Hydrogen peroxide

experimental_model

Primary airway epithelial cultures and human oral-KI exposure; separate experimental arms.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Culture antiviral activity and human secretion measurements do not establish prevention or treatment of human infection.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

Airway cells supplied the oxidant needed by the enzyme.

primary_references

Enhancement of respiratory mucosal antiviral defenses by the oxidation of iodide. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21441383/ · DOI 10.1165/rcmb.2010-0329oc

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 88–94

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Primary airway epithelial cultures and human oral-KI exposure; separate experimental arms. · source_derived_draft · unverified_draft

## ki-air-peroxide Airway cells supplied the oxidant needed by the enzyme. Differentiated airway epithelia supplied sufficient peroxide for antiviral activity when LPO and iodide were added. Model: Primary airway epithelial cultures and human oral-KI exposure; separate experimental arms. Limitations: Culture antiviral activity and human secretion measurements do not establish prevention or treatment of human infection. Evidence location: Primary abstract Enhancement of respiratory mucosal antiviral defenses by the oxidation of iodide. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21441383/ · DOI 10.1165/rcmb.2010-0329oc

experimental_model

Purified LPO transient kinetics; pH 7, 15 °C; preparation species unresolved in abstract.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Purified enzyme kinetics; concentrations, substrate competition and reaction order determine relevance in tissues.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

Peroxide activates the enzyme before iodide oxidation.

primary_references

Reaction of lactoperoxidase compound I with halides and thiocyanate. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12269834/ · DOI 10.1021/bi026326x

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 184–190

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Purified LPO transient kinetics; pH 7, 15 °C; preparation species unresolved in abstract. · source_derived_draft · unverified_draft

## ki-lpo-activate Peroxide activates the enzyme before iodide oxidation. H2O2 formed LPO compound I with second-order rate constant (1.1 ± 0.1) × 10^7 M−1 s−1. Model: Purified LPO transient kinetics; pH 7, 15 °C; preparation species unresolved in abstract. Limitations: Purified enzyme kinetics; concentrations, substrate competition and reaction order determine relevance in tissues. Evidence location: Primary abstract Reaction of lactoperoxidase compound I with halides and thiocyanate. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12269834/ · DOI 10.1021/bi026326x

cross_nutrient

true

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/10187846.json", "json_field": "abstractText", "text_sha256": "97f8a86c7effd5754e2b61c65d769de9e86678a7398c5eb20a0e88ac49a8fdbb", "text_characters": 1855, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

CHO cells expressing human TPO; additional primary thyroid cultures

exposure

10 micromolar H2O2, 10 minutes.

limitations

Authors interpret activation through covalent heme attachment; no direct nutrient-intake intervention.

nutrient_topic

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

organism

Homo sapiens protein; Cricetulus griseus host cells

plain_language

Peroxide exposure helped activate surface TPO in this cell model.

primary_references

[iodine-syn-tpo1999] Role of heme in intracellular trafficking of thyroperoxidase and involvement of H2O2 generated at the apical surface of thyroid cells in autocatalytic covalent heme binding. (1999). https://pubmed.ncbi.nlm.nih.gov/10187846/ DOI: 10.1074/jbc.274.15.10533

tissue_or_cell_type

CHO cell surface

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 590–602

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CHO cells expressing human TPO; additional primary thyroid cultures · source_derived_draft · unverified_draft

### iodine-syn-peroxide-tpo-activation Exposing human TPO-expressing CHO cells to 10 micromolar H2O2 for 10 minutes increased cell-surface peroxidase activity by 65%. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Peroxide exposure helped activate surface TPO in this cell model. organism: Homo sapiens protein; Cricetulus griseus host cells tissue_or_cell_type: CHO cell surface experimental_model: CHO cells expressing human TPO; additional primary thyroid cultures limitations: Authors interpret activation through covalent heme attachment; no direct nutrient-intake intervention. exposure: 10 micromolar H2O2, 10 minutes. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/10187846.json", "json_field": "abstractText", "text_sha256": "97f8a86c7effd5754e2b61c65d769de9e86678a7398c5eb20a0e88ac49a8fdbb", "text_characters": 1855, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tpo1999] Role of heme in intracellular trafficking of thyroperoxidase and involvement of H2O2 generated at the apical surface of thyroid cells in autocatalytic covalent heme binding. (1999). https://pubmed.ncbi.nlm.nih.gov/10187846/ DOI: 10.1074/jbc.274.15.10533

