Ferric iron

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Ferrous iron (tested_ion); Manganese(II) ion (comparison_ion); TMEM165 Golgi cation-homeostasis protein (affected_protein)

evidence_span

{"source_cache": "artifacts/manganese-glycosylation-sources/serum2020.txt", "locator": "Results and Figure 8; comparative ion rescue", "file_sha256": "203365df4c837f50483da9ec16cb0882674cf4903bbda21aa7374205d72ade69", "start_char": 8502, "end_char": 9711, "text_sha256": "beb10a451c339fb08a468255ff298f79c3617f1b83b0c2f4a31a4470d2e46aa6", "text_characters": 1209}

experimental_model

TMEM165-knockout HEK cell cultures with different fetal bovine serum lots

exposure

Fe(II), Fe(III) or Mn(II), each at 5 micromolar for 16 hours in the Figure 8 comparison.

limitations

Serum manganese contributes to the result but is not the sole determinant. These are medium concentrations, not blood thresholds or supplementation regimens.

nutrient_topic

Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese

organism

Homo sapiens

plain_language

Iron changed this cellular readout but did not act as an equivalent manganese replacement.

primary_references

[mn-gly-serum2020] Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. (2020). https://pubmed.ncbi.nlm.nih.gov/31415112/ DOI: 10.1002/jimd.12161

tissue_or_cell_type

Golgi glycosylation in HEK cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 852–864

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · TMEM165-knockout HEK cell cultures with different fetal bovine serum lots · source_derived_draft · unverified_draft

### mn-gly-iron-glycan-partial At 5 micromolar, both Fe(III) and Fe(II) produced partially glycosylated LAMP2 forms; manganese was more effective in the compared culture conditions. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron changed this cellular readout but did not act as an equivalent manganese replacement. organism: Homo sapiens tissue_or_cell_type: Golgi glycosylation in HEK cells experimental_model: TMEM165-knockout HEK cell cultures with different fetal bovine serum lots limitations: Serum manganese contributes to the result but is not the sole determinant. These are medium concentrations, not blood thresholds or supplementation regimens. exposure: Fe(II), Fe(III) or Mn(II), each at 5 micromolar for 16 hours in the Figure 8 comparison. cross_nutrient: Ferrous iron (tested_ion); Manganese(II) ion (comparison_ion); TMEM165 Golgi cation-homeostasis protein (affected_protein) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/serum2020.txt", "locator": "Results and Figure 8; comparative ion rescue", "file_sha256": "203365df4c837f50483da9ec16cb0882674cf4903bbda21aa7374205d72ade69", "start_char": 8502, "end_char": 9711, "text_sha256": "beb10a451c339fb08a468255ff298f79c3617f1b83b0c2f4a31a4470d2e46aa6", "text_characters": 1209} [mn-gly-serum2020] Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. (2020). https://pubmed.ncbi.nlm.nih.gov/31415112/ DOI: 10.1002/jimd.12161

evidence_access

Primary abstract

experimental_model

Spectroscopy, mass spectrometry and electrochemistry.

limitations

Solvent-specific chemistry does not establish intestinal iron depletion.

nutrient_topic

Luteolin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Luteolin / 3′,4′,5,7-tetrahydroxyflavone

plain_language

Iron binding depends on chemical conditions.

primary_references

Spectroscopic and electrochemical studies on the evaluation of the radical scavenging activities of luteolin by chelating iron · 2014 · https://pubs.rsc.org/en/content/articlelanding/2014/ra/c4ra01396d · DOI 10.1039/C4RA01396D

Luteolin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 300–306

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Spectroscopy, mass spectrometry and electrochemistry. · source_derived_draft · unverified_draft

## luteolin-iron-binding Iron binding depends on chemical conditions. Luteolin formed a 1:1 Fe(III) complex in ethanol, with the B-ring catechol assigned as the binding site. Model: Spectroscopy, mass spectrometry and electrochemistry. Limitations: Solvent-specific chemistry does not establish intestinal iron depletion. Evidence access: Primary abstract Spectroscopic and electrochemical studies on the evaluation of the radical scavenging activities of luteolin by chelating iron · 2014 · https://pubs.rsc.org/en/content/articlelanding/2014/ra/c4ra01396d · DOI 10.1039/C4RA01396D

evidence_access

Primary abstract

experimental_model

Cell-free EXAFS spectroscopy; acidic aqueous solutions at pH 2 and 4.

limitations

Chemical binding does not establish human intestinal uptake or correction of iron deficiency.

nutrient_topic

Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)

plain_language

The organic fraction bound ferric iron.

primary_references

EXAFS study on the reactions between iron and fulvic acid in acid aqueous solutions. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18504967/ · DOI 10.1021/es072092z

Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 92–98

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free EXAFS spectroscopy; acidic aqueous solutions at pH 2 and 4. · source_derived_draft · unverified_draft

## fulvic-acid-iron-complex The organic fraction bound ferric iron. The tested fulvic fraction formed iron(III) complexes within 15 minutes. Model: Cell-free EXAFS spectroscopy; acidic aqueous solutions at pH 2 and 4. Limitations: Chemical binding does not establish human intestinal uptake or correction of iron deficiency. Evidence access: Primary abstract EXAFS study on the reactions between iron and fulvic acid in acid aqueous solutions. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18504967/ · DOI 10.1021/es072092z

acting_entity

s-allylcysteine

dose

Not specified in accessed abstract

duration

Not specified in accessed abstract

evidence_access

Primary abstract

experimental_comparison

SAC in metal-binding and oxidative challenge assays

experimental_model

Ferrozine, electrochemistry and rat brain homogenate

interpretation_status

Source-derived research curation; not independent primary verification

limitations

Does not establish iron depletion, removal from human tissues or treatment of iron overload.

nutrient_topic

S-allylcysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · S-allyl-L-cysteine / SAC

organism

Cell-free assays and rat brain preparation

plain_language

A second oxidation state was examined.

