Nutrient chapter

Gamma-nonalactone

C9H16O2; CAS 104-61-0; nonan-4-olide / 5-pentyloxolan-2-one. Flavor and fragrance lactone, not an established essential nutrient or therapy. Generic records do not resolve enantiomer composition unless stated; FDA GSRS registers CAS 104-61-0 as racemic. Distinct from delta-nonalactone, gamma-decalactone, gamma-butyrolactone and GHB. Identity: https://precision.fda.gov/ginas/app/ui/substances/99a11123-4b6b-41c5-b472-a70449e3a6b4

23 recorded mechanisms · 1 availability situations · 1 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

  1. Gamma-nonalactone evoked a calcium response in human-TRPV1-expressing HEK293 cells.

    Gamma-nonalactone → Human transient receptor potential vanilloid 1 / TRPV1 source_derived_draftungraded
    Experimental context and source evidence
    dose
    Gamma-nonalactone 2 mM; six replicates; separate concentration-response series
    duration
    Acute fluorescence response; precise recording window not specified in accessed methods
    evidence_access
    Primary full-text methods/results inspected; PubMed metadata where indexed.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Human TRPV1 or TRPA1 stably expressed in Flp-In HEK293 cells
    limitations
    Millimolar assay exposure is not dietary tissue exposure or clinical analgesia. Above 5 mM assay artifacts prevented reliable lactone EC50 fitting. Human receptor species confirmed in methods.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Human TRPV1 or TRPA1 stably expressed in Flp-In HEK293 cells
    plain_language
    Gamma-nonalactone evoked a calcium response in human-TRPV1-expressing HEK293 cells.
    primary_references
    Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023
    route
    In vitro bath addition
    tissue
    Fluo8 NW calcium-flux assay

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 15–24

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human TRPV1 or TRPA1 stably expressed in Flp-In HEK293 cells · source_derived_draft · unverified_draft

    ## gamma-nonalactone-trpv1-activation Gamma-nonalactone evoked a calcium response in human-TRPV1-expressing HEK293 cells. Model/species: Human TRPV1 or TRPA1 stably expressed in Flp-In HEK293 cells Tissue: Fluo8 NW calcium-flux assay Exposure: Gamma-nonalactone 2 mM; six replicates; separate concentration-response series Route: In vitro bath addition Duration: Acute fluorescence response; precise recording window not specified in accessed methods Limits: Millimolar assay exposure is not dietary tissue exposure or clinical analgesia. Above 5 mM assay artifacts prevented reliable lactone EC50 fitting. Human receptor species confirmed in methods. Primary reference: Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.
    Complete structured claim and evidence

  2. Gamma-nonalactone evoked a calcium response in human-TRPA1-expressing HEK293 cells.

    Gamma-nonalactone → Human TRPA1 ion channel source_derived_draftungraded
    Experimental context and source evidence
    dose
    Gamma-nonalactone 2 mM; six replicates; separate concentration-response series
    duration
    Acute fluorescence response; precise recording window not specified in accessed methods
    evidence_access
    Primary full-text methods/results inspected; PubMed metadata where indexed.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Human TRPV1 or TRPA1 stably expressed in Flp-In HEK293 cells
    limitations
    Millimolar assay exposure is not dietary tissue exposure or clinical analgesia. Above 5 mM assay artifacts prevented reliable lactone EC50 fitting. Human receptor species confirmed in methods.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Human TRPV1 or TRPA1 stably expressed in Flp-In HEK293 cells
    plain_language
    Gamma-nonalactone evoked a calcium response in human-TRPA1-expressing HEK293 cells.
    primary_references
    Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023
    route
    In vitro bath addition
    tissue
    Fluo8 NW calcium-flux assay

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 26–35

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human TRPV1 or TRPA1 stably expressed in Flp-In HEK293 cells · source_derived_draft · unverified_draft

    ## gamma-nonalactone-trpa1-activation Gamma-nonalactone evoked a calcium response in human-TRPA1-expressing HEK293 cells. Model/species: Human TRPV1 or TRPA1 stably expressed in Flp-In HEK293 cells Tissue: Fluo8 NW calcium-flux assay Exposure: Gamma-nonalactone 2 mM; six replicates; separate concentration-response series Route: In vitro bath addition Duration: Acute fluorescence response; precise recording window not specified in accessed methods Limits: Millimolar assay exposure is not dietary tissue exposure or clinical analgesia. Above 5 mM assay artifacts prevented reliable lactone EC50 fitting. Human receptor species confirmed in methods. Primary reference: Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.
    Complete structured claim and evidence

  3. Lower gamma-nonalactone concentrations shifted the capsaicin response toward greater sensitivity with little change in maximum response.

    Gamma-nonalactone → Human transient receptor potential vanilloid 1 / TRPV1 source_derived_draftungraded
    Experimental context and source evidence
    dose
    Gamma-nonalactone 0.64 or 1.28 mM with a capsaicin concentration series
    duration
    Acute calcium response
    evidence_access
    Primary full-text methods/results inspected; PubMed metadata where indexed.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Human TRPV1-expressing HEK293 cells
    limitations
    Functional curve shifts do not directly locate a binding site. No human pungency or pain outcome was tested.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Human TRPV1-expressing HEK293 cells
    plain_language
    Lower gamma-nonalactone concentrations shifted the capsaicin response toward greater sensitivity with little change in maximum response.
    primary_references
    Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023
    route
    In vitro co-application
    tissue
    Capsaicin concentration-response assay

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 37–46

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human TRPV1-expressing HEK293 cells · source_derived_draft · unverified_draft

    ## gamma-nonalactone-capsaicin-low Lower gamma-nonalactone concentrations shifted the capsaicin response toward greater sensitivity with little change in maximum response. Model/species: Human TRPV1-expressing HEK293 cells Tissue: Capsaicin concentration-response assay Exposure: Gamma-nonalactone 0.64 or 1.28 mM with a capsaicin concentration series Route: In vitro co-application Duration: Acute calcium response Limits: Functional curve shifts do not directly locate a binding site. No human pungency or pain outcome was tested. Primary reference: Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.
    Complete structured claim and evidence