evidence_span

{"source_cache": "artifacts/glutathione-research/9642155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "701b6cbdc44486c0b9423d7c30f52b282f1407958c7dde45d4aa1d3751718a72", "start_char": 0, "end_char": 1538, "text_sha256": "701b6cbdc44486c0b9423d7c30f52b282f1407958c7dde45d4aa1d3751718a72"}

experimental_model

Purified GAPDH oxidation and radiolabeled disulfide assays

exposure

Hydrogen peroxide versus GSSG and glutaredoxin

limitations

This particular assay separates oxidation from glutathionylation; it does not establish one universal effect for all modified proteins.

nutrient_topic

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

organism

Human GAPDH; human or bacterial glutaredoxin

plain_language

The kind of chemical modification mattered.

primary_references

[glutathione-p9642155] Studies on the mechanism of oxidative modification of human glyceraldehyde-3-phosphate dehydrogenase by glutathione: catalysis by glutaredoxin. (1998). https://pubmed.ncbi.nlm.nih.gov/9642155/ DOI: 10.1006/bbrc.1998.8695

tissue_or_cell_type

Cell-free enzyme system

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 853–864

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified GAPDH oxidation and radiolabeled disulfide assays · source_derived_draft · unverified_draft

### glutathione-gapdh-peroxide Direct hydrogen-peroxide oxidation inhibited GAPDH activity in the comparison. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kind of chemical modification mattered. organism: Human GAPDH; human or bacterial glutaredoxin tissue_or_cell_type: Cell-free enzyme system experimental_model: Purified GAPDH oxidation and radiolabeled disulfide assays limitations: This particular assay separates oxidation from glutathionylation; it does not establish one universal effect for all modified proteins. exposure: Hydrogen peroxide versus GSSG and glutaredoxin evidence_span: {"source_cache": "artifacts/glutathione-research/9642155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "701b6cbdc44486c0b9423d7c30f52b282f1407958c7dde45d4aa1d3751718a72", "start_char": 0, "end_char": 1538, "text_sha256": "701b6cbdc44486c0b9423d7c30f52b282f1407958c7dde45d4aa1d3751718a72"} [glutathione-p9642155] Studies on the mechanism of oxidative modification of human glyceraldehyde-3-phosphate dehydrogenase by glutathione: catalysis by glutaredoxin. (1998). https://pubmed.ncbi.nlm.nih.gov/9642155/ DOI: 10.1006/bbrc.1998.8695

cross_nutrient

false

evidence_location

Full text lines 105–107; Fig. 1B–D

experimental_model

Primary cardiomyocyte exposure and Langendorff-perfused rat hearts

exposure

Cardiomyocytes: 1–100 micromolar H2O2, 30 minutes; perfused hearts: 100 micromolar H2O2, 20 minutes.

limitations

DTT sensitivity supports mixed disulfides. Antioxidant protection or improved organ function was not established by this endpoint. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Rattus norvegicus

plain_language

Oxidative stress caused CoA to form reversible bonds with protein cysteines.

primary_references

[b5-met-coalation2017] Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells. (2017). https://pubmed.ncbi.nlm.nih.gov/28341808/ DOI: 10.1042/bcj20170129

tissue_or_cell_type

Adult cardiomyocytes and isolated heart

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1047–1059

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary cardiomyocyte exposure and Langendorff-perfused rat hearts · source_derived_draft · unverified_draft

