Nutrient chapter

L-Ergothioneine

Ergothioneine is a food-derived, sulfur-containing histidine derivative whose cellular availability depends on transport. This collection connects SLC22A4 and SLC22A15 uptake to sodium, carnosine, carnitine and thiamine; redox chemistry to vitamin C, glutathione and copper; and microbial synthesis to histidine, SAM, cysteine, iron and PLP. It also records vascular, immune, mitochondrial, microbial and brain mechanisms. Human uptake, dialysis depletion, preliminary clinical findings and animal experiments retain separate evidence labels. Shared pathways support discovery questions without proving supplement synergy or a human deficiency threshold.

102 recorded mechanisms · 15 availability situations · 10 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.

Expression of human SLC22A4 in HEK293 cells produced efficient, sodium-dependent ergothioneine uptake and intracellular retention.
Human ergothioneine transporter OCTN1 / SLC22A4 → L-Ergothioneine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human transporter expressed in HEK293 cells.
limitations
Expression experiments do not quantify uptake in every human tissue.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
A specific carrier lets cells build an ergothioneine pool.
primary_references
Discovery of the ergothioneine transporter. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15795384/ · DOI 10.1073/pnas.0408624102
transport_effect
raises Sodium-dependent ergothioneine uptake with intracellular retention.
transport_pool
the expressing cell Sodium-dependent ergothioneine uptake with intracellular retention.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 16–22
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human transporter expressed in HEK293 cells. · source_derived_draft · unverified_draft
## ergothioneine-slc22a4-uptake A specific carrier lets cells build an ergothioneine pool. Expression of human SLC22A4 in HEK293 cells produced efficient, sodium-dependent ergothioneine uptake and intracellular retention. Model: Human transporter expressed in HEK293 cells. Limitations: Expression experiments do not quantify uptake in every human tissue. Evidence access: Primary abstract Discovery of the ergothioneine transporter. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15795384/ · DOI 10.1073/pnas.0408624102
Complete structured claim and evidence
Rat Slc22a4-mediated ergothioneine uptake was saturable, pH-sensitive and sodium-dependent, with approximately 1:1 sodium:substrate stoichiometry.
Rat ergothioneine transporter Octn1 / Slc22a4 → L-Ergothioneine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat transporter in HEK293 cells; uptake also examined in rat PC12 cells.
limitations
Rat measurements; no demonstrated benefit from increasing dietary salt.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
The carrier couples entry to sodium.
primary_references
Functional characterization of ergothioneine transport by rat organic cation/carnitine transporter Octn1 (slc22a4). · 2008 · https://pubmed.ncbi.nlm.nih.gov/18670092/ · DOI 10.1248/bpb.31.1580
transport_effect
raises Saturable, pH-sensitive, sodium-dependent ergothioneine uptake.
transport_pool
the expressing cell Saturable, pH-sensitive, sodium-dependent ergothioneine uptake.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 24–30
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat transporter in HEK293 cells; uptake also examined in rat PC12 cells. · source_derived_draft · unverified_draft
## ergothioneine-sodium-coupling-rat The carrier couples entry to sodium. Rat Slc22a4-mediated ergothioneine uptake was saturable, pH-sensitive and sodium-dependent, with approximately 1:1 sodium:substrate stoichiometry. Model: Rat transporter in HEK293 cells; uptake also examined in rat PC12 cells. Limitations: Rat measurements; no demonstrated benefit from increasing dietary salt. Evidence access: Primary abstract Functional characterization of ergothioneine transport by rat organic cation/carnitine transporter Octn1 (slc22a4). · 2008 · https://pubmed.ncbi.nlm.nih.gov/18670092/ · DOI 10.1248/bpb.31.1580
Complete structured claim and evidence
Wild-type human SLC22A4 did not mediate carnitine transport in the comparative HEK293 expression assay.
Human ergothioneine transporter OCTN1 / SLC22A4 → L-Carnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Wild-type human SLC22A4/SLC22A5 transport comparison.
limitations
Assay-specific discrimination; engineered mutants have different properties.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
The historical carrier name does not mean carnitine uses this route.
primary_references
Substrate discrimination by ergothioneine transporter SLC22A4 and carnitine transporter SLC22A5: gain-of-function by interchange of selected amino acids. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19814996/ · DOI 10.1016/j.bbamem.2009.09.019
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 32–38
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Wild-type human SLC22A4/SLC22A5 transport comparison. · source_derived_draft · unverified_draft
## ergothioneine-slc22a4-not-carnitine The historical carrier name does not mean carnitine uses this route. Wild-type human SLC22A4 did not mediate carnitine transport in the comparative HEK293 expression assay. Model: Wild-type human SLC22A4/SLC22A5 transport comparison. Limitations: Assay-specific discrimination; engineered mutants have different properties. Evidence access: Primary abstract Substrate discrimination by ergothioneine transporter SLC22A4 and carnitine transporter SLC22A5: gain-of-function by interchange of selected amino acids. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19814996/ · DOI 10.1016/j.bbamem.2009.09.019
Complete structured claim and evidence
Wild-type human SLC22A5 did not transport ergothioneine in the comparative expression assay.
Human carnitine transporter OCTN2 / SLC22A5 → L-Ergothioneine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human wild-type transporters expressed in HEK293 cells.
limitations
Related sequence does not establish substrate interchangeability.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
The main carnitine carrier cannot be assumed to carry ergothioneine.
primary_references
Substrate discrimination by ergothioneine transporter SLC22A4 and carnitine transporter SLC22A5: gain-of-function by interchange of selected amino acids. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19814996/ · DOI 10.1016/j.bbamem.2009.09.019
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 40–46
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human wild-type transporters expressed in HEK293 cells. · source_derived_draft · unverified_draft
## ergothioneine-slc22a5-not-ergo The main carnitine carrier cannot be assumed to carry ergothioneine. Wild-type human SLC22A5 did not transport ergothioneine in the comparative expression assay. Model: Human wild-type transporters expressed in HEK293 cells. Limitations: Related sequence does not establish substrate interchangeability. Evidence access: Primary abstract Substrate discrimination by ergothioneine transporter SLC22A4 and carnitine transporter SLC22A5: gain-of-function by interchange of selected amino acids. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19814996/ · DOI 10.1016/j.bbamem.2009.09.019
Complete structured claim and evidence
Human SLC22A15 expression enabled uptake of ergothioneine in HEK293 substrate assays.
Human solute carrier SLC22A15 → L-Ergothioneine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Metabolomic screening and uptake assays in transfected human cells.
limitations
Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
An additional carrier connects ergothioneine to the transport network.
primary_references
Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R
transport_effect
raises Expression enabled uptake in HEK293 substrate assays.
transport_pool
the expressing cell Expression enabled uptake in HEK293 substrate assays.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 48–54
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Metabolomic screening and uptake assays in transfected human cells. · source_derived_draft · unverified_draft
## ergothioneine-slc22a15-ergo An additional carrier connects ergothioneine to the transport network. Human SLC22A15 expression enabled uptake of ergothioneine in HEK293 substrate assays. Model: Metabolomic screening and uptake assays in transfected human cells. Limitations: Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures. Evidence access: Primary abstract Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R
Complete structured claim and evidence
Human SLC22A15 expression enabled uptake of carnosine in HEK293 substrate assays.
Human solute carrier SLC22A15 → L-Carnosine / beta-alanyl-L-histidine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Metabolomic screening and uptake assays in transfected human cells.
limitations
Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
An additional carrier connects carnosine to the transport network.
primary_references
Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R
transport_effect
raises Expression enabled uptake in HEK293 substrate assays.
transport_pool
the expressing cell Expression enabled uptake in HEK293 substrate assays.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 56–62
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Metabolomic screening and uptake assays in transfected human cells. · source_derived_draft · unverified_draft
## ergothioneine-slc22a15-carnosine An additional carrier connects carnosine to the transport network. Human SLC22A15 expression enabled uptake of carnosine in HEK293 substrate assays. Model: Metabolomic screening and uptake assays in transfected human cells. Limitations: Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures. Evidence access: Primary abstract Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R
Complete structured claim and evidence
Human SLC22A15 expression enabled uptake of carnitine in HEK293 substrate assays.
Human solute carrier SLC22A15 → L-Carnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Metabolomic screening and uptake assays in transfected human cells.
limitations
Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
An additional carrier connects carnitine to the transport network.
primary_references
Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R
transport_effect
raises Expression enabled uptake in HEK293 substrate assays.
transport_pool
the expressing cell Expression enabled uptake in HEK293 substrate assays.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 64–70
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Metabolomic screening and uptake assays in transfected human cells. · source_derived_draft · unverified_draft
## ergothioneine-slc22a15-carnitine An additional carrier connects carnitine to the transport network. Human SLC22A15 expression enabled uptake of carnitine in HEK293 substrate assays. Model: Metabolomic screening and uptake assays in transfected human cells. Limitations: Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures. Evidence access: Primary abstract Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R
Complete structured claim and evidence
Human SLC22A15 expression enabled uptake of thiamine in HEK293 substrate assays.
Human solute carrier SLC22A15 → Thiamine (vitamin B1) source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Metabolomic screening and uptake assays in transfected human cells.
limitations
Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
An additional carrier connects thiamine to the transport network.
primary_references
Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R
transport_effect
raises Expression enabled uptake in HEK293 substrate assays.
transport_pool
the expressing cell Expression enabled uptake in HEK293 substrate assays.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 72–78
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Metabolomic screening and uptake assays in transfected human cells. · source_derived_draft · unverified_draft
## ergothioneine-slc22a15-thiamine An additional carrier connects thiamine to the transport network. Human SLC22A15 expression enabled uptake of thiamine in HEK293 substrate assays. Model: Metabolomic screening and uptake assays in transfected human cells. Limitations: Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures. Evidence access: Primary abstract Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R
Complete structured claim and evidence
RNA-interference depletion of SLC22A4 made human cultured cells more susceptible to oxidant-associated mitochondrial DNA damage.
Human ergothioneine transporter OCTN1 / SLC22A4 → Human cultured-cell mitochondrial DNA damage source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human cell RNA-interference and oxidant challenges.
limitations
Does not establish the identity of a mitochondrial membrane transporter.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Removing the entry route weakens cellular protection.
primary_references
The unusual amino acid L-ergothioneine is a physiologic cytoprotectant. · 2010 · https://pubmed.ncbi.nlm.nih.gov/19911007/ · DOI 10.1038/cdd.2009.163
trigger_kind
machinery_impairment Imported condition classification; unverified.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 80–86
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell RNA-interference and oxidant challenges. · source_derived_draft · unverified_draft
## ergothioneine-hela-transporter-loss Removing the entry route weakens cellular protection. RNA-interference depletion of SLC22A4 made human cultured cells more susceptible to oxidant-associated mitochondrial DNA damage. Model: Human cell RNA-interference and oxidant challenges. Limitations: Does not establish the identity of a mitochondrial membrane transporter. Evidence access: Primary abstract The unusual amino acid L-ergothioneine is a physiologic cytoprotectant. · 2010 · https://pubmed.ncbi.nlm.nih.gov/19911007/ · DOI 10.1038/cdd.2009.163
Complete structured claim and evidence
SLC22A4-depleted human cells showed increased protein oxidation and lipid peroxidation under oxidative stress.
Human ergothioneine transporter OCTN1 / SLC22A4 → Human cultured-cell lipid peroxidation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human cultured cells with transporter knockdown.
limitations
Not a human dietary deficiency syndrome; linked outcomes share one study.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
The consequences extend beyond DNA.
primary_references
The unusual amino acid L-ergothioneine is a physiologic cytoprotectant. · 2010 · https://pubmed.ncbi.nlm.nih.gov/19911007/ · DOI 10.1038/cdd.2009.163
trigger_kind
machinery_impairment Imported condition classification; unverified.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 88–94
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cultured cells with transporter knockdown. · source_derived_draft · unverified_draft
## ergothioneine-hela-lipid-loss The consequences extend beyond DNA. SLC22A4-depleted human cells showed increased protein oxidation and lipid peroxidation under oxidative stress. Model: Human cultured cells with transporter knockdown. Limitations: Not a human dietary deficiency syndrome; linked outcomes share one study. Evidence access: Primary abstract The unusual amino acid L-ergothioneine is a physiologic cytoprotectant. · 2010 · https://pubmed.ncbi.nlm.nih.gov/19911007/ · DOI 10.1038/cdd.2009.163
Complete structured claim and evidence
Zebrafish ETT knockout lowered ergothioneine content by more than 1000-fold.
Zebrafish ergothioneine transporter ETT → Zebrafish whole-body ergothioneine content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Retroviral insertion into transporter exon 1.
limitations
No obvious gross morphology or behavior difference was reported; do not transfer sole-transporter status to humans.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
In this animal model, the transporter controls nearly the entire pool.
primary_references
Knockout of the ergothioneine transporter ETT in zebrafish results in increased 8-oxoguanine levels. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25746775/ · DOI 10.1016/j.freeradbiomed.2015.02.026
trigger_kind
machinery_impairment Imported condition classification; unverified.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 96–102
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Retroviral insertion into transporter exon 1. · source_derived_draft · unverified_draft
## ergothioneine-zebrafish-loss In this animal model, the transporter controls nearly the entire pool. Zebrafish ETT knockout lowered ergothioneine content by more than 1000-fold. Model: Retroviral insertion into transporter exon 1. Limitations: No obvious gross morphology or behavior difference was reported; do not transfer sole-transporter status to humans. Evidence access: Primary abstract Knockout of the ergothioneine transporter ETT in zebrafish results in increased 8-oxoguanine levels. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25746775/ · DOI 10.1016/j.freeradbiomed.2015.02.026
Complete structured claim and evidence
ETT-knockout zebrafish had 3.8-fold higher skin 8-oxoguanine; lipid-oxidation differences appeared after lead or copper stress.
Zebrafish ergothioneine transporter ETT → Zebrafish skin 8-oxoguanine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Whole-fish and skin analyses; basal versus metal-stressed conditions.
limitations
A stress-dependent phenotype does not identify one exclusive antioxidant reaction.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Loss of protection can become clearer under stress.
primary_references
Knockout of the ergothioneine transporter ETT in zebrafish results in increased 8-oxoguanine levels. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25746775/ · DOI 10.1016/j.freeradbiomed.2015.02.026
trigger_kind
machinery_impairment Imported condition classification; unverified.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 104–110
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Whole-fish and skin analyses; basal versus metal-stressed conditions. · source_derived_draft · unverified_draft
## ergothioneine-zebrafish-oxidation Loss of protection can become clearer under stress. ETT-knockout zebrafish had 3.8-fold higher skin 8-oxoguanine; lipid-oxidation differences appeared after lead or copper stress. Model: Whole-fish and skin analyses; basal versus metal-stressed conditions. Limitations: A stress-dependent phenotype does not identify one exclusive antioxidant reaction. Evidence access: Primary abstract Knockout of the ergothioneine transporter ETT in zebrafish results in increased 8-oxoguanine levels. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25746775/ · DOI 10.1016/j.freeradbiomed.2015.02.026
Complete structured claim and evidence
In pulse-radiolysis assays, ascorbate rapidly reduced the one-electron-oxidized ergothioneine transient back toward ergothioneine, forming ascorbyl radicals.
L-Ascorbate → Ergothioneine one-electron oxidation transient source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cell-free reaction; reported rate constant 6.3 x 10^8 M^-1 s^-1.
limitations
Chemical kinetics do not establish tissue flux or a required supplement combination.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Vitamin C can repair an oxidized ergothioneine intermediate.
primary_references
One-electron oxidation of ergothioneine and analogues investigated by pulse radiolysis: redox reaction involving ergothioneine and vitamin C. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8615839/ · DOI 10.1042/bj3150625
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 112–118
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free reaction; reported rate constant 6.3 x 10^8 M^-1 s^-1. · source_derived_draft · unverified_draft
## ergothioneine-ascorbate-repair Vitamin C can repair an oxidized ergothioneine intermediate. In pulse-radiolysis assays, ascorbate rapidly reduced the one-electron-oxidized ergothioneine transient back toward ergothioneine, forming ascorbyl radicals. Model: Cell-free reaction; reported rate constant 6.3 x 10^8 M^-1 s^-1. Limitations: Chemical kinetics do not establish tissue flux or a required supplement combination. Evidence access: Primary abstract One-electron oxidation of ergothioneine and analogues investigated by pulse radiolysis: redox reaction involving ergothioneine and vitamin C. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8615839/ · DOI 10.1042/bj3150625
Complete structured claim and evidence
Ergothioneine bound copper(I), rather than copper(II), and formed a redox-inactive complex in the tested chemical systems.
L-Ergothioneine → Copper(I) ion source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Spectroscopy and competition against histidine/phenanthroline.
limitations
This is not demonstrated copper depletion in humans.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Copper oxidation state matters for binding.
primary_references
Ergothioneine prevents copper-induced oxidative damage to DNA and protein by forming a redox-inactive ergothioneine-copper complex. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21047085/ · DOI 10.1021/tx100214t
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 120–126
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Spectroscopy and competition against histidine/phenanthroline. · source_derived_draft · unverified_draft
## ergothioneine-copper-binding Copper oxidation state matters for binding. Ergothioneine bound copper(I), rather than copper(II), and formed a redox-inactive complex in the tested chemical systems. Model: Spectroscopy and competition against histidine/phenanthroline. Limitations: This is not demonstrated copper depletion in humans. Evidence access: Primary abstract Ergothioneine prevents copper-induced oxidative damage to DNA and protein by forming a redox-inactive ergothioneine-copper complex. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21047085/ · DOI 10.1021/tx100214t
Complete structured claim and evidence
Ergothioneine at 0.1-1 mM protected DNA and albumin against 0.1 mM copper with ascorbate or peroxide.
Ergothioneine-copper(I) complex → Copper-driven DNA and protein oxidation in chemical assays source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cell-free copper/ascorbate and copper/peroxide systems.
limitations
Exposure and free-metal speciation limit extrapolation.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Binding the catalyst can protect several targets.
primary_references