primary_references

[18422331] Antioxidant and iron-binding properties of curcumin, capsaicin, and S-allylcysteine reduce oxidative stress in rat brain homogenate. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18422331/ · DOI 10.1021/jf0734931

route

In vitro

tissue_or_cell_type

Ferrozine, electrochemistry and rat brain homogenate

S-allylcysteine: sulfur signaling, redox responses and cross-nutrient mechanisms (2026-09-20) · lines 122–129

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Ferrozine, electrochemistry and rat brain homogenate · source_derived_draft · unverified_draft

## s-allylcysteine-iron-iii-binding A second oxidation state was examined. Electrochemical measurements supported SAC binding of Fe3+; rat-brain assays also showed reduced iron-associated lipid peroxidation. Model: Ferrozine, electrochemistry and rat brain homogenate Limitations: Does not establish iron depletion, removal from human tissues or treatment of iron overload. Evidence access: Primary abstract [18422331] Antioxidant and iron-binding properties of curcumin, capsaicin, and S-allylcysteine reduce oxidative stress in rat brain homogenate. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18422331/ · DOI 10.1021/jf0734931 Structured context: {"organism": "Cell-free assays and rat brain preparation", "tissue_or_cell_type": "Ferrozine, electrochemistry and rat brain homogenate", "dose": "Not specified in accessed abstract", "duration": "Not specified in accessed abstract", "route": "In vitro", "experimental_comparison": "SAC in metal-binding and oxidative challenge assays", "acting_entity": "s-allylcysteine", "interpretation_status": "Source-derived research curation; not independent primary verification"}

evidence_span

{"source_cache": "artifacts/nasunin-research/10100509.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c9b0aa305d8c03dd6b8fe8c1fae505dc50b3347a43c00387e01d4e36ecd04c09", "start_char": 0, "end_char": 1400, "text_sha256": "c9b0aa305d8c03dd6b8fe8c1fae505dc50b3347a43c00387e01d4e36ecd04c09"}

experimental_model

ESR spin trapping, spectrophotometry and tissue-homogenate oxidation

exposure

Nasunin isolated from Chouja eggplant; 1 micromolar homogenate experiment

limitations

Homogenates do not establish brain entry or neuronal protection after oral intake. SOD-equivalent units are assay calibration, not SOD induction.

nutrient_topic

Nasunin research collection; topical membership is not evidence of a direct dietary effect. · Nasunin

organism

Cell-free chemistry and rat brain homogenates

plain_language

Binding iron can change its chemical availability.

primary_references

[nasunin-p10100509] Antioxidant activity of nasunin, an anthocyanin in eggplant. (1998). https://pubmed.ncbi.nlm.nih.gov/10100509/

tissue_or_cell_type

Iron complex formation and lipid oxidation

Nasunin: identity, redox chemistry and nutrient connections (2026-09-17) · lines 536–547

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ESR spin trapping, spectrophotometry and tissue-homogenate oxidation · source_derived_draft · unverified_draft

### nasunin-ferric-complex Spectrophotometry indicated a 2:1 nasunin:Fe(III) complex. Condition category: normal nutrient_topic: Nasunin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Binding iron can change its chemical availability. organism: Cell-free chemistry and rat brain homogenates tissue_or_cell_type: Iron complex formation and lipid oxidation experimental_model: ESR spin trapping, spectrophotometry and tissue-homogenate oxidation limitations: Homogenates do not establish brain entry or neuronal protection after oral intake. SOD-equivalent units are assay calibration, not SOD induction. exposure: Nasunin isolated from Chouja eggplant; 1 micromolar homogenate experiment evidence_span: {"source_cache": "artifacts/nasunin-research/10100509.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c9b0aa305d8c03dd6b8fe8c1fae505dc50b3347a43c00387e01d4e36ecd04c09", "start_char": 0, "end_char": 1400, "text_sha256": "c9b0aa305d8c03dd6b8fe8c1fae505dc50b3347a43c00387e01d4e36ecd04c09"} [nasunin-p10100509] Antioxidant activity of nasunin, an anthocyanin in eggplant. (1998). https://pubmed.ncbi.nlm.nih.gov/10100509/

evidence_span

{"source_cache": "artifacts/chlorogenic_acid-research/9501514.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb573ad7da5b27974eff1c3a31d52becf53a72ffe3216703743aab82eacef1b7", "start_char": 0, "end_char": 797, "text_sha256": "eb573ad7da5b27974eff1c3a31d52becf53a72ffe3216703743aab82eacef1b7"}

experimental_model

Spectroscopy, ESR, NMR and iron-driven lipid-oxidation experiments

exposure

CGA concentration series; iron-EDTA and iron-ADP comparisons

limitations

Chemical prevention of radical formation is distinct from radical scavenging. These assays do not measure human mineral stores, oral chelation therapy or clinical disease prevention.

nutrient_topic

Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. · Chlorogenic acid / 5-O-caffeoylquinic acid

organism

Cell-free chemistry and bovine liver microsomes

plain_language

Preventing a radical from forming differs from catching one after it forms.

primary_references

[chlorogenic_acid-p9501514] Iron chelation by chlorogenic acid as a natural antioxidant. (1998). https://pubmed.ncbi.nlm.nih.gov/9501514/ DOI: 10.1271/bbb.62.22

tissue_or_cell_type

Ferric complexes, Fenton-type chemistry and microsomal lipids

Chlorogenic acid: metabolism, signaling and nutrient connections (2026-09-17) · lines 711–722

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Spectroscopy, ESR, NMR and iron-driven lipid-oxidation experiments · source_derived_draft · unverified_draft

