Component

Human pyrroline-5-carboxylate reductase 1 / PYCR1

Context-specific entity; species, compartment and exposure are stated on each claim.

8 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. Reducing PYCR1 in human mammary cancer-associated fibroblasts lowered proline supply for collagen production and decreased collagen deposition.

    Human pyrroline-5-carboxylate reductase 1 / PYCR1 → Collagen deposition by human cancer-associated fibroblasts source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human CAF knockdown and matrix measurements; xenograft experiments separately examined tumor consequences.
    limitations
    This is a tumor-associated fibroblast model, not a trial of ordinary wound healing. 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
    Endogenous synthesis can limit matrix production in activated fibroblasts.
    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
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 254–260

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human CAF knockdown and matrix measurements; xenograft experiments separately examined tumor consequences. · source_derived_draft · unverified_draft

    ## l-proline-collagen-pycr1 Endogenous synthesis can limit matrix production in activated fibroblasts. Reducing PYCR1 in human mammary cancer-associated fibroblasts lowered proline supply for collagen production and decreased collagen deposition. Model: Human CAF knockdown and matrix measurements; xenograft experiments separately examined tumor consequences. Limitations: This is a tumor-associated fibroblast model, not a trial of ordinary wound healing. 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

  2. Fibroblasts from people with PYCR1-related cutis laxa showed altered mitochondrial morphology and membrane potential and greater apoptosis during oxidative stress.

    Human pyrroline-5-carboxylate reductase 1 / PYCR1 → Mitochondrial integrity in PYCR1-deficient human fibroblasts source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human genetic families and patient fibroblasts.
    limitations
    The clinical disorder is not shown to be an isolated dietary proline deficiency or reliably corrected by proline supplementation. Correction record: Author correction PMID 35064218 / DOI 10.1038/s41588-022-01013-2 adds an omitted funding acknowledgment for Hulya Kayserili (TUBITAK SBAG-108S418). The notice does not report a change to the mechanism results. https://www.nature.com/articles/s41588-022-01013-2
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    An enzyme defect can affect connective tissue and cellular stress handling together.
    primary_references
    Mutations in PYCR1 cause cutis laxa with progeroid features. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19648921/ · DOI 10.1038/ng.413
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 150–156

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human genetic families and patient fibroblasts. · source_derived_draft · unverified_draft

    ## l-proline-pycr1-genetic An enzyme defect can affect connective tissue and cellular stress handling together. Fibroblasts from people with PYCR1-related cutis laxa showed altered mitochondrial morphology and membrane potential and greater apoptosis during oxidative stress. Model: Human genetic families and patient fibroblasts. Limitations: The clinical disorder is not shown to be an isolated dietary proline deficiency or reliably corrected by proline supplementation. Correction record: Author correction PMID 35064218 / DOI 10.1038/s41588-022-01013-2 adds an omitted funding acknowledgment for Hulya Kayserili (TUBITAK SBAG-108S418). The notice does not report a change to the mechanism results. https://www.nature.com/articles/s41588-022-01013-2 Evidence access: Primary abstract Mutations in PYCR1 cause cutis laxa with progeroid features. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19648921/ · DOI 10.1038/ng.413
    Complete structured claim and evidence

  3. PYCR1 loss increased hypoxia-associated cell death in three-dimensional cancer cultures and tumors in vivo.

    Human pyrroline-5-carboxylate reductase 1 / PYCR1 → Hypoxic survival of PYCR1-manipulated human cancer cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human cancer-cell PYCR1 depletion/knockout and xenograft experiments.
    limitations
    This is a context-specific vulnerability and is not proof of systemic proline deficiency.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    A cell may need the synthesis reaction itself, not merely a measured pool of the final amino acid.
    primary_references
    Proline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35108535/ · DOI 10.1016/j.celrep.2022.110320
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 358–364

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell PYCR1 depletion/knockout and xenograft experiments. · source_derived_draft · unverified_draft

    ## l-proline-pycr1-hypoxic-loss A cell may need the synthesis reaction itself, not merely a measured pool of the final amino acid. PYCR1 loss increased hypoxia-associated cell death in three-dimensional cancer cultures and tumors in vivo. Model: Human cancer-cell PYCR1 depletion/knockout and xenograft experiments. Limitations: This is a context-specific vulnerability and is not proof of systemic proline deficiency. Evidence access: Primary full text Proline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35108535/ · DOI 10.1016/j.celrep.2022.110320
    Complete structured claim and evidence

  4. In hypoxic cancer models, increased PYCR1-dependent proline synthesis oxidized NADH and helped sustain TCA-cycle activity.