### b5-met-oxidant-coalation Hydrogen peroxide exposure induced DTT-sensitive protein CoAlation in isolated rat cardiomyocytes and perfused rat hearts. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Oxidative stress caused CoA to form reversible bonds with protein cysteines. organism: Rattus norvegicus tissue_or_cell_type: Adult cardiomyocytes and isolated heart experimental_model: Primary cardiomyocyte exposure and Langendorff-perfused rat hearts limitations: DTT sensitivity supports mixed disulfides. Antioxidant protection or improved organ function was not established by this endpoint. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Cardiomyocytes: 1–100 micromolar H2O2, 30 minutes; perfused hearts: 100 micromolar H2O2, 20 minutes. cross_nutrient: false evidence_location: Full text lines 105–107; Fig. 1B–D [b5-met-coalation2017] Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells. (2017). https://pubmed.ncbi.nlm.nih.gov/28341808/ DOI: 10.1042/bcj20170129

evidence_span

{"source_cache": "artifacts/phosphorus-research/42247296.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76", "start_char": 0, "end_char": 1041, "text_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76"}

experimental_model

Osteosarcoma-cell signaling with in-vivo tumor experiments

exposure

Elevated phosphate challenges and receptor activation experiments

limitations

New 2026 mechanism in tumor models; blood-Pi/tumor-growth association is not proof that dietary phosphorus causes human cancer. No specific transporter or oxidized residue number is invented from the abstract.

nutrient_topic

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

organism

Osteosarcoma cellular and animal systems; precise species not fully resolved from abstract

plain_language

A redox change reached the receptor protein.

primary_references

[phosphorus-p42247296] Unconventional activation of the proto-oncogene FGFR1 by extracellular phosphate via H2O2-mediated kinase oxidation. (2026). https://pubmed.ncbi.nlm.nih.gov/42247296/ DOI: 10.1016/j.celrep.2026.117504

tissue_or_cell_type

Plasma-membrane/mitochondrial phosphate handling and FGFR1 signaling

Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 880–891

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Osteosarcoma-cell signaling with in-vivo tumor experiments · source_derived_draft · unverified_draft

### phosphorus-peroxide-fgfr The phosphate-associated hydrogen-peroxide burst oxidized critical cysteine and methionine residues of FGFR1. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: A redox change reached the receptor protein. organism: Osteosarcoma cellular and animal systems; precise species not fully resolved from abstract tissue_or_cell_type: Plasma-membrane/mitochondrial phosphate handling and FGFR1 signaling experimental_model: Osteosarcoma-cell signaling with in-vivo tumor experiments limitations: New 2026 mechanism in tumor models; blood-Pi/tumor-growth association is not proof that dietary phosphorus causes human cancer. No specific transporter or oxidized residue number is invented from the abstract. exposure: Elevated phosphate challenges and receptor activation experiments evidence_span: {"source_cache": "artifacts/phosphorus-research/42247296.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76", "start_char": 0, "end_char": 1041, "text_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76"} [phosphorus-p42247296] Unconventional activation of the proto-oncogene FGFR1 by extracellular phosphate via H2O2-mediated kinase oxidation. (2026). https://pubmed.ncbi.nlm.nih.gov/42247296/ DOI: 10.1016/j.celrep.2026.117504

experimental_model

Rose bengal plus 540-nm light; up to 100 mM KI; microbial assays and a mouse skin-abrasion model.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Local photochemical system, not an effect of oral KI alone. Peroxyiodide intermediates were proposed, not directly established.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

This reaction produced peroxide rather than universally removing it.

primary_references

Potassium Iodide Potentiates Antimicrobial Photodynamic Inactivation Mediated by Rose Bengal in In Vitro and In Vivo Studies. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28438946/ · DOI 10.1128/aac.00467-17

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 328–334

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Rose bengal plus 540-nm light; up to 100 mM KI; microbial assays and a mouse skin-abrasion model. · source_derived_draft · unverified_draft

## ki-pdt-peroxide This reaction produced peroxide rather than universally removing it. The illuminated mixture generated peroxide measured by Amplex Red. Model: Rose bengal plus 540-nm light; up to 100 mM KI; microbial assays and a mouse skin-abrasion model. Limitations: Local photochemical system, not an effect of oral KI alone. Peroxyiodide intermediates were proposed, not directly established. Evidence location: Full-text Figure 4B Potassium Iodide Potentiates Antimicrobial Photodynamic Inactivation Mediated by Rose Bengal in In Vitro and In Vivo Studies. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28438946/ · DOI 10.1128/aac.00467-17

experimental_model

In-vitro polymorphonuclear leukocytes; tested drug concentrations reported as 10 micromolar–millimolar.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Assay effects do not identify a unique molecular target or establish universal antioxidant action.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