### chlorogenic_acid-fenton-prevention The ferric CGA complex did not support Fenton-type hydroxyl-radical generation under the tested conditions. Condition category: normal nutrient_topic: Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Preventing a radical from forming differs from catching one after it forms. organism: Cell-free chemistry and bovine liver microsomes tissue_or_cell_type: Ferric complexes, Fenton-type chemistry and microsomal lipids experimental_model: Spectroscopy, ESR, NMR and iron-driven lipid-oxidation experiments limitations: Chemical prevention of radical formation is distinct from radical scavenging. These assays do not measure human mineral stores, oral chelation therapy or clinical disease prevention. exposure: CGA concentration series; iron-EDTA and iron-ADP comparisons evidence_span: {"source_cache": "artifacts/chlorogenic_acid-research/9501514.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb573ad7da5b27974eff1c3a31d52becf53a72ffe3216703743aab82eacef1b7", "start_char": 0, "end_char": 797, "text_sha256": "eb573ad7da5b27974eff1c3a31d52becf53a72ffe3216703743aab82eacef1b7"} [chlorogenic_acid-p9501514] Iron chelation by chlorogenic acid as a natural antioxidant. (1998). https://pubmed.ncbi.nlm.nih.gov/9501514/ DOI: 10.1271/bbb.62.22

evidence_span

{"source_cache": "artifacts/chlorogenic_acid-research/9501514.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb573ad7da5b27974eff1c3a31d52becf53a72ffe3216703743aab82eacef1b7", "start_char": 0, "end_char": 797, "text_sha256": "eb573ad7da5b27974eff1c3a31d52becf53a72ffe3216703743aab82eacef1b7"}

experimental_model

Spectroscopy, ESR, NMR and iron-driven lipid-oxidation experiments

exposure

CGA concentration series; iron-EDTA and iron-ADP comparisons

limitations

Chemical prevention of radical formation is distinct from radical scavenging. These assays do not measure human mineral stores, oral chelation therapy or clinical disease prevention.

nutrient_topic

Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. · Chlorogenic acid / 5-O-caffeoylquinic acid

organism

Cell-free chemistry and bovine liver microsomes

plain_language

Binding a metal changes which reactions it can catalyze.

primary_references

[chlorogenic_acid-p9501514] Iron chelation by chlorogenic acid as a natural antioxidant. (1998). https://pubmed.ncbi.nlm.nih.gov/9501514/ DOI: 10.1271/bbb.62.22

tissue_or_cell_type

Ferric complexes, Fenton-type chemistry and microsomal lipids

Chlorogenic acid: metabolism, signaling and nutrient connections (2026-09-17) · lines 698–709

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Spectroscopy, ESR, NMR and iron-driven lipid-oxidation experiments · source_derived_draft · unverified_draft

### chlorogenic_acid-ferric-complex Spectroscopy, ESR and NMR supported formation of a CGA-iron complex. Condition category: normal nutrient_topic: Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Binding a metal changes which reactions it can catalyze. organism: Cell-free chemistry and bovine liver microsomes tissue_or_cell_type: Ferric complexes, Fenton-type chemistry and microsomal lipids experimental_model: Spectroscopy, ESR, NMR and iron-driven lipid-oxidation experiments limitations: Chemical prevention of radical formation is distinct from radical scavenging. These assays do not measure human mineral stores, oral chelation therapy or clinical disease prevention. exposure: CGA concentration series; iron-EDTA and iron-ADP comparisons evidence_span: {"source_cache": "artifacts/chlorogenic_acid-research/9501514.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb573ad7da5b27974eff1c3a31d52becf53a72ffe3216703743aab82eacef1b7", "start_char": 0, "end_char": 797, "text_sha256": "eb573ad7da5b27974eff1c3a31d52becf53a72ffe3216703743aab82eacef1b7"} [chlorogenic_acid-p9501514] Iron chelation by chlorogenic acid as a natural antioxidant. (1998). https://pubmed.ncbi.nlm.nih.gov/9501514/ DOI: 10.1271/bbb.62.22

evidence_span

{"source_cache": "artifacts/chlorogenic_acid-research/9501514.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb573ad7da5b27974eff1c3a31d52becf53a72ffe3216703743aab82eacef1b7", "start_char": 0, "end_char": 797, "text_sha256": "eb573ad7da5b27974eff1c3a31d52becf53a72ffe3216703743aab82eacef1b7"}

experimental_model

Spectroscopy, ESR, NMR and iron-driven lipid-oxidation experiments

exposure

CGA concentration series; iron-EDTA and iron-ADP comparisons

limitations

Chemical prevention of radical formation is distinct from radical scavenging. These assays do not measure human mineral stores, oral chelation therapy or clinical disease prevention.

nutrient_topic

Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. · Chlorogenic acid / 5-O-caffeoylquinic acid

organism

Cell-free chemistry and bovine liver microsomes

plain_language

Protection in a tissue preparation is retained with its experimental scope.

primary_references

[chlorogenic_acid-p9501514] Iron chelation by chlorogenic acid as a natural antioxidant. (1998). https://pubmed.ncbi.nlm.nih.gov/9501514/ DOI: 10.1271/bbb.62.22

tissue_or_cell_type

Ferric complexes, Fenton-type chemistry and microsomal lipids

Chlorogenic acid: metabolism, signaling and nutrient connections (2026-09-17) · lines 724–735

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Spectroscopy, ESR, NMR and iron-driven lipid-oxidation experiments · source_derived_draft · unverified_draft

### chlorogenic_acid-microsomal-oxidation CGA reduced iron-induced bovine microsomal lipid peroxidation in a concentration-dependent manner. Condition category: normal nutrient_topic: Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Protection in a tissue preparation is retained with its experimental scope. organism: Cell-free chemistry and bovine liver microsomes tissue_or_cell_type: Ferric complexes, Fenton-type chemistry and microsomal lipids experimental_model: Spectroscopy, ESR, NMR and iron-driven lipid-oxidation experiments limitations: Chemical prevention of radical formation is distinct from radical scavenging. These assays do not measure human mineral stores, oral chelation therapy or clinical disease prevention. exposure: CGA concentration series; iron-EDTA and iron-ADP comparisons evidence_span: {"source_cache": "artifacts/chlorogenic_acid-research/9501514.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb573ad7da5b27974eff1c3a31d52becf53a72ffe3216703743aab82eacef1b7", "start_char": 0, "end_char": 797, "text_sha256": "eb573ad7da5b27974eff1c3a31d52becf53a72ffe3216703743aab82eacef1b7"} [chlorogenic_acid-p9501514] Iron chelation by chlorogenic acid as a natural antioxidant. (1998). https://pubmed.ncbi.nlm.nih.gov/9501514/ DOI: 10.1271/bbb.62.22

evidence_span

{"source_cache": "artifacts/copper-research/16274220.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976", "start_char": 0, "end_char": 1880, "text_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976"}

experimental_model

Purified recombinant human hephaestin

exposure

Fe(II) substrate and apotransferrin assays

limitations

Soluble recombinant construct; average measured copper loading of 3.13 atoms is not a universal mature-protein stoichiometry.