Ergothioneine prevents copper-induced oxidative damage to DNA and protein by forming a redox-inactive ergothioneine-copper complex. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21047085/ · DOI 10.1021/tx100214t
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 128–134
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free copper/ascorbate and copper/peroxide systems. · source_derived_draft · unverified_draft
## ergothioneine-copper-oxidation Binding the catalyst can protect several targets. Ergothioneine at 0.1-1 mM protected DNA and albumin against 0.1 mM copper with ascorbate or peroxide. Model: Cell-free copper/ascorbate and copper/peroxide systems. Limitations: Exposure and free-metal speciation limit extrapolation. Evidence access: Primary abstract Ergothioneine prevents copper-induced oxidative damage to DNA and protein by forming a redox-inactive ergothioneine-copper complex. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21047085/ · DOI 10.1021/tx100214t
Complete structured claim and evidence
At pH 7.4, ergothioneine and hercynine generated different products after chemically generated singlet oxygen exposure.
L-Ergothioneine → Singlet molecular oxygen source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
LC-MS analysis with a thermal singlet-oxygen donor.
limitations
Product-based reaction model; not proof that this is its exclusive physiological function.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
The sulfur atom changes the reaction route.
primary_references
Ergothioneine stands out from hercynine in the reaction with singlet oxygen: Resistance to glutathione and TRIS in the generation of specific products indicates high reactivity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29074402/ · DOI 10.1016/j.freeradbiomed.2017.10.372
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · LC-MS analysis with a thermal singlet-oxygen donor. · source_derived_draft · unverified_draft
## ergothioneine-singlet-oxygen The sulfur atom changes the reaction route. At pH 7.4, ergothioneine and hercynine generated different products after chemically generated singlet oxygen exposure. Model: LC-MS analysis with a thermal singlet-oxygen donor. Limitations: Product-based reaction model; not proof that this is its exclusive physiological function. Evidence access: Primary abstract Ergothioneine stands out from hercynine in the reaction with singlet oxygen: Resistance to glutathione and TRIS in the generation of specific products indicates high reactivity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29074402/ · DOI 10.1016/j.freeradbiomed.2017.10.372
Complete structured claim and evidence
In the singlet-oxygen assay, 5 mM glutathione almost abolished net ergothioneine loss even though formation of selected products persisted.
GSH → L-Ergothioneine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cell-free singlet-oxygen chemistry.
limitations
Regeneration was proposed; its complete cellular enzymatic cycle was not established.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Glutathione changes the fate of oxidized ergothioneine.
primary_references
Ergothioneine stands out from hercynine in the reaction with singlet oxygen: Resistance to glutathione and TRIS in the generation of specific products indicates high reactivity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29074402/ · DOI 10.1016/j.freeradbiomed.2017.10.372
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free singlet-oxygen chemistry. · source_derived_draft · unverified_draft
## ergothioneine-glutathione-preservation Glutathione changes the fate of oxidized ergothioneine. In the singlet-oxygen assay, 5 mM glutathione almost abolished net ergothioneine loss even though formation of selected products persisted. Model: Cell-free singlet-oxygen chemistry. Limitations: Regeneration was proposed; its complete cellular enzymatic cycle was not established. Evidence access: Primary abstract Ergothioneine stands out from hercynine in the reaction with singlet oxygen: Resistance to glutathione and TRIS in the generation of specific products indicates high reactivity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29074402/ · DOI 10.1016/j.freeradbiomed.2017.10.372
Complete structured claim and evidence
Ergothioneine protected against peroxynitrite-induced tyrosine nitration in vitro.
L-Ergothioneine → Tyrosine nitration in peroxynitrite assays source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Chemical antioxidant assays.
limitations
Not evidence of removal of all reactive nitrogen species in vivo.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Protection includes a nitrogen-derived oxidant.
primary_references
Antioxidant action of ergothioneine: assessment of its ability to scavenge peroxynitrite. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9070285/ · DOI 10.1006/bbrc.1997.6109
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Chemical antioxidant assays. · source_derived_draft · unverified_draft
## ergothioneine-peroxynitrite-nitration Protection includes a nitrogen-derived oxidant. Ergothioneine protected against peroxynitrite-induced tyrosine nitration in vitro. Model: Chemical antioxidant assays. Limitations: Not evidence of removal of all reactive nitrogen species in vivo. Evidence access: Primary abstract Antioxidant action of ergothioneine: assessment of its ability to scavenge peroxynitrite. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9070285/ · DOI 10.1006/bbrc.1997.6109
Complete structured claim and evidence
Ergothioneine limited peroxynitrite-mediated inactivation of alpha-1-antiproteinase in vitro.
L-Ergothioneine → Alpha-1-antiproteinase preparation in peroxynitrite assays source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Biochemical protein-activity assay.
limitations
Preparation-specific result; no clinical lung-disease benefit established.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Oxidant defense can preserve a protein function.
primary_references
Antioxidant action of ergothioneine: assessment of its ability to scavenge peroxynitrite. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9070285/ · DOI 10.1006/bbrc.1997.6109
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Biochemical protein-activity assay. · source_derived_draft · unverified_draft
## ergothioneine-antiproteinase-protection Oxidant defense can preserve a protein function. Ergothioneine limited peroxynitrite-mediated inactivation of alpha-1-antiproteinase in vitro. Model: Biochemical protein-activity assay. Limitations: Preparation-specific result; no clinical lung-disease benefit established. Evidence access: Primary abstract Antioxidant action of ergothioneine: assessment of its ability to scavenge peroxynitrite. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9070285/ · DOI 10.1006/bbrc.1997.6109
Complete structured claim and evidence
Reconstituted Mycobacterium smegmatis biosynthesis used a methyltransferase to add three methyl groups to the histidine alpha-amino group, producing hercynine.
Mycobacterium smegmatis EgtD → L-Histidine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant bacterial enzyme pathway.
limitations
Humans have no established equivalent ergothioneine biosynthetic pathway.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Microbes first modify histidine before adding sulfur.
primary_references
In vitro reconstitution of Mycobacterial ergothioneine biosynthesis. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20420449/ · DOI 10.1021/ja101721e
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant bacterial enzyme pathway. · source_derived_draft · unverified_draft
## ergothioneine-histidine-methylation Microbes first modify histidine before adding sulfur. Reconstituted Mycobacterium smegmatis biosynthesis used a methyltransferase to add three methyl groups to the histidine alpha-amino group, producing hercynine. Model: Recombinant bacterial enzyme pathway. Limitations: Humans have no established equivalent ergothioneine biosynthetic pathway. Evidence access: Primary abstract In vitro reconstitution of Mycobacterial ergothioneine biosynthesis. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20420449/ · DOI 10.1021/ja101721e
Complete structured claim and evidence
Reconstituted Mycobacterium smegmatis biosynthesis required an iron(II)-dependent oxidative sulfurization step.
Mycobacterium smegmatis EgtB → Hercynine / N-alpha-trimethylhistidine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified bacterial pathway.
limitations
Does not mean iron supplements increase human synthesis.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Iron supports a microbial synthesis enzyme.
primary_references
In vitro reconstitution of Mycobacterial ergothioneine biosynthesis. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20420449/ · DOI 10.1021/ja101721e
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified bacterial pathway. · source_derived_draft · unverified_draft
## ergothioneine-bacterial-iron-step Iron supports a microbial synthesis enzyme. Reconstituted Mycobacterium smegmatis biosynthesis required an iron(II)-dependent oxidative sulfurization step. Model: Purified bacterial pathway. Limitations: Does not mean iron supplements increase human synthesis. Evidence access: Primary abstract In vitro reconstitution of Mycobacterial ergothioneine biosynthesis. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20420449/ · DOI 10.1021/ja101721e
Complete structured claim and evidence
Mycobacterium thermoresistibile EgtB coupled gamma-glutamylcysteine to hercynine through an oxygen-dependent C-S bond-forming reaction.
Mycobacterium thermoresistibile EgtB → Gamma-glutamylcysteine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Crystal structure and enzyme mechanism study.
limitations
Non-heme iron coordination supports a proposed radical mechanism, not direct observation of every intermediate.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
A cysteine-containing precursor supplies sulfur.
primary_references
Structure of the sulfoxide synthase EgtB from the ergothioneine biosynthetic pathway. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25597398/ · DOI 10.1002/anie.201410045
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Crystal structure and enzyme mechanism study. · source_derived_draft · unverified_draft
## ergothioneine-egtb-sulfur-donor A cysteine-containing precursor supplies sulfur. Mycobacterium thermoresistibile EgtB coupled gamma-glutamylcysteine to hercynine through an oxygen-dependent C-S bond-forming reaction. Model: Crystal structure and enzyme mechanism study. Limitations: Non-heme iron coordination supports a proposed radical mechanism, not direct observation of every intermediate. Evidence access: Primary abstract Structure of the sulfoxide synthase EgtB from the ergothioneine biosynthetic pathway. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25597398/ · DOI 10.1002/anie.201410045
Complete structured claim and evidence
Mycobacterium smegmatis EgtC removes the glutamyl portion of the ergothioneine-pathway sulfur adduct.
Mycobacterium smegmatis EgtC → Hercynyl-gamma-glutamylcysteine sulfoxide source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Substrate-bound bacterial EgtC structure.
limitations
Not human glutathione breakdown; EgtC homologs can have other functions.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
A separate enzyme removes the carrier part of the sulfur donor.
primary_references
Structure of the Ergothioneine-Biosynthesis Amidohydrolase EgtC. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26079795/ · DOI 10.1002/cbic.201500168
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Substrate-bound bacterial EgtC structure. · source_derived_draft · unverified_draft
## ergothioneine-egtc-amide A separate enzyme removes the carrier part of the sulfur donor. Mycobacterium smegmatis EgtC removes the glutamyl portion of the ergothioneine-pathway sulfur adduct. Model: Substrate-bound bacterial EgtC structure. Limitations: Not human glutathione breakdown; EgtC homologs can have other functions. Evidence access: Primary abstract Structure of the Ergothioneine-Biosynthesis Amidohydrolase EgtC. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26079795/ · DOI 10.1002/cbic.201500168
Complete structured claim and evidence
Purified Mycobacterium smegmatis EgtE catalyzed a PLP-dependent C-S lyase reaction in ergothioneine biosynthesis.
PLP → Mycobacterium smegmatis EgtE source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified bacterial EgtE with thioether/sulfoxide substrates and reductant comparisons.
limitations
No demonstrated B6-dependent synthesis in human cells.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
The active vitamin B6 cofactor participates in microbial synthesis.
primary_references
Mechanistic studies of a novel C-S lyase in ergothioneine biosynthesis: the involvement of a sulfenic acid intermediate. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26149121/ · DOI 10.1038/srep11870
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified bacterial EgtE with thioether/sulfoxide substrates and reductant comparisons. · source_derived_draft · unverified_draft
## ergothioneine-egte-plp The active vitamin B6 cofactor participates in microbial synthesis. Purified Mycobacterium smegmatis EgtE catalyzed a PLP-dependent C-S lyase reaction in ergothioneine biosynthesis. Model: Purified bacterial EgtE with thioether/sulfoxide substrates and reductant comparisons. Limitations: No demonstrated B6-dependent synthesis in human cells. Evidence access: Primary abstract Mechanistic studies of a novel C-S lyase in ergothioneine biosynthesis: the involvement of a sulfenic acid intermediate. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26149121/ · DOI 10.1038/srep11870
Complete structured claim and evidence
Biochemical characterization of Mycobacterium smegmatis EgtE supported sulfoxide substrate processing through a sulfenic-acid intermediate toward ergothioneine.
Mycobacterium smegmatis EgtE → Hercynylcysteine sulfoxide source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
In vitro enzyme characterization.
limitations
Intermediate assignment is mechanistically supported; full intracellular flux was not measured.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Sulfur is retained while the cysteine carbon scaffold is removed.
primary_references
Mechanistic studies of a novel C-S lyase in ergothioneine biosynthesis: the involvement of a sulfenic acid intermediate. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26149121/ · DOI 10.1038/srep11870
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · In vitro enzyme characterization. · source_derived_draft · unverified_draft
## ergothioneine-egte-sulfenic Sulfur is retained while the cysteine carbon scaffold is removed. Biochemical characterization of Mycobacterium smegmatis EgtE supported sulfoxide substrate processing through a sulfenic-acid intermediate toward ergothioneine. Model: In vitro enzyme characterization. Limitations: Intermediate assignment is mechanistically supported; full intracellular flux was not measured. Evidence access: Primary abstract Mechanistic studies of a novel C-S lyase in ergothioneine biosynthesis: the involvement of a sulfenic acid intermediate. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26149121/ · DOI 10.1038/srep11870
Complete structured claim and evidence
Chlorobium limicola enzymes synthesized ergothioneine without oxygen through a rhodanese-like sulfur-transfer route.
Chlorobium limicola EanB → L-Ergothioneine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Enzymes from a strictly anaerobic green sulfur bacterium.
limitations
Anaerobic production does not establish a non-antioxidant function in humans.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
An alternative microbial route does not need oxygen.
primary_references
Anaerobic Origin of Ergothioneine. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28786519/ · DOI 10.1002/anie.201705932
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Enzymes from a strictly anaerobic green sulfur bacterium. · source_derived_draft · unverified_draft
## ergothioneine-anaerobic-synthesis An alternative microbial route does not need oxygen. Chlorobium limicola enzymes synthesized ergothioneine without oxygen through a rhodanese-like sulfur-transfer route. Model: Enzymes from a strictly anaerobic green sulfur bacterium. Limitations: Anaerobic production does not establish a non-antioxidant function in humans. Evidence access: Primary abstract Anaerobic Origin of Ergothioneine. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28786519/ · DOI 10.1002/anie.201705932
Complete structured claim and evidence
Structural and kinetic analyses of Chlorobium limicola EanB supported sulfurization of hercynine in anaerobic ergothioneine synthesis.
Chlorobium limicola EanB → Hercynine / N-alpha-trimethylhistidine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Bacterial enzyme crystal structure and kinetics.
limitations
Do not project this microbial enzyme onto human tissues.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Different machinery can produce the same compound.
primary_references
Structural and Mechanistic Basis for Anaerobic Ergothioneine Biosynthesis. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30943021/ · DOI 10.1021/jacs.8b12596
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 224–230
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Bacterial enzyme crystal structure and kinetics. · source_derived_draft · unverified_draft
## ergothioneine-eanb-mechanism Different machinery can produce the same compound. Structural and kinetic analyses of Chlorobium limicola EanB supported sulfurization of hercynine in anaerobic ergothioneine synthesis. Model: Bacterial enzyme crystal structure and kinetics. Limitations: Do not project this microbial enzyme onto human tissues. Evidence access: Primary abstract Structural and Mechanistic Basis for Anaerobic Ergothioneine Biosynthesis. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30943021/ · DOI 10.1021/jacs.8b12596
Complete structured claim and evidence
Streptococcus pneumoniae spd_1642-1643 encoded an ergothioneine-specific ABC uptake transporter.
Streptococcus pneumoniae EgtU ABC transporter → L-Ergothioneine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Bacterial transporter genetics and structure.
limitations
Not evidence that oral ergothioneine worsens a human infection.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Some bacteria acquire ergothioneine instead of making it.
primary_references
Discovery and structure of a widespread bacterial ABC transporter specific for ergothioneine. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36481738/ · DOI 10.1038/s41467-022-35277-3
transport_effect
raises Encoded an ergothioneine-specific ABC uptake transporter.
transport_pool
the bacterial cytoplasm Encoded an ergothioneine-specific ABC uptake transporter.
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Bacterial transporter genetics and structure. · source_derived_draft · unverified_draft
## ergothioneine-bacterial-uptake Some bacteria acquire ergothioneine instead of making it. Streptococcus pneumoniae spd_1642-1643 encoded an ergothioneine-specific ABC uptake transporter. Model: Bacterial transporter genetics and structure. Limitations: Not evidence that oral ergothioneine worsens a human infection. Evidence access: Primary abstract Discovery and structure of a widespread bacterial ABC transporter specific for ergothioneine. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36481738/ · DOI 10.1038/s41467-022-35277-3
Complete structured claim and evidence
The Streptococcus pneumoniae EgtUC domain recognized the betaine and thioimidazole portions of ergothioneine with high specificity.
Streptococcus pneumoniae EgtU solute-binding domain EgtUC → L-Ergothioneine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Ligand-bound bacterial transporter-domain structure.
limitations
Substrate recognition is distinct from ATP-driven translocation.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
A binding component selects the cargo.
primary_references
Discovery and structure of a widespread bacterial ABC transporter specific for ergothioneine. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36481738/ · DOI 10.1038/s41467-022-35277-3
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 240–246
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Ligand-bound bacterial transporter-domain structure. · source_derived_draft · unverified_draft
## ergothioneine-egtuc-binding A binding component selects the cargo. The Streptococcus pneumoniae EgtUC domain recognized the betaine and thioimidazole portions of ergothioneine with high specificity. Model: Ligand-bound bacterial transporter-domain structure. Limitations: Substrate recognition is distinct from ATP-driven translocation. Evidence access: Primary abstract Discovery and structure of a widespread bacterial ABC transporter specific for ergothioneine. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36481738/ · DOI 10.1038/s41467-022-35277-3
Complete structured claim and evidence
In ergothioneine-controlled culture medium, wild-type Helicobacter pylori required available ergothioneine to outcompete its transporter-deficient strain.
L-Ergothioneine → Helicobacter pylori competitive fitness in ergothioneine-controlled medium source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Affinity-resin depletion and bacterial competition in vitro.
limitations
Controlled medium depletion; not a human nutritional diagnosis or infection outcome.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
External supply and uptake machinery act together.
primary_references
An affinity-based depletion strategy for evaluating the effects of ergothioneine on bacterial physiology. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40068683/ · DOI 10.1016/j.chembiol.2025.02.004
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 248–254
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Affinity-resin depletion and bacterial competition in vitro. · source_derived_draft · unverified_draft
## ergothioneine-bacterial-availability External supply and uptake machinery act together. In ergothioneine-controlled culture medium, wild-type Helicobacter pylori required available ergothioneine to outcompete its transporter-deficient strain. Model: Affinity-resin depletion and bacterial competition in vitro. Limitations: Controlled medium depletion; not a human nutritional diagnosis or infection outcome. Evidence access: Primary abstract An affinity-based depletion strategy for evaluating the effects of ergothioneine on bacterial physiology. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40068683/ · DOI 10.1016/j.chembiol.2025.02.004
Complete structured claim and evidence