  4. At 2.56 mM, gamma-nonalactone reduced capsaicin sensitivity and maximum response.

    Gamma-nonalactone → Human transient receptor potential vanilloid 1 / TRPV1 source_derived_draftungraded
    Experimental context and source evidence
    dose
    Gamma-nonalactone 2.56 mM with a capsaicin concentration series
    duration
    Acute calcium response
    evidence_access
    Primary full-text methods/results inspected; PubMed metadata where indexed.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Human TRPV1-expressing HEK293 cells
    limitations
    Concentration-dependent mixed modulation; not a potent selective antagonist or established dietary interaction.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Human TRPV1-expressing HEK293 cells
    plain_language
    At 2.56 mM, gamma-nonalactone reduced capsaicin sensitivity and maximum response.
    primary_references
    Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023
    route
    In vitro co-application
    tissue
    Capsaicin concentration-response assay

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 48–57

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human TRPV1-expressing HEK293 cells · source_derived_draft · unverified_draft

    ## gamma-nonalactone-capsaicin-high At 2.56 mM, gamma-nonalactone reduced capsaicin sensitivity and maximum response. Model/species: Human TRPV1-expressing HEK293 cells Tissue: Capsaicin concentration-response assay Exposure: Gamma-nonalactone 2.56 mM with a capsaicin concentration series Route: In vitro co-application Duration: Acute calcium response Limits: Concentration-dependent mixed modulation; not a potent selective antagonist or established dietary interaction. Primary reference: Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.
    Complete structured claim and evidence

  5. Gamma-nonalactone shifted the AITC response rightward without reducing its maximum.

    Gamma-nonalactone → Human TRPA1 ion channel source_derived_draftungraded
    Experimental context and source evidence
    dose
    Gamma-nonalactone 2.56 mM with an AITC concentration series
    duration
    Acute calcium response
    evidence_access
    Primary full-text methods/results inspected; PubMed metadata where indexed.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Human TRPA1-expressing HEK293 cells
    limitations
    Authors interpret an agonist interaction; the retained maximum does not establish pure antagonism. Delta-dodecalactone antagonism must not be assigned to gamma-nonalactone.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Human TRPA1-expressing HEK293 cells
    plain_language
    Gamma-nonalactone shifted the AITC response rightward without reducing its maximum.
    primary_references
    Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023
    route
    In vitro co-application
    tissue
    AITC concentration-response assay

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 59–68

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human TRPA1-expressing HEK293 cells · source_derived_draft · unverified_draft

    ## gamma-nonalactone-aitc-curve Gamma-nonalactone shifted the AITC response rightward without reducing its maximum. Model/species: Human TRPA1-expressing HEK293 cells Tissue: AITC concentration-response assay Exposure: Gamma-nonalactone 2.56 mM with an AITC concentration series Route: In vitro co-application Duration: Acute calcium response Limits: Authors interpret an agonist interaction; the retained maximum does not establish pure antagonism. Delta-dodecalactone antagonism must not be assigned to gamma-nonalactone. Primary reference: Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.
    Complete structured claim and evidence

  6. Capsazepine inhibited the gamma-nonalactone-evoked TRPV1 calcium response.

    Capsazepine → Calcium response of human-TRPV1-expressing HEK293 cells source_derived_draftungraded
    Experimental context and source evidence
    dose
    Gamma-nonalactone 2 mM; capsazepine 1 micromolar or A-967079 1 micromolar
    duration
    Acute fluorescence assay
    evidence_access
    Primary full-text methods/results inspected; PubMed metadata where indexed.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Human TRPV1 or TRPA1 expressed in HEK293 cells
    limitations
    Pharmacological specificity controls support channel involvement; they do not establish a binding pocket or oral therapeutic exposure.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Human TRPV1 or TRPA1 expressed in HEK293 cells
    plain_language
    Capsazepine inhibited the gamma-nonalactone-evoked TRPV1 calcium response.
    primary_references
    Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023
    route
    In vitro co-exposure
    tissue
    Receptor antagonist controls

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 70–79

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human TRPV1 or TRPA1 expressed in HEK293 cells · source_derived_draft · unverified_draft

    ## gamma-nonalactone-capsazepine-control Capsazepine inhibited the gamma-nonalactone-evoked TRPV1 calcium response. Model/species: Human TRPV1 or TRPA1 expressed in HEK293 cells Tissue: Receptor antagonist controls Exposure: Gamma-nonalactone 2 mM; capsazepine 1 micromolar or A-967079 1 micromolar Route: In vitro co-exposure Duration: Acute fluorescence assay Limits: Pharmacological specificity controls support channel involvement; they do not establish a binding pocket or oral therapeutic exposure. Primary reference: Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.
    Complete structured claim and evidence

  7. A-967079 inhibited the gamma-nonalactone-evoked TRPA1 calcium response.

    A-967079 → Calcium response of human-TRPA1-expressing HEK293 cells source_derived_draftungraded
    Experimental context and source evidence
    dose
    Gamma-nonalactone 2 mM; capsazepine 1 micromolar or A-967079 1 micromolar
    duration
    Acute fluorescence assay
    evidence_access
    Primary full-text methods/results inspected; PubMed metadata where indexed.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Human TRPV1 or TRPA1 expressed in HEK293 cells
    limitations
    Pharmacological specificity controls support channel involvement; they do not establish a binding pocket or oral therapeutic exposure.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Human TRPV1 or TRPA1 expressed in HEK293 cells
    plain_language
    A-967079 inhibited the gamma-nonalactone-evoked TRPA1 calcium response.
    primary_references
    Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023
    route
    In vitro co-exposure
    tissue
    Receptor antagonist controls

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 81–90

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human TRPV1 or TRPA1 expressed in HEK293 cells · source_derived_draft · unverified_draft

    ## gamma-nonalactone-a967079-control A-967079 inhibited the gamma-nonalactone-evoked TRPA1 calcium response. Model/species: Human TRPV1 or TRPA1 expressed in HEK293 cells Tissue: Receptor antagonist controls Exposure: Gamma-nonalactone 2 mM; capsazepine 1 micromolar or A-967079 1 micromolar Route: In vitro co-exposure Duration: Acute fluorescence assay Limits: Pharmacological specificity controls support channel involvement; they do not establish a binding pocket or oral therapeutic exposure. Primary reference: Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.
    Complete structured claim and evidence

