Component

4-Hydroxyproline

4-Hydroxyproline. Species, exposure and limitations are retained in each linked 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 acts on it

  1. 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

  2. Purified truncated human PRODH2/HYPDH contained one FAD and showed approximately twelvefold higher catalytic efficiency for hydroxyproline than proline.

    Human hydroxyproline dehydrogenase / PRODH2 → 4-Hydroxyproline source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human recombinant catalytic core, residues 157–515; substrate kinetics.
    limitations
    PRODH2 is not simply a second interchangeable proline oxidase.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    Hydroxyproline uses a related but distinct breakdown enzyme.
    primary_references
    Proline dehydrogenase 2 (PRODH2) is a hydroxyproline dehydrogenase (HYPDH) and molecular target for treating primary hyperoxaluria. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25697095/ · DOI 10.1042/BJ20141159

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 278–284

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant catalytic core, residues 157–515; substrate kinetics. · source_derived_draft · unverified_draft

    ## l-proline-hypdh-specificity Hydroxyproline uses a related but distinct breakdown enzyme. Purified truncated human PRODH2/HYPDH contained one FAD and showed approximately twelvefold higher catalytic efficiency for hydroxyproline than proline. Model: Human recombinant catalytic core, residues 157–515; substrate kinetics. Limitations: PRODH2 is not simply a second interchangeable proline oxidase. Evidence access: Primary abstract Proline dehydrogenase 2 (PRODH2) is a hydroxyproline dehydrogenase (HYPDH) and molecular target for treating primary hyperoxaluria. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25697095/ · DOI 10.1042/BJ20141159
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Ascorbate is required for hydroxylation of proline residues in procollagen, hydroxyproline stabilises the collagen triple-helical structure, and consequently ascorbate stimulates procollagen secretion.

    L-Ascorbate → Procollagen secretion source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/hbot-research/1720597.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b769da8d030351b117b7a349262e9b52d54aab00ca3a2679900cb1372006bc31", "start_char": 0, "end_char": 1015, "text_sha256": "b769da8d030351b117b7a349262e9b52d54aab00ca3a2679900cb1372006bc31"}
    experimental_model
    Ascorbate-deficient guinea pigs, fasting controls, and cells cultured in scorbutic serum
    exposure
    Vitamin C deficiency, with fasting plus ascorbate supplementation as a comparison
    limitations
    The study separates a direct hydroxylation defect from a growth-factor-mediated one, so it argues against reading scurvy as pure under-hydroxylation.
    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
    Guinea pig and cultured cells
    plain_language
    Without vitamin C the collagen cannot be stiffened properly and does not leave the cell.
    primary_references
    [hbot-p1720597] Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. (1991). https://pubmed.ncbi.nlm.nih.gov/1720597/ DOI: 10.1093/ajcn/54.6.1135s
    tissue_or_cell_type
    Connective tissue
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 907–918

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ascorbate-deficient guinea pigs, fasting controls, and cells cultured in scorbutic serum · source_derived_draft · unverified_draft

    ### hbot-ascorbate-procollagen Ascorbate is required for hydroxylation of proline residues in procollagen, hydroxyproline stabilises the collagen triple-helical structure, and consequently ascorbate stimulates procollagen secretion. Condition category: nutrient_deficiency 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: Without vitamin C the collagen cannot be stiffened properly and does not leave the cell. organism: Guinea pig and cultured cells tissue_or_cell_type: Connective tissue experimental_model: Ascorbate-deficient guinea pigs, fasting controls, and cells cultured in scorbutic serum limitations: The study separates a direct hydroxylation defect from a growth-factor-mediated one, so it argues against reading scurvy as pure under-hydroxylation. exposure: Vitamin C deficiency, with fasting plus ascorbate supplementation as a comparison evidence_span: {"source_cache": "artifacts/hbot-research/1720597.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b769da8d030351b117b7a349262e9b52d54aab00ca3a2679900cb1372006bc31", "start_char": 0, "end_char": 1015, "text_sha256": "b769da8d030351b117b7a349262e9b52d54aab00ca3a2679900cb1372006bc31"} [hbot-p1720597] Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. (1991). https://pubmed.ncbi.nlm.nih.gov/1720597/ DOI: 10.1093/ajcn/54.6.1135s
    Complete structured claim and evidence

  2. Quinone acceptors including CoQ1 reacted more efficiently than oxygen during purified human HYPDH turnover, supporting a dehydrogenase mechanism.