nutrient_topic

Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

organism

Human protein produced in baby hamster kidney cells

plain_language

A copper enzyme changes iron into the form needed for the next transport step.

primary_references

[copper-p16274220] Recombinant expression and functional characterization of human hephaestin: a multicopper oxidase with ferroxidase activity. (2005). https://pubmed.ncbi.nlm.nih.gov/16274220/ DOI: 10.1021/bi051559k

tissue_or_cell_type

Purified soluble hephaestin construct

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 767–778

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human hephaestin · source_derived_draft · unverified_draft

### copper-heph-ferroxidation Recombinant copper-containing human hephaestin oxidized Fe(II), with an apparent substrate Km of 2.1 micromolar. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A copper enzyme changes iron into the form needed for the next transport step. organism: Human protein produced in baby hamster kidney cells tissue_or_cell_type: Purified soluble hephaestin construct experimental_model: Purified recombinant human hephaestin limitations: Soluble recombinant construct; average measured copper loading of 3.13 atoms is not a universal mature-protein stoichiometry. exposure: Fe(II) substrate and apotransferrin assays evidence_span: {"source_cache": "artifacts/copper-research/16274220.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976", "start_char": 0, "end_char": 1880, "text_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976"} [copper-p16274220] Recombinant expression and functional characterization of human hephaestin: a multicopper oxidase with ferroxidase activity. (2005). https://pubmed.ncbi.nlm.nih.gov/16274220/ DOI: 10.1021/bi051559k

evidence_span

{"source_cache": "artifacts/copper-research/16274220.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976", "start_char": 0, "end_char": 1880, "text_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976"}

experimental_model

Purified recombinant human hephaestin

exposure

Fe(II) substrate and apotransferrin assays

limitations

Soluble recombinant construct; average measured copper loading of 3.13 atoms is not a universal mature-protein stoichiometry.

nutrient_topic

Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

organism

Human protein produced in baby hamster kidney cells

plain_language

Copper-dependent iron processing helps load iron onto its blood carrier.

primary_references

[copper-p16274220] Recombinant expression and functional characterization of human hephaestin: a multicopper oxidase with ferroxidase activity. (2005). https://pubmed.ncbi.nlm.nih.gov/16274220/ DOI: 10.1021/bi051559k

tissue_or_cell_type

Purified soluble hephaestin construct

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 780–791

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human hephaestin · source_derived_draft · unverified_draft

### copper-heph-transferrin-loading Human hephaestin catalyzed diferric transferrin formation from Fe(II) and apotransferrin in vitro. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper-dependent iron processing helps load iron onto its blood carrier. organism: Human protein produced in baby hamster kidney cells tissue_or_cell_type: Purified soluble hephaestin construct experimental_model: Purified recombinant human hephaestin limitations: Soluble recombinant construct; average measured copper loading of 3.13 atoms is not a universal mature-protein stoichiometry. exposure: Fe(II) substrate and apotransferrin assays evidence_span: {"source_cache": "artifacts/copper-research/16274220.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976", "start_char": 0, "end_char": 1880, "text_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976"} [copper-p16274220] Recombinant expression and functional characterization of human hephaestin: a multicopper oxidase with ferroxidase activity. (2005). https://pubmed.ncbi.nlm.nih.gov/16274220/ DOI: 10.1021/bi051559k

evidence_access

Primary abstract

experimental_model

Human transferrin binding experiments under normoxic conditions.

limitations

Does not establish systemic iron deficiency or competition magnitude at dietary exposures.

nutrient_topic

Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium

plain_language

Vanadium can occupy available metal-binding sites without stripping out all bound iron.

primary_references

Vanadium(V/IV)-Transferrin Binding Disrupts the Transferrin Cycle and Reduces Vanadium Uptake and Antiproliferative Activity in Human Lung Cancer Cells. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32578416/ · DOI 10.1021/acs.inorgchem.0c00926

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 190–196

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human transferrin binding experiments under normoxic conditions. · source_derived_draft · unverified_draft

## vanadium-tf-binding Vanadium can occupy available metal-binding sites without stripping out all bound iron. V(V) and V(IV) bound vacant transferrin iron-binding sites in culture medium even with a 20-fold molar excess of albumin, without displacing already-bound Fe(III) under those conditions. Model: Human transferrin binding experiments under normoxic conditions. Limitations: Does not establish systemic iron deficiency or competition magnitude at dietary exposures. Evidence access: Primary abstract Vanadium(V/IV)-Transferrin Binding Disrupts the Transferrin Cycle and Reduces Vanadium Uptake and Antiproliferative Activity in Human Lung Cancer Cells. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32578416/ · DOI 10.1021/acs.inorgchem.0c00926

evidence_access

Primary full text

experimental_model

Human protein crystallography; 5 mM compound and crystallization conditions.

limitations

Reaction/crystal structure does not demonstrate the same species dominates human blood.

nutrient_topic

Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium

plain_language

The species bound to a protein can differ from the compound originally added.

primary_references

First crystal structure of an adduct formed upon reaction of a vanadium compound with human serum transferrin. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41545537/ · DOI 10.1038/s42004-026-01891-1

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 214–220

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human protein crystallography; 5 mM compound and crystallization conditions. · source_derived_draft · unverified_draft

## vanadium-tf-crystal-transformation The species bound to a protein can differ from the compound originally added. Crystals of C-lobe-ferric human transferrin exposed to vanadyl acetylacetonate contained a two-vanadium(V) unit linked to Tyr188 rather than intact V(IV) acetylacetonate. Model: Human protein crystallography; 5 mM compound and crystallization conditions. Limitations: Reaction/crystal structure does not demonstrate the same species dominates human blood. Evidence access: Primary full text First crystal structure of an adduct formed upon reaction of a vanadium compound with human serum transferrin. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41545537/ · DOI 10.1038/s42004-026-01891-1

evidence_span

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experimental_model

Iron-coordination spectroscopy and mitochondrial challenge

exposure

Assay-defined ferric iron-mangiferin complex

limitations

Defined chemical form and calcium context explain the different response; no clinical iron/mangiferin co-dosing recommendation.