  8. EGTA treatment suppressed the gamma-nonalactone-evoked TRPA1 calcium signal.

    EGTA → Calcium response of human-TRPA1-expressing HEK293 cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    dose
    Gamma-nonalactone 2 mM and EGTA 5 mM
    duration
    Acute fluorescence assay
    evidence_access
    Primary full-text methods/results inspected; PubMed metadata where indexed.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Human TRPV1 or TRPA1 expressed in HEK293 cells
    limitations
    Experimental extracellular calcium removal is not dietary calcium deficiency. A calcium-flux readout cannot establish every downstream cellular consequence.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Human TRPV1 or TRPA1 expressed in HEK293 cells
    plain_language
    EGTA treatment suppressed the gamma-nonalactone-evoked TRPA1 calcium signal.
    primary_references
    Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023
    route
    In vitro calcium chelation
    tissue
    Extracellular calcium-chelation control
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 92–101

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human TRPV1 or TRPA1 expressed in HEK293 cells · source_derived_draft · unverified_draft

    ## gamma-nonalactone-egta-trpa1 EGTA treatment suppressed the gamma-nonalactone-evoked TRPA1 calcium signal. Model/species: Human TRPV1 or TRPA1 expressed in HEK293 cells Tissue: Extracellular calcium-chelation control Exposure: Gamma-nonalactone 2 mM and EGTA 5 mM Route: In vitro calcium chelation Duration: Acute fluorescence assay Limits: Experimental extracellular calcium removal is not dietary calcium deficiency. A calcium-flux readout cannot establish every downstream cellular consequence. Primary reference: Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.
    Complete structured claim and evidence

  9. Purified human PON1 hydrolyzed gamma-nonalactone at 144.7 +/- 11.3 micromol/min/mg.

    Human paraoxonase 1 / PON1 → Gamma-nonalactone source_derived_draftungraded
    Experimental context and source evidence
    dose
    Gamma-nonalactone 1 mM; Table 2 specific activities from 2-4 measurements
    duration
    PON2 non-detection tested up to 10 min at 37 C; exact positive-rate sampling interval not recovered
    evidence_access
    Primary publisher Table 2, footnote and surrounding results plus PubMed abstract; complete assay methods not recovered.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Purified recombinant human PON1, PON2 and PON3, expressed in insect cells
    limitations
    Gamma-nonalactone is a substrate, not a demonstrated PON activator. Buffer details were not recovered from the accessed table excerpt; physiological clearance and calcium-deficiency effects are unmeasured.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Purified recombinant human PON1, PON2 and PON3, expressed in insect cells
    plain_language
    Purified human PON1 hydrolyzed gamma-nonalactone at 144.7 +/- 11.3 micromol/min/mg.
    primary_references
    Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. (2005). https://pubmed.ncbi.nlm.nih.gov/15772423/ DOI: 10.1194/jlr.M400511-JLR200
    route
    In vitro enzyme/substrate incubation
    tissue
    Cell-free lactone-hydrolysis assay

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 103–112

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Purified recombinant human PON1, PON2 and PON3, expressed in insect cells · source_derived_draft · unverified_draft

    ## gamma-nonalactone-pon1-substrate Purified human PON1 hydrolyzed gamma-nonalactone at 144.7 +/- 11.3 micromol/min/mg. Model/species: Purified recombinant human PON1, PON2 and PON3, expressed in insect cells Tissue: Cell-free lactone-hydrolysis assay Exposure: Gamma-nonalactone 1 mM; Table 2 specific activities from 2-4 measurements Route: In vitro enzyme/substrate incubation Duration: PON2 non-detection tested up to 10 min at 37 C; exact positive-rate sampling interval not recovered Limits: Gamma-nonalactone is a substrate, not a demonstrated PON activator. Buffer details were not recovered from the accessed table excerpt; physiological clearance and calcium-deficiency effects are unmeasured. Primary reference: Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. (2005). https://pubmed.ncbi.nlm.nih.gov/15772423/ DOI: 10.1194/jlr.M400511-JLR200 Access: Primary publisher Table 2, footnote and surrounding results plus PubMed abstract; complete assay methods not recovered.
    Complete structured claim and evidence

  10. Purified human PON3 hydrolyzed gamma-nonalactone at 30.9 +/- 2.7 micromol/min/mg.

    Human paraoxonase 3 / PON3 → Gamma-nonalactone source_derived_draftungraded
    Experimental context and source evidence
    dose
    Gamma-nonalactone 1 mM; Table 2 specific activities from 2-4 measurements
    duration
    PON2 non-detection tested up to 10 min at 37 C; exact positive-rate sampling interval not recovered
    evidence_access
    Primary publisher Table 2, footnote and surrounding results plus PubMed abstract; complete assay methods not recovered.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Purified recombinant human PON1, PON2 and PON3, expressed in insect cells
    limitations
    Gamma-nonalactone is a substrate, not a demonstrated PON activator. Buffer details were not recovered from the accessed table excerpt; physiological clearance and calcium-deficiency effects are unmeasured.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Purified recombinant human PON1, PON2 and PON3, expressed in insect cells
    plain_language
    Purified human PON3 hydrolyzed gamma-nonalactone at 30.9 +/- 2.7 micromol/min/mg.
    primary_references
    Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. (2005). https://pubmed.ncbi.nlm.nih.gov/15772423/ DOI: 10.1194/jlr.M400511-JLR200
    route
    In vitro enzyme/substrate incubation
    tissue
    Cell-free lactone-hydrolysis assay

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 114–123

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Purified recombinant human PON1, PON2 and PON3, expressed in insect cells · source_derived_draft · unverified_draft

    ## gamma-nonalactone-pon3-substrate Purified human PON3 hydrolyzed gamma-nonalactone at 30.9 +/- 2.7 micromol/min/mg. Model/species: Purified recombinant human PON1, PON2 and PON3, expressed in insect cells Tissue: Cell-free lactone-hydrolysis assay Exposure: Gamma-nonalactone 1 mM; Table 2 specific activities from 2-4 measurements Route: In vitro enzyme/substrate incubation Duration: PON2 non-detection tested up to 10 min at 37 C; exact positive-rate sampling interval not recovered Limits: Gamma-nonalactone is a substrate, not a demonstrated PON activator. Buffer details were not recovered from the accessed table excerpt; physiological clearance and calcium-deficiency effects are unmeasured. Primary reference: Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. (2005). https://pubmed.ncbi.nlm.nih.gov/15772423/ DOI: 10.1194/jlr.M400511-JLR200 Access: Primary publisher Table 2, footnote and surrounding results plus PubMed abstract; complete assay methods not recovered.
    Complete structured claim and evidence

