascorbate mattered most.
    nutrient_topic
    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy
    organism
    Human cells
    plain_language
    Vitamin C’s job here is to keep the enzyme’s iron in the right state.
    primary_references
    [hbot-p24495550] Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. (2014). https://pubmed.ncbi.nlm.nih.gov/24495550/ DOI: 10.1016/j.freeradbiomed.2014.01.033
    tissue_or_cell_type
    Cytosol and nucleus

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 998–1009

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors · source_derived_draft · unverified_draft

    ### hbot-ascorbate-iron-site The findings suggest that ascorbate acts primarily to stabilise and reduce the iron atom in the hydroxylase active site, and that the asparagine hydroxylase controlling HIF-1 transcriptional activity is particularly susceptible to fluctuations in intracellular ascorbate. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Vitamin C’s job here is to keep the enzyme’s iron in the right state. organism: Human cells tissue_or_cell_type: Cytosol and nucleus experimental_model: Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors limitations: Establishes an effect of intracellular ascorbate on the HIF response. The iron-competing inhibitors are the conditions where ascorbate mattered most. exposure: Intracellular ascorbate loading with CoCl2, NiCl2, desferrioxamine, dimethyloxalylglycine or hypoxia evidence_span: {"source_cache": "artifacts/hbot-research/24495550.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a", "start_char": 0, "end_char": 1497, "text_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a"} [hbot-p24495550] Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. (2014). https://pubmed.ncbi.nlm.nih.gov/24495550/ DOI: 10.1016/j.freeradbiomed.2014.01.033
    Complete structured claim and evidence

  2. The initial rate and extent of PHD2-catalysed hydroxylation of two prolyl sites in human HIF-1alpha, and of FIH-catalysed asparaginyl hydroxylation, were increased in the presence of ascorbate; these are Fe(II) and 2-oxoglutarate-dependent oxygenases.

    L-Ascorbate → PHD2-catalysed prolyl hydroxylation of HIF-1alpha source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/hbot-research/20055761.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3b9ac610e9510ed4f2fd2ed696009ab95dadac196fff3a7fe1644f03ed29d1dd", "start_char": 0, "end_char": 1322, "text_sha256": "3b9ac610e9510ed4f2fd2ed696009ab95dadac196fff3a7fe1644f03ed29d1dd"}
    experimental_model
    Enzyme assays of PHD2 and FIH with ascorbate, ascorbate analogues and alternative reducing agents
    exposure
    Prolyl and asparaginyl hydroxylation with and without ascorbate, glutathione or dithiothreitol
    limitations
    Purified-enzyme kinetics. It identifies which part of the ascorbate molecule matters, and shows other reductants substitute only partially.
    nutrient_topic
    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy
    organism
    Human enzymes
    plain_language
    Vitamin C makes the enzyme that destroys the low-oxygen signal work faster.
    primary_references
    [hbot-p20055761] Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. (2010). https://pubmed.ncbi.nlm.nih.gov/20055761/ DOI: 10.1042/bj20091609
    tissue_or_cell_type
    Purified enzyme with HIF-1alpha peptides

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 959–970

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme assays of PHD2 and FIH with ascorbate, ascorbate analogues and alternative reducing agents · source_derived_draft · unverified_draft

    ### hbot-ascorbate-stimulates-phd The initial rate and extent of PHD2-catalysed hydroxylation of two prolyl sites in human HIF-1alpha, and of FIH-catalysed asparaginyl hydroxylation, were increased in the presence of ascorbate; these are Fe(II) and 2-oxoglutarate-dependent oxygenases. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Vitamin C makes the enzyme that destroys the low-oxygen signal work faster. organism: Human enzymes tissue_or_cell_type: Purified enzyme with HIF-1alpha peptides experimental_model: Enzyme assays of PHD2 and FIH with ascorbate, ascorbate analogues and alternative reducing agents limitations: Purified-enzyme kinetics. It identifies which part of the ascorbate molecule matters, and shows other reductants substitute only partially. exposure: Prolyl and asparaginyl hydroxylation with and without ascorbate, glutathione or dithiothreitol evidence_span: {"source_cache": "artifacts/hbot-research/20055761.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3b9ac610e9510ed4f2fd2ed696009ab95dadac196fff3a7fe1644f03ed29d1dd", "start_char": 0, "end_char": 1322, "text_sha256": "3b9ac610e9510ed4f2fd2ed696009ab95dadac196fff3a7fe1644f03ed29d1dd"} [hbot-p20055761] Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. (2010). https://pubmed.ncbi.nlm.nih.gov/20055761/ DOI: 10.1042/bj20091609
    Complete structured claim and evidence

  3. Ascorbate inhibited HIF-1 activity most dramatically under all mechanisms of iron competition, and HIF-1-dependent gene expression was prevented even under conditions that allowed HIF-1alpha protein stabilisation.

    L-Ascorbate → HIF-1 transcriptional activity source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/hbot-research/24495550.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a", "start_char": 0, "end_char": 1497, "text_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a"}
    experimental_model
    Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors
    exposure
    Intracellular ascorbate loading with CoCl2, NiCl2, desferrioxamine, dimethyloxalylglycine or hypoxia
    limitations
    Establishes an effect of intracellular ascorbate on the HIF response. The iron-competing inhibitors are the conditions where ascorbate mattered most.
    nutrient_topic
    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy
    organism
    Human cells
    plain_language
    Vitamin C shuts down the low-oxygen gene programme even when the protein itself survives.
    primary_references
    [hbot-p24495550] Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. (2014). https://pubmed.ncbi.nlm.nih.gov/24495550/ DOI: 10.1016/j.freeradbiomed.2014.01.033
    tissue_or_cell_type
    Cytosol and nucleus

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 985–996

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors · source_derived_draft · unverified_draft

    ### hbot-ascorbate-suppresses-hif Ascorbate inhibited HIF-1 activity most dramatically under all mechanisms of iron competition, and HIF-1-dependent gene expression was prevented even under conditions that allowed HIF-1alpha protein stabilisation. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Vitamin C shuts down the low-oxygen gene programme even when the protein itself survives. organism: Human cells tissue_or_cell_type: Cytosol and nucleus experimental_model: Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors limitations: Establishes an effect of intracellular ascorbate on the HIF response. The iron-competing inhibitors are the conditions where ascorbate mattered most. exposure: Intracellular ascorbate loading with CoCl2, NiCl2, desferrioxamine, dimethyloxalylglycine or hypoxia evidence_span: {"source_cache": "artifacts/hbot-research/24495550.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a", "start_char": 0, "end_char": 1497, "text_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a"} [hbot-p24495550] Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. (2014). https://pubmed.ncbi.nlm.nih.gov/24495550/ DOI: 10.1016/j.freeradbiomed.2014.01.033
    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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