Component

Spermine

Study-scoped entity; inspect species, exposure and experimental limitations on each claim.

17 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. Spermine still potentiated NMDA current in the presence of agmatine, supporting distinct interaction sites for the two compounds.

    Spermine → Rat NMDA-type glutamate receptors, subunits unresolved source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Rat hippocampal-neuron electrophysiology.
    limitations
    This is a cellular interaction, not evidence that co-supplementation is beneficial.
    nutrient_topic
    Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate
    plain_language
    Two connected polyamine-related molecules can push the same channel in different directions.
    primary_references
    Agmatine selectively blocks the N-methyl-D-aspartate subclass of glutamate receptor channels in rat hippocampal neurons. · 1999 · https://pubmed.ncbi.nlm.nih.gov/9918557/

    Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 268–274

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat hippocampal-neuron electrophysiology. · source_derived_draft · unverified_draft

    ## agmatine-sulfate-spermine-nmda Two connected polyamine-related molecules can push the same channel in different directions. Spermine still potentiated NMDA current in the presence of agmatine, supporting distinct interaction sites for the two compounds. Model: Rat hippocampal-neuron electrophysiology. Limitations: This is a cellular interaction, not evidence that co-supplementation is beneficial. Evidence access: Primary abstract Agmatine selectively blocks the N-methyl-D-aspartate subclass of glutamate receptor channels in rat hippocampal neurons. · 1999 · https://pubmed.ncbi.nlm.nih.gov/9918557/
    Complete structured claim and evidence

  2. Spermine bound human DHPS and generated a smaller NADH fluorescence response than spermidine.

    Spermine → DHPS source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Single-turnover fluorescence and structural assays; apparent spermine KD about 81 micromolar.
    limitations
    The assay probes an initial reaction step, not successful cellular replacement of spermidine for complete eIF5A hypusination.
    nutrient_topic
    Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Spermidine
    plain_language
    A related polyamine can participate in part of the chemistry.
    primary_references
    Half Way to Hypusine-Structural Basis for Substrate Recognition by Human Deoxyhypusine Synthase. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32235505/ · DOI 10.3390/biom10040522

    Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 30–36

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Single-turnover fluorescence and structural assays; apparent spermine KD about 81 micromolar. · source_derived_draft · unverified_draft

    ## spermidine-spermine-first-step A related polyamine can participate in part of the chemistry. Spermine bound human DHPS and generated a smaller NADH fluorescence response than spermidine. Model: Single-turnover fluorescence and structural assays; apparent spermine KD about 81 micromolar. Limitations: The assay probes an initial reaction step, not successful cellular replacement of spermidine for complete eIF5A hypusination. Evidence access: Primary full text Half Way to Hypusine-Structural Basis for Substrate Recognition by Human Deoxyhypusine Synthase. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32235505/ · DOI 10.3390/biom10040522
    Complete structured claim and evidence

What acts on it

  1. The recombinant human PAOX preparation did not efficiently oxidize unacetylated spermine.

    Human N1-acetylpolyamine oxidase / PAOX → Spermine source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Purified enzyme comparison.
    limitations
    Do not substitute PAOX for SMOX in the graph.
    nutrient_topic
    Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Spermidine
    plain_language
    Acetylation changes substrate recognition.
    primary_references
    Properties of recombinant human N1-acetylpolyamine oxidase (hPAO): potential role in determining drug sensitivity. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15791459/ · DOI 10.1007/s00280-004-0936-5

    Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 110–116

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified enzyme comparison. · source_derived_draft · unverified_draft

    ## spermidine-paox-spermine-null Acetylation changes substrate recognition. The recombinant human PAOX preparation did not efficiently oxidize unacetylated spermine. Model: Purified enzyme comparison. Limitations: Do not substitute PAOX for SMOX in the graph. Evidence access: Primary abstract Properties of recombinant human N1-acetylpolyamine oxidase (hPAO): potential role in determining drug sensitivity. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15791459/ · DOI 10.1007/s00280-004-0936-5
    Complete structured claim and evidence