  11. Purified human PON2 showed no detectable gamma-nonalactone hydrolysis under the reported conditions.

    Human paraoxonase 2 / PON2 → Gamma-nonalactone source_derived_draftungraded
    Experimental context and source evidence
    dose
    Gamma-nonalactone 1 mM; Table 2 specific activities from 2-4 measurements
    duration
    PON2 non-detection tested up to 10 min at 37 C; exact positive-rate sampling interval not recovered
    evidence_access
    Primary publisher Table 2, footnote and surrounding results plus PubMed abstract; complete assay methods not recovered.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Purified recombinant human PON1, PON2 and PON3, expressed in insect cells
    limitations
    Gamma-nonalactone is a substrate, not a demonstrated PON activator. Buffer details were not recovered from the accessed table excerpt; physiological clearance and calcium-deficiency effects are unmeasured.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Purified recombinant human PON1, PON2 and PON3, expressed in insect cells
    plain_language
    Purified human PON2 showed no detectable gamma-nonalactone hydrolysis under the reported conditions.
    primary_references
    Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. (2005). https://pubmed.ncbi.nlm.nih.gov/15772423/ DOI: 10.1194/jlr.M400511-JLR200
    route
    In vitro enzyme/substrate incubation
    tissue
    Cell-free lactone-hydrolysis assay

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 125–134

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Purified recombinant human PON1, PON2 and PON3, expressed in insect cells · source_derived_draft · unverified_draft

    ## gamma-nonalactone-pon2-null Purified human PON2 showed no detectable gamma-nonalactone hydrolysis under the reported conditions. Model/species: Purified recombinant human PON1, PON2 and PON3, expressed in insect cells Tissue: Cell-free lactone-hydrolysis assay Exposure: Gamma-nonalactone 1 mM; Table 2 specific activities from 2-4 measurements Route: In vitro enzyme/substrate incubation Duration: PON2 non-detection tested up to 10 min at 37 C; exact positive-rate sampling interval not recovered Limits: Gamma-nonalactone is a substrate, not a demonstrated PON activator. Buffer details were not recovered from the accessed table excerpt; physiological clearance and calcium-deficiency effects are unmeasured. Primary reference: Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. (2005). https://pubmed.ncbi.nlm.nih.gov/15772423/ DOI: 10.1194/jlr.M400511-JLR200 Access: Primary publisher Table 2, footnote and surrounding results plus PubMed abstract; complete assay methods not recovered.
    Complete structured claim and evidence

  12. Gamma-nonalactone was identified among products formed during HNE biotransformation in murine astrocytes.

    4-Hydroxy-2-nonenal / HNE → Gamma-nonalactone source_derived_draftungraded
    Experimental context and source evidence
    dose
    trans-4-Hydroxy-2-nonenal 1, 5 or 15 micromolar
    duration
    10 min
    evidence_access
    Primary PubMed abstract; unresolved method details explicitly retained.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Murine astrocyte cultures
    limitations
    Product identified in an HNE-metabolism study; specific formation enzymes, flux fraction and human relevance remain unresolved. The pyrrole-forming toxicity described for 4-oxo-nonanal is not a gamma-nonalactone finding.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Murine astrocyte cultures
    plain_language
    Gamma-nonalactone was identified among products formed during HNE biotransformation in murine astrocytes.
    primary_references
    Astrocytic biotransformation of trans-4-hydroxy-2-nonenal is dose-dependent. (2006). https://pubmed.ncbi.nlm.nih.gov/16780364/ DOI: 10.1021/tx0600393
    route
    In vitro precursor addition
    tissue
    HNE biotransformation products

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    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Murine astrocyte cultures · source_derived_draft · unverified_draft

    ## gamma-nonalactone-hne-metabolite Gamma-nonalactone was identified among products formed during HNE biotransformation in murine astrocytes. Model/species: Murine astrocyte cultures Tissue: HNE biotransformation products Exposure: trans-4-Hydroxy-2-nonenal 1, 5 or 15 micromolar Route: In vitro precursor addition Duration: 10 min Limits: Product identified in an HNE-metabolism study; specific formation enzymes, flux fraction and human relevance remain unresolved. The pyrrole-forming toxicity described for 4-oxo-nonanal is not a gamma-nonalactone finding. Primary reference: Astrocytic biotransformation of trans-4-hydroxy-2-nonenal is dose-dependent. (2006). https://pubmed.ncbi.nlm.nih.gov/16780364/ DOI: 10.1021/tx0600393 Access: Primary PubMed abstract; unresolved method details explicitly retained.
    Complete structured claim and evidence

  13. The lowest-alpha-tocopherol beef-fat group showed the greatest gamma-nonalactone rise during storage: 51.4 ppb, 11.7 times the prestorage level.

    Alpha-tocopherol → Gamma-nonalactone source_derived_draftungraded
    Experimental context and source evidence
    dose
    Groups differing in alpha-tocopherol content; lowest 2.9 ppm, highest 28.8 ppm
    duration
    7 days at 2 C
    evidence_access
    Primary PubMed abstract; unresolved method details explicitly retained.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Rendered fat from marbled beef; bovine food matrix
    limitations
    Food oxidation and partitioning are not human nutrient metabolism. The abstract supports a matrix-dependent association, not an intake recommendation or gamma-nonalactone-induced vitamin E depletion.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Rendered fat from marbled beef; bovine food matrix
    plain_language
    The lowest-alpha-tocopherol beef-fat group showed the greatest gamma-nonalactone rise during storage: 51.4 ppb, 11.7 times the prestorage level.
    primary_references
    Effect of α-tocopherol on lactone formation in marbled beef and changes in lactone volatility during storage. (2012). https://pubmed.ncbi.nlm.nih.gov/22583190/ DOI: 10.1111/j.1750-3841.2012.02694.x
    route
    Food-matrix storage; no human administration
    tissue
    Stored-fat headspace and lactone quantitation

