Component

Ferrous iron / Fe(II)

Ferrous iron / Fe(II). Species, exposure and limitations are retained in each linked 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. A prolyl-4-hydroxylase, a functional homologue of human 2-oxoglutarate-dependent dioxygenases with essential roles in collagen biosynthesis and oxygen sensing, accumulated a C-H-cleaving high-spin Fe(IV)-oxo intermediate with a large substrate deuterium kinetic isotope effect on its decay.

    Ferrous iron / Fe(II) → The high-spin Fe(IV)-oxo reaction intermediate of a 2-oxoglutarate dioxygenase source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/hbot-research/17003127.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8c7def7926cf3f7a38d874fe22494fa3b72477ed41bdd2baee407cab4ea0d96d", "start_char": 0, "end_char": 1302, "text_sha256": "8c7def7926cf3f7a38d874fe22494fa3b72477ed41bdd2baee407cab4ea0d96d"}
    experimental_model
    Stopped-flow, optical absorption and Mossbauer spectroscopy of a prolyl-4-hydroxylase reaction
    exposure
    Catalysis with saturating substrates and deuterated substrate
    limitations
    Spectroscopy on a functional homologue, not the human enzyme. It identifies the chemical intermediate that does the work.
    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
    Bacterial enzyme homologous to the human enzymes
    plain_language
    The iron atom briefly becomes a highly reactive form that rips a hydrogen off the target carbon.
    primary_references
    [hbot-p17003127] Direct spectroscopic detection of a C-H-cleaving high-spin Fe(IV) complex in a prolyl-4-hydroxylase. (2006). https://pubmed.ncbi.nlm.nih.gov/17003127/ DOI: 10.1073/pnas.0604005103
    tissue_or_cell_type
    Purified enzyme

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 894–905

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stopped-flow, optical absorption and Mossbauer spectroscopy of a prolyl-4-hydroxylase reaction · source_derived_draft · unverified_draft

    ### hbot-fe-iv-intermediate A prolyl-4-hydroxylase, a functional homologue of human 2-oxoglutarate-dependent dioxygenases with essential roles in collagen biosynthesis and oxygen sensing, accumulated a C-H-cleaving high-spin Fe(IV)-oxo intermediate with a large substrate deuterium kinetic isotope effect on its decay. 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: The iron atom briefly becomes a highly reactive form that rips a hydrogen off the target carbon. organism: Bacterial enzyme homologous to the human enzymes tissue_or_cell_type: Purified enzyme experimental_model: Stopped-flow, optical absorption and Mossbauer spectroscopy of a prolyl-4-hydroxylase reaction limitations: Spectroscopy on a functional homologue, not the human enzyme. It identifies the chemical intermediate that does the work. exposure: Catalysis with saturating substrates and deuterated substrate evidence_span: {"source_cache": "artifacts/hbot-research/17003127.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8c7def7926cf3f7a38d874fe22494fa3b72477ed41bdd2baee407cab4ea0d96d", "start_char": 0, "end_char": 1302, "text_sha256": "8c7def7926cf3f7a38d874fe22494fa3b72477ed41bdd2baee407cab4ea0d96d"} [hbot-p17003127] Direct spectroscopic detection of a C-H-cleaving high-spin Fe(IV) complex in a prolyl-4-hydroxylase. (2006). https://pubmed.ncbi.nlm.nih.gov/17003127/ DOI: 10.1073/pnas.0604005103
    Complete structured claim and evidence

What acts on it

  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

Where it participates (unsigned role)

  1. 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

  2. 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

  3. Prolyl 4-hydroxylase catalyses formation of 4-hydroxyproline in collagens by hydroxylating proline residues in X-Pro-Gly sequences, and the reaction requires Fe2+, 2-oxoglutarate, O2 and ascorbate, involving oxidative decarboxylation of 2-oxoglutarate.

    Molecular oxygen → 4-Hydroxyproline source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/hbot-research/2537773.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe", "start_char": 0, "end_char": 2024, "text_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe"}
    experimental_model
    Review of prolyl 4-hydroxylase enzymology and subunit structure
    exposure
    Hydroxylation of proline in X-Pro-Gly sequences
    limitations
    An authoritative enzymology review rather than a single experiment. It is the source for the cosubstrate list, which is the point at which oxygen, iron and vitamin C meet in collagen synthesis.
    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
    Mammalian enzyme
    plain_language
    Making collagen needs oxygen, iron, vitamin C and a Krebs-cycle acid, all four at once.
    primary_references
    [hbot-p2537773] Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit. (1989). https://pubmed.ncbi.nlm.nih.gov/2537773/ DOI: 10.1096/fasebj.3.5.2537773
    tissue_or_cell_type
    Endoplasmic reticulum

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 855–866

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of prolyl 4-hydroxylase enzymology and subunit structure · source_derived_draft · unverified_draft

    ### hbot-p4h-cosubstrates Prolyl 4-hydroxylase catalyses formation of 4-hydroxyproline in collagens by hydroxylating proline residues in X-Pro-Gly sequences, and the reaction requires Fe2+, 2-oxoglutarate, O2 and ascorbate, involving oxidative decarboxylation of 2-oxoglutarate. 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: Making collagen needs oxygen, iron, vitamin C and a Krebs-cycle acid, all four at once. organism: Mammalian enzyme tissue_or_cell_type: Endoplasmic reticulum experimental_model: Review of prolyl 4-hydroxylase enzymology and subunit structure limitations: An authoritative enzymology review rather than a single experiment. It is the source for the cosubstrate list, which is the point at which oxygen, iron and vitamin C meet in collagen synthesis. exposure: Hydroxylation of proline in X-Pro-Gly sequences evidence_span: {"source_cache": "artifacts/hbot-research/2537773.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe", "start_char": 0, "end_char": 2024, "text_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe"} [hbot-p2537773] Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit. (1989). https://pubmed.ncbi.nlm.nih.gov/2537773/ DOI: 10.1096/fasebj.3.5.2537773
    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