nutrient_topic

Mangiferin research collection; topical membership is not evidence of a direct dietary effect. · Mangiferin

organism

Rattus norvegicus and cell-free chemistry

plain_language

The metal-bound form is represented separately.

primary_references

[mangiferin-p17068204] Fe(III) shifts the mitochondria permeability transition-eliciting capacity of mangiferin to protection of organelle. (2007). https://pubmed.ncbi.nlm.nih.gov/17068204/ DOI: 10.1124/jpet.106.112003

tissue_or_cell_type

Isolated mitochondria

Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 731–742

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Iron-coordination spectroscopy and mitochondrial challenge · source_derived_draft · unverified_draft

### mangiferin-ferric-complex Electrochemical and spectroscopic analyses supported coordination of ferric iron with mangiferin. Condition category: normal nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The metal-bound form is represented separately. organism: Rattus norvegicus and cell-free chemistry tissue_or_cell_type: Isolated mitochondria experimental_model: Iron-coordination spectroscopy and mitochondrial challenge limitations: Defined chemical form and calcium context explain the different response; no clinical iron/mangiferin co-dosing recommendation. exposure: Assay-defined ferric iron-mangiferin complex evidence_span: {"source_cache": "artifacts/mangiferin-research/17068204.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d0b364cee6629228fe7bc41446a0e2ddfe62b9274d77d4781ca7439aedfbb64", "start_char": 0, "end_char": 1172, "text_sha256": "1d0b364cee6629228fe7bc41446a0e2ddfe62b9274d77d4781ca7439aedfbb64"} [mangiferin-p17068204] Fe(III) shifts the mitochondria permeability transition-eliciting capacity of mangiferin to protection of organelle. (2007). https://pubmed.ncbi.nlm.nih.gov/17068204/ DOI: 10.1124/jpet.106.112003

evidence_span

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experimental_model

Isolated mitochondrial and iron-redox assays

exposure

10 micromolar mangiferin and 50 micromolar ferrous citrate in one protection experiment

limitations

In vitro iron complexing is not evidence that oral mangiferin depletes body iron or treats iron overload.

nutrient_topic

Mangiferin research collection; topical membership is not evidence of a direct dietary effect. · Mangiferin

organism

Rattus norvegicus and cell-free chemistry

plain_language

The iron oxidation state shifted.

primary_references

[mangiferin-p15878708] Iron complexing activity of mangiferin, a naturally occurring glucosylxanthone, inhibits mitochondrial lipid peroxidation induced by Fe2+-citrate. (2005). https://pubmed.ncbi.nlm.nih.gov/15878708/ DOI: 10.1016/j.ejphar.2005.03.007

tissue_or_cell_type

Liver mitochondria

Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 679–690

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated mitochondrial and iron-redox assays · source_derived_draft · unverified_draft

### mangiferin-iron-oxidation Mangiferin accelerated ferrous iron autoxidation in the tested system. Condition category: normal nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The iron oxidation state shifted. organism: Rattus norvegicus and cell-free chemistry tissue_or_cell_type: Liver mitochondria experimental_model: Isolated mitochondrial and iron-redox assays limitations: In vitro iron complexing is not evidence that oral mangiferin depletes body iron or treats iron overload. exposure: 10 micromolar mangiferin and 50 micromolar ferrous citrate in one protection experiment evidence_span: {"source_cache": "artifacts/mangiferin-research/15878708.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e29d024822df85f1aa0b737bb4123c869646d737c15bf05f1dc72b047a45eef3", "start_char": 0, "end_char": 1966, "text_sha256": "e29d024822df85f1aa0b737bb4123c869646d737c15bf05f1dc72b047a45eef3"} [mangiferin-p15878708] Iron complexing activity of mangiferin, a naturally occurring glucosylxanthone, inhibits mitochondrial lipid peroxidation induced by Fe2+-citrate. (2005). https://pubmed.ncbi.nlm.nih.gov/15878708/ DOI: 10.1016/j.ejphar.2005.03.007

evidence_span

{"source_cache": "artifacts/mangiferin-research/15878708.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e29d024822df85f1aa0b737bb4123c869646d737c15bf05f1dc72b047a45eef3", "start_char": 0, "end_char": 1966, "text_sha256": "e29d024822df85f1aa0b737bb4123c869646d737c15bf05f1dc72b047a45eef3"}

experimental_model

Isolated mitochondrial and iron-redox assays

exposure

10 micromolar mangiferin and 50 micromolar ferrous citrate in one protection experiment

limitations

In vitro iron complexing is not evidence that oral mangiferin depletes body iron or treats iron overload.

nutrient_topic

Mangiferin research collection; topical membership is not evidence of a direct dietary effect. · Mangiferin

organism

Rattus norvegicus and cell-free chemistry

plain_language

Iron binding changed a reaction involving vitamin C.

primary_references

[mangiferin-p15878708] Iron complexing activity of mangiferin, a naturally occurring glucosylxanthone, inhibits mitochondrial lipid peroxidation induced by Fe2+-citrate. (2005). https://pubmed.ncbi.nlm.nih.gov/15878708/ DOI: 10.1016/j.ejphar.2005.03.007

tissue_or_cell_type

Liver mitochondria

Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 692–703

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated mitochondrial and iron-redox assays · source_derived_draft · unverified_draft