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 147–156

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Rendered fat from marbled beef; bovine food matrix · source_derived_draft · unverified_draft

    ## gamma-nonalactone-vitamin-e-matrix The lowest-alpha-tocopherol beef-fat group showed the greatest gamma-nonalactone rise during storage: 51.4 ppb, 11.7 times the prestorage level. Model/species: Rendered fat from marbled beef; bovine food matrix Tissue: Stored-fat headspace and lactone quantitation Exposure: Groups differing in alpha-tocopherol content; lowest 2.9 ppm, highest 28.8 ppm Route: Food-matrix storage; no human administration Duration: 7 days at 2 C Limits: Food oxidation and partitioning are not human nutrient metabolism. The abstract supports a matrix-dependent association, not an intake recommendation or gamma-nonalactone-induced vitamin E depletion. Primary reference: Effect of α-tocopherol on lactone formation in marbled beef and changes in lactone volatility during storage. (2012). https://pubmed.ncbi.nlm.nih.gov/22583190/ DOI: 10.1111/j.1750-3841.2012.02694.x Access: Primary PubMed abstract; unresolved method details explicitly retained.
    Complete structured claim and evidence

  14. Labeled-precursor experiments demonstrated conversion of 4-oxononanoic acid into gamma-nonalactone during yeast fermentation.

    4-Oxononanoic acid → Gamma-nonalactone source_derived_draftungraded
    Experimental context and source evidence
    dose
    Labeled d6-4-oxononanoic acid; experimental spike concentration not given in abstract
    duration
    Fermentation interval not specified in accessed abstract
    evidence_access
    Primary PubMed abstract; unresolved method details explicitly retained.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Saccharomyces cerevisiae alcoholic fermentation and grape/wine analyses
    limitations
    Tracer evidence establishes precursor conversion in yeast; it does not establish a human pathway or identify individual reductase enzymes.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Saccharomyces cerevisiae alcoholic fermentation and grape/wine analyses
    plain_language
    Labeled-precursor experiments demonstrated conversion of 4-oxononanoic acid into gamma-nonalactone during yeast fermentation.
    primary_references
    Aromatic Potential of Bordeaux Grape Cultivars: Identification and Assays on 4-Oxononanoic Acid, a γ-Nonalactone Precursor. (2020). https://pubmed.ncbi.nlm.nih.gov/32955257/ DOI: 10.1021/acs.jafc.0c04171
    route
    Microbial precursor biotransformation
    tissue
    Fermenting must

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 158–167

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Saccharomyces cerevisiae alcoholic fermentation and grape/wine analyses · source_derived_draft · unverified_draft

    ## gamma-nonalactone-yeast-precursor Labeled-precursor experiments demonstrated conversion of 4-oxononanoic acid into gamma-nonalactone during yeast fermentation. Model/species: Saccharomyces cerevisiae alcoholic fermentation and grape/wine analyses Tissue: Fermenting must Exposure: Labeled d6-4-oxononanoic acid; experimental spike concentration not given in abstract Route: Microbial precursor biotransformation Duration: Fermentation interval not specified in accessed abstract Limits: Tracer evidence establishes precursor conversion in yeast; it does not establish a human pathway or identify individual reductase enzymes. Primary reference: Aromatic Potential of Bordeaux Grape Cultivars: Identification and Assays on 4-Oxononanoic Acid, a γ-Nonalactone Precursor. (2020). https://pubmed.ncbi.nlm.nih.gov/32955257/ DOI: 10.1021/acs.jafc.0c04171 Access: Primary PubMed abstract; unresolved method details explicitly retained.
    Complete structured claim and evidence

  15. The yeast biotransformation of 4-oxononanoic acid favored the R gamma-nonalactone enantiomer.

    4-Oxononanoic acid → (R)-Gamma-nonalactone source_derived_draftungraded
    Experimental context and source evidence
    dose
    Labeled d6-4-oxononanoic acid; experimental spike concentration not given in abstract
    duration
    Fermentation interval not specified in accessed abstract
    evidence_access
    Primary PubMed abstract; unresolved method details explicitly retained.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Saccharomyces cerevisiae alcoholic fermentation and grape/wine analyses
    limitations
    Tracer evidence establishes precursor conversion in yeast; it does not establish a human pathway or identify individual reductase enzymes.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Saccharomyces cerevisiae alcoholic fermentation and grape/wine analyses
    plain_language
    The yeast biotransformation of 4-oxononanoic acid favored the R gamma-nonalactone enantiomer.
    primary_references
    Aromatic Potential of Bordeaux Grape Cultivars: Identification and Assays on 4-Oxononanoic Acid, a γ-Nonalactone Precursor. (2020). https://pubmed.ncbi.nlm.nih.gov/32955257/ DOI: 10.1021/acs.jafc.0c04171
    route
    Microbial precursor biotransformation
    tissue
    Fermenting must

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 169–178

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Saccharomyces cerevisiae alcoholic fermentation and grape/wine analyses · source_derived_draft · unverified_draft

    ## gamma-nonalactone-yeast-r-selectivity The yeast biotransformation of 4-oxononanoic acid favored the R gamma-nonalactone enantiomer. Model/species: Saccharomyces cerevisiae alcoholic fermentation and grape/wine analyses Tissue: Fermenting must Exposure: Labeled d6-4-oxononanoic acid; experimental spike concentration not given in abstract Route: Microbial precursor biotransformation Duration: Fermentation interval not specified in accessed abstract Limits: Tracer evidence establishes precursor conversion in yeast; it does not establish a human pathway or identify individual reductase enzymes. Primary reference: Aromatic Potential of Bordeaux Grape Cultivars: Identification and Assays on 4-Oxononanoic Acid, a γ-Nonalactone Precursor. (2020). https://pubmed.ncbi.nlm.nih.gov/32955257/ DOI: 10.1021/acs.jafc.0c04171 Access: Primary PubMed abstract; unresolved method details explicitly retained.
    Complete structured claim and evidence

