Component

Collagen-bound proline residues

Peptidyl proline in a collagen-like chain; not free dietary proline.

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. Human pancreatic cancer cells took up collagen fragments and used collagen-derived proline in metabolism under nutrient-limited culture conditions.

    Collagen-bound proline residues → Collagen-derived proline metabolism in human pancreatic cancer cells source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human PDAC culture and tracer experiments under limited fuel availability.
    limitations
    Collagen uptake, peptide digestion and proline oxidation are distinct steps; no effect of oral collagen supplements is demonstrated.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    A tissue matrix can become a nutrient reservoir for cells.
    primary_references
    Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28685754/ · DOI 10.1038/ncomms16031

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 374–380

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC culture and tracer experiments under limited fuel availability. · source_derived_draft · unverified_draft

    ## l-proline-pdac-collagen-fuel A tissue matrix can become a nutrient reservoir for cells. Human pancreatic cancer cells took up collagen fragments and used collagen-derived proline in metabolism under nutrient-limited culture conditions. Model: Human PDAC culture and tracer experiments under limited fuel availability. Limitations: Collagen uptake, peptide digestion and proline oxidation are distinct steps; no effect of oral collagen supplements is demonstrated. Evidence access: Primary full text Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28685754/ · DOI 10.1038/ncomms16031
    Complete structured claim and evidence

What acts on it

  1. Purified chick collagen prolyl hydroxylase completed approximately 15–30 rapid catalytic cycles in 5–10 seconds without added ascorbate before activity declined.

    Chick collagen prolyl 4-hydroxylase preparation → Collagen-bound proline residues source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.
    experimental_model
    Purified chick-embryo collagen prolyl hydroxylase kinetics
    exposure
    Ascorbate omitted or added in purified-enzyme assays; initial 5–10 seconds versus approximately 1 minute.
    limitations
    Purified assay with cofactor omission; does not quantify a dietary requirement or establish an identical turnover number in human cells.
    nutrient_topic
    Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
    organism
    Gallus gallus
    plain_language
    The collagen enzyme can start working without vitamin C, but sustained work needs vitamin C support.
    primary_references
    [myllyla1978] The role of ascorbate in the prolyl hydroxylase reaction. (1978). https://pubmed.ncbi.nlm.nih.gov/212056/ DOI: 10.1016/0006-291x(78)91010-0
    tissue_or_cell_type
    Chick embryo enzyme preparation

    Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 572–583

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified chick-embryo collagen prolyl hydroxylase kinetics · source_derived_draft · unverified_draft

    ### vc-enzyme-initial-p4h-turnover Purified chick collagen prolyl hydroxylase completed approximately 15–30 rapid catalytic cycles in 5–10 seconds without added ascorbate before activity declined. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The collagen enzyme can start working without vitamin C, but sustained work needs vitamin C support. organism: Gallus gallus tissue_or_cell_type: Chick embryo enzyme preparation experimental_model: Purified chick-embryo collagen prolyl hydroxylase kinetics limitations: Purified assay with cofactor omission; does not quantify a dietary requirement or establish an identical turnover number in human cells. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Ascorbate omitted or added in purified-enzyme assays; initial 5–10 seconds versus approximately 1 minute. [myllyla1978] The role of ascorbate in the prolyl hydroxylase reaction. (1978). https://pubmed.ncbi.nlm.nih.gov/212056/ DOI: 10.1016/0006-291x(78)91010-0
    Complete structured claim and evidence

Where it participates (unsigned role)

  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. Carbon-13 glutamine tracing in human mammary cancer-associated fibroblasts demonstrated incorporation of newly synthesized proline into COL1A1 peptides.

    L-Glutamine → Human collagen type I alpha 1 / COL1A1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human fibroblast cultures; 2 mM labeled glutamine for 72 hours in the collagen-peptide experiment.
    limitations
    Atom tracing does not show that dietary glutamine or proline is the limiting substrate in a person. Correction record: Author correction PMID 35927357 / DOI 10.1038/s42255-022-00632-7 corrects the author surname Riero-Domingo to Riera-Domingo. It does not report a change to the experimental results. https://www.nature.com/articles/s42255-022-00632-7
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    Collagen-building cells can make their own proline from glutamine.
    primary_references
    Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35760868/ · DOI 10.1038/s42255-022-00582-0

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 246–252

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human fibroblast cultures; 2 mM labeled glutamine for 72 hours in the collagen-peptide experiment. · source_derived_draft · unverified_draft

    ## l-proline-collagen-carbon Collagen-building cells can make their own proline from glutamine. Carbon-13 glutamine tracing in human mammary cancer-associated fibroblasts demonstrated incorporation of newly synthesized proline into COL1A1 peptides. Model: Human fibroblast cultures; 2 mM labeled glutamine for 72 hours in the collagen-peptide experiment. Limitations: Atom tracing does not show that dietary glutamine or proline is the limiting substrate in a person. Correction record: Author correction PMID 35927357 / DOI 10.1038/s42255-022-00632-7 corrects the author surname Riero-Domingo to Riera-Domingo. It does not report a change to the experimental results. https://www.nature.com/articles/s42255-022-00632-7 Evidence access: Primary full text Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35760868/ · DOI 10.1038/s42255-022-00582-0
    Complete structured claim and evidence

  3. In chick collagen hydroxylase assays, complete proline hydroxylation was coupled to 2-oxoglutarate decarboxylation while ascorbate was not consumed in most catalytic cycles.

    Chick collagen prolyl 4-hydroxylase preparation → 2-Oxoglutarate source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.
    experimental_model
    Purified chick prolyl and partially purified lysyl collagen hydroxylases
    exposure
    Peptide substrate present or absent; uncoupled 2-oxoglutarate decarboxylation assays.
    limitations
    This statement concerns coupled turnover; it must not be transferred to copper monooxygenases.
    nutrient_topic
    Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
    organism
    Gallus gallus
    plain_language
    Vitamin C is not a one-for-one consumed ingredient in every successful collagen hydroxylation.
    primary_references
    [myllyla1984] Ascorbate is consumed stoichiometrically in the uncoupled reactions catalyzed by prolyl 4-hydroxylase and lysyl hydroxylase. (1984). https://pubmed.ncbi.nlm.nih.gov/6325436/ DOI: 10.1016/s0021-9258(18)91023-9
    tissue_or_cell_type
    Chick embryo enzyme preparations

    Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 585–596

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified chick prolyl and partially purified lysyl collagen hydroxylases · source_derived_draft · unverified_draft

    ### vc-enzyme-coupled-ascorbate-use In chick collagen hydroxylase assays, complete proline hydroxylation was coupled to 2-oxoglutarate decarboxylation while ascorbate was not consumed in most catalytic cycles. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C is not a one-for-one consumed ingredient in every successful collagen hydroxylation. organism: Gallus gallus tissue_or_cell_type: Chick embryo enzyme preparations experimental_model: Purified chick prolyl and partially purified lysyl collagen hydroxylases limitations: This statement concerns coupled turnover; it must not be transferred to copper monooxygenases. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Peptide substrate present or absent; uncoupled 2-oxoglutarate decarboxylation assays. [myllyla1984] Ascorbate is consumed stoichiometrically in the uncoupled reactions catalyzed by prolyl 4-hydroxylase and lysyl hydroxylase. (1984). https://pubmed.ncbi.nlm.nih.gov/6325436/ DOI: 10.1016/s0021-9258(18)91023-9
    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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