### mangiferin-iron-vitamin-c Mangiferin prevented ascorbate-driven ferric iron reduction in vitro. Condition category: normal nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron binding changed a reaction involving vitamin C. organism: Rattus norvegicus and cell-free chemistry tissue_or_cell_type: Liver mitochondria experimental_model: Isolated mitochondrial and iron-redox assays limitations: In vitro iron complexing is not evidence that oral mangiferin depletes body iron or treats iron overload. exposure: 10 micromolar mangiferin and 50 micromolar ferrous citrate in one protection experiment evidence_span: {"source_cache": "artifacts/mangiferin-research/15878708.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e29d024822df85f1aa0b737bb4123c869646d737c15bf05f1dc72b047a45eef3", "start_char": 0, "end_char": 1966, "text_sha256": "e29d024822df85f1aa0b737bb4123c869646d737c15bf05f1dc72b047a45eef3"} [mangiferin-p15878708] Iron complexing activity of mangiferin, a naturally occurring glucosylxanthone, inhibits mitochondrial lipid peroxidation induced by Fe2+-citrate. (2005). https://pubmed.ncbi.nlm.nih.gov/15878708/ DOI: 10.1016/j.ejphar.2005.03.007

evidence_access

Primary abstract

experimental_model

Cell-free EXAFS study of the specified fulvic fraction.

limitations

Stomach-like acidity alone does not reproduce food, digestion, mucosal transport or human pharmacokinetics.

nutrient_topic

Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)

plain_language

Acidity changed the iron-redox outcome.

primary_references

EXAFS study on the reactions between iron and fulvic acid in acid aqueous solutions. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18504967/ · DOI 10.1021/es072092z

Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 100–106

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free EXAFS study of the specified fulvic fraction. · source_derived_draft · unverified_draft

## fulvic-acid-iron-redox Acidity changed the iron-redox outcome. Iron(III) reduction to iron(II) occurred over time at pH 2 but was not significant at pH 4. Model: Cell-free EXAFS study of the specified fulvic fraction. Limitations: Stomach-like acidity alone does not reproduce food, digestion, mucosal transport or human pharmacokinetics. Evidence access: Primary abstract EXAFS study on the reactions between iron and fulvic acid in acid aqueous solutions. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18504967/ · DOI 10.1021/es072092z

dose

Assay-specific submicromolar to micromolar concentrations; oral arm 300 mL beet juice with 120 mg betanin

duration

Kinetic assays; urine collected 2-4 h after ingestion

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

literature_reviewed; source-derived curation, not universally established human effects

experimental_model

Cell-free biochemical systems and four human volunteers

limitations

Chemical activity does not establish clinical efficacy or a dietary iron interaction.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Cell-free biochemical systems and four human volunteers

plain_language

Added betanin inhibited iron-redox-driven lipid peroxidation in cell-free lipid preparations.

primary_references

Betalains--a new class of dietary cationized antioxidants. (2001). https://pubmed.ncbi.nlm.nih.gov/11714300/ DOI: 10.1021/jf010456f

route

In vitro addition; separate oral juice arm

tissue

Lipid emulsions, membranes, LDL; urine arm separate

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 27–35

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Cell-free biochemical systems and four human volunteers · source_derived_draft · unverified_draft

## betalains-betanin-iron-oxidation Added betanin inhibited iron-redox-driven lipid peroxidation in cell-free lipid preparations. Model/species: Cell-free biochemical systems and four human volunteers Tissue: Lipid emulsions, membranes, LDL; urine arm separate Exposure: Assay-specific submicromolar to micromolar concentrations; oral arm 300 mL beet juice with 120 mg betanin Route: In vitro addition; separate oral juice arm Duration: Kinetic assays; urine collected 2-4 h after ingestion Limits: Chemical activity does not establish clinical efficacy or a dietary iron interaction. Primary reference: Betalains--a new class of dietary cationized antioxidants. (2001). https://pubmed.ncbi.nlm.nih.gov/11714300/ DOI: 10.1021/jf010456f

cross_nutrient

Vitamin C changes availability of iron for uptake; not proof that all iron absorption requires added vitamin C.

experimental_model

Differentiated human Caco-2 monolayers; apical ferric nitrilotriacetate and transepithelial transport assays.

exposure

Apical 10 micromolar Fe(III) as 1 Fe:2 NTA, varied ascorbic acid, ascorbate oxidase and Fe(II) chelators.

limitations

Chelator/oxidase interventions support redox dependence; the experiment does not identify every human intestinal transport step.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Homo sapiens

plain_language

Changing iron’s chemical state helped the intestinal-model cells acquire it.

primary_references

[c-han1995] Reduction of Fe(III) is required for uptake of nonheme iron by Caco-2 cells (1995). https://pubmed.ncbi.nlm.nih.gov/7738689/ DOI: 10.1093/jn/125.5.1291

tissue_or_cell_type

Human Caco-2 apical cell surface and culture medium

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1554–1565

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated human Caco-2 monolayers; apical ferric nitrilotriacetate and transepithelial transport assays. · source_derived_draft · unverified_draft

### c-iron-ferric-reduction-uptake Ascorbate enhanced ferric-NTA iron uptake; ascorbate oxidase and Fe(II) chelators inhibited the enhancement, supporting a required Fe(III)-to-Fe(II) reduction step in this cell model. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing iron’s chemical state helped the intestinal-model cells acquire it. organism: Homo sapiens tissue_or_cell_type: Human Caco-2 apical cell surface and culture medium experimental_model: Differentiated human Caco-2 monolayers; apical ferric nitrilotriacetate and transepithelial transport assays. limitations: Chelator/oxidase interventions support redox dependence; the experiment does not identify every human intestinal transport step. exposure: Apical 10 micromolar Fe(III) as 1 Fe:2 NTA, varied ascorbic acid, ascorbate oxidase and Fe(II) chelators. cross_nutrient: Vitamin C changes availability of iron for uptake; not proof that all iron absorption requires added vitamin C. [c-han1995] Reduction of Fe(III) is required for uptake of nonheme iron by Caco-2 cells (1995). https://pubmed.ncbi.nlm.nih.gov/7738689/ DOI: 10.1093/jn/125.5.1291

cross_nutrient

true

evidence_location

Figure 1a–b; treatment Methods

experimental_model

Human LNCaP and PC-3 monolayers in RPMI-1640 +10% FCS; MTT and crystal-violet viability assays

exposure

5 or 10 mM freshly neutralized ascorbic acid, 2 h, then wash/recovery; FAC adds 5–30 µM iron to medium containing 5.6 ±1.3 µM total iron.