  16. The reported sensory detection threshold for R-gamma-nonalactone was 66 micrograms/L.

    (R)-Gamma-nonalactone → Human gamma-nonalactone aroma detection source_derived_draftungraded
    Experimental context and source evidence
    dose
    R and S gamma-nonalactone concentration series
    duration
    Threshold-testing interval not specified in abstract
    evidence_access
    Primary PubMed abstract; unresolved method details explicitly retained.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Human sensory detection tests reported with grape/wine enantiomer study
    limitations
    Enantiomer thresholds depend on matrix and protocol. No olfactory receptor identity or general threshold across foods is established.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Human sensory detection tests reported with grape/wine enantiomer study
    plain_language
    The reported sensory detection threshold for R-gamma-nonalactone was 66 micrograms/L.
    primary_references
    Aromatic Potential of Bordeaux Grape Cultivars: Identification and Assays on 4-Oxononanoic Acid, a γ-Nonalactone Precursor. (2020). https://pubmed.ncbi.nlm.nih.gov/32955257/ DOI: 10.1021/acs.jafc.0c04171
    route
    Sensory exposure; exact test matrix and panel size unresolved in accessed abstract
    tissue
    Olfactory perception

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    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human sensory detection tests reported with grape/wine enantiomer study · source_derived_draft · unverified_draft

    ## gamma-nonalactone-r-odor-threshold The reported sensory detection threshold for R-gamma-nonalactone was 66 micrograms/L. Model/species: Human sensory detection tests reported with grape/wine enantiomer study Tissue: Olfactory perception Exposure: R and S gamma-nonalactone concentration series Route: Sensory exposure; exact test matrix and panel size unresolved in accessed abstract Duration: Threshold-testing interval not specified in abstract Limits: Enantiomer thresholds depend on matrix and protocol. No olfactory receptor identity or general threshold across foods is established. Primary reference: Aromatic Potential of Bordeaux Grape Cultivars: Identification and Assays on 4-Oxononanoic Acid, a γ-Nonalactone Precursor. (2020). https://pubmed.ncbi.nlm.nih.gov/32955257/ DOI: 10.1021/acs.jafc.0c04171 Access: Primary PubMed abstract; unresolved method details explicitly retained.
    Complete structured claim and evidence

  17. The reported sensory detection threshold for S-gamma-nonalactone was 35 micrograms/L.

    (S)-Gamma-nonalactone → Human gamma-nonalactone aroma detection source_derived_draftungraded
    Experimental context and source evidence
    dose
    R and S gamma-nonalactone concentration series
    duration
    Threshold-testing interval not specified in abstract
    evidence_access
    Primary PubMed abstract; unresolved method details explicitly retained.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Human sensory detection tests reported with grape/wine enantiomer study
    limitations
    Enantiomer thresholds depend on matrix and protocol. No olfactory receptor identity or general threshold across foods is established.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Human sensory detection tests reported with grape/wine enantiomer study
    plain_language
    The reported sensory detection threshold for S-gamma-nonalactone was 35 micrograms/L.
    primary_references
    Aromatic Potential of Bordeaux Grape Cultivars: Identification and Assays on 4-Oxononanoic Acid, a γ-Nonalactone Precursor. (2020). https://pubmed.ncbi.nlm.nih.gov/32955257/ DOI: 10.1021/acs.jafc.0c04171
    route
    Sensory exposure; exact test matrix and panel size unresolved in accessed abstract
    tissue
    Olfactory perception

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 191–200

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human sensory detection tests reported with grape/wine enantiomer study · source_derived_draft · unverified_draft

    ## gamma-nonalactone-s-odor-threshold The reported sensory detection threshold for S-gamma-nonalactone was 35 micrograms/L. Model/species: Human sensory detection tests reported with grape/wine enantiomer study Tissue: Olfactory perception Exposure: R and S gamma-nonalactone concentration series Route: Sensory exposure; exact test matrix and panel size unresolved in accessed abstract Duration: Threshold-testing interval not specified in abstract Limits: Enantiomer thresholds depend on matrix and protocol. No olfactory receptor identity or general threshold across foods is established. Primary reference: Aromatic Potential of Bordeaux Grape Cultivars: Identification and Assays on 4-Oxononanoic Acid, a γ-Nonalactone Precursor. (2020). https://pubmed.ncbi.nlm.nih.gov/32955257/ DOI: 10.1021/acs.jafc.0c04171 Access: Primary PubMed abstract; unresolved method details explicitly retained.
    Complete structured claim and evidence

  18. Gamma-nonalactone at 51 micromolar increased locomotion during cocaine exposure from about 49% to 88% of control.

    Gamma-nonalactone → Locomotion of Dugesia tigrina planarians source_derived_draftungraded
    Experimental context and source evidence
    dose
    Gamma-nonalactone 25-51 micromolar with cocaine 200 micromolar; artificial pond water with 0.1% DMSO
    duration
    10 min incubation followed by 5 min locomotion recording
    evidence_access
    Primary full-text methods/results inspected; PubMed metadata where indexed.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Dugesia tigrina planarians
    limitations
    A narrow nonhuman behavioral response; molecular target and mammalian relevance are unknown. No addiction-treatment efficacy or use protocol is established.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Dugesia tigrina planarians
    plain_language
    Gamma-nonalactone at 51 micromolar increased locomotion during cocaine exposure from about 49% to 88% of control.
    primary_references
    Minimal structural requirements of alkyl γ-lactones capable of antagonizing the cocaine-induced motility decrease in planarians. (2011). https://pubmed.ncbi.nlm.nih.gov/21878350/ DOI: 10.1016/j.pbb.2011.08.013
    route
    Whole-worm bath co-exposure
    tissue
    Grid-crossing locomotion assay

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 202–211

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Dugesia tigrina planarians · source_derived_draft · unverified_draft

    ## gamma-nonalactone-cocaine-motility Gamma-nonalactone at 51 micromolar increased locomotion during cocaine exposure from about 49% to 88% of control. Model/species: Dugesia tigrina planarians Tissue: Grid-crossing locomotion assay Exposure: Gamma-nonalactone 25-51 micromolar with cocaine 200 micromolar; artificial pond water with 0.1% DMSO Route: Whole-worm bath co-exposure Duration: 10 min incubation followed by 5 min locomotion recording Limits: A narrow nonhuman behavioral response; molecular target and mammalian relevance are unknown. No addiction-treatment efficacy or use protocol is established. Primary reference: Minimal structural requirements of alkyl γ-lactones capable of antagonizing the cocaine-induced motility decrease in planarians. (2011). https://pubmed.ncbi.nlm.nih.gov/21878350/ DOI: 10.1016/j.pbb.2011.08.013 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.
    Complete structured claim and evidence