KI lowered a peroxide assay readout in immune cells.

primary_references

Effects of potassium iodide, colchicine and dapsone on the generation of polymorphonuclear leukocyte-derived oxygen intermediates. · 1982 · https://pubmed.ncbi.nlm.nih.gov/7104217/ · DOI 10.1111/j.1365-2133.1982.tb00340.x

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 288–294

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · In-vitro polymorphonuclear leukocytes; tested drug concentrations reported as 10 micromolar–millimolar. · source_derived_draft · unverified_draft

## ki-pmn-peroxide KI lowered a peroxide assay readout in immune cells. KI suppressed the measured PMN-derived hydrogen-peroxide signal. Model: In-vitro polymorphonuclear leukocytes; tested drug concentrations reported as 10 micromolar–millimolar. Limitations: Assay effects do not identify a unique molecular target or establish universal antioxidant action. Evidence location: Primary abstract Effects of potassium iodide, colchicine and dapsone on the generation of polymorphonuclear leukocyte-derived oxygen intermediates. · 1982 · https://pubmed.ncbi.nlm.nih.gov/7104217/ · DOI 10.1111/j.1365-2133.1982.tb00340.x

evidence_access

Primary abstract

experimental_model

Purified porcine enzyme oxidative half-reaction.

limitations

This chemistry alone does not demonstrate oxidative injury after human oral supplementation.

nutrient_topic

D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate

plain_language

Clearing D-aspartate also generates a peroxide-handling requirement.

primary_references

Functional and structural characterization of D-aspartate oxidase from porcine kidney: non-Michaelis kinetics due to substrate activation. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17234685/ · DOI 10.1093/jb/mvm041

D-Aspartate: synthesis, clearance, neural and endocrine 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 · Purified porcine enzyme oxidative half-reaction. · source_derived_draft · unverified_draft

## d-aspartate-ddo-peroxide Clearing D-aspartate also generates a peroxide-handling requirement. Reoxidation of reduced FAD by oxygen during porcine DDO turnover produced hydrogen peroxide. Model: Purified porcine enzyme oxidative half-reaction. Limitations: This chemistry alone does not demonstrate oxidative injury after human oral supplementation. Evidence access: Primary abstract Functional and structural characterization of D-aspartate oxidase from porcine kidney: non-Michaelis kinetics due to substrate activation. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17234685/ · DOI 10.1093/jb/mvm041

cross_nutrient

false

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/16651268.json", "json_field": "abstractText", "text_sha256": "9fa3bbca756141f9c8e8c334e58db29c97d930b117e5697ac91f28a0f41c92a0", "text_characters": 1357, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

Human DUOX2/DUOXA2 heterologous coexpression

exposure

Human DUOX2 with versus without DUOXA2.

limitations

Does not establish a dietary vitamin threshold.

nutrient_topic

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

organism

Homo sapiens proteins; heterologous cells

plain_language

The maturation factor makes the peroxide-producing enzyme functional.

primary_references

[iodine-syn-duoxa2006] Identification of the maturation factor for dual oxidase. Evolution of an eukaryotic operon equivalent. (2006). https://pubmed.ncbi.nlm.nih.gov/16651268/ DOI: 10.1074/jbc.c600095200

tissue_or_cell_type

Cell surface

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 506–518

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DUOX2/DUOXA2 heterologous coexpression · source_derived_draft · unverified_draft