    Human pyrroline-5-carboxylate reductase 1 / PYCR1 → NADH source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human cancer-cell hypoxia experiments and three-dimensional/xenograft models.
    limitations
    A benefit to tumor-cell survival is not a health benefit of supplementation; proline production is part of the reaction that consumes NADH.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    Making proline can also help rebalance mitochondrial reducing power.
    primary_references
    Proline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35108535/ · DOI 10.1016/j.celrep.2022.110320

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 350–356

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell hypoxia experiments and three-dimensional/xenograft models. · source_derived_draft · unverified_draft

    ## l-proline-pycr1-hypoxic-redox Making proline can also help rebalance mitochondrial reducing power. In hypoxic cancer models, increased PYCR1-dependent proline synthesis oxidized NADH and helped sustain TCA-cycle activity. Model: Human cancer-cell hypoxia experiments and three-dimensional/xenograft models. Limitations: A benefit to tumor-cell survival is not a health benefit of supplementation; proline production is part of the reaction that consumes NADH. Evidence access: Primary full text Proline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35108535/ · DOI 10.1016/j.celrep.2022.110320
    Complete structured claim and evidence

  5. Recombinant human PYCR1 reduced P5C to proline with NADH or NADPH; in the tested conditions its specific activity was higher with NADH.

    Human pyrroline-5-carboxylate reductase 1 / PYCR1 → L-Proline source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Purified human enzyme; comparison with 0.1 mM P5C and 0.1 mM reduced cofactor, 37 degrees C.
    limitations
    Cofactor preference depends on assay conditions and does not make the alternative cofactor unusable.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    One mitochondrial enzyme finishes the synthesis of proline.
    primary_references
    Functional specialization in proline biosynthesis of melanoma. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23024808/ · DOI 10.1371/journal.pone.0045190

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 14–20

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human enzyme; comparison with 0.1 mM P5C and 0.1 mM reduced cofactor, 37 degrees C. · source_derived_draft · unverified_draft

    ## l-proline-pycr1-reduction One mitochondrial enzyme finishes the synthesis of proline. Recombinant human PYCR1 reduced P5C to proline with NADH or NADPH; in the tested conditions its specific activity was higher with NADH. Model: Purified human enzyme; comparison with 0.1 mM P5C and 0.1 mM reduced cofactor, 37 degrees C. Limitations: Cofactor preference depends on assay conditions and does not make the alternative cofactor unusable. Evidence access: Primary full text Functional specialization in proline biosynthesis of melanoma. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23024808/ · DOI 10.1371/journal.pone.0045190
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. 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

  2. Isotope tracing with gene silencing linked glutamine/glutamate-derived proline mainly to PYCR1/PYCR2 and ornithine-derived proline mainly to PYCRL in human melanoma cells.

    L-Ornithine → L-Proline source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Lu1205 cells; 1 mM labeled precursors for eight hours; ornithine labeling required omission of extracellular proline.
    limitations
    The ornithine experiment used conditions the authors regarded as likely nonphysiological; no universal exclusive routing rule is inferred.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    Two precursor routes can feed the same product through differently placed enzymes.
    primary_references
    Functional specialization in proline biosynthesis of melanoma. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23024808/ · DOI 10.1371/journal.pone.0045190

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 38–44

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Lu1205 cells; 1 mM labeled precursors for eight hours; ornithine labeling required omission of extracellular proline. · source_derived_draft · unverified_draft

    ## l-proline-precursor-routing Two precursor routes can feed the same product through differently placed enzymes. Isotope tracing with gene silencing linked glutamine/glutamate-derived proline mainly to PYCR1/PYCR2 and ornithine-derived proline mainly to PYCRL in human melanoma cells. Model: Lu1205 cells; 1 mM labeled precursors for eight hours; ornithine labeling required omission of extracellular proline. Limitations: The ornithine experiment used conditions the authors regarded as likely nonphysiological; no universal exclusive routing rule is inferred. Evidence access: Primary full text Functional specialization in proline biosynthesis of melanoma. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23024808/ · DOI 10.1371/journal.pone.0045190
    Complete structured claim and evidence

  3. Proline inhibited recombinant PYCR2 more strongly than PYCR1 or PYCRL; approximate apparent inhibition constants were 0.1, 0.6 and 8 mM, respectively.

    L-Proline → Human pyrroline-5-carboxylate reductase 2 / PYCR2 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Purified human enzymes; product-inhibition assays, with PYCR2 losing about 90% activity at 0.3 mM proline.
    limitations
    These assay concentrations are not blood targets or supplement recommendations.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    Accumulating product can slow further production, with unequal sensitivity among enzymes.
    primary_references
    Functional specialization in proline biosynthesis of melanoma. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23024808/ · DOI 10.1371/journal.pone.0045190

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 46–52

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human enzymes; product-inhibition assays, with PYCR2 losing about 90% activity at 0.3 mM proline. · source_derived_draft · unverified_draft

    ## l-proline-product-feedback Accumulating product can slow further production, with unequal sensitivity among enzymes. Proline inhibited recombinant PYCR2 more strongly than PYCR1 or PYCRL; approximate apparent inhibition constants were 0.1, 0.6 and 8 mM, respectively. Model: Purified human enzymes; product-inhibition assays, with PYCR2 losing about 90% activity at 0.3 mM proline. Limitations: These assay concentrations are not blood targets or supplement recommendations. Evidence access: Primary full text Functional specialization in proline biosynthesis of melanoma. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23024808/ · DOI 10.1371/journal.pone.0045190
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

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