  19. Gamma-nonalactone at 75-100 micromolar did not prevent the cocaine-associated locomotion decrease.

    Gamma-nonalactone → Locomotion of Dugesia tigrina planarians source_derived_draftungraded
    Experimental context and source evidence
    dose
    Gamma-nonalactone 75-100 micromolar with cocaine 200 micromolar
    duration
    10 min incubation followed by 5 min recording
    evidence_access
    Primary full-text methods/results inspected; PubMed metadata where indexed.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Dugesia tigrina planarians
    limitations
    Loss of protection at higher concentrations is not a scientific conflict with the lower-dose response; it occurs in the same study.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Dugesia tigrina planarians
    plain_language
    Gamma-nonalactone at 75-100 micromolar did not prevent the cocaine-associated locomotion decrease.
    primary_references
    Minimal structural requirements of alkyl γ-lactones capable of antagonizing the cocaine-induced motility decrease in planarians. (2011). https://pubmed.ncbi.nlm.nih.gov/21878350/ DOI: 10.1016/j.pbb.2011.08.013
    route
    Whole-worm bath co-exposure
    tissue
    Grid-crossing locomotion assay

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 213–222

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Dugesia tigrina planarians · source_derived_draft · unverified_draft

    ## gamma-nonalactone-cocaine-range-limit Gamma-nonalactone at 75-100 micromolar did not prevent the cocaine-associated locomotion decrease. Model/species: Dugesia tigrina planarians Tissue: Grid-crossing locomotion assay Exposure: Gamma-nonalactone 75-100 micromolar with cocaine 200 micromolar Route: Whole-worm bath co-exposure Duration: 10 min incubation followed by 5 min recording Limits: Loss of protection at higher concentrations is not a scientific conflict with the lower-dose response; it occurs in the same study. Primary reference: Minimal structural requirements of alkyl γ-lactones capable of antagonizing the cocaine-induced motility decrease in planarians. (2011). https://pubmed.ncbi.nlm.nih.gov/21878350/ DOI: 10.1016/j.pbb.2011.08.013 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.
    Complete structured claim and evidence

  20. Gamma-nonalactone alone reduced planarian locomotion at higher concentrations, with an IC50 of 181 +/- 18 micromolar.

    Gamma-nonalactone → Locomotion of Dugesia tigrina planarians source_derived_draftungraded
    Experimental context and source evidence
    dose
    Gamma-nonalactone concentration series without cocaine
    duration
    10 min incubation followed by 5 min recording
    evidence_access
    Primary full-text methods/results inspected; PubMed metadata where indexed.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Dugesia tigrina planarians
    limitations
    Behavioral impairment is not direct evidence for DAT, GABA receptors, or a human toxic dose. Compound alone at 51 micromolar did not significantly change locomotion.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Dugesia tigrina planarians
    plain_language
    Gamma-nonalactone alone reduced planarian locomotion at higher concentrations, with an IC50 of 181 +/- 18 micromolar.
    primary_references
    Minimal structural requirements of alkyl γ-lactones capable of antagonizing the cocaine-induced motility decrease in planarians. (2011). https://pubmed.ncbi.nlm.nih.gov/21878350/ DOI: 10.1016/j.pbb.2011.08.013
    route
    Whole-worm bath exposure
    tissue
    Grid-crossing locomotion assay

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 224–233

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Dugesia tigrina planarians · source_derived_draft · unverified_draft

    ## gamma-nonalactone-motility-alone Gamma-nonalactone alone reduced planarian locomotion at higher concentrations, with an IC50 of 181 +/- 18 micromolar. Model/species: Dugesia tigrina planarians Tissue: Grid-crossing locomotion assay Exposure: Gamma-nonalactone concentration series without cocaine Route: Whole-worm bath exposure Duration: 10 min incubation followed by 5 min recording Limits: Behavioral impairment is not direct evidence for DAT, GABA receptors, or a human toxic dose. Compound alone at 51 micromolar did not significantly change locomotion. Primary reference: Minimal structural requirements of alkyl γ-lactones capable of antagonizing the cocaine-induced motility decrease in planarians. (2011). https://pubmed.ncbi.nlm.nih.gov/21878350/ DOI: 10.1016/j.pbb.2011.08.013 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.
    Complete structured claim and evidence

  21. Adding gamma-nonalactone increased rated sweetness of 5% sucrose solution by a reported 23.0% at the optimal tested concentration.

    Gamma-nonalactone → Human perceived sweetness of sucrose solution source_derived_draftungraded
    Experimental context and source evidence
    dose
    Gamma-nonalactone concentration series; optimal sweetness reported at 10 mg/kg solution; propylene glycol used at 0.1-0.2% for poorly soluble compounds
    duration
    Acute sensory sessions; at least 2 min between samples
    evidence_access
    Primary full-text methods/results inspected; PubMed metadata where indexed.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Ten trained human sensory evaluators; five men and five women, mean age 24 years
    limitations
    Small trained panel and matrix-specific perception, not a glycemic or dietary-intake trial. Docking and molecular dynamics do not prove T1R2/T1R3 activation or binding.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Ten trained human sensory evaluators; five men and five women, mean age 24 years
    plain_language
    Adding gamma-nonalactone increased rated sweetness of 5% sucrose solution by a reported 23.0% at the optimal tested concentration.
    primary_references
    Sweetness enhancement and mechanism by sweet aroma compounds in the sucrose solution using sensory, electronic tongue, molecular docking, and molecular dynamics simulation. (2026). https://pubmed.ncbi.nlm.nih.gov/41884462/ DOI: 10.1016/j.fochx.2026.103753
    route
    Oral tasting followed by expectoration
    tissue
    Sweetness ratings in 5% sucrose solution