    Human hydroxyproline dehydrogenase / PRODH2 → Coenzyme Q1, experimental ubiquinone analogue source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Truncated purified human HYPDH; quinone analogue and oxygen comparisons.
    limitations
    CoQ10 as the physiological acceptor is inferred, not directly measured in intact human tissues; this does not demonstrate benefit from CoQ10 supplements.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    Hydroxyproline breakdown can feed a quinone electron-transfer route.
    primary_references
    Proline dehydrogenase 2 (PRODH2) is a hydroxyproline dehydrogenase (HYPDH) and molecular target for treating primary hyperoxaluria. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25697095/ · DOI 10.1042/BJ20141159

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 286–292

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Truncated purified human HYPDH; quinone analogue and oxygen comparisons. · source_derived_draft · unverified_draft

    ## l-proline-hypdh-electrons Hydroxyproline breakdown can feed a quinone electron-transfer route. Quinone acceptors including CoQ1 reacted more efficiently than oxygen during purified human HYPDH turnover, supporting a dehydrogenase mechanism. Model: Truncated purified human HYPDH; quinone analogue and oxygen comparisons. Limitations: CoQ10 as the physiological acceptor is inferred, not directly measured in intact human tissues; this does not demonstrate benefit from CoQ10 supplements. Evidence access: Primary abstract Proline dehydrogenase 2 (PRODH2) is a hydroxyproline dehydrogenase (HYPDH) and molecular target for treating primary hyperoxaluria. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25697095/ · DOI 10.1042/BJ20141159
    Complete structured claim and evidence

  3. Prodh2 deletion reduced urinary oxalate in mouse hyperoxaluria models; combined Grhpr/Prodh2 deletion prevented kidney calcium-oxalate deposition during a 1% hydroxyproline diet.

    Mouse hydroxyproline dehydrogenase / Prodh2 → Hydroxyproline-derived urinary oxalate in mouse hyperoxaluria models source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Genetic mouse models, including Grhpr knockout and a 1% hydroxyproline diet.
    limitations
    Hydroxyproline loading is not equivalent to free proline intake; human efficacy of pathway inhibition was not established.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    A collagen-derived amino acid can feed an oxalate-producing pathway under specific conditions.
    primary_references
    The effects of the inactivation of Hydroxyproline dehydrogenase on urinary oxalate and glycolate excretion in mouse models of primary hyperoxaluria. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31821850/ · DOI 10.1016/j.bbadis.2019.165633
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 294–300

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Genetic mouse models, including Grhpr knockout and a 1% hydroxyproline diet. · source_derived_draft · unverified_draft

    ## l-proline-hypdh-oxalate A collagen-derived amino acid can feed an oxalate-producing pathway under specific conditions. Prodh2 deletion reduced urinary oxalate in mouse hyperoxaluria models; combined Grhpr/Prodh2 deletion prevented kidney calcium-oxalate deposition during a 1% hydroxyproline diet. Model: Genetic mouse models, including Grhpr knockout and a 1% hydroxyproline diet. Limitations: Hydroxyproline loading is not equivalent to free proline intake; human efficacy of pathway inhibition was not established. Evidence access: Primary abstract The effects of the inactivation of Hydroxyproline dehydrogenase on urinary oxalate and glycolate excretion in mouse models of primary hyperoxaluria. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31821850/ · DOI 10.1016/j.bbadis.2019.165633
    Complete structured claim and evidence

  4. Human prolidase hydrolyzes dipeptides with C-terminal proline or hydroxyproline; substrate- and product-bound structures explain its terminal peptide-cleavage reaction.

    Human prolidase / PEPD → L-Proline source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Recombinant human wild-type prolidase, high-resolution substrate/product complexes.
    limitations
    This does not mean prolidase by itself cleaves an intact collagen triple helix.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    Recycling a proline-containing peptide requires a suitable peptidase.
    primary_references
    Substrate specificity and reaction mechanism of human prolidase. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28677335/ · DOI 10.1111/febs.14158

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 262–268

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human wild-type prolidase, high-resolution substrate/product complexes. · source_derived_draft · unverified_draft

    ## l-proline-pepd-recycling Recycling a proline-containing peptide requires a suitable peptidase. Human prolidase hydrolyzes dipeptides with C-terminal proline or hydroxyproline; substrate- and product-bound structures explain its terminal peptide-cleavage reaction. Model: Recombinant human wild-type prolidase, high-resolution substrate/product complexes. Limitations: This does not mean prolidase by itself cleaves an intact collagen triple helix. Evidence access: Primary abstract Substrate specificity and reaction mechanism of human prolidase. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28677335/ · DOI 10.1111/febs.14158
    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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