### iodine-syn-duoxa-functional Coexpressing DUOXA2 reconstituted functional human DUOX2-dependent hydrogen-peroxide generation. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The maturation factor makes the peroxide-producing enzyme functional. organism: Homo sapiens proteins; heterologous cells tissue_or_cell_type: Cell surface experimental_model: Human DUOX2/DUOXA2 heterologous coexpression limitations: Does not establish a dietary vitamin threshold. exposure: Human DUOX2 with versus without DUOXA2. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/16651268.json", "json_field": "abstractText", "text_sha256": "9fa3bbca756141f9c8e8c334e58db29c97d930b117e5697ac91f28a0f41c92a0", "text_characters": 1357, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-duoxa2006] Identification of the maturation factor for dual oxidase. Evolution of an eukaryotic operon equivalent. (2006). https://pubmed.ncbi.nlm.nih.gov/16651268/ DOI: 10.1074/jbc.c600095200

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/18042646.json", "json_field": "abstractText", "text_sha256": "99a0667a0a4036b9ad94f59e6ba82a4c80c7f4b4228f11029f63db5c5b811da7", "text_characters": 1847, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

Human genetic case finding and heterologous DUOX2 reconstitution

exposure

Y246X mutant versus wild-type DUOXA2 in reconstitution.

limitations

Loss of enzyme machinery, not iodine or riboflavin shortage.

nutrient_topic

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

organism

Homo sapiens proteins

plain_language

This truncated helper protein could not support peroxide production.

primary_references

[iodine-syn-duoxa2008] Biallelic inactivation of the dual oxidase maturation factor 2 (DUOXA2) gene as a novel cause of congenital hypothyroidism. (2008). https://pubmed.ncbi.nlm.nih.gov/18042646/ DOI: 10.1210/jc.2007-2020

tissue_or_cell_type

Heterologous cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 534–546

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human genetic case finding and heterologous DUOX2 reconstitution · source_derived_draft · unverified_draft

### iodine-syn-duoxa-mutant-function Human DUOXA2 p.Y246X failed to reconstitute DUOX2 activity in vitro. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This truncated helper protein could not support peroxide production. organism: Homo sapiens proteins tissue_or_cell_type: Heterologous cells experimental_model: Human genetic case finding and heterologous DUOX2 reconstitution limitations: Loss of enzyme machinery, not iodine or riboflavin shortage. exposure: Y246X mutant versus wild-type DUOXA2 in reconstitution. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/18042646.json", "json_field": "abstractText", "text_sha256": "99a0667a0a4036b9ad94f59e6ba82a4c80c7f4b4228f11029f63db5c5b811da7", "text_characters": 1847, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-duoxa2008] Biallelic inactivation of the dual oxidase maturation factor 2 (DUOXA2) gene as a novel cause of congenital hypothyroidism. (2008). https://pubmed.ncbi.nlm.nih.gov/18042646/ DOI: 10.1210/jc.2007-2020

availability_state

Severe selenium deficiency reduces selenium-dependent thyroid redox capacity.

experimental_scope

Biochemical redox mechanism in severe deficiency; autoimmune disease is a separate, multifactorial outcome.

limitations

This does not make deficiency a sufficient cause of Hashimoto thyroiditis or thyroid antibodies. No antibody or treatment benefit is inferred.

trigger_kind

nutrient_deficiency

Selenium deficiency: a mechanism-first reference · lines 331–338

Supplied selenium deficiency reference · supports · Supplied reference; verify the primary study and experimental context. · source_derived_draft · unverified_draft

Thyroid-hormone synthesis requires locally generated H₂O₂: TSH signaling → DUOX2/DUOXA2 generates H₂O₂ near the apical membrane → TPO uses H₂O₂ to oxidize iodide and iodinate thyroglobulin → antioxidant systems limit peroxide spillover and lipid/protein damage Selenoproteins such as GPXs and thioredoxin reductases contribute to thyroid redox control. Severe selenium deficiency can reduce this defensive capacity, but Hashimoto thyroiditis is multifactorial; selenium deficiency is not a sufficient one-step cause of anti-TPO or anti-thyroglobulin autoimmunity.

acting_entity

s-allylcysteine

dose

Assay-specific millimolar IC50 values

duration

Not specified in accessed abstract

evidence_access

Primary abstract

experimental_comparison

SAC concentration series versus corresponding reference scavengers

experimental_model

Reactive-species scavenging systems

interpretation_status

Source-derived research curation; not independent primary verification

limitations