limitations

FAC supplementation changes iron speciation as well as concentration; matching plasma total iron does not reconstruct transferrin binding or tissue interstitial chemistry. No clinical efficacy conclusion.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Homo sapiens

plain_language

In this medium, extra iron protected the prostate cancer cells from high-concentration vitamin C.

primary_references

[c-reg-mojic] Extracellular iron diminishes anticancer effects of vitamin C: an in vitro study. (2014). https://pubmed.ncbi.nlm.nih.gov/25092529/ DOI: 10.1038/srep05955

tissue_or_cell_type

Prostate carcinoma cells

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1285–1297

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human LNCaP and PC-3 monolayers in RPMI-1640 +10% FCS; MTT and crystal-violet viability assays · source_derived_draft · unverified_draft

### c-reg-extracellular-iron-cytoprotection Supplementing RPMI/FCS with as little as 5 µM iron as FAC prevented the marked viability loss caused by 5–10 mM ascorbate in LNCaP and PC-3 cultures; protection also occurred at higher tested iron additions. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this medium, extra iron protected the prostate cancer cells from high-concentration vitamin C. organism: Homo sapiens tissue_or_cell_type: Prostate carcinoma cells experimental_model: Human LNCaP and PC-3 monolayers in RPMI-1640 +10% FCS; MTT and crystal-violet viability assays limitations: FAC supplementation changes iron speciation as well as concentration; matching plasma total iron does not reconstruct transferrin binding or tissue interstitial chemistry. No clinical efficacy conclusion. exposure: 5 or 10 mM freshly neutralized ascorbic acid, 2 h, then wash/recovery; FAC adds 5–30 µM iron to medium containing 5.6 ±1.3 µM total iron. cross_nutrient: true evidence_location: Figure 1a–b; treatment Methods [c-reg-mojic] Extracellular iron diminishes anticancer effects of vitamin C: an in vitro study. (2014). https://pubmed.ncbi.nlm.nih.gov/25092529/ DOI: 10.1038/srep05955

cross_nutrient

true

evidence_location

Figure 1D–E; Figure S1A–C

experimental_model

Recombinant murine TET1 catalytic domain expressed in E. coli; methylated 86-mer DNA ELISA assay

exposure

1.5 µM TET1-CD, 0.5 µM DNA, 1 mM 2-oxoglutarate, 10 or 100 µM iron; sodium L-ascorbate 1 mM; pH 6.8 versus pH 8.0.

limitations

This does not directly measure free iron inside cells or establish a dietary iron/ascorbate requirement.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Mus musculus protein expressed in Escherichia coli

plain_language

Vitamin C helped restore the usable iron needed by this isolated DNA-modifying enzyme.

primary_references

[c-reg-hore] Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms. (2016). https://pubmed.ncbi.nlm.nih.gov/27729528/ DOI: 10.1073/pnas.1608679113

tissue_or_cell_type

Cell-free

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1019–1031

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant murine TET1 catalytic domain expressed in E. coli; methylated 86-mer DNA ELISA assay · source_derived_draft · unverified_draft

### c-reg-tet-iron-reduction-rescue Ascorbate restored murine TET1-CD activity with ferric iron or under pH 8.0 conditions that rapidly oxidized Fe(II); iron-redox measurements support provision of reduced iron as the rescue mechanism. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C helped restore the usable iron needed by this isolated DNA-modifying enzyme. organism: Mus musculus protein expressed in Escherichia coli tissue_or_cell_type: Cell-free experimental_model: Recombinant murine TET1 catalytic domain expressed in E. coli; methylated 86-mer DNA ELISA assay limitations: This does not directly measure free iron inside cells or establish a dietary iron/ascorbate requirement. exposure: 1.5 µM TET1-CD, 0.5 µM DNA, 1 mM 2-oxoglutarate, 10 or 100 µM iron; sodium L-ascorbate 1 mM; pH 6.8 versus pH 8.0. cross_nutrient: true evidence_location: Figure 1D–E; Figure S1A–C [c-reg-hore] Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms. (2016). https://pubmed.ncbi.nlm.nih.gov/27729528/ DOI: 10.1073/pnas.1608679113

evidence_span

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experimental_model

Transporter/reductase discovery and expression assays

exposure

Cybrd1 expression and physiological modulation of iron absorption

limitations

Shows ferric reductase activity; not proof that this is the only reductase or universally indispensable in vivo.

nutrient_topic

Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron

organism

Mouse Cybrd1 expressed in Xenopus oocytes and cultured cells

plain_language

Before nonheme iron enters through the ferrous-iron transporter, an enzyme can help convert it to the required chemical form.

primary_references

[iron-p11230685] An iron-regulated ferric reductase associated with the absorption of dietary iron. (2001). https://pubmed.ncbi.nlm.nih.gov/11230685/ DOI: 10.1126/science.1057206

tissue_or_cell_type

Duodenal brush border and expression systems

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 381–392

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter/reductase discovery and expression assays · source_derived_draft · unverified_draft

### iron-dcytb-reduction Duodenal Cybrd1 expression induced ferric reductase activity in oocytes and cultured cells and localized to the enterocyte brush border. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Before nonheme iron enters through the ferrous-iron transporter, an enzyme can help convert it to the required chemical form. organism: Mouse Cybrd1 expressed in Xenopus oocytes and cultured cells tissue_or_cell_type: Duodenal brush border and expression systems experimental_model: Transporter/reductase discovery and expression assays limitations: Shows ferric reductase activity; not proof that this is the only reductase or universally indispensable in vivo. exposure: Cybrd1 expression and physiological modulation of iron absorption evidence_span: {"source_cache": "artifacts/iron-research/11230685.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3ef2e0a58c59707a044f0507c68aa61988718dfc97611b6664705468a5efa32", "start_char": 0, "end_char": 824, "text_sha256": "e3ef2e0a58c59707a044f0507c68aa61988718dfc97611b6664705468a5efa32"} [iron-p11230685] An iron-regulated ferric reductase associated with the absorption of dietary iron. (2001). https://pubmed.ncbi.nlm.nih.gov/11230685/ DOI: 10.1126/science.1057206

evidence_span

{"source_cache": "artifacts/iron-research/8369307.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff", "start_char": 0, "end_char": 1709, "text_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff"}

experimental_model

Ferroxidase kinetics and site-directed mutants

exposure

Fe(II) oxidation by oxygen; H-chain mutations and zinc inhibition

limitations

In-vitro metal concentrations and H/L composition determine kinetics; this does not establish a dietary zinc effect on human iron stores.