  2. Human spermine-synthase substrate/product structures and mutagenesis support aminopropyl transfer to spermidine.

    Spermidine → Spermine source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human SMS structures and catalytic assays.
    limitations
    A pathway connection does not mean arginine is always rate limiting.
    nutrient_topic
    L-Arginine collection; tissue, species, dose and formulation distinctions retained. · L-Arginine
    plain_language
    The polyamine pathway extends beyond spermidine.
    primary_references
    Crystal structure of human spermine synthase: implications of substrate binding and catalytic mechanism. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18367445/ · DOI 10.1074/jbc.m710323200

    L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 158–164

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human SMS structures and catalytic assays. · source_derived_draft · unverified_draft

    ## arg-sms The polyamine pathway extends beyond spermidine. Human spermine-synthase substrate/product structures and mutagenesis support aminopropyl transfer to spermidine. Model: Human SMS structures and catalytic assays. Limitations: A pathway connection does not mean arginine is always rate limiting. Evidence access: Primary abstract Crystal structure of human spermine synthase: implications of substrate binding and catalytic mechanism. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18367445/ · DOI 10.1074/jbc.m710323200
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Agmatine promoted an antizyme-mRNA frameshift producing full-length antizyme; anti-antizyme antibody or antizyme inhibitor suppressed associated inhibitory activity.

    Agmatine → Agmatine-dependent antizyme translational frameshift in the 1998 experiments source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Cell and translation assays; exact construct and cell species not resolved in accessed abstract.
    limitations
    This is not assigned to a human isoform without checking the complete preparation.
    nutrient_topic
    Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate
    plain_language
    It can influence production of a regulator of polyamine metabolism.
    primary_references
    Agmatine suppresses proliferation by frameshift induction of antizyme and attenuation of cellular polyamine levels. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9624108/ · DOI 10.1074/jbc.273.25.15313

    Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 340–346

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell and translation assays; exact construct and cell species not resolved in accessed abstract. · source_derived_draft · unverified_draft

    ## agmatine-sulfate-antizyme-frameshift It can influence production of a regulator of polyamine metabolism. Agmatine promoted an antizyme-mRNA frameshift producing full-length antizyme; anti-antizyme antibody or antizyme inhibitor suppressed associated inhibitory activity. Model: Cell and translation assays; exact construct and cell species not resolved in accessed abstract. Limitations: This is not assigned to a human isoform without checking the complete preparation. Evidence access: Primary abstract Agmatine suppresses proliferation by frameshift induction of antizyme and attenuation of cellular polyamine levels. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9624108/ · DOI 10.1074/jbc.273.25.15313
    Complete structured claim and evidence

  2. Transformed mouse NIH/3T3 cells took up agmatine through an energy- and membrane-potential-dependent saturable system with apparent Km 2.5 micromolar.

    Mouse transformed NIH/3T3 polyamine transport system → Agmatine source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Mouse transformed fibroblast transport experiments.
    limitations
    The molecular transporter gene was not identified; this system is not automatically OCT2 or MATE1.
    nutrient_topic
    Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate
    plain_language
    Different cells can have much higher-affinity uptake than a single recombinant transporter.
    primary_references
    Polyamine transport system mediates agmatine transport in mammalian cells. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11401856/ · DOI 10.1152/ajpcell.2001.281.1.C329
    transport_effect
    raises Cells took up agmatine through an energy- and membrane-potential-dependent saturable system.
    transport_pool
    the expressing cell Cells took up agmatine through an energy- and membrane-potential-dependent saturable system.

    Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 60–66

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse transformed fibroblast transport experiments. · source_derived_draft · unverified_draft

    ## agmatine-sulfate-polyamine-carrier Different cells can have much higher-affinity uptake than a single recombinant transporter. Transformed mouse NIH/3T3 cells took up agmatine through an energy- and membrane-potential-dependent saturable system with apparent Km 2.5 micromolar. Model: Mouse transformed fibroblast transport experiments. Limitations: The molecular transporter gene was not identified; this system is not automatically OCT2 or MATE1. Evidence access: Primary abstract Polyamine transport system mediates agmatine transport in mammalian cells. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11401856/ · DOI 10.1152/ajpcell.2001.281.1.C329
    Complete structured claim and evidence

  3. Polyamines inhibited MATE1-mediated agmatine transport, whereas L-arginine did not inhibit it in the tested system.

    Polyamine competitor pool in the human MATE1 agmatine assay → Human MATE1-mediated agmatine transport source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human MATE1-expressing HEK293 cells.
    limitations
    The primary abstract groups the polyamine competitors; no individual potency rank is assigned.
    nutrient_topic
    Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate
    plain_language
    A shared precursor is not necessarily a transport competitor.
    primary_references
    OCT2 and MATE1 provide bidirectional agmatine transport. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21128598/ · DOI 10.1021/mp100180a

    Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 52–58

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human MATE1-expressing HEK293 cells. · source_derived_draft · unverified_draft

    ## agmatine-sulfate-polyamine-competition A shared precursor is not necessarily a transport competitor. Polyamines inhibited MATE1-mediated agmatine transport, whereas L-arginine did not inhibit it in the tested system. Model: Human MATE1-expressing HEK293 cells. Limitations: The primary abstract groups the polyamine competitors; no individual potency rank is assigned. Evidence access: Primary abstract OCT2 and MATE1 provide bidirectional agmatine transport. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21128598/ · DOI 10.1021/mp100180a
    Complete structured claim and evidence

  4. Agmatine lowered intracellular polyamines and suppressed transformed-cell proliferation; polyamine supplementation reversed growth suppression.

    Polyamine supplementation pool in the 1998 agmatine experiments → Agmatine-associated growth suppression in the 1998 transformed-cell model source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Transformed-cell supplementation experiment.
    limitations
    The accessed abstract reports polyamine supplementation as a group, not a spermidine-only rescue or cancer therapy.
    nutrient_topic
    Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate
    plain_language
    Restoring a downstream pool changed the cellular outcome.
    primary_references
    Agmatine suppresses proliferation by frameshift induction of antizyme and attenuation of cellular polyamine levels. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9624108/ · DOI 10.1074/jbc.273.25.15313

    Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 348–354

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Transformed-cell supplementation experiment. · source_derived_draft · unverified_draft

    ## agmatine-sulfate-polyamine-rescue Restoring a downstream pool changed the cellular outcome. Agmatine lowered intracellular polyamines and suppressed transformed-cell proliferation; polyamine supplementation reversed growth suppression. Model: Transformed-cell supplementation experiment. Limitations: The accessed abstract reports polyamine supplementation as a group, not a spermidine-only rescue or cancer therapy. Evidence access: Primary abstract Agmatine suppresses proliferation by frameshift induction of antizyme and attenuation of cellular polyamine levels. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9624108/ · DOI 10.1074/jbc.273.25.15313
    Complete structured claim and evidence

  5. Rat hepatocytes exhibited high-affinity agmatine uptake with Km 0.03 mM; the system also transported putrescine but not arginine, spermidine or spermine.

    Rat hepatocyte high-affinity agmatine uptake → Agmatine source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Primary rat hepatocyte cultures and radiolabeled substrate.
    limitations
    Different selectivity from other polyamine uptake systems is a context difference, not a universal contradiction.
    nutrient_topic
    Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate
    plain_language
    Competition depends on which cell and transport route is being studied.
    primary_references
    Transport and metabolism of agmatine in rat hepatocyte cultures. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11179960/ · DOI 10.1046/j.1432-1327.2001.01955.x
    transport_effect
    raises Hepatocytes showed high-affinity agmatine uptake with a Km of 0.03 mM.
    transport_pool
    the hepatocyte interior Hepatocytes showed high-affinity agmatine uptake with a Km of 0.03 mM.

    Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 76–82

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary rat hepatocyte cultures and radiolabeled substrate. · source_derived_draft · unverified_draft

    ## agmatine-sulfate-rat-liver-uptake Competition depends on which cell and transport route is being studied. Rat hepatocytes exhibited high-affinity agmatine uptake with Km 0.03 mM; the system also transported putrescine but not arginine, spermidine or spermine. Model: Primary rat hepatocyte cultures and radiolabeled substrate. Limitations: Different selectivity from other polyamine uptake systems is a context difference, not a universal contradiction. Evidence access: Primary abstract Transport and metabolism of agmatine in rat hepatocyte cultures. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11179960/ · DOI 10.1046/j.1432-1327.2001.01955.x
    Complete structured claim and evidence

  6. Agmatine present in culture medium competitively inhibited radiolabeled polyamine uptake, increasing apparent Km.

    Agmatine → Rat pulmonary-endothelial polyamine uptake source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Rat pulmonary endothelial transport kinetics.
    limitations
    No universal human polyamine depletion magnitude or clinical supplement interaction is established.
    nutrient_topic
    Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate
    plain_language
    Immediate transport competition can coexist with slower regulation of protein expression.
    primary_references
    Regulation of ornithine decarboxylase activity and polyamine transport by agmatine in rat pulmonary artery endothelial cells. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11160620/

    Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 364–370

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat pulmonary endothelial transport kinetics. · source_derived_draft · unverified_draft

    ## agmatine-sulfate-rat-polyamine-competition Immediate transport competition can coexist with slower regulation of protein expression. Agmatine present in culture medium competitively inhibited radiolabeled polyamine uptake, increasing apparent Km. Model: Rat pulmonary endothelial transport kinetics. Limitations: No universal human polyamine depletion magnitude or clinical supplement interaction is established. Evidence access: Primary abstract Regulation of ornithine decarboxylase activity and polyamine transport by agmatine in rat pulmonary artery endothelial cells. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11160620/
    Complete structured claim and evidence

  7. About 10% of taken-up agmatine label entered the polyamine pool in rat hepatocyte cultures.

    Agmatine → Rat hepatocyte agmatine-derived labeled polyamine pool source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Primary rat hepatocytes with radiotracer.
    limitations
    The abstract reports a polyamine pool, not a putrescine-only percentage or purified human AGMAT reaction.
    nutrient_topic
    Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate
    plain_language
    Agmatine can feed polyamine metabolism in a defined preparation.
    primary_references
    Transport and metabolism of agmatine in rat hepatocyte cultures. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11179960/ · DOI 10.1046/j.1432-1327.2001.01955.x

    Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 100–106

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary rat hepatocytes with radiotracer. · source_derived_draft · unverified_draft

    ## agmatine-sulfate-rat-polyamine-production Agmatine can feed polyamine metabolism in a defined preparation. About 10% of taken-up agmatine label entered the polyamine pool in rat hepatocyte cultures. Model: Primary rat hepatocytes with radiotracer. Limitations: The abstract reports a polyamine pool, not a putrescine-only percentage or purified human AGMAT reaction. Evidence access: Primary abstract Transport and metabolism of agmatine in rat hepatocyte cultures. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11179960/ · DOI 10.1046/j.1432-1327.2001.01955.x
    Complete structured claim and evidence

  8. Spermidine stimulated OAZ1 +1 frameshifting in engineered yeast; its response lacked the cooperativity seen with putrescine and spermine.