The reconstituted bacterial catabolic pathway began with ergothionase and generated trimethylamine as one endpoint.
Bacterial ergothionase in the reconstituted catabolic pathway → L-Ergothioneine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Five-step in vitro bacterial pathway reconstruction.
limitations
This study does not establish human gut production of TMAO from dietary ergothioneine.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Bacterial breakdown can release a methylated amine.
primary_references
In Vitro Reconstitution of a Five-Step Pathway for Bacterial Ergothioneine Catabolism. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33544568/ · DOI 10.1021/acschembio.0c00968
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 256–262
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Five-step in vitro bacterial pathway reconstruction. · source_derived_draft · unverified_draft
## ergothioneine-ergothionase Bacterial breakdown can release a methylated amine. The reconstituted bacterial catabolic pathway began with ergothionase and generated trimethylamine as one endpoint. Model: Five-step in vitro bacterial pathway reconstruction. Limitations: This study does not establish human gut production of TMAO from dietary ergothioneine. Evidence access: Primary abstract In Vitro Reconstitution of a Five-Step Pathway for Bacterial Ergothioneine Catabolism. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33544568/ · DOI 10.1021/acschembio.0c00968
Complete structured claim and evidence
Paenibacillus thiourocanate hydratase had structural features distinguishing it from histidine-pathway urocanate hydratases.
Paenibacillus sp. thiourocanate hydratase → Thiourocanate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Enzyme structure within the reconstituted bacterial pathway.
limitations
Do not substitute a human histidine-degradation enzyme for this bacterial activity.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
A related-looking enzyme handles a different intermediate.
primary_references
In Vitro Reconstitution of a Five-Step Pathway for Bacterial Ergothioneine Catabolism. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33544568/ · DOI 10.1021/acschembio.0c00968
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 264–270
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Enzyme structure within the reconstituted bacterial pathway. · source_derived_draft · unverified_draft
## ergothioneine-catabolic-hydratase A related-looking enzyme handles a different intermediate. Paenibacillus thiourocanate hydratase had structural features distinguishing it from histidine-pathway urocanate hydratases. Model: Enzyme structure within the reconstituted bacterial pathway. Limitations: Do not substitute a human histidine-degradation enzyme for this bacterial activity. Evidence access: Primary abstract In Vitro Reconstitution of a Five-Step Pathway for Bacterial Ergothioneine Catabolism. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33544568/ · DOI 10.1021/acschembio.0c00968
Complete structured claim and evidence
The reconstituted bacterial pathway converted ergothioneine into glutamate, trimethylamine, hydrogen sulfide, carbon dioxide and ammonia.
L-Ergothioneine → Hydrogen sulfide / H2S source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
In vitro five-step bacterial enzyme system.
limitations
Environmental gene distribution does not quantify human intestinal flux.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
The sulfur and carbon skeleton enter separate products.
primary_references
In Vitro Reconstitution of a Five-Step Pathway for Bacterial Ergothioneine Catabolism. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33544568/ · DOI 10.1021/acschembio.0c00968
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 272–278
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · In vitro five-step bacterial enzyme system. · source_derived_draft · unverified_draft
## ergothioneine-catabolic-products The sulfur and carbon skeleton enter separate products. The reconstituted bacterial pathway converted ergothioneine into glutamate, trimethylamine, hydrogen sulfide, carbon dioxide and ammonia. Model: In vitro five-step bacterial enzyme system. Limitations: Environmental gene distribution does not quantify human intestinal flux. Evidence access: Primary abstract In Vitro Reconstitution of a Five-Step Pathway for Bacterial Ergothioneine Catabolism. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33544568/ · DOI 10.1021/acschembio.0c00968
Complete structured claim and evidence
SLC22A4 siRNA reduced ergothioneine uptake and abolished its cytoprotection in human brain microvascular endothelial cells.
Human ergothioneine transporter OCTN1 / SLC22A4 → Human endothelial oxidant-associated cell injury source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Cultured human cells challenged with oxidant generators or high glucose.
limitations
Transport dependence does not locate ergothioneine inside mitochondria.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Protection depended on getting the compound inside.
primary_references
Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured human cells challenged with oxidant generators or high glucose. · source_derived_draft · unverified_draft
## ergothioneine-endothelial-entry-loss Protection depended on getting the compound inside. SLC22A4 siRNA reduced ergothioneine uptake and abolished its cytoprotection in human brain microvascular endothelial cells. Model: Cultured human cells challenged with oxidant generators or high glucose. Limitations: Transport dependence does not locate ergothioneine inside mitochondria. Evidence access: Primary abstract Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049
Complete structured claim and evidence
Ergothioneine decreased NOX1 expression in the human endothelial-cell study.
L-Ergothioneine → Human NADPH oxidase 1 / NOX1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human brain microvascular endothelial cells.
limitations
Expression change, not demonstrated direct NOX1 inhibition.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
The response included a lower oxidant-generating enzyme signal.
primary_references
Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 288–294
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human brain microvascular endothelial cells. · source_derived_draft · unverified_draft
## ergothioneine-endothelial-nox1 The response included a lower oxidant-generating enzyme signal. Ergothioneine decreased NOX1 expression in the human endothelial-cell study. Model: Human brain microvascular endothelial cells. Limitations: Expression change, not demonstrated direct NOX1 inhibition. Evidence access: Primary abstract Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049
Complete structured claim and evidence
Ergothioneine increased glutathione reductase expression in human brain microvascular endothelial cells.
L-Ergothioneine → Glutathione reductase / GSR source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cultured human endothelial cells.
limitations
GSR expression does not establish increased flux or correction of riboflavin deficiency.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
This connects the response to glutathione recycling.
primary_references
Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 296–302
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured human endothelial cells. · source_derived_draft · unverified_draft
## ergothioneine-endothelial-gsr This connects the response to glutathione recycling. Ergothioneine increased glutathione reductase expression in human brain microvascular endothelial cells. Model: Cultured human endothelial cells. Limitations: GSR expression does not establish increased flux or correction of riboflavin deficiency. Evidence access: Primary abstract Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049
Complete structured claim and evidence
Ergothioneine increased catalase expression in human brain microvascular endothelial cells.
L-Ergothioneine → Human catalase / CAT source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cultured human endothelial cells.
limitations
Not evidence that ergothioneine supplies heme or iron.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Peroxide-removing machinery was part of the response.
primary_references
Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 304–310
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured human endothelial cells. · source_derived_draft · unverified_draft
## ergothioneine-endothelial-catalase Peroxide-removing machinery was part of the response. Ergothioneine increased catalase expression in human brain microvascular endothelial cells. Model: Cultured human endothelial cells. Limitations: Not evidence that ergothioneine supplies heme or iron. Evidence access: Primary abstract Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049
Complete structured claim and evidence
Ergothioneine protected isolated rat basilar-artery relaxation during oxidative/high-glucose stress and improved responses after chronic treatment in diabetic rats.
L-Ergothioneine → Rat basilar-artery acetylcholine-induced relaxation source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Isolated arteries and streptozotocin-diabetic rats.
limitations
Separate from human cardiovascular outcome evidence.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
The vascular effect was also measured at the artery level.
primary_references
Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 312–318
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated arteries and streptozotocin-diabetic rats. · source_derived_draft · unverified_draft
## ergothioneine-rat-vascular-function The vascular effect was also measured at the artery level. Ergothioneine protected isolated rat basilar-artery relaxation during oxidative/high-glucose stress and improved responses after chronic treatment in diabetic rats. Model: Isolated arteries and streptozotocin-diabetic rats. Limitations: Separate from human cardiovascular outcome evidence. Evidence access: Primary abstract Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049
Complete structured claim and evidence
Ergothioneine at 0.1-0.3 mM reduced IL-1beta-induced vascular cell adhesion molecule 1 expression in human aortic endothelial cells.
L-Ergothioneine → Human vascular cell adhesion molecule 1 / VCAM1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
16-hour pretreatment, then 6-hour cytokine challenge.
limitations
Cell-culture result; not established prevention of human atherosclerosis.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
The endothelial surface expressed fewer adhesion signals.
primary_references
The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21091247/ · DOI 10.1089/jmf.2009.0194
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 16-hour pretreatment, then 6-hour cytokine challenge. · source_derived_draft · unverified_draft
## ergothioneine-adhesion-human-vcam1 The endothelial surface expressed fewer adhesion signals. Ergothioneine at 0.1-0.3 mM reduced IL-1beta-induced vascular cell adhesion molecule 1 expression in human aortic endothelial cells. Model: 16-hour pretreatment, then 6-hour cytokine challenge. Limitations: Cell-culture result; not established prevention of human atherosclerosis. Evidence access: Primary abstract The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21091247/ · DOI 10.1089/jmf.2009.0194
Complete structured claim and evidence
Ergothioneine at 0.1-0.3 mM reduced IL-1beta-induced intercellular adhesion molecule 1 expression in human aortic endothelial cells.
L-Ergothioneine → Human intercellular adhesion molecule 1 / ICAM1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
16-hour pretreatment, then 6-hour cytokine challenge.
limitations
Cell-culture result; not established prevention of human atherosclerosis.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
The endothelial surface expressed fewer adhesion signals.
primary_references
The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21091247/ · DOI 10.1089/jmf.2009.0194
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 16-hour pretreatment, then 6-hour cytokine challenge. · source_derived_draft · unverified_draft
## ergothioneine-adhesion-human-icam1 The endothelial surface expressed fewer adhesion signals. Ergothioneine at 0.1-0.3 mM reduced IL-1beta-induced intercellular adhesion molecule 1 expression in human aortic endothelial cells. Model: 16-hour pretreatment, then 6-hour cytokine challenge. Limitations: Cell-culture result; not established prevention of human atherosclerosis. Evidence access: Primary abstract The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21091247/ · DOI 10.1089/jmf.2009.0194
Complete structured claim and evidence
Ergothioneine at 0.1-0.3 mM reduced IL-1beta-induced E-selectin expression in human aortic endothelial cells.
L-Ergothioneine → Human E-selectin source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
16-hour pretreatment, then 6-hour cytokine challenge.
limitations
Cell-culture result; not established prevention of human atherosclerosis.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
The endothelial surface expressed fewer adhesion signals.
primary_references
The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21091247/ · DOI 10.1089/jmf.2009.0194
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 336–342
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 16-hour pretreatment, then 6-hour cytokine challenge. · source_derived_draft · unverified_draft
## ergothioneine-adhesion-sele The endothelial surface expressed fewer adhesion signals. Ergothioneine at 0.1-0.3 mM reduced IL-1beta-induced E-selectin expression in human aortic endothelial cells. Model: 16-hour pretreatment, then 6-hour cytokine challenge. Limitations: Cell-culture result; not established prevention of human atherosclerosis. Evidence access: Primary abstract The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21091247/ · DOI 10.1089/jmf.2009.0194
Complete structured claim and evidence
At 1-3 mM pretreatment, ergothioneine reduced U937 monocyte attachment to IL-1beta-stimulated human aortic endothelial cells.
L-Ergothioneine → Human U937 monocyte adhesion to endothelial cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human cultured-cell binding assay.
limitations
High in vitro exposure; the cells and adhesion markers belong to one study.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
A functional adhesion measurement followed the expression changes.
primary_references
The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21091247/ · DOI 10.1089/jmf.2009.0194
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 344–350
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cultured-cell binding assay. · source_derived_draft · unverified_draft
## ergothioneine-monocyte-binding A functional adhesion measurement followed the expression changes. At 1-3 mM pretreatment, ergothioneine reduced U937 monocyte attachment to IL-1beta-stimulated human aortic endothelial cells. Model: Human cultured-cell binding assay. Limitations: High in vitro exposure; the cells and adhesion markers belong to one study. Evidence access: Primary abstract The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21091247/ · DOI 10.1089/jmf.2009.0194
Complete structured claim and evidence
In the endothelial high-glucose experiment, ergothioneine increased SIRT1/SIRT6 expression and reduced senescence-associated responses.
L-Ergothioneine → SIRT6 in endothelial high-glucose study, species unresolved source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
0.01-1 mM pretreatment; highest protection at 0.5 mM, then 25 mM glucose.
limitations
Abstract does not identify the endothelial species; protein nodes remain preparation-specific.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Stress protection involved cell-regulatory enzymes.
primary_references
Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27101740/ · DOI 10.1016/j.freeradbiomed.2016.04.013
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 0.01-1 mM pretreatment; highest protection at 0.5 mM, then 25 mM glucose. · source_derived_draft · unverified_draft
## ergothioneine-sirtuin-expression Stress protection involved cell-regulatory enzymes. In the endothelial high-glucose experiment, ergothioneine increased SIRT1/SIRT6 expression and reduced senescence-associated responses. Model: 0.01-1 mM pretreatment; highest protection at 0.5 mM, then 25 mM glucose. Limitations: Abstract does not identify the endothelial species; protein nodes remain preparation-specific. Evidence access: Primary abstract Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27101740/ · DOI 10.1016/j.freeradbiomed.2016.04.013
Complete structured claim and evidence
SIRT1 activity inhibition or SIRT6 siRNA abolished ergothioneine protection against high-glucose-induced endothelial senescence.
SIRT1 inhibition or SIRT6 silencing in endothelial assay → Endothelial-cell high-glucose-induced senescence, preparation specified source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Endothelial-cell pharmacological and genetic perturbation.
limitations
Dependence is stronger than expression association, but does not show direct binding or supply of NAD.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Blocking the regulatory machinery removed protection.
primary_references
Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27101740/ · DOI 10.1016/j.freeradbiomed.2016.04.013
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Endothelial-cell pharmacological and genetic perturbation. · source_derived_draft · unverified_draft
## ergothioneine-sirtuin-dependence Blocking the regulatory machinery removed protection. SIRT1 activity inhibition or SIRT6 siRNA abolished ergothioneine protection against high-glucose-induced endothelial senescence. Model: Endothelial-cell pharmacological and genetic perturbation. Limitations: Dependence is stronger than expression association, but does not show direct binding or supply of NAD. Evidence access: Primary abstract Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27101740/ · DOI 10.1016/j.freeradbiomed.2016.04.013
Complete structured claim and evidence
Ergothioneine treatment reduced inflammatory and matrix-degrading responses in IL-1beta-stimulated mouse chondrocytes through a reported Sirt6/NF-kappaB axis.
L-Ergothioneine → Mouse chondrocyte NF-kappaB-associated inflammation source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse chondrocytes; 10 ng/mL IL-1beta; DMM mouse OA model.
limitations
Not human osteoarthritis treatment evidence; direct Sirt6 binding is not established by this abstract.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Cartilage cells provide another signaling context.
primary_references
Ergothioneine inhibits the progression of osteoarthritis via the Sirt6/NF-κB axis both in vitro and in vivo. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37156032/ · DOI 10.1016/j.intimp.2023.110211
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse chondrocytes; 10 ng/mL IL-1beta; DMM mouse OA model. · source_derived_draft · unverified_draft
## ergothioneine-mouse-cartilage Cartilage cells provide another signaling context. Ergothioneine treatment reduced inflammatory and matrix-degrading responses in IL-1beta-stimulated mouse chondrocytes through a reported Sirt6/NF-kappaB axis. Model: Mouse chondrocytes; 10 ng/mL IL-1beta; DMM mouse OA model. Limitations: Not human osteoarthritis treatment evidence; direct Sirt6 binding is not established by this abstract. Evidence access: Primary abstract Ergothioneine inhibits the progression of osteoarthritis via the Sirt6/NF-κB axis both in vitro and in vivo. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37156032/ · DOI 10.1016/j.intimp.2023.110211
Complete structured claim and evidence
Adding 1 mM ergothioneine for 24 hours reduced IL-18 production in placental explants from women with gestational diabetes.
L-Ergothioneine → Human interleukin 18 / IL18 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human placental explants; comparison with NLRP3 inhibitor MCC950.
limitations
Ex vivo result, not a pregnancy intervention trial or proof of direct NLRP3 binding.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Inflammatory output fell in tissue studied outside the body.
primary_references
L-ergothioneine reduces mitochondrial-driven NLRP3 activation in gestational diabetes mellitus. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38029485/ · DOI 10.1016/j.jri.2023.104171
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human placental explants; comparison with NLRP3 inhibitor MCC950. · source_derived_draft · unverified_draft
## ergothioneine-placenta-il18 Inflammatory output fell in tissue studied outside the body. Adding 1 mM ergothioneine for 24 hours reduced IL-18 production in placental explants from women with gestational diabetes. Model: Human placental explants; comparison with NLRP3 inhibitor MCC950. Limitations: Ex vivo result, not a pregnancy intervention trial or proof of direct NLRP3 binding. Evidence access: Primary abstract L-ergothioneine reduces mitochondrial-driven NLRP3 activation in gestational diabetes mellitus. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38029485/ · DOI 10.1016/j.jri.2023.104171
Complete structured claim and evidence
Ergothioneine limited 6-hydroxydopamine-associated mitochondrial depolarization and mitochondrial ROS increases in human iPSC-derived dopaminergic neurons and SH-SY5Y cells.
L-Ergothioneine → Human dopaminergic-cell mitochondrial membrane potential source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human cell cultures exposed to 6-OHDA.
limitations
A neurotoxin model is not a Parkinson disease clinical trial.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Mitochondrial function was protected in a neuronal injury model.
primary_references
Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38929132/ · DOI 10.3390/antiox13060693
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell cultures exposed to 6-OHDA. · source_derived_draft · unverified_draft
## ergothioneine-dopaminergic-mitochondria Mitochondrial function was protected in a neuronal injury model. Ergothioneine limited 6-hydroxydopamine-associated mitochondrial depolarization and mitochondrial ROS increases in human iPSC-derived dopaminergic neurons and SH-SY5Y cells. Model: Human cell cultures exposed to 6-OHDA. Limitations: A neurotoxin model is not a Parkinson disease clinical trial. Evidence access: Primary abstract Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38929132/ · DOI 10.3390/antiox13060693
Complete structured claim and evidence