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 235–244

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    ## gamma-nonalactone-sucrose-sweetness Adding gamma-nonalactone increased rated sweetness of 5% sucrose solution by a reported 23.0% at the optimal tested concentration. Model/species: Ten trained human sensory evaluators; five men and five women, mean age 24 years Tissue: Sweetness ratings in 5% sucrose solution Exposure: Gamma-nonalactone concentration series; optimal sweetness reported at 10 mg/kg solution; propylene glycol used at 0.1-0.2% for poorly soluble compounds Route: Oral tasting followed by expectoration Duration: Acute sensory sessions; at least 2 min between samples Limits: Small trained panel and matrix-specific perception, not a glycemic or dietary-intake trial. Docking and molecular dynamics do not prove T1R2/T1R3 activation or binding. Primary reference: Sweetness enhancement and mechanism by sweet aroma compounds in the sucrose solution using sensory, electronic tongue, molecular docking, and molecular dynamics simulation. (2026). https://pubmed.ncbi.nlm.nih.gov/41884462/ DOI: 10.1016/j.fochx.2026.103753 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.
    Complete structured claim and evidence

  22. The gamma-nonalactone aroma detection threshold in 5% sucrose was reported as 0.0047 mg/kg solution.

    Gamma-nonalactone → Human gamma-nonalactone aroma detection source_derived_draftungraded
    Experimental context and source evidence
    dose
    Gamma-nonalactone serial dilution; reported threshold 0.0047 mg/kg
    duration
    Repeated threshold trials
    evidence_access
    Primary full-text methods/results inspected; PubMed metadata where indexed.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Ten trained human sensory evaluators
    limitations
    The water comparison was a literature reference, not a matched experiment. Do not equate detection threshold with the much larger sweetness-optimization concentration.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Ten trained human sensory evaluators
    plain_language
    The gamma-nonalactone aroma detection threshold in 5% sucrose was reported as 0.0047 mg/kg solution.
    primary_references
    Sweetness enhancement and mechanism by sweet aroma compounds in the sucrose solution using sensory, electronic tongue, molecular docking, and molecular dynamics simulation. (2026). https://pubmed.ncbi.nlm.nih.gov/41884462/ DOI: 10.1016/j.fochx.2026.103753
    route
    Sensory testing in sucrose solution
    tissue
    Three-alternative forced-choice aroma detection in 5% sucrose

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 246–255

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Ten trained human sensory evaluators · source_derived_draft · unverified_draft

    ## gamma-nonalactone-sucrose-aroma-threshold The gamma-nonalactone aroma detection threshold in 5% sucrose was reported as 0.0047 mg/kg solution. Model/species: Ten trained human sensory evaluators Tissue: Three-alternative forced-choice aroma detection in 5% sucrose Exposure: Gamma-nonalactone serial dilution; reported threshold 0.0047 mg/kg Route: Sensory testing in sucrose solution Duration: Repeated threshold trials Limits: The water comparison was a literature reference, not a matched experiment. Do not equate detection threshold with the much larger sweetness-optimization concentration. Primary reference: Sweetness enhancement and mechanism by sweet aroma compounds in the sucrose solution using sensory, electronic tongue, molecular docking, and molecular dynamics simulation. (2026). https://pubmed.ncbi.nlm.nih.gov/41884462/ DOI: 10.1016/j.fochx.2026.103753 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.
    Complete structured claim and evidence

  23. The human lactulose time course showed no apparent increasing trend in gamma-nonalactone skin emission.

    Lactulose → Gamma-nonalactone emission from human forearm skin source_derived_draftungraded
    Experimental context and source evidence
    dose
    Lactulose 4 g/day; no administered gamma-nonalactone
    duration
    2 weeks; baseline days 1-2 and follow-up days 6, 10 and 17
    evidence_access
    Primary full-text methods/results inspected; PubMed metadata where indexed.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Exploratory healthy-human lactulose study; six participants in time-course cohort, ten in expanded correlation analysis
    limitations
    Small uncontrolled study; no apparent C9 trend is not proof of universal absence of effect. Significant C10/C11 increases must not be transferred to C9 gamma-nonalactone; SCFA mediation remains proposed.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Exploratory healthy-human lactulose study; six participants in time-course cohort, ten in expanded correlation analysis
    plain_language
    The human lactulose time course showed no apparent increasing trend in gamma-nonalactone skin emission.
    primary_references
    Influence of Ingestion of Lactulose on gamma-Lactones Emanating from Human Skin Surface (2023). https://www.mdpi.com/2076-3417/13/6/3930 DOI: 10.3390/app13063930
    route
    Oral lactulose; passive skin-gas sampling
    tissue
    Forearm volatile emission measured by passive sampling and GC-MS

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 257–266

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Exploratory healthy-human lactulose study; six participants in time-course cohort, ten in expanded correlation analysis · source_derived_draft · unverified_draft

    ## gamma-nonalactone-lactulose-skin-null The human lactulose time course showed no apparent increasing trend in gamma-nonalactone skin emission. Model/species: Exploratory healthy-human lactulose study; six participants in time-course cohort, ten in expanded correlation analysis Tissue: Forearm volatile emission measured by passive sampling and GC-MS Exposure: Lactulose 4 g/day; no administered gamma-nonalactone Route: Oral lactulose; passive skin-gas sampling Duration: 2 weeks; baseline days 1-2 and follow-up days 6, 10 and 17 Limits: Small uncontrolled study; no apparent C9 trend is not proof of universal absence of effect. Significant C10/C11 increases must not be transferred to C9 gamma-nonalactone; SCFA mediation remains proposed. Primary reference: Influence of Ingestion of Lactulose on gamma-Lactones Emanating from Human Skin Surface (2023). https://www.mdpi.com/2076-3417/13/6/3930 DOI: 10.3390/app13063930 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.
    Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

Calcium chelation suppresses the lactone-evoked TRPA1 calcium readout

Condition: machinery_impairment · Experimental EGTA 5 mM during gamma-nonalactone 2 mM exposure.

Normal role: Gamma-nonalactone produces a channel-associated calcium-flux response.

Recorded consequence: The TRPA1 calcium signal is suppressed.

Scope: Acute in vitro extracellular-calcium chelation.

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

  • Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20)Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

    Open questions in this collection

    Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

      Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

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      Evidence, AI assistance and curation standards