    Spermidine → Saccharomyces cerevisiae Oaz1 antizyme source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Yeast strains with synthesis/interconversion deletions and reporter modeling.
    limitations
    Do not transfer the quantitative yeast response to human OAZ1.
    nutrient_topic
    Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Spermidine
    plain_language
    Polyamine abundance feeds back into synthesis control.
    primary_references
    Translational recoding as a feedback controller: systems approaches reveal polyamine-specific effects on the antizyme ribosomal frameshift. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21303766/ · DOI 10.1093/nar/gkq1349

    Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 478–484

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Yeast strains with synthesis/interconversion deletions and reporter modeling. · source_derived_draft · unverified_draft

    ## spermidine-antizyme-feedback Polyamine abundance feeds back into synthesis control. Spermidine stimulated OAZ1 +1 frameshifting in engineered yeast; its response lacked the cooperativity seen with putrescine and spermine. Model: Yeast strains with synthesis/interconversion deletions and reporter modeling. Limitations: Do not transfer the quantitative yeast response to human OAZ1. Evidence access: Primary full text Translational recoding as a feedback controller: systems approaches reveal polyamine-specific effects on the antizyme ribosomal frameshift. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21303766/ · DOI 10.1093/nar/gkq1349
    Complete structured claim and evidence

  9. ATP13A2 supports lysosomal polyamine export to cytosol after endocytic uptake; spermine had the highest tested affinity.

    Human ATP13A2 / PARK9 → Human lysosome-to-cytosol polyamine export source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Purified human transporter and cellular transport experiments.
    limitations
    Polyamine-class result; strongest affinity was for spermine, not necessarily spermidine.
    nutrient_topic
    Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Spermidine
    plain_language
    A molecule can enter a cell yet remain trapped in a compartment.
    primary_references
    ATP13A2 deficiency disrupts lysosomal polyamine export. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31996848/ · DOI 10.1038/s41586-020-1968-7

    Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 118–124

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human transporter and cellular transport experiments. · source_derived_draft · unverified_draft

    ## spermidine-atp13a2-export A molecule can enter a cell yet remain trapped in a compartment. ATP13A2 supports lysosomal polyamine export to cytosol after endocytic uptake; spermine had the highest tested affinity. Model: Purified human transporter and cellular transport experiments. Limitations: Polyamine-class result; strongest affinity was for spermine, not necessarily spermidine. Evidence access: Primary abstract ATP13A2 deficiency disrupts lysosomal polyamine export. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31996848/ · DOI 10.1038/s41586-020-1968-7
    Complete structured claim and evidence

  10. Spermidine inhibited rat-testis deoxyhypusine hydroxylase in vitro, less potently than spermine.

    Spermidine → Rat deoxyhypusine hydroxylase / Dohh source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Rat testis enzyme; comparative polyamine inhibition kinetics.
    limitations
    High-concentration enzyme inhibition is not a contradiction of cellular hypusination rescue; no human inhibitory threshold established.
    nutrient_topic
    Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Spermidine
    plain_language
    More substrate upstream does not guarantee more activity downstream.
    primary_references
    Inhibition of deoxyhypusine hydroxylase by polyamines and by a deoxyhypusine peptide. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2765563/ · DOI 10.1016/0167-4838(89)90195-7

    Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 70–76

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat testis enzyme; comparative polyamine inhibition kinetics. · source_derived_draft · unverified_draft

    ## spermidine-dohh-high-polyamine More substrate upstream does not guarantee more activity downstream. Spermidine inhibited rat-testis deoxyhypusine hydroxylase in vitro, less potently than spermine. Model: Rat testis enzyme; comparative polyamine inhibition kinetics. Limitations: High-concentration enzyme inhibition is not a contradiction of cellular hypusination rescue; no human inhibitory threshold established. Evidence access: Primary abstract Inhibition of deoxyhypusine hydroxylase by polyamines and by a deoxyhypusine peptide. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2765563/ · DOI 10.1016/0167-4838(89)90195-7
    Complete structured claim and evidence