Ergothioneine limited ATP loss, protein carbonylation and tyrosine hydroxylase loss in the human 6-OHDA cell experiments.
L-Ergothioneine → Human dopaminergic-cell ATP content source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human iPSC-derived neurons and neuroblastoma cells.
limitations
These correlated outcomes do not identify a single direct mitochondrial target.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Protection involved energy and dopamine-related cell markers.
primary_references
Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38929132/ · DOI 10.3390/antiox13060693
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human iPSC-derived neurons and neuroblastoma cells. · source_derived_draft · unverified_draft
## ergothioneine-dopaminergic-atp Protection involved energy and dopamine-related cell markers. Ergothioneine limited ATP loss, protein carbonylation and tyrosine hydroxylase loss in the human 6-OHDA cell experiments. Model: Human iPSC-derived neurons and neuroblastoma cells. Limitations: These correlated outcomes do not identify a single direct mitochondrial target. Evidence access: Primary abstract Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38929132/ · DOI 10.3390/antiox13060693
Complete structured claim and evidence
Verapamil abrogated ergothioneine protection in the human neuronal-cell study.
Verapamil → Ergothioneine-associated human neuronal cytoprotection source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
6-OHDA challenge with verapamil hydrochloride.
limitations
Verapamil is nonspecific; this experiment alone cannot prove exclusive SLC22A4 mediation.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
A transport-inhibiting drug weakened protection.
primary_references
Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38929132/ · DOI 10.3390/antiox13060693
trigger_kind
machinery_impairment Imported condition classification; unverified.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 400–406
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 6-OHDA challenge with verapamil hydrochloride. · source_derived_draft · unverified_draft
## ergothioneine-neuronal-verapamil A transport-inhibiting drug weakened protection. Verapamil abrogated ergothioneine protection in the human neuronal-cell study. Model: 6-OHDA challenge with verapamil hydrochloride. Limitations: Verapamil is nonspecific; this experiment alone cannot prove exclusive SLC22A4 mediation. Evidence access: Primary abstract Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38929132/ · DOI 10.3390/antiox13060693
Complete structured claim and evidence
Ergothioneine reduced cisplatin-associated auditory threshold shifts by about 30 dB in the mouse comparison.
L-Ergothioneine → Mouse auditory response during cisplatin exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cisplatin-exposed mice; cell experiments examined antioxidant signaling.
limitations
Does not establish safe cotreatment in cancer patients or preserved antitumor efficacy.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Protection extended to an experimental hearing injury.
primary_references
The Antioxidant Ergothioneine Alleviates Cisplatin-Induced Hearing Loss Through the Nrf2 Pathway. · 2025 · https://pubmed.ncbi.nlm.nih.gov/38770822/ · DOI 10.1089/ars.2024.0648
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cisplatin-exposed mice; cell experiments examined antioxidant signaling. · source_derived_draft · unverified_draft
## ergothioneine-cochlear-defense Protection extended to an experimental hearing injury. Ergothioneine reduced cisplatin-associated auditory threshold shifts by about 30 dB in the mouse comparison. Model: Cisplatin-exposed mice; cell experiments examined antioxidant signaling. Limitations: Does not establish safe cotreatment in cancer patients or preserved antitumor efficacy. Evidence access: Primary abstract The Antioxidant Ergothioneine Alleviates Cisplatin-Induced Hearing Loss Through the Nrf2 Pathway. · 2025 · https://pubmed.ncbi.nlm.nih.gov/38770822/ · DOI 10.1089/ars.2024.0648
Complete structured claim and evidence
Nrf2 silencing supported Nrf2 dependence of ergothioneine protection in the cisplatin ototoxicity study.
Nrf2 silencing in the cochlear-cell experimental model → Ergothioneine-associated cochlear-cell antioxidant response source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Cell and mouse ototoxicity study; abstract does not resolve species of the silenced preparation.
limitations
No direct NRF2 binding demonstrated; preparation-specific node avoids assigning this silencing result to a human protein.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Disabling antioxidant signaling weakened protection.
primary_references
The Antioxidant Ergothioneine Alleviates Cisplatin-Induced Hearing Loss Through the Nrf2 Pathway. · 2025 · https://pubmed.ncbi.nlm.nih.gov/38770822/ · DOI 10.1089/ars.2024.0648
trigger_kind
machinery_impairment Imported condition classification; unverified.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 416–422
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell and mouse ototoxicity study; abstract does not resolve species of the silenced preparation. · source_derived_draft · unverified_draft
## ergothioneine-nrf2-dependence Disabling antioxidant signaling weakened protection. Nrf2 silencing supported Nrf2 dependence of ergothioneine protection in the cisplatin ototoxicity study. Model: Cell and mouse ototoxicity study; abstract does not resolve species of the silenced preparation. Limitations: No direct NRF2 binding demonstrated; preparation-specific node avoids assigning this silencing result to a human protein. Evidence access: Primary abstract The Antioxidant Ergothioneine Alleviates Cisplatin-Induced Hearing Loss Through the Nrf2 Pathway. · 2025 · https://pubmed.ncbi.nlm.nih.gov/38770822/ · DOI 10.1089/ars.2024.0648
Complete structured claim and evidence
Chronic olanzapine treatment in mice reduced blood and brain ergothioneine alongside altered microbiota and cognitive deficits.
Olanzapine → Mouse brain ergothioneine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse treatment, multi-omics and microbiota-transplant experiments.
limitations
Association among microbial taxa and metabolite levels does not resolve every biosynthetic flux.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
A medicine-associated ecosystem change coincided with a lower pool.
primary_references
Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020
trigger_kind
biomarker_context Imported condition classification; unverified.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 424–430
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse treatment, multi-omics and microbiota-transplant experiments. · source_derived_draft · unverified_draft
## ergothioneine-olanzapine-mouse-pool A medicine-associated ecosystem change coincided with a lower pool. Chronic olanzapine treatment in mice reduced blood and brain ergothioneine alongside altered microbiota and cognitive deficits. Model: Mouse treatment, multi-omics and microbiota-transplant experiments. Limitations: Association among microbial taxa and metabolite levels does not resolve every biosynthetic flux. Evidence access: Primary abstract Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020
Complete structured claim and evidence
The study also found lower blood ergothioneine in olanzapine-treated patients.
Olanzapine → Human blood ergothioneine concentration, compartment specified source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Patient blood comparison within a mainly mechanistic animal study.
limitations
Not evidence that supplementation improves cognition in these patients.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
A human blood observation accompanied the mouse work.
primary_references
Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020
trigger_kind
biomarker_context Imported condition classification; unverified.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 432–438
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Patient blood comparison within a mainly mechanistic animal study. · source_derived_draft · unverified_draft
## ergothioneine-olanzapine-human-marker A human blood observation accompanied the mouse work. The study also found lower blood ergothioneine in olanzapine-treated patients. Model: Patient blood comparison within a mainly mechanistic animal study. Limitations: Not evidence that supplementation improves cognition in these patients. Evidence access: Primary abstract Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020
Complete structured claim and evidence
Ergothioneine supplementation inhibited hippocampal PTP1B-associated signaling and mitigated synaptic/cognitive impairment in olanzapine-treated mice.
L-Ergothioneine → Mouse protein tyrosine phosphatase 1B / Ptpn1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse gut-brain study with supplementation.
limitations
Abstract supports inhibition but does not establish a direct binding site or human efficacy.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
A phosphatase links the compound to a brain signaling pathway.
primary_references
Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 440–446
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse gut-brain study with supplementation. · source_derived_draft · unverified_draft
## ergothioneine-mouse-ptp1b-inhibition A phosphatase links the compound to a brain signaling pathway. Ergothioneine supplementation inhibited hippocampal PTP1B-associated signaling and mitigated synaptic/cognitive impairment in olanzapine-treated mice. Model: Mouse gut-brain study with supplementation. Limitations: Abstract supports inhibition but does not establish a direct binding site or human efficacy. Evidence access: Primary abstract Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020
Complete structured claim and evidence
Hippocampal neuronal-specific PTP1B deletion prevented olanzapine-induced synaptic and cognitive deficits in mice.
Mouse protein tyrosine phosphatase 1B / Ptpn1 → Mouse cognitive/synaptic response during antipsychotic exposure source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Cell-type-specific mouse genetic intervention.
limitations
Does not mean ergothioneine reproduces every consequence of genetic deletion.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Removing the proposed target tested its role in the injury pathway.
primary_references
Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020
trigger_kind
machinery_impairment Imported condition classification; unverified.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 448–454
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-type-specific mouse genetic intervention. · source_derived_draft · unverified_draft
## ergothioneine-mouse-ptp1b-deletion Removing the proposed target tested its role in the injury pathway. Hippocampal neuronal-specific PTP1B deletion prevented olanzapine-induced synaptic and cognitive deficits in mice. Model: Cell-type-specific mouse genetic intervention. Limitations: Does not mean ergothioneine reproduces every consequence of genetic deletion. Evidence access: Primary abstract Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020
Complete structured claim and evidence
In a 10-man crossover study, mushroom meals containing 8 or 16 grams of mushroom powder produced postprandial erythrocyte ergothioneine uptake.
Agaricus bisporus mushroom test meal → Human erythrocyte ergothioneine concentration source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Acute human mushroom-meal study.
limitations
Grams refer to mushroom powder, not pure ergothioneine; food-matrix effects cannot be assigned to this compound alone.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Food-derived ergothioneine reaches the blood-cell pool.
primary_references
The bioavailability of ergothioneine from mushrooms (Agaricus bisporus) and the acute effects on antioxidant capacity and biomarkers of inflammation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22230474/ · DOI 10.1016/j.ypmed.2011.12.028
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 456–462
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Acute human mushroom-meal study. · source_derived_draft · unverified_draft
## ergothioneine-mushroom-bioavailability Food-derived ergothioneine reaches the blood-cell pool. In a 10-man crossover study, mushroom meals containing 8 or 16 grams of mushroom powder produced postprandial erythrocyte ergothioneine uptake. Model: Acute human mushroom-meal study. Limitations: Grams refer to mushroom powder, not pure ergothioneine; food-matrix effects cannot be assigned to this compound alone. Evidence access: Primary abstract The bioavailability of ergothioneine from mushrooms (Agaricus bisporus) and the acute effects on antioxidant capacity and biomarkers of inflammation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22230474/ · DOI 10.1016/j.ypmed.2011.12.028
Complete structured claim and evidence
Oral pure ergothioneine increased plasma and whole-blood concentrations in healthy volunteers, with urinary recovery below 4% of the administered amount.
L-Ergothioneine → Human blood ergothioneine concentration, compartment specified source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human oral uptake/pharmacokinetic study.
limitations
Blood measurements do not establish tissue-specific sufficiency.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
The body retained much of the measured exposure.
primary_references
Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27488221/ · DOI 10.1089/ars.2016.6778
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 464–470
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human oral uptake/pharmacokinetic study. · source_derived_draft · unverified_draft
## ergothioneine-human-retention The body retained much of the measured exposure. Oral pure ergothioneine increased plasma and whole-blood concentrations in healthy volunteers, with urinary recovery below 4% of the administered amount. Model: Human oral uptake/pharmacokinetic study. Limitations: Blood measurements do not establish tissue-specific sufficiency. Evidence access: Primary abstract Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27488221/ · DOI 10.1089/ars.2016.6778
Complete structured claim and evidence
Human whole-blood ergothioneine correlated with hercynine and S-methyl-ergothioneine, consistent with possible metabolism.
Human blood ergothioneine concentration, compartment specified → S-Methyl-ergothioneine source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human oral-administration study.
limitations
Correlation does not identify the human enzymes or prove every conversion direction.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Related molecules may help trace its fate.
primary_references
Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27488221/ · DOI 10.1089/ars.2016.6778
trigger_kind
biomarker_context Imported condition classification; unverified.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 472–478
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human oral-administration study. · source_derived_draft · unverified_draft
## ergothioneine-human-metabolite-markers Related molecules may help trace its fate. Human whole-blood ergothioneine correlated with hercynine and S-methyl-ergothioneine, consistent with possible metabolism. Model: Human oral-administration study. Limitations: Correlation does not identify the human enzymes or prove every conversion direction. Evidence access: Primary abstract Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27488221/ · DOI 10.1089/ars.2016.6778
Complete structured claim and evidence
Most oxidative-damage and inflammation marker changes after pure ergothioneine administration were not statistically significant.
L-Ergothioneine → Human oxidative-damage/inflammation biomarkers during ergothioneine intake source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Healthy-volunteer pharmacokinetic study.
limitations
Some downward trends were reported; trends are not confirmed treatment effects.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Measured uptake did not establish a broad biomarker benefit.
primary_references
Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27488221/ · DOI 10.1089/ars.2016.6778
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 480–486
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Healthy-volunteer pharmacokinetic study. · source_derived_draft · unverified_draft
## ergothioneine-human-oxidation-null Measured uptake did not establish a broad biomarker benefit. Most oxidative-damage and inflammation marker changes after pure ergothioneine administration were not statistically significant. Model: Healthy-volunteer pharmacokinetic study. Limitations: Some downward trends were reported; trends are not confirmed treatment effects. Evidence access: Primary abstract Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27488221/ · DOI 10.1089/ars.2016.6778
Complete structured claim and evidence
In 3236 initially CVD- and diabetes-free participants, higher baseline ergothioneine predicted lower coronary disease and mortality over a median 21.4 years.
Human blood ergothioneine concentration, compartment specified → Human cardiovascular/mortality association with baseline ergothioneine source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Malmo Diet and Cancer observational cohort; adjusted associations.
limitations
Healthy dietary pattern and other confounding prevent a causal supplement conclusion.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
A higher blood marker tracked better long-term outcomes.
primary_references
Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31672783/ · DOI 10.1136/heartjnl-2019-315485
trigger_kind
biomarker_context Imported condition classification; unverified.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 488–494
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Malmo Diet and Cancer observational cohort; adjusted associations. · source_derived_draft · unverified_draft
## ergothioneine-cv-observational A higher blood marker tracked better long-term outcomes. In 3236 initially CVD- and diabetes-free participants, higher baseline ergothioneine predicted lower coronary disease and mortality over a median 21.4 years. Model: Malmo Diet and Cancer observational cohort; adjusted associations. Limitations: Healthy dietary pattern and other confounding prevent a causal supplement conclusion. Evidence access: Primary abstract Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31672783/ · DOI 10.1136/heartjnl-2019-315485
Complete structured claim and evidence
A 19-person randomized MCI pilot reported improved verbal-learning performance with 25 mg ergothioneine three times weekly for one year.
L-Ergothioneine → Human verbal-learning response in ergothioneine MCI pilot source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Double-blind placebo-controlled pilot; adults at least 60 years old.
limitations
Small trial, not established dementia prevention; blood safety markers cannot exclude uncommon adverse effects.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
A small human trial found a preliminary cognitive signal.
primary_references
Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: A pilot study. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39544014/ · DOI 10.1177/13872877241291253
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 496–502
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Double-blind placebo-controlled pilot; adults at least 60 years old. · source_derived_draft · unverified_draft
## ergothioneine-mci-pilot A small human trial found a preliminary cognitive signal. A 19-person randomized MCI pilot reported improved verbal-learning performance with 25 mg ergothioneine three times weekly for one year. Model: Double-blind placebo-controlled pilot; adults at least 60 years old. Limitations: Small trial, not established dementia prevention; blood safety markers cannot exclude uncommon adverse effects. Evidence access: Primary abstract Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: A pilot study. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39544014/ · DOI 10.1177/13872877241291253
Complete structured claim and evidence
Plasma neurofilament light remained stable in the ergothioneine arm of the 19-person MCI pilot while increasing in placebo recipients.
L-Ergothioneine → Human plasma neurofilament-light response in ergothioneine pilot source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Same one-year trial as the verbal-learning record.
limitations
Not an independent replication or proof of reduced neurodegeneration.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
A blood injury marker accompanied the learning result.
primary_references
Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: A pilot study. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39544014/ · DOI 10.1177/13872877241291253
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 504–510
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same one-year trial as the verbal-learning record. · source_derived_draft · unverified_draft
## ergothioneine-mci-nfl A blood injury marker accompanied the learning result. Plasma neurofilament light remained stable in the ergothioneine arm of the 19-person MCI pilot while increasing in placebo recipients. Model: Same one-year trial as the verbal-learning record. Limitations: Not an independent replication or proof of reduced neurodegeneration. Evidence access: Primary abstract Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: A pilot study. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39544014/ · DOI 10.1177/13872877241291253
Complete structured claim and evidence
Daily oral ergothioneine at approximately 4-5 mg/kg from seven weeks of age extended lifespan in male mice.
L-Ergothioneine → Male-mouse lifespan during lifelong ergothioneine exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Male-mouse lifelong drinking-water exposure.
limitations
Not demonstrated human longevity or a human dose; sex and lifelong exposure matter.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
An animal lifespan experiment supports further investigation.
primary_references
Ergothioneine promotes longevity and healthy aging in male mice. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38446314/ · DOI 10.1007/s11357-024-01111-5
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 512–518
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Male-mouse lifelong drinking-water exposure. · source_derived_draft · unverified_draft