nutrient_topic

Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron

organism

Human recombinant ferritin and human liver apoferritin

plain_language

Ferritin does chemical work to package iron, not just physical storage.

primary_references

[iron-p8369307] Ferroxidase kinetics of human liver apoferritin, recombinant H-chain apoferritin, and site-directed mutants. (1993). https://pubmed.ncbi.nlm.nih.gov/8369307/ DOI: 10.1021/bi00087a015

tissue_or_cell_type

Purified ferritin subunits/assemblies

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 615–626

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ferroxidase kinetics and site-directed mutants · source_derived_draft · unverified_draft

### iron-ferritin-h-oxidation Human H-chain ferritin catalyzed Fe(II) oxidation; mutation of its proposed ferroxidase ligands Glu62 and His65 abolished most activity. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Ferritin does chemical work to package iron, not just physical storage. organism: Human recombinant ferritin and human liver apoferritin tissue_or_cell_type: Purified ferritin subunits/assemblies experimental_model: Ferroxidase kinetics and site-directed mutants limitations: In-vitro metal concentrations and H/L composition determine kinetics; this does not establish a dietary zinc effect on human iron stores. exposure: Fe(II) oxidation by oxygen; H-chain mutations and zinc inhibition evidence_span: {"source_cache": "artifacts/iron-research/8369307.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff", "start_char": 0, "end_char": 1709, "text_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff"} [iron-p8369307] Ferroxidase kinetics of human liver apoferritin, recombinant H-chain apoferritin, and site-directed mutants. (1993). https://pubmed.ncbi.nlm.nih.gov/8369307/ DOI: 10.1021/bi00087a015

evidence_span

{"source_cache": "artifacts/iron-research/16227996.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd6e35b6ea534163d0db76cbdec2fa6c3c2dd998b0a1f66d9f16479bcb87711b", "start_char": 0, "end_char": 1006, "text_sha256": "cd6e35b6ea534163d0db76cbdec2fa6c3c2dd998b0a1f66d9f16479bcb87711b"}

experimental_model

Positional cloning, overexpression and deficient-mouse experiments

exposure

Steap3 deficiency and overexpression

limitations

A dominant erythroid reduction pathway, not proof of equal dependence in every tissue.

nutrient_topic

Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron

organism

Mice and mouse Steap3 expression systems

plain_language

Iron released from transferrin needs another chemical reduction step before it can leave the endosome.

primary_references

[iron-p16227996] Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. (2005). https://pubmed.ncbi.nlm.nih.gov/16227996/ DOI: 10.1038/ng1658

tissue_or_cell_type

Erythroid endosomes

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 446–457

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Positional cloning, overexpression and deficient-mouse experiments · source_derived_draft · unverified_draft

### iron-steap-reduction Steap3 colocalized with transferrin-cycle endosomes and promoted iron reduction and transferrin-dependent iron uptake. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron released from transferrin needs another chemical reduction step before it can leave the endosome. organism: Mice and mouse Steap3 expression systems tissue_or_cell_type: Erythroid endosomes experimental_model: Positional cloning, overexpression and deficient-mouse experiments limitations: A dominant erythroid reduction pathway, not proof of equal dependence in every tissue. exposure: Steap3 deficiency and overexpression evidence_span: {"source_cache": "artifacts/iron-research/16227996.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd6e35b6ea534163d0db76cbdec2fa6c3c2dd998b0a1f66d9f16479bcb87711b", "start_char": 0, "end_char": 1006, "text_sha256": "cd6e35b6ea534163d0db76cbdec2fa6c3c2dd998b0a1f66d9f16479bcb87711b"} [iron-p16227996] Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. (2005). https://pubmed.ncbi.nlm.nih.gov/16227996/ DOI: 10.1038/ng1658

evidence_span

{"source_cache": "artifacts/iron-research/6300903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852", "start_char": 0, "end_char": 906, "text_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852"}

experimental_model

Receptor binding at controlled pH and transferrin cycle analysis

exposure

Apotransferrin and diferric transferrin binding at acidic versus neutral pH

limitations

The indexed abstract does not identify the cell line; its experiments support a pH-dependent trafficking model, not direct measures of whole-body iron turnover.

nutrient_topic

Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron

organism

Cultured-cell transferrin receptor system

plain_language

The carrier gives up its iron inside an acidic compartment but stays attached to its return transport.

primary_references

[iron-p6300903] pH and the recycling of transferrin during receptor-mediated endocytosis. (1983). https://pubmed.ncbi.nlm.nih.gov/6300903/ DOI: 10.1073/pnas.80.8.2258

tissue_or_cell_type

Cell surface and endosomal recycling model

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 420–431

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor binding at controlled pH and transferrin cycle analysis · source_derived_draft · unverified_draft

### iron-tf-acidic-release The transferrin-cycle model supported by the binding experiments releases iron in acidified endosomes while apotransferrin remains receptor-bound. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The carrier gives up its iron inside an acidic compartment but stays attached to its return transport. organism: Cultured-cell transferrin receptor system tissue_or_cell_type: Cell surface and endosomal recycling model experimental_model: Receptor binding at controlled pH and transferrin cycle analysis limitations: The indexed abstract does not identify the cell line; its experiments support a pH-dependent trafficking model, not direct measures of whole-body iron turnover. exposure: Apotransferrin and diferric transferrin binding at acidic versus neutral pH evidence_span: {"source_cache": "artifacts/iron-research/6300903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852", "start_char": 0, "end_char": 906, "text_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852"} [iron-p6300903] pH and the recycling of transferrin during receptor-mediated endocytosis. (1983). https://pubmed.ncbi.nlm.nih.gov/6300903/ DOI: 10.1073/pnas.80.8.2258