  11. The same trial found increased plasma spermine exposure after oral spermidine.

    Spermidine → Human plasma spermine concentration source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Twelve-person crossover trial; 15 mg/day, five days.
    limitations
    Presystemic conversion was an interpretation, not proven by an isotope tracer; the fasting spermine comparison was not significant.
    nutrient_topic
    Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Spermidine
    plain_language
    A related metabolite changed instead.
    primary_references
    High-Dose Spermidine Supplementation Does Not Increase Spermidine Levels in Blood Plasma and Saliva of Healthy Adults: A Randomized Placebo-Controlled Pharmacokinetic and Metabolomic Study. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37111071/ · DOI 10.3390/nu15081852
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 558–564

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Twelve-person crossover trial; 15 mg/day, five days. · source_derived_draft · unverified_draft

    ## spermidine-human-spermine A related metabolite changed instead. The same trial found increased plasma spermine exposure after oral spermidine. Model: Twelve-person crossover trial; 15 mg/day, five days. Limitations: Presystemic conversion was an interpretation, not proven by an isotope tracer; the fasting spermine comparison was not significant. Evidence access: Primary full text High-Dose Spermidine Supplementation Does Not Increase Spermidine Levels in Blood Plasma and Saliva of Healthy Adults: A Randomized Placebo-Controlled Pharmacokinetic and Metabolomic Study. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37111071/ · DOI 10.3390/nu15081852
    Complete structured claim and evidence

  12. Human PAOX oxidized N1-acetylspermine with Km 0.85 micromolar and kcat 31.7 per second.

    Human N1-acetylpolyamine oxidase / PAOX → N1-Acetylspermine source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Purified human enzyme.
    limitations
    Substrate specificity differs from SMOX; enzyme turnover is not whole-body turnover.
    nutrient_topic
    Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Spermidine
    plain_language
    Back-conversion depends on which polyamine was acetylated.
    primary_references
    Properties of recombinant human N1-acetylpolyamine oxidase (hPAO): potential role in determining drug sensitivity. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15791459/ · DOI 10.1007/s00280-004-0936-5

    Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 102–108

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human enzyme. · source_derived_draft · unverified_draft

    ## spermidine-paox-acetylspermine Back-conversion depends on which polyamine was acetylated. Human PAOX oxidized N1-acetylspermine with Km 0.85 micromolar and kcat 31.7 per second. Model: Purified human enzyme. Limitations: Substrate specificity differs from SMOX; enzyme turnover is not whole-body turnover. Evidence access: Primary abstract Properties of recombinant human N1-acetylpolyamine oxidase (hPAO): potential role in determining drug sensitivity. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15791459/ · DOI 10.1007/s00280-004-0936-5
    Complete structured claim and evidence

  13. The product-bound SMS structure supplied a mechanistic explanation for inhibition by methylthioadenosine.

    5′-Methylthioadenosine → Human spermine synthase / SMS source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human SMS structural and biochemical study.
    limitations
    Product inhibition is not a measured dietary-arginine effect.
    nutrient_topic
    L-Arginine collection; tissue, species, dose and formulation distinctions retained. · L-Arginine
    plain_language
    A reaction product can slow its own production pathway.
    primary_references
    Crystal structure of human spermine synthase: implications of substrate binding and catalytic mechanism. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18367445/ · DOI 10.1074/jbc.m710323200

    L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 166–172

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human SMS structural and biochemical study. · source_derived_draft · unverified_draft

    ## arg-sms-inhibition A reaction product can slow its own production pathway. The product-bound SMS structure supplied a mechanistic explanation for inhibition by methylthioadenosine. Model: Human SMS structural and biochemical study. Limitations: Product inhibition is not a measured dietary-arginine effect. Evidence access: Primary abstract Crystal structure of human spermine synthase: implications of substrate binding and catalytic mechanism. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18367445/ · DOI 10.1074/jbc.m710323200
    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