## ergothioneine-male-mouse-lifespan An animal lifespan experiment supports further investigation. Daily oral ergothioneine at approximately 4-5 mg/kg from seven weeks of age extended lifespan in male mice. Model: Male-mouse lifelong drinking-water exposure. Limitations: Not demonstrated human longevity or a human dose; sex and lifelong exposure matter. Evidence access: Primary abstract Ergothioneine promotes longevity and healthy aging in male mice. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38446314/ · DOI 10.1007/s11357-024-01111-5
Complete structured claim and evidence
Ergothioneine-treated aging male mice showed preserved learning/memory with changes in neurogenesis, TDP43 aggregation and microglial phenotype.
L-Ergothioneine → Male-mouse hippocampal aging outcomes during ergothioneine intake source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Same lifelong mouse experiment as the lifespan record.
limitations
These associations do not identify one necessary mediator.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Several brain changes accompanied the behavioral result.
primary_references
Ergothioneine promotes longevity and healthy aging in male mice. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38446314/ · DOI 10.1007/s11357-024-01111-5
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 520–526
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same lifelong mouse experiment as the lifespan record. · source_derived_draft · unverified_draft
## ergothioneine-male-mouse-brain-aging Several brain changes accompanied the behavioral result. Ergothioneine-treated aging male mice showed preserved learning/memory with changes in neurogenesis, TDP43 aggregation and microglial phenotype. Model: Same lifelong mouse experiment as the lifespan record. Limitations: These associations do not identify one necessary mediator. Evidence access: Primary abstract Ergothioneine promotes longevity and healthy aging in male mice. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38446314/ · DOI 10.1007/s11357-024-01111-5
Complete structured claim and evidence
Hemodialysis cleared ergothioneine at 146 +/- 36 mL/min in the measured cohort, exceeding urinary removal in controls and CKD participants.
Human hemodialysis → L-Ergothioneine source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
11 hemodialysis, 12 advanced CKD and 12 control participants.
limitations
Removal measured; clinical benefit from replacing the solute remains untested.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Dialysis can bypass the kidney retention mechanism.
primary_references
Depletion by Hemodialysis of the Antioxidant Ergothioneine. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39869777/ · DOI 10.34067/KID.0000000645
trigger_kind
biomarker_context Imported condition classification; unverified.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 528–534
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 11 hemodialysis, 12 advanced CKD and 12 control participants. · source_derived_draft · unverified_draft
## ergothioneine-hemodialysis-clearance Dialysis can bypass the kidney retention mechanism. Hemodialysis cleared ergothioneine at 146 +/- 36 mL/min in the measured cohort, exceeding urinary removal in controls and CKD participants. Model: 11 hemodialysis, 12 advanced CKD and 12 control participants. Limitations: Removal measured; clinical benefit from replacing the solute remains untested. Evidence access: Primary abstract Depletion by Hemodialysis of the Antioxidant Ergothioneine. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39869777/ · DOI 10.34067/KID.0000000645
Complete structured claim and evidence
Erythrocyte ergothioneine averaged 8% of control levels in hemodialysis participants and 24% in advanced CKD participants.
Human hemodialysis → Human erythrocyte ergothioneine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Cross-group measurements plus clearance assessment.
limitations
Diet, disease and clearance may all contribute; no universal deficiency cutoff.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
The blood-cell pool was substantially lower.
primary_references
Depletion by Hemodialysis of the Antioxidant Ergothioneine. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39869777/ · DOI 10.34067/KID.0000000645
trigger_kind
biomarker_context Imported condition classification; unverified.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 536–542
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cross-group measurements plus clearance assessment. · source_derived_draft · unverified_draft
## ergothioneine-hemodialysis-rbc The blood-cell pool was substantially lower. Erythrocyte ergothioneine averaged 8% of control levels in hemodialysis participants and 24% in advanced CKD participants. Model: Cross-group measurements plus clearance assessment. Limitations: Diet, disease and clearance may all contribute; no universal deficiency cutoff. Evidence access: Primary abstract Depletion by Hemodialysis of the Antioxidant Ergothioneine. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39869777/ · DOI 10.34067/KID.0000000645
Complete structured claim and evidence
In a later comparison, erythrocyte ergothioneine averaged 34% of control levels during peritoneal dialysis versus 10% during hemodialysis.
Human peritoneal dialysis → Human erythrocyte ergothioneine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
16 peritoneal dialysis, 16 hemodialysis and 15 controls.
limitations
Percentages belong to this cohort, not a contradiction of the earlier study; replacement benefits remain unknown.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Different dialysis routes were associated with different depletion.
primary_references
Ergothioneine Depletion in Peritoneal Dialysis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41411056/ · DOI 10.34067/KID.0000001105
trigger_kind
biomarker_context Imported condition classification; unverified.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 544–550
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 16 peritoneal dialysis, 16 hemodialysis and 15 controls. · source_derived_draft · unverified_draft
## ergothioneine-peritoneal-rbc Different dialysis routes were associated with different depletion. In a later comparison, erythrocyte ergothioneine averaged 34% of control levels during peritoneal dialysis versus 10% during hemodialysis. Model: 16 peritoneal dialysis, 16 hemodialysis and 15 controls. Limitations: Percentages belong to this cohort, not a contradiction of the earlier study; replacement benefits remain unknown. Evidence access: Primary abstract Ergothioneine Depletion in Peritoneal Dialysis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41411056/ · DOI 10.34067/KID.0000001105
Complete structured claim and evidence
Mycobacterium smegmatis EgtD uses SAM-dependent methyl transfer to convert histidine into hercynine.
S-Adenosyl-L-methionine → Mycobacterium smegmatis EgtD source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Apo and ligand-bound enzyme structures.
limitations
No evidence that human ergothioneine consumption drains SAM; humans lack this established synthesis pathway.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
The microbial synthesis branch connects to methyl-donor chemistry.
primary_references
Structural insights into the histidine trimethylation activity of EgtD from Mycobacterium smegmatis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25251321/ · DOI 10.1016/j.bbrc.2014.09.058
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 552–558
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Apo and ligand-bound enzyme structures. · source_derived_draft · unverified_draft
## ergothioneine-egtd-sam The microbial synthesis branch connects to methyl-donor chemistry. Mycobacterium smegmatis EgtD uses SAM-dependent methyl transfer to convert histidine into hercynine. Model: Apo and ligand-bound enzyme structures. Limitations: No evidence that human ergothioneine consumption drains SAM; humans lack this established synthesis pathway. Evidence access: Primary abstract Structural insights into the histidine trimethylation activity of EgtD from Mycobacterium smegmatis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25251321/ · DOI 10.1016/j.bbrc.2014.09.058
Complete structured claim and evidence
The described Mycobacterium smegmatis pathway uses EgtA to condense glutamate and cysteine into gamma-glutamylcysteine.
Mycobacterium smegmatis EgtA → Gamma-glutamylcysteine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text, pathway background citing original reconstitution
experimental_model
Pathway description in the primary EgtE paper, citing the original reconstitution.
limitations
This step is cited background, not a new EgtA experiment in this paper; microbial and human pathways remain separate.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
A separately encoded enzyme prepares the sulfur donor.
primary_references
Mechanistic studies of a novel C-S lyase in ergothioneine biosynthesis: the involvement of a sulfenic acid intermediate. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26149121/ · DOI 10.1038/srep11870
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 560–566
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pathway description in the primary EgtE paper, citing the original reconstitution. · source_derived_draft · unverified_draft
## ergothioneine-egta-precursor A separately encoded enzyme prepares the sulfur donor. The described Mycobacterium smegmatis pathway uses EgtA to condense glutamate and cysteine into gamma-glutamylcysteine. Model: Pathway description in the primary EgtE paper, citing the original reconstitution. Limitations: This step is cited background, not a new EgtA experiment in this paper; microbial and human pathways remain separate. Evidence access: Primary full text, pathway background citing original reconstitution Mechanistic studies of a novel C-S lyase in ergothioneine biosynthesis: the involvement of a sulfenic acid intermediate. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26149121/ · DOI 10.1038/srep11870
Complete structured claim and evidence
Ergothioneine increased superoxide dismutase expression in the human endothelial-cell experiment.
L-Ergothioneine → Human endothelial superoxide dismutase, isoform unresolved source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human brain microvascular endothelial cells.
limitations
Abstract does not resolve SOD1 versus SOD2; do not infer a specific copper, zinc or manganese requirement from this result.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Another oxidant-handling enzyme accompanied the response.
primary_references
Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 568–574
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human brain microvascular endothelial cells. · source_derived_draft · unverified_draft
## ergothioneine-endothelial-sod Another oxidant-handling enzyme accompanied the response. Ergothioneine increased superoxide dismutase expression in the human endothelial-cell experiment. Model: Human brain microvascular endothelial cells. Limitations: Abstract does not resolve SOD1 versus SOD2; do not infer a specific copper, zinc or manganese requirement from this result. Evidence access: Primary abstract Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049
Complete structured claim and evidence
The 2015 Mycobacterium tuberculosis study reported PknD phosphorylation of EgtD at Thr213 in vitro and in a cell-based system.
Mycobacterium tuberculosis protein kinase PknD → Mycobacterium tuberculosis EgtD / Rv3701c source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Bacterial kinase assays and cell-based phosphorylation evidence.
limitations
The kinase-substrate assignment was directly challenged by the 2020 reexamination; not settled regulation.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
One study reported a kinase-controlled synthesis switch.
primary_references
Regulation of Ergothioneine Biosynthesis and Its Effect on Mycobacterium tuberculosis Growth and Infectivity. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26229105/ · DOI 10.1074/jbc.M115.648642
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 576–582
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Bacterial kinase assays and cell-based phosphorylation evidence. · source_derived_draft · unverified_draft
## ergothioneine-pknd-positive One study reported a kinase-controlled synthesis switch. The 2015 Mycobacterium tuberculosis study reported PknD phosphorylation of EgtD at Thr213 in vitro and in a cell-based system. Model: Bacterial kinase assays and cell-based phosphorylation evidence. Limitations: The kinase-substrate assignment was directly challenged by the 2020 reexamination; not settled regulation. Evidence access: Primary abstract Regulation of Ergothioneine Biosynthesis and Its Effect on Mycobacterium tuberculosis Growth and Infectivity. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26229105/ · DOI 10.1074/jbc.M115.648642
Complete structured claim and evidence
The 2020 reexamination found that Mycobacterium tuberculosis EgtD was not a PknD substrate under its in vitro conditions.
Mycobacterium tuberculosis protein kinase PknD → Mycobacterium tuberculosis EgtD / Rv3701c source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
In vitro kinase reassessment; active-site accessibility considered structurally.
limitations
A negative in vitro result does not alone exclude every cellular condition; matched protocols are needed.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
A later study did not reproduce the proposed kinase reaction.
primary_references
Reexamination of the Ergothioneine Biosynthetic Methyltransferase EgtD from Mycobacterium tuberculosis as a Protein Kinase Substrate. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32614492/ · DOI 10.1002/cbic.202000232
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 584–590
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · In vitro kinase reassessment; active-site accessibility considered structurally. · source_derived_draft · unverified_draft
## ergothioneine-pknd-negative A later study did not reproduce the proposed kinase reaction. The 2020 reexamination found that Mycobacterium tuberculosis EgtD was not a PknD substrate under its in vitro conditions. Model: In vitro kinase reassessment; active-site accessibility considered structurally. Limitations: A negative in vitro result does not alone exclude every cellular condition; matched protocols are needed. Evidence access: Primary abstract Reexamination of the Ergothioneine Biosynthetic Methyltransferase EgtD from Mycobacterium tuberculosis as a Protein Kinase Substrate. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32614492/ · DOI 10.1002/cbic.202000232
Complete structured claim and evidence
EgtD T213E failed to restore ergothioneine synthesis in a Mycobacterium tuberculosis egtD-deletion strain, unlike T213A.
Mycobacterium tuberculosis EgtD T213E mutant → Mycobacterium tuberculosis ergothioneine synthesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mutant complementation in the 2015 study.
limitations
A phosphomimetic mutation is not direct evidence of physiological phosphorylation, particularly at an active-site residue.
nutrient_topic
Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
plain_language
Changing this residue disrupted restoration of synthesis.
primary_references
Regulation of Ergothioneine Biosynthesis and Its Effect on Mycobacterium tuberculosis Growth and Infectivity. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26229105/ · DOI 10.1074/jbc.M115.648642
trigger_kind
machinery_impairment Imported condition classification; unverified.
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 592–598
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mutant complementation in the 2015 study. · source_derived_draft · unverified_draft
## ergothioneine-egtd-mutant Changing this residue disrupted restoration of synthesis. EgtD T213E failed to restore ergothioneine synthesis in a Mycobacterium tuberculosis egtD-deletion strain, unlike T213A. Model: Mutant complementation in the 2015 study. Limitations: A phosphomimetic mutation is not direct evidence of physiological phosphorylation, particularly at an active-site residue. Evidence access: Primary abstract Regulation of Ergothioneine Biosynthesis and Its Effect on Mycobacterium tuberculosis Growth and Infectivity. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26229105/ · DOI 10.1074/jbc.M115.648642
Complete structured claim and evidence
Human OCTN2 expression increased sodium-dependent carnitine uptake with an apparent Km of 4.34 micromolar.
Human carnitine transporter OCTN2 / SLC22A5 → L-Carnitine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sodium-research/9685390.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08cdedaad32299795a52b81183d565d2b476b7a190b2af7b950c829f8c11ddf6", "start_char": 0, "end_char": 1549, "text_sha256": "08cdedaad32299795a52b81183d565d2b476b7a190b2af7b950c829f8c11ddf6"}
experimental_model
Cloning and functional expression
exposure
Radiolabeled carnitine uptake and sodium dependence
limitations
Expression assay; dietary sodium intake, mitochondrial fatty-acid oxidation and clinical supplementation were not directly tested.
nutrient_topic
Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium
organism
Human OCTN2 in HEK293 cells
plain_language
The sodium gradient helps bring carnitine into cells.
primary_references
[sodium-p9685390] Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. (1998). https://pubmed.ncbi.nlm.nih.gov/9685390/ DOI: 10.1074/jbc.273.32.20378
tissue_or_cell_type
Cell plasma membrane
transport_effect
raises Expression increased sodium-dependent carnitine uptake.
transport_pool
the expressing cell Expression increased sodium-dependent carnitine uptake.
Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 616–627
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning and functional expression · source_derived_draft · unverified_draft
### sodium-octn2-carnitine Human OCTN2 expression increased sodium-dependent carnitine uptake with an apparent Km of 4.34 micromolar. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The sodium gradient helps bring carnitine into cells. organism: Human OCTN2 in HEK293 cells tissue_or_cell_type: Cell plasma membrane experimental_model: Cloning and functional expression limitations: Expression assay; dietary sodium intake, mitochondrial fatty-acid oxidation and clinical supplementation were not directly tested. exposure: Radiolabeled carnitine uptake and sodium dependence evidence_span: {"source_cache": "artifacts/sodium-research/9685390.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08cdedaad32299795a52b81183d565d2b476b7a190b2af7b950c829f8c11ddf6", "start_char": 0, "end_char": 1549, "text_sha256": "08cdedaad32299795a52b81183d565d2b476b7a190b2af7b950c829f8c11ddf6"} [sodium-p9685390] Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. (1998). https://pubmed.ncbi.nlm.nih.gov/9685390/ DOI: 10.1074/jbc.273.32.20378
Complete structured claim and evidence
Human OCTN2 transport measurements were consistent with approximately one sodium ion accompanying each carnitine molecule.
Human carnitine transporter OCTN2 / SLC22A5 → L-Carnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human OCTN2 expressed in HEK293 cells.
limitations
Does not imply that eating more salt improves carnitine uptake.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Cell entry depends on a sodium-coupled transporter.
primary_references
Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10525100/
transport_effect
raises Sodium-coupled, with about one sodium ion accompanying each carnitine molecule inward.
transport_pool
the expressing cell Sodium-coupled, with about one sodium ion accompanying each carnitine molecule inward.
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 42–48
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human OCTN2 expressed in HEK293 cells. · source_derived_draft · unverified_draft
## l-carnitine-octn2-sodium Cell entry depends on a sodium-coupled transporter. Human OCTN2 transport measurements were consistent with approximately one sodium ion accompanying each carnitine molecule. Model: Human OCTN2 expressed in HEK293 cells. Limitations: Does not imply that eating more salt improves carnitine uptake. Evidence access: Primary abstract Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10525100/
Complete structured claim and evidence
GSR reduces one glutathione-disulfide molecule to two reduced glutathione molecules using the NADPH/FAD catalytic relay.
Glutathione reductase / GSR → GSSG source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-FAD supports GSH recycling; selenium-dependent GPX use of GSH is a separate reaction.
evidence_location
Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes
experimental_model
Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls.
exposure
Purified-enzyme assay
limitations
GSR is not glutathione peroxidase; this record does not show that B2 improves selenium repletion.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
This enzyme recycles glutathione after oxidation.
primary_references
[berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083
tissue_or_cell_type
Purified human GSR
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1332–1344
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. · source_derived_draft · unverified_draft
### b2-gsr-gssg-to-gsh GSR reduces one glutathione-disulfide molecule to two reduced glutathione molecules using the NADPH/FAD catalytic relay. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This enzyme recycles glutathione after oxidation. organism: Homo sapiens tissue_or_cell_type: Purified human GSR experimental_model: Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. limitations: GSR is not glutathione peroxidase; this record does not show that B2 improves selenium repletion. exposure: Purified-enzyme assay cross_nutrient: B2-FAD supports GSH recycling; selenium-dependent GPX use of GSH is a separate reaction. evidence_location: Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes [berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083
Complete structured claim and evidence
Marginally B2-deficient subjects had lower erythrocyte glutathione reductase activity than controls across the study comparison.
Riboflavin (vitamin B2) → Erythrocyte glutathione reductase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B2 supports a component of glutathione recycling; this is not proof of universal glutathione exhaustion.
experimental_model
Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions.
exposure
Red-cell age-fraction enzyme/cofactor assays, glutathione, hemoglobin species and peroxide susceptibility; observational comparison.
limitations
Observational age-fraction study; reduced glutathione itself was not among the significant between-group differences.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
A B2-dependent recycling enzyme was less active in red cells from the deficient group.
primary_references
[b2-powers1981] Riboflavin deficiency in man: effects on haemoglobin and reduced glutathione in erythrocytes of different ages (1981). https://pubmed.ncbi.nlm.nih.gov/7284295/ DOI: 10.1079/bjn19810031
tissue_or_cell_type
Human clinical setting
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1692–1703
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions. · source_derived_draft · unverified_draft
### b2-deficiency-redcell-gsr Marginally B2-deficient subjects had lower erythrocyte glutathione reductase activity than controls across the study comparison. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A B2-dependent recycling enzyme was less active in red cells from the deficient group. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions. limitations: Observational age-fraction study; reduced glutathione itself was not among the significant between-group differences. exposure: Red-cell age-fraction enzyme/cofactor assays, glutathione, hemoglobin species and peroxide susceptibility; observational comparison. cross_nutrient: B2 supports a component of glutathione recycling; this is not proof of universal glutathione exhaustion. [b2-powers1981] Riboflavin deficiency in man: effects on haemoglobin and reduced glutathione in erythrocytes of different ages (1981). https://pubmed.ncbi.nlm.nih.gov/7284295/ DOI: 10.1079/bjn19810031
Complete structured claim and evidence
Purified rat liver thioredoxin reductase decreased ascorbyl radical measured by electron paramagnetic resonance while consuming NADPH; DHA controls could not explain the signal.
Rat thioredoxin reductase 1 / Txnrd1 → Ascorbyl radical source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Purified rat liver enzyme, dialyzed cytosol and microsomes from control/selenium-deficient rats
exposure
Low-micromolar ascorbyl radical generated by ascorbate oxidase
limitations
Purified assay; radical and DHA reduction are distinct reactions.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Rattus norvegicus
plain_language
The reductase can also recycle the one-electron vitamin C radical.
primary_references
[may1998] Reduction of the ascorbyl free radical to ascorbate by thioredoxin reductase. (1998). https://pubmed.ncbi.nlm.nih.gov/9722529/ DOI: 10.1074/jbc.273.36.23039
tissue_or_cell_type
Purified liver enzyme
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 416–427
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified rat liver enzyme, dialyzed cytosol and microsomes from control/selenium-deficient rats · source_derived_draft · unverified_draft
### vc-transport-txnrd-radical Purified rat liver thioredoxin reductase decreased ascorbyl radical measured by electron paramagnetic resonance while consuming NADPH; DHA controls could not explain the signal. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The reductase can also recycle the one-electron vitamin C radical. organism: Rattus norvegicus tissue_or_cell_type: Purified liver enzyme experimental_model: Purified rat liver enzyme, dialyzed cytosol and microsomes from control/selenium-deficient rats limitations: Purified assay; radical and DHA reduction are distinct reactions. exposure: Low-micromolar ascorbyl radical generated by ascorbate oxidase cross_nutrient: true [may1998] Reduction of the ascorbyl free radical to ascorbate by thioredoxin reductase. (1998). https://pubmed.ncbi.nlm.nih.gov/9722529/ DOI: 10.1074/jbc.273.36.23039
Complete structured claim and evidence
Dialyzed liver cytosol from selenium-deficient rats lost NADPH-dependent ascorbyl-radical reducing activity attributed to thioredoxin reductase.
Selenium → Ascorbyl radical reduction to ascorbate source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
experimental_model
Purified rat liver enzyme, dialyzed cytosol and microsomes from control/selenium-deficient rats
exposure
Dietary selenium depletion; isolated dialyzed cytosol
limitations
Activity assignment also used inhibitor sensitivity; this is a fraction assay, not a direct human outcome.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Rattus norvegicus
plain_language
Selenium deficiency impaired radical recycling in the rat liver’s soluble fraction.
primary_references
[may1998] Reduction of the ascorbyl free radical to ascorbate by thioredoxin reductase. (1998). https://pubmed.ncbi.nlm.nih.gov/9722529/ DOI: 10.1074/jbc.273.36.23039
tissue_or_cell_type
Liver cytosol
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 429–440
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified rat liver enzyme, dialyzed cytosol and microsomes from control/selenium-deficient rats · source_derived_draft · unverified_draft
### vc-transport-selenium-cytosolic-radical Dialyzed liver cytosol from selenium-deficient rats lost NADPH-dependent ascorbyl-radical reducing activity attributed to thioredoxin reductase. Condition category: nutrient_deficiency nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Selenium deficiency impaired radical recycling in the rat liver’s soluble fraction. organism: Rattus norvegicus tissue_or_cell_type: Liver cytosol experimental_model: Purified rat liver enzyme, dialyzed cytosol and microsomes from control/selenium-deficient rats limitations: Activity assignment also used inhibitor sensitivity; this is a fraction assay, not a direct human outcome. exposure: Dietary selenium depletion; isolated dialyzed cytosol cross_nutrient: true [may1998] Reduction of the ascorbyl free radical to ascorbate by thioredoxin reductase. (1998). https://pubmed.ncbi.nlm.nih.gov/9722529/ DOI: 10.1074/jbc.273.36.23039
Complete structured claim and evidence
Human SIRT1 removes acetylation from histone H4 Lys16 in an NAD+-dependent reaction.
SIRT1 → Histone H4 acetylated at K16 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human enzyme assays and cultured-cell SIRT1 perturbation.
limitations
This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome.
organism
Human
plain_language
A different enzyme removes a lysine modification using NAD+.
primary_references
[sirt1-2004] Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin (2004). https://pubmed.ncbi.nlm.nih.gov/15469825/ DOI: 10.1016/j.molcel.2004.08.031
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 537–545
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme assays and cultured-cell SIRT1 perturbation. · source_derived_draft · unverified_draft
### sirt1-h4k16-deacetylation Human SIRT1 removes acetylation from histone H4 Lys16 in an NAD+-dependent reaction. Plain language: A different enzyme removes a lysine modification using NAD+. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human enzyme assays and cultured-cell SIRT1 perturbation. limitations: This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [sirt1-2004] Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin (2004). https://pubmed.ncbi.nlm.nih.gov/15469825/ DOI: 10.1016/j.molcel.2004.08.031
Complete structured claim and evidence
Mass spectrometry detected ergothioneine entry into isolated mitochondria and mitochondrial presence after treating cells and animals.
L-Ergothioneine → Ergothioneine uptake into isolated mammalian mitochondria source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract; numerical exposures and tissue-specific methods not available in the abstract.
experimental_model
Isolated mitochondria, treated cells and animals; tissue and dose details not extracted from the abstract.
interpretation_status
Source-derived research curation; not independent raw-data verification.
limitations
Mitochondrial localisation alone does not establish disease prevention or identify the membrane transporter.
nutrient_topic
Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine
plain_language
Cell entry and mitochondrial entry are separate transport questions.
primary_references
Fong et al. Ergothioneine and mitochondria: An important protective mechanism? DOI 10.1016/j.bbrc.2024.150269; PMID 38909533; https://pubmed.ncbi.nlm.nih.gov/38909533/
source_locator
Abstract
Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 25–25
Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Isolated mitochondria, treated cells and animals; tissue and dose details not extracted from the abstract. · source_derived_draft · unverified_draft
Mass spectrometry detected ergothioneine entry into isolated mitochondria and mitochondrial presence after treating cells and animals.
Complete structured claim and evidence
Slc22a4 knockout impaired but did not abolish ergothioneine uptake by isolated mouse mitochondria.
Mouse ergothioneine transporter Octn1 / Slc22a4 → Ergothioneine uptake into isolated mouse mitochondria source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary indexed abstract; numerical exposures and tissue-specific methods not available in the abstract.
experimental_condition
non-knockout mitochondrial comparison knockout · Mouse ergothioneine transporter Octn1 / Slc22a4 Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "Octn1/Slc22a4 knockout", "comparator": "non-knockout mitochondrial comparison", "endpoint": "mitochondrial ergothioneine uptake", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "mouse-slc22a4", "state": "knockout"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mitochondria isolated from Octn1-knockout mouse tissues.
interpretation_status
Source-derived research curation; not independent raw-data verification.
limitations
Residual uptake does not prove which alternative transporter operates, nor that OCTN1 normally resides on the mitochondrial membrane.
nutrient_topic
Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine
plain_language
An alternative mitochondrial uptake route remains possible.
primary_references
Fong et al. Ergothioneine and mitochondria: An important protective mechanism? DOI 10.1016/j.bbrc.2024.150269; PMID 38909533; https://pubmed.ncbi.nlm.nih.gov/38909533/
source_locator
Abstract, knockout comparison
trigger_kind
machinery_impairment Imported condition classification; unverified.
Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 33–33
Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Mitochondria isolated from Octn1-knockout mouse tissues. · source_derived_draft · unverified_draft
Slc22a4 knockout impaired but did not abolish ergothioneine uptake by isolated mouse mitochondria.
Complete structured claim and evidence
Human MPST2 is a mitochondrial-targeted splice isoform of MPST, distinct from cytosolic MPST1.
Human MPST mitochondrial isoform 2 → Human mercaptopyruvate sulfurtransferase / MPST source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract and figure descriptions.
experimental_model
Recombinant human isoform characterization and sequence organisation.
interpretation_status
Source-derived research curation; not independent raw-data verification.
limitations
An isoform relationship is identity/navigation, not a signed activation effect; it does not collapse mouse and human proteins.
nutrient_topic
Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine
plain_language
This is the same human enzyme family with a specific splice form.
primary_references
Yadav et al. Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations. DOI 10.1074/jbc.RA120.012616; PMID 32179647; https://pubmed.ncbi.nlm.nih.gov/32179647/
source_locator
Abstract and Figure 1
Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 41–41
Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Recombinant human isoform characterization and sequence organisation. · source_derived_draft · unverified_draft
Human MPST2 is a mitochondrial-targeted splice isoform of MPST, distinct from cytosolic MPST1.
Complete structured claim and evidence
Ergothioneine bound purified human MPST2 in ITC and NMR experiments.
L-Ergothioneine → Human MPST mitochondrial isoform 2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.
experimental_model
Purified recombinant human MPST mitochondrial isoform 2.
interpretation_status
Source-derived research curation; not independent raw-data verification.
limitations
Binding is measured; docking poses and proposed sulfur-acceptor chemistry are not equivalent to a measured covalent intermediate. Ambiguous OCR binding constants are omitted.
nutrient_topic
Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine
organism
Homo sapiens
plain_language
Ergothioneine has an experimentally identified enzyme target.
primary_references
Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/
protein_isoform
MPST2 · Human MPST mitochondrial isoform 2
source_locator
Figure 3E; Figures S3E-S3G; Results
Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 49–49
Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Purified recombinant human MPST mitochondrial isoform 2. · source_derived_draft · unverified_draft
Ergothioneine bound purified human MPST2 in ITC and NMR experiments.
Complete structured claim and evidence
Ergothioneine plus 3-mercaptopyruvate supported H2S release by recombinant human MPST.
L-Ergothioneine → Hydrogen sulfide / H2S source_derived_draftungraded
Experimental context and source evidence
assay_pH
11
evidence_access
Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.
experimental_condition
substrate conditions without ergothioneine added · L-Ergothioneine Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
substrate conditions without ergothioneine present · 3-Mercaptopyruvate Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "ergothioneine plus 3-mercaptopyruvate", "comparator": "substrate conditions without ergothioneine", "endpoint": "AzMC H2S-associated signal", "effect_direction": "increase", "combination": "joint", "conditions": [{"entity_slug": "ergothioneine", "state": "added"}, {"entity_slug": "3-mercaptopyruvate", "state": "present"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Purified human MPST activity assay using AzMC; reported buffer pH 11.
interpretation_status
Source-derived research curation; not independent raw-data verification.
limitations
The alkaline biochemical assay does not establish the same flux at physiological pH. Product signal is not proof of a structurally identified ergothioneine persulfide.
nutrient_topic
Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine
plain_language
Enzyme activation still needs its sulfur substrate.
primary_references
Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/
source_locator
Figure 3G; Figure S3K; STAR Methods, Recombinant MPST activity
Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 57–57
Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Purified human MPST activity assay using AzMC; reported buffer pH 11. · source_derived_draft · unverified_draft
Ergothioneine plus 3-mercaptopyruvate supported H2S release by recombinant human MPST.
Complete structured claim and evidence
Without 3-mercaptopyruvate, ergothioneine produced no detected H2S in the MPST and isolated-mitochondria assays.
L-Ergothioneine → Hydrogen sulfide / H2S source_derived_draftungraded
Experimental context and source evidence
evidence_access
Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.
experimental_condition
substrate-omission baseline controls present · L-Ergothioneine Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
substrate-omission baseline controls omitted · 3-Mercaptopyruvate Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "ergothioneine with 3-mercaptopyruvate omitted", "comparator": "substrate-omission baseline controls", "endpoint": "detectable H2S signal", "effect_direction": "no_detected_change", "combination": "joint", "conditions": [{"entity_slug": "ergothioneine", "state": "present"}, {"entity_slug": "3-mercaptopyruvate", "state": "omitted"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Recombinant MPST and isolated mitochondria; substrate-omission controls.
interpretation_status
Source-derived research curation; not independent raw-data verification.
limitations
This control is not evidence of a human 3-mercaptopyruvate deficiency threshold or a universal inability to release sulfur in other systems.
nutrient_topic
Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine
plain_language
Ergothioneine alone did not replace the substrate.
primary_references
Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/
source_locator
Figures S3K-S3L; Results
Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 65–65
Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Recombinant MPST and isolated mitochondria; substrate-omission controls. · source_derived_draft · unverified_draft
Without 3-mercaptopyruvate, ergothioneine produced no detected H2S in the MPST and isolated-mitochondria assays.
Complete structured claim and evidence
Ergothioneine increased basal and maximal respiration in wild-type human HeLa cells.
L-Ergothioneine → Basal and maximal respiration in ergothioneine-treated human HeLa cells source_derived_draftungraded
Experimental context and source evidence
dose
500 micromolar
duration
72 hours
evidence_access
Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.
experimental_condition
vehicle in wild-type HeLa cells added · L-Ergothioneine Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "500 micromolar ergothioneine for 72 hours", "comparator": "vehicle in wild-type HeLa cells", "endpoint": "basal and maximal oxygen consumption", "effect_direction": "increase", "combination": "single", "conditions": [{"entity_slug": "ergothioneine", "state": "added"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human HeLa cells; 500 micromolar ergothioneine for 72 hours, as stated unambiguously in supplementary Figure S2.
interpretation_status
Source-derived research curation; not independent raw-data verification.
limitations
Cancer-cell culture at this exposure is not a clinical supplementation result or proof of a nutritional requirement.
nutrient_topic
Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine
organism
Homo sapiens
plain_language
A human cell model showed a respiratory response.
primary_references
Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/
source_locator
Figure S2E, wild-type panels
Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 73–73
Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Human HeLa cells; 500 micromolar ergothioneine for 72 hours, as stated unambiguously in supplementary Figure S2. · source_derived_draft · unverified_draft
Ergothioneine increased basal and maximal respiration in wild-type human HeLa cells.
Complete structured claim and evidence
MPST-deleted HeLa cells showed no significant respiratory increase with ergothioneine versus vehicle.
L-Ergothioneine → Basal and maximal respiration in ergothioneine-treated human HeLa cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.
experimental_condition
vehicle in MPST-deleted HeLa cells 500 micromolar, 72 hours · L-Ergothioneine Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
vehicle in MPST-deleted HeLa cells CRISPR-Cas9 deletion · Human mercaptopyruvate sulfurtransferase / MPST Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "ergothioneine in MPST-deleted HeLa cells", "comparator": "vehicle in MPST-deleted HeLa cells", "endpoint": "basal and maximal oxygen consumption", "effect_direction": "no_detected_change", "combination": "joint", "conditions": [{"entity_slug": "ergothioneine", "state": "500 micromolar, 72 hours"}, {"entity_slug": "mpst", "state": "CRISPR-Cas9 deletion"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
CRISPR-Cas9 MPST-deleted human HeLa cells; 500 micromolar ergothioneine for 72 hours.
interpretation_status
Source-derived research curation; not independent raw-data verification.
limitations
The comparison is ergothioneine versus vehicle within knockout cells. It does not show that every protective action requires MPST, or that human dietary low intake mimics knockout.
nutrient_topic
Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine
plain_language
Loss of the target removed this measured response.
primary_references
Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/
source_locator
Figures S2E-S2F; Results
trigger_kind
machinery_impairment Imported condition classification; unverified.
Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 81–81
Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · CRISPR-Cas9 MPST-deleted human HeLa cells; 500 micromolar ergothioneine for 72 hours. · source_derived_draft · unverified_draft
MPST-deleted HeLa cells showed no significant respiratory increase with ergothioneine versus vehicle.
Complete structured claim and evidence
Four weeks of endurance training enriched ergothioneine in mouse skeletal-muscle mitochondrial isolates.
Voluntary wheel endurance training in mice → Ergothioneine concentration in mouse skeletal-muscle mitochondrial isolates source_derived_draftungraded
Experimental context and source evidence
evidence_access
Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.
experimental_condition
sedentary MITO-Tag mice four weeks · Voluntary wheel endurance training in mice Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "four-week voluntary wheel training", "comparator": "sedentary MITO-Tag mice", "endpoint": "muscle mitochondrial ergothioneine concentration", "effect_direction": "increase", "combination": "single", "conditions": [{"entity_slug": "mouse-voluntary-wheel-training", "state": "four weeks"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
MITO-Tag mice; gastrocnemius mitochondrial immunoprecipitation and targeted metabolomics.
interpretation_status
Source-derived research curation; not independent raw-data verification.
limitations
This is tissue-specific metabolite enrichment, not proof of a human deficiency threshold or the transport mechanism.
nutrient_topic
Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine
plain_language
Exercise changed the mitochondrial pool, not just intake.
primary_references
Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/
source_locator
Figure 1D-F
Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 89–89
Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · MITO-Tag mice; gastrocnemius mitochondrial immunoprecipitation and targeted metabolomics. · source_derived_draft · unverified_draft
Four weeks of endurance training enriched ergothioneine in mouse skeletal-muscle mitochondrial isolates.
Complete structured claim and evidence
Muscle PGC-1alpha overexpression increased Slc22a4 mRNA and protein in mice.
Mouse PGC-1alpha / Ppargc1a → Mouse ergothioneine transporter Octn1 / Slc22a4 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.
experimental_condition
wild-type mice muscle overexpression · Mouse PGC-1alpha / Ppargc1a Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "muscle-specific PGC-1alpha overexpression", "comparator": "wild-type mice", "endpoint": "Slc22a4 mRNA and protein", "effect_direction": "increase", "combination": "single", "conditions": [{"entity_slug": "mouse-ppargc1a", "state": "muscle overexpression"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
MCK-PGC-1alpha mice, gastrocnemius muscle, versus wild-type controls.
interpretation_status
Source-derived research curation; not independent raw-data verification.
limitations
Overexpression differs from physiological exercise and human diet; increased transporter abundance is not itself a measured transport flux.
nutrient_topic
Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine
plain_language
A regulatory programme can alter transporter abundance.
primary_references
Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/
source_locator
Figure 2D-E
Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 97–97
Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · MCK-PGC-1alpha mice, gastrocnemius muscle, versus wild-type controls. · source_derived_draft · unverified_draft
Muscle PGC-1alpha overexpression increased Slc22a4 mRNA and protein in mice.
Complete structured claim and evidence
PGC-1alpha-overexpressing mouse muscle contained more ergothioneine than control muscle.
Mouse PGC-1alpha / Ppargc1a → Ergothioneine concentration in mouse gastrocnemius muscle source_derived_draftungraded
Experimental context and source evidence
evidence_access
Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.
experimental_condition
wild-type mice muscle overexpression · Mouse PGC-1alpha / Ppargc1a Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "muscle-specific PGC-1alpha overexpression", "comparator": "wild-type mice", "endpoint": "whole-muscle ergothioneine concentration", "effect_direction": "increase", "combination": "single", "conditions": [{"entity_slug": "mouse-ppargc1a", "state": "muscle overexpression"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
MCK-PGC-1alpha mice; whole gastrocnemius metabolomics.
interpretation_status
Source-derived research curation; not independent raw-data verification.
limitations
Whole-muscle concentration is not the isolated mitochondrial pool. This does not establish that transporter upregulation is the only causal route.
nutrient_topic
Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine
plain_language
The muscle pool changed alongside transporter expression.
primary_references
Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/
source_locator
Figure 2F
Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 105–105
Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · MCK-PGC-1alpha mice; whole gastrocnemius metabolomics. · source_derived_draft · unverified_draft
PGC-1alpha-overexpressing mouse muscle contained more ergothioneine than control muscle.
Complete structured claim and evidence
An ergothioneine-enriched diet improved endurance performance in trained wild-type mice.
L-Ergothioneine → Endurance performance in the mouse ergothioneine diet experiment source_derived_draftungraded
Experimental context and source evidence
evidence_access
Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.
experimental_condition
control diet during the same training training · Voluntary wheel endurance training in mice Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
control diet during the same training diet enrichment · L-Ergothioneine Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "ergothioneine-enriched diet during endurance training", "comparator": "control diet during the same training", "endpoint": "wheel-running endurance performance", "effect_direction": "increase", "combination": "joint", "conditions": [{"entity_slug": "ergothioneine", "state": "diet enrichment"}, {"entity_slug": "mouse-voluntary-wheel-training", "state": "training"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Diet pre-feeding followed by voluntary wheel endurance training in mice.
interpretation_status
Source-derived research curation; not independent raw-data verification.
limitations
Diet plus training is a joint setting, not an ergothioneine-only sedentary intervention or a demonstrated human effect. The dose is not converted into a human recommendation.
nutrient_topic
Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine
plain_language
The target pathway has a measured mouse functional outcome.
primary_references
Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/
source_locator
Figure 4B-D; Figures S5C-S5D
Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 113–113
Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Diet pre-feeding followed by voluntary wheel endurance training in mice. · source_derived_draft · unverified_draft
An ergothioneine-enriched diet improved endurance performance in trained wild-type mice.
Complete structured claim and evidence
Mpst-null mice showed no endurance advantage from the ergothioneine-enriched diet versus control diet.
L-Ergothioneine → Endurance performance in the mouse ergothioneine diet experiment source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.
experimental_condition
control diet in trained Mpst-null mice training · Voluntary wheel endurance training in mice Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
control diet in trained Mpst-null mice diet enrichment · L-Ergothioneine Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
control diet in trained Mpst-null mice null · Mouse mercaptopyruvate sulfurtransferase / Mpst Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "ergothioneine-enriched diet in trained Mpst-null mice", "comparator": "control diet in trained Mpst-null mice", "endpoint": "endurance performance", "effect_direction": "no_detected_change", "combination": "joint", "conditions": [{"entity_slug": "ergothioneine", "state": "diet enrichment"}, {"entity_slug": "mouse-mpst", "state": "null"}, {"entity_slug": "mouse-voluntary-wheel-training", "state": "training"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mpst-null mouse diet and training comparison.
interpretation_status
Source-derived research curation; not independent raw-data verification.
limitations
This is a within-genotype diet comparison during training, not evidence of dietary ergothioneine deficiency or a universal requirement for all ergothioneine effects.
nutrient_topic
Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine
plain_language
Removing the mouse target removed the diet-associated performance benefit.
primary_references
Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/
source_locator
Figure 4G-J; Figures S5F-S5K
trigger_kind
machinery_impairment Imported condition classification; unverified.
Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 121–121
Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Mpst-null mouse diet and training comparison. · source_derived_draft · unverified_draft
Mpst-null mice showed no endurance advantage from the ergothioneine-enriched diet versus control diet.
Complete structured claim and evidence
Bound FAD cycles between reduction by sulfide and oxidation by ubiquinone during human SQOR catalysis.
FAD → Human sulfide:quinone oxidoreductase / SQOR source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract and figure descriptions.
experimental_model
Purified human sulfide:quinone oxidoreductase; transient kinetics and flavin spectroscopy.
interpretation_status
Source-derived research curation; not independent raw-data verification.
limitations
Enzyme-bound FAD is not extracellular FMN. This study did not test dietary B2 deficiency or combined B2 and ergothioneine treatment.
nutrient_topic
Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine
plain_language
Sulfur disposal has a flavin-dependent electron relay.
primary_references
Mishanina et al. Transient Kinetic Analysis of Hydrogen Sulfide Oxidation Catalyzed by Human Sulfide Quinone Oxidoreductase. DOI 10.1074/jbc.M115.682369; PMID 26318450; https://pubmed.ncbi.nlm.nih.gov/26318450/
source_locator
Abstract and Figure 1
Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 129–129
Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Purified human sulfide:quinone oxidoreductase; transient kinetics and flavin spectroscopy. · source_derived_draft · unverified_draft
Bound FAD cycles between reduction by sulfide and oxidation by ubiquinone during human SQOR catalysis.
Complete structured claim and evidence
Nanodisc-embedded human SQOR transferred sulfane sulfur to glutathione; kinetics supported GSH as the predominant physiological acceptor.
Human sulfide:quinone oxidoreductase / SQOR → Glutathione persulfide / GSSH source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary indexed abstract. Physiological acceptor assignment is a kinetic interpretation, not a direct measurement of flux in a patient.
experimental_model
Purified human SQOR in nanodiscs; steady-state and rapid-kinetic assays.
interpretation_status
Source-derived research curation; not independent raw-data verification.
limitations
Predominant acceptor is a kinetic interpretation; alternative acceptors can work in other assay conditions. Ergothioneine and nutrient depletion were not tested.
nutrient_topic
Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine
plain_language
Glutathione also participates in disposal of sulfide-derived sulfur.
primary_references
Landry et al. H2S oxidation by nanodisc-embedded human sulfide quinone oxidoreductase. DOI 10.1074/jbc.M117.788547; PMID 28512131; https://pubmed.ncbi.nlm.nih.gov/28512131/
source_locator
Abstract
Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 137–137
Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Purified human SQOR in nanodiscs; steady-state and rapid-kinetic assays. · source_derived_draft · unverified_draft
Nanodisc-embedded human SQOR transferred sulfane sulfur to glutathione; kinetics supported GSH as the predominant physiological acceptor.
Complete structured claim and evidence
Human MPST transfers sulfur from 3-mercaptopyruvate to its active-site Cys248, releasing pyruvate and forming an enzyme-bound persulfide.
Human mercaptopyruvate sulfurtransferase / MPST → 3-Mercaptopyruvate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and primary figure descriptions
experimental_model
Purified human MPST structure and kinetics at pH 7.4.
limitations
The upstream cysteine transamination is pathway context; this experiment does not identify its dominant human tissue isoenzyme.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A cysteine-derived intermediate hands sulfur to an enzyme before it reaches another acceptor.
primary_references
Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23698001/ · DOI 10.1074/jbc.M113.466177
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 452–458
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human MPST structure and kinetics at pH 7.4. · source_derived_draft · unverified_draft
## l-cysteine-mpst-sulfur-transfer A cysteine-derived intermediate hands sulfur to an enzyme before it reaches another acceptor. Human MPST transfers sulfur from 3-mercaptopyruvate to its active-site Cys248, releasing pyruvate and forming an enzyme-bound persulfide. Model: Purified human MPST structure and kinetics at pH 7.4. Limitations: The upstream cysteine transamination is pathway context; this experiment does not identify its dominant human tissue isoenzyme. Evidence access: Primary abstract and primary figure descriptions Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23698001/ · DOI 10.1074/jbc.M113.466177
Complete structured claim and evidence
Human MPST supported H2S production with thioredoxin and several low-molecular-weight acceptors, including cysteine, glutathione and dihydrolipoic acid.
Human mercaptopyruvate sulfurtransferase / MPST → Thiol acceptors in purified human MPST assays source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and primary figure descriptions
experimental_model
Purified human MPST kinetics; concentrations and acceptors varied.
limitations
Some small-thiol assays used millimolar concentrations; these are not demonstrated effects of oral cysteine or lipoic acid.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Sharing a sulfur-transfer route does not make these acceptors equally effective inside cells.
primary_references
Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23698001/ · DOI 10.1074/jbc.M113.466177
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 460–466
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human MPST kinetics; concentrations and acceptors varied. · source_derived_draft · unverified_draft
## l-cysteine-mpst-acceptor-choice Sharing a sulfur-transfer route does not make these acceptors equally effective inside cells. Human MPST supported H2S production with thioredoxin and several low-molecular-weight acceptors, including cysteine, glutathione and dihydrolipoic acid. Model: Purified human MPST kinetics; concentrations and acceptors varied. Limitations: Some small-thiol assays used millimolar concentrations; these are not demonstrated effects of oral cysteine or lipoic acid. Evidence access: Primary abstract and primary figure descriptions Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23698001/ · DOI 10.1074/jbc.M113.466177
Complete structured claim and evidence
Thioredoxin showed substrate inhibition in human MPST assays and increased the apparent Km for 3-mercaptopyruvate relative to other acceptors.
Thioredoxin / TXN → Human mercaptopyruvate sulfurtransferase / MPST source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant human MPST isoform kinetics.
limitations
Predicted tissue sulfur allocation was based on simulations; no human dietary response was measured.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
More of a redox partner did not simply produce a faster reaction.
primary_references
Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32179647/ · DOI 10.1074/jbc.RA120.012616
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 468–474
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human MPST isoform kinetics. · source_derived_draft · unverified_draft
## l-cysteine-mpst-thioredoxin-inhibition More of a redox partner did not simply produce a faster reaction. Thioredoxin showed substrate inhibition in human MPST assays and increased the apparent Km for 3-mercaptopyruvate relative to other acceptors. Model: Recombinant human MPST isoform kinetics. Limitations: Predicted tissue sulfur allocation was based on simulations; no human dietary response was measured. Evidence access: Primary abstract Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32179647/ · DOI 10.1074/jbc.RA120.012616
Complete structured claim and evidence
N-acetylcysteine was a poor MPST sulfur acceptor in the reported kinetic experiments.
N-Acetyl-L-cysteine → Human mercaptopyruvate sulfurtransferase / MPST source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant human MPST assays.
limitations
This does not negate NAC metabolism to cysteine or its other mechanisms.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A cysteine precursor does not necessarily substitute for cysteine in each chemical reaction.
primary_references
Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32179647/ · DOI 10.1074/jbc.RA120.012616
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 476–482
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human MPST assays. · source_derived_draft · unverified_draft
## l-cysteine-mpst-nac-distinction A cysteine precursor does not necessarily substitute for cysteine in each chemical reaction. N-acetylcysteine was a poor MPST sulfur acceptor in the reported kinetic experiments. Model: Recombinant human MPST assays. Limitations: This does not negate NAC metabolism to cysteine or its other mechanisms. Evidence access: Primary abstract Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32179647/ · DOI 10.1074/jbc.RA120.012616
Complete structured claim and evidence
CoQ serves as electron acceptor for SQOR at the start of mitochondrial sulfide oxidation.
Human sulfide:quinone oxidoreductase / SQOR → Ubiquinone source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coq10-research/27856618.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8b98767d3bed9661c05c7b82b55817b6d9912abd8bfc9dd9d59ca9763025485", "start_char": 0, "end_char": 1261, "text_sha256": "a8b98767d3bed9661c05c7b82b55817b6d9912abd8bfc9dd9d59ca9763025485"}
experimental_model
Patient fibroblasts, biosynthesis inhibition and mouse genetics
exposure
Genetic or pharmacological CoQ depletion and in-vitro repletion
limitations
Tissue-specific disease models; mouse residual percentages are not diagnostic human thresholds.
nutrient_topic
Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system
organism
Human fibroblasts/HeLa cells and Pdss2 mutant mice
plain_language
CoQ connects energy metabolism to sulfur disposal.
primary_references
[coq10-p27856618] Coenzyme Q deficiency causes impairment of the sulfide oxidation pathway. (2017). https://pubmed.ncbi.nlm.nih.gov/27856618/ DOI: 10.15252/emmm.201606356
tissue_or_cell_type
Sulfide oxidation and tissue CoQ
Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 528–539
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient fibroblasts, biosynthesis inhibition and mouse genetics · source_derived_draft · unverified_draft
### coq10-sqor-electron-acceptor CoQ serves as electron acceptor for SQOR at the start of mitochondrial sulfide oxidation. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CoQ connects energy metabolism to sulfur disposal. organism: Human fibroblasts/HeLa cells and Pdss2 mutant mice tissue_or_cell_type: Sulfide oxidation and tissue CoQ experimental_model: Patient fibroblasts, biosynthesis inhibition and mouse genetics limitations: Tissue-specific disease models; mouse residual percentages are not diagnostic human thresholds. exposure: Genetic or pharmacological CoQ depletion and in-vitro repletion evidence_span: {"source_cache": "artifacts/coq10-research/27856618.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8b98767d3bed9661c05c7b82b55817b6d9912abd8bfc9dd9d59ca9763025485", "start_char": 0, "end_char": 1261, "text_sha256": "a8b98767d3bed9661c05c7b82b55817b6d9912abd8bfc9dd9d59ca9763025485"} [coq10-p27856618] Coenzyme Q deficiency causes impairment of the sulfide oxidation pathway. (2017). https://pubmed.ncbi.nlm.nih.gov/27856618/ DOI: 10.15252/emmm.201606356
Complete structured claim and evidence
Human RFK phosphorylates riboflavin to FMN using ATP, yielding ADP; this precedes FLAD1-mediated FAD synthesis.
Riboflavin kinase / RFK → Riboflavin (vitamin B2) source_derived_draftungraded
Experimental context and source evidence
evidence_location
Abstract and product-bound structure
experimental_model
Human RFK structural and catalytic mechanism study
exposure
Purified RFK with flavin and adenine nucleotide ligands.
limitations
Reaction chemistry does not imply RFK controls every tissue flavin pool to the same extent.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
RFK performs the first activation step from riboflavin to FMN.
primary_references
[transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t
tissue_or_cell_type
Purified protein
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 293–304
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RFK structural and catalytic mechanism study · source_derived_draft · unverified_draft
### transport-rfk-phosphorylation Human RFK phosphorylates riboflavin to FMN using ATP, yielding ADP; this precedes FLAD1-mediated FAD synthesis. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: RFK performs the first activation step from riboflavin to FMN. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Human RFK structural and catalytic mechanism study limitations: Reaction chemistry does not imply RFK controls every tissue flavin pool to the same extent. exposure: Purified RFK with flavin and adenine nucleotide ligands. evidence_location: Abstract and product-bound structure [transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t
Complete structured claim and evidence
Recombinant human FLAD1 isoforms 1 and 2 exhibited FAD synthetase activity; isoform 2 was purified, and activity required MgCl2.
Human FAD synthetase isoform 2 → FAD source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2 activation and Mg-dependent FAD synthesis provide a biochemical partner to B1-dependent complexes; direct transfer of newly made FAD to DLD was not tested.
evidence
[{"paper_key": "brizio-2006-fad", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Recombinant human FLAD1 isoforms expressed in E. coli.
limitations
No tissue Mg threshold or combined B1/B2 deficiency experiment.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The flavin used by E3 must first be made from the riboflavin pathway. This distinct magnesium-dependent synthesis reaction should not be confused with magnesium binding to B1 enzymes.
primary_references
[brizio-2006-fad] Over-expression in Escherichia coli and characterization of two recombinant isoforms of human FAD synthetase (2006). https://pubmed.ncbi.nlm.nih.gov/16643857/ DOI: 10.1016/j.bbrc.2006.04.003
tissue_or_cell_type
Purified/expressed proteins
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 745–757
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human FLAD1 isoforms expressed in E. coli. · source_derived_draft · unverified_draft
### b1-fad-b2-cofactor-synthesis Recombinant human FLAD1 isoforms 1 and 2 exhibited FAD synthetase activity; isoform 2 was purified, and activity required MgCl2. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The flavin used by E3 must first be made from the riboflavin pathway. This distinct magnesium-dependent synthesis reaction should not be confused with magnesium binding to B1 enzymes. organism: Homo sapiens tissue_or_cell_type: Purified/expressed proteins experimental_model: Recombinant human FLAD1 isoforms expressed in E. coli. limitations: No tissue Mg threshold or combined B1/B2 deficiency experiment. evidence: [{"paper_key": "brizio-2006-fad", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B2 activation and Mg-dependent FAD synthesis provide a biochemical partner to B1-dependent complexes; direct transfer of newly made FAD to DLD was not tested. nutrient: Thiamine (vitamin B1) [brizio-2006-fad] Over-expression in Escherichia coli and characterization of two recombinant isoforms of human FAD synthetase (2006). https://pubmed.ncbi.nlm.nih.gov/16643857/ DOI: 10.1016/j.bbrc.2006.04.003
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.

Cellular entry can be the limiting step

Condition: machinery_impairment · SLC22A4 RNA interference in human cultured cells.

Normal role: Available ergothioneine can enter through transporters and participate in context-dependent redox or signaling responses.

Recorded consequence: Reduced protection against DNA, lipid and endothelial injury.

Scope: Species, exposure and manipulation are specified on each linked primary-source record.

Transporter loss reduces mitochondrial uptake but leaves a residual route

Condition: machinery_impairment · Mouse Slc22a4/Octn1 genetic knockout.

Normal role: Ergothioneine can enter mitochondrial preparations.

Recorded consequence: Mitochondrial uptake was impaired but remained detectable.

Scope: The 2024 isolated mouse mitochondrial experiment.

Transporter deletion nearly empties the animal pool

Condition: machinery_impairment · Zebrafish ETT knockout.

Normal role: Available ergothioneine can enter through transporters and participate in context-dependent redox or signaling responses.

Recorded consequence: Very low ergothioneine and increased skin oxidation marker.

Scope: Species, exposure and manipulation are specified on each linked primary-source record.

MPST deletion removes a measured ergothioneine respiratory response

Condition: machinery_impairment · CRISPR-Cas9 MPST deletion.

Normal role: Ergothioneine increased respiration in wild-type HeLa cells.

Recorded consequence: No significant respiratory increase versus vehicle in the deleted cells.

Scope: Human cancer-cell model; specified exposure and oxygen-consumption endpoint.

Sirtuin perturbation removes a protective response

Condition: machinery_impairment · SIRT1 inhibition or SIRT6 siRNA in endothelial cells.

Normal role: Available ergothioneine can enter through transporters and participate in context-dependent redox or signaling responses.

Recorded consequence: High-glucose senescence protection is lost.

Scope: Species, exposure and manipulation are specified on each linked primary-source record.

Mouse Mpst loss removes the dietary endurance response

Condition: machinery_impairment · Mouse Mpst genetic loss.

Normal role: An enriched ergothioneine diet improved endurance in trained wild-type mice.

Recorded consequence: No significant endurance advantage from enriched versus control diet within the null genotype.

Scope: Mouse diet and voluntary-wheel training study.

A nonspecific transporter inhibitor changes neuronal protection

Condition: machinery_impairment · Verapamil in human neuronal cultures.

Normal role: Available ergothioneine can enter through transporters and participate in context-dependent redox or signaling responses.

Recorded consequence: Ergothioneine-associated protection is abrogated, without exclusive target identification.

Scope: Species, exposure and manipulation are specified on each linked primary-source record.

Antioxidant signaling is part of the hearing-cell response

Condition: machinery_impairment · Nrf2 silencing in the experimental cochlear model.

Normal role: Available ergothioneine can enter through transporters and participate in context-dependent redox or signaling responses.

Recorded consequence: Protective signaling weakens.

Scope: Species, exposure and manipulation are specified on each linked primary-source record.

Removing an injury-pathway target prevents deficits

Condition: machinery_impairment · Hippocampal neuronal PTP1B deletion in mice.

Normal role: Available ergothioneine can enter through transporters and participate in context-dependent redox or signaling responses.

Recorded consequence: Olanzapine-associated deficits are prevented.

Scope: Species, exposure and manipulation are specified on each linked primary-source record.

Environmental shortage changes bacterial competition

Condition: nutrient_deficiency · Affinity depletion of ergothioneine from bacterial medium.

Normal role: Available ergothioneine can enter through transporters and participate in context-dependent redox or signaling responses.

Recorded consequence: Wild-type transporter-dependent competitive advantage requires available substrate.

Scope: Species, exposure and manipulation are specified on each linked primary-source record.

Dialysis removal accompanies low circulating pools

Condition: biomarker_context · Hemodialysis or peritoneal dialysis in human cohorts.

Normal role: Available ergothioneine can enter through transporters and participate in context-dependent redox or signaling responses.

Recorded consequence: Measured clearance and low erythrocyte concentrations; benefit of repletion remains unknown.

Scope: Species, exposure and manipulation are specified on each linked primary-source record.

Drug-associated lower pools need causal interpretation

Condition: biomarker_context · Chronic antipsychotic exposure in mice and a human blood comparison.

Normal role: Available ergothioneine can enter through transporters and participate in context-dependent redox or signaling responses.

Recorded consequence: Lower blood/brain measurements are separate from mouse target interventions.

Scope: Species, exposure and manipulation are specified on each linked primary-source record.

Related blood compounds can track intake

Condition: biomarker_context · Pure ergothioneine administration in healthy people.

Normal role: Available ergothioneine can enter through transporters and participate in context-dependent redox or signaling responses.

Recorded consequence: Correlated hercynine and S-methyl-ergothioneine suggest metabolism but do not identify enzymes.

Scope: Species, exposure and manipulation are specified on each linked primary-source record.

A circulating marker predicts outcomes without proving prevention

Condition: biomarker_context · Baseline plasma ergothioneine in a prospective cohort.

Normal role: Available ergothioneine can enter through transporters and participate in context-dependent redox or signaling responses.

Recorded consequence: Higher levels correlate with lower cardiovascular and mortality risk.

Scope: Species, exposure and manipulation are specified on each linked primary-source record.

A changed active-site residue blocks synthesis rescue

Condition: machinery_impairment · EgtD deletion followed by T213E or T213A complementation in M. tuberculosis.

Normal role: Available ergothioneine can enter through transporters and participate in context-dependent redox or signaling responses.

Recorded consequence: The T213E protein fails to restore ergothioneine; the physiological phosphorylation interpretation remains disputed.

Scope: Species, exposure and manipulation are specified on each linked primary-source record.

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.

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02)Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · unverified_draftRead preserved source
Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19)AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19)AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19)AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
L-Lysine: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. 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.

Does PknD phosphorylate EgtD to regulate microbial ergothioneine synthesis?The 2015 primary study reported PknD-dependent EgtD Thr213 phosphorylation in vitro and in a cell-based system. The 2020 primary reexamination directly tested and rejected EgtD as a PknD substrate under its in vitro conditions. This is a research disagreement, not correction of ledger wording.Read the recorded disagreement

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.

Which transporter accounts for mitochondrial ergothioneine uptake remaining after mouse Octn1 loss?The knockout result supports residual uptake but identifies no alternative membrane transporter.
What are the verified binding and exposure units in the original publisher PDF?Some main-text indexed OCR replaces micro-unit symbols with milli-unit symbols. No ambiguous binding constant or main-text concentration was imported; check original figure pixels before a quantitative update.
Does the recombinant MPST/ergothioneine effect persist at physiological pH and with directly identified sulfur intermediates?The reported activity assay uses pH 11. Direct binding and cellular genetic evidence do not establish the exact chemical intermediate or physiological reaction rate.
Do low tissue ergothioneine pools cause a validated human deficiency syndrome through MPST?Transporter/target knockout, culture exposure and mouse exercise findings cannot set a human dietary deficiency threshold.
Which tissue-specific cysteine transamination route supplies 3-mercaptopyruvate during an ergothioneine response?Existing MPST evidence establishes substrate use, not a universal human isoenzyme, PLP bottleneck or nutritional B6 interaction.

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

Evidence, AI assistance and curation standards

L-Ergothioneine

The mechanisms

Expression of human SLC22A4 in HEK293 cells produced efficient, sodium-dependent ergothioneine uptake and intracellular retention.

Rat Slc22a4-mediated ergothioneine uptake was saturable, pH-sensitive and sodium-dependent, with approximately 1:1 sodium:substrate stoichiometry.

Wild-type human SLC22A4 did not mediate carnitine transport in the comparative HEK293 expression assay.

Wild-type human SLC22A5 did not transport ergothioneine in the comparative expression assay.

Human SLC22A15 expression enabled uptake of ergothioneine in HEK293 substrate assays.

Human SLC22A15 expression enabled uptake of carnosine in HEK293 substrate assays.

Human SLC22A15 expression enabled uptake of carnitine in HEK293 substrate assays.

Human SLC22A15 expression enabled uptake of thiamine in HEK293 substrate assays.

RNA-interference depletion of SLC22A4 made human cultured cells more susceptible to oxidant-associated mitochondrial DNA damage.

SLC22A4-depleted human cells showed increased protein oxidation and lipid peroxidation under oxidative stress.

Zebrafish ETT knockout lowered ergothioneine content by more than 1000-fold.

ETT-knockout zebrafish had 3.8-fold higher skin 8-oxoguanine; lipid-oxidation differences appeared after lead or copper stress.

In pulse-radiolysis assays, ascorbate rapidly reduced the one-electron-oxidized ergothioneine transient back toward ergothioneine, forming ascorbyl radicals.

Ergothioneine bound copper(I), rather than copper(II), and formed a redox-inactive complex in the tested chemical systems.

Ergothioneine at 0.1-1 mM protected DNA and albumin against 0.1 mM copper with ascorbate or peroxide.

At pH 7.4, ergothioneine and hercynine generated different products after chemically generated singlet oxygen exposure.

In the singlet-oxygen assay, 5 mM glutathione almost abolished net ergothioneine loss even though formation of selected products persisted.

Ergothioneine protected against peroxynitrite-induced tyrosine nitration in vitro.

Ergothioneine limited peroxynitrite-mediated inactivation of alpha-1-antiproteinase in vitro.

Reconstituted Mycobacterium smegmatis biosynthesis used a methyltransferase to add three methyl groups to the histidine alpha-amino group, producing hercynine.

Reconstituted Mycobacterium smegmatis biosynthesis required an iron(II)-dependent oxidative sulfurization step.

Mycobacterium thermoresistibile EgtB coupled gamma-glutamylcysteine to hercynine through an oxygen-dependent C-S bond-forming reaction.

Mycobacterium smegmatis EgtC removes the glutamyl portion of the ergothioneine-pathway sulfur adduct.

Purified Mycobacterium smegmatis EgtE catalyzed a PLP-dependent C-S lyase reaction in ergothioneine biosynthesis.

Biochemical characterization of Mycobacterium smegmatis EgtE supported sulfoxide substrate processing through a sulfenic-acid intermediate toward ergothioneine.

Chlorobium limicola enzymes synthesized ergothioneine without oxygen through a rhodanese-like sulfur-transfer route.

Structural and kinetic analyses of Chlorobium limicola EanB supported sulfurization of hercynine in anaerobic ergothioneine synthesis.

Streptococcus pneumoniae spd_1642-1643 encoded an ergothioneine-specific ABC uptake transporter.

The Streptococcus pneumoniae EgtUC domain recognized the betaine and thioimidazole portions of ergothioneine with high specificity.

In ergothioneine-controlled culture medium, wild-type Helicobacter pylori required available ergothioneine to outcompete its transporter-deficient strain.

The reconstituted bacterial catabolic pathway began with ergothionase and generated trimethylamine as one endpoint.

Paenibacillus thiourocanate hydratase had structural features distinguishing it from histidine-pathway urocanate hydratases.

The reconstituted bacterial pathway converted ergothioneine into glutamate, trimethylamine, hydrogen sulfide, carbon dioxide and ammonia.

SLC22A4 siRNA reduced ergothioneine uptake and abolished its cytoprotection in human brain microvascular endothelial cells.

Ergothioneine decreased NOX1 expression in the human endothelial-cell study.

Ergothioneine increased glutathione reductase expression in human brain microvascular endothelial cells.

Ergothioneine increased catalase expression in human brain microvascular endothelial cells.

Ergothioneine protected isolated rat basilar-artery relaxation during oxidative/high-glucose stress and improved responses after chronic treatment in diabetic rats.

Ergothioneine at 0.1-0.3 mM reduced IL-1beta-induced vascular cell adhesion molecule 1 expression in human aortic endothelial cells.

Ergothioneine at 0.1-0.3 mM reduced IL-1beta-induced intercellular adhesion molecule 1 expression in human aortic endothelial cells.

Ergothioneine at 0.1-0.3 mM reduced IL-1beta-induced E-selectin expression in human aortic endothelial cells.

At 1-3 mM pretreatment, ergothioneine reduced U937 monocyte attachment to IL-1beta-stimulated human aortic endothelial cells.

In the endothelial high-glucose experiment, ergothioneine increased SIRT1/SIRT6 expression and reduced senescence-associated responses.

SIRT1 activity inhibition or SIRT6 siRNA abolished ergothioneine protection against high-glucose-induced endothelial senescence.

Ergothioneine treatment reduced inflammatory and matrix-degrading responses in IL-1beta-stimulated mouse chondrocytes through a reported Sirt6/NF-kappaB axis.

Adding 1 mM ergothioneine for 24 hours reduced IL-18 production in placental explants from women with gestational diabetes.

Ergothioneine limited 6-hydroxydopamine-associated mitochondrial depolarization and mitochondrial ROS increases in human iPSC-derived dopaminergic neurons and SH-SY5Y cells.

Ergothioneine limited ATP loss, protein carbonylation and tyrosine hydroxylase loss in the human 6-OHDA cell experiments.

Verapamil abrogated ergothioneine protection in the human neuronal-cell study.

Ergothioneine reduced cisplatin-associated auditory threshold shifts by about 30 dB in the mouse comparison.

Nrf2 silencing supported Nrf2 dependence of ergothioneine protection in the cisplatin ototoxicity study.

Chronic olanzapine treatment in mice reduced blood and brain ergothioneine alongside altered microbiota and cognitive deficits.

The study also found lower blood ergothioneine in olanzapine-treated patients.

Ergothioneine supplementation inhibited hippocampal PTP1B-associated signaling and mitigated synaptic/cognitive impairment in olanzapine-treated mice.

Hippocampal neuronal-specific PTP1B deletion prevented olanzapine-induced synaptic and cognitive deficits in mice.

In a 10-man crossover study, mushroom meals containing 8 or 16 grams of mushroom powder produced postprandial erythrocyte ergothioneine uptake.

Oral pure ergothioneine increased plasma and whole-blood concentrations in healthy volunteers, with urinary recovery below 4% of the administered amount.

Human whole-blood ergothioneine correlated with hercynine and S-methyl-ergothioneine, consistent with possible metabolism.

Most oxidative-damage and inflammation marker changes after pure ergothioneine administration were not statistically significant.

In 3236 initially CVD- and diabetes-free participants, higher baseline ergothioneine predicted lower coronary disease and mortality over a median 21.4 years.

A 19-person randomized MCI pilot reported improved verbal-learning performance with 25 mg ergothioneine three times weekly for one year.

Plasma neurofilament light remained stable in the ergothioneine arm of the 19-person MCI pilot while increasing in placebo recipients.

Daily oral ergothioneine at approximately 4-5 mg/kg from seven weeks of age extended lifespan in male mice.

Ergothioneine-treated aging male mice showed preserved learning/memory with changes in neurogenesis, TDP43 aggregation and microglial phenotype.

Hemodialysis cleared ergothioneine at 146 +/- 36 mL/min in the measured cohort, exceeding urinary removal in controls and CKD participants.

Erythrocyte ergothioneine averaged 8% of control levels in hemodialysis participants and 24% in advanced CKD participants.

In a later comparison, erythrocyte ergothioneine averaged 34% of control levels during peritoneal dialysis versus 10% during hemodialysis.

Mycobacterium smegmatis EgtD uses SAM-dependent methyl transfer to convert histidine into hercynine.

The described Mycobacterium smegmatis pathway uses EgtA to condense glutamate and cysteine into gamma-glutamylcysteine.

Ergothioneine increased superoxide dismutase expression in the human endothelial-cell experiment.

The 2015 Mycobacterium tuberculosis study reported PknD phosphorylation of EgtD at Thr213 in vitro and in a cell-based system.

The 2020 reexamination found that Mycobacterium tuberculosis EgtD was not a PknD substrate under its in vitro conditions.

EgtD T213E failed to restore ergothioneine synthesis in a Mycobacterium tuberculosis egtD-deletion strain, unlike T213A.

Human OCTN2 expression increased sodium-dependent carnitine uptake with an apparent Km of 4.34 micromolar.

Human OCTN2 transport measurements were consistent with approximately one sodium ion accompanying each carnitine molecule.

GSR reduces one glutathione-disulfide molecule to two reduced glutathione molecules using the NADPH/FAD catalytic relay.

Marginally B2-deficient subjects had lower erythrocyte glutathione reductase activity than controls across the study comparison.

Purified rat liver thioredoxin reductase decreased ascorbyl radical measured by electron paramagnetic resonance while consuming NADPH; DHA controls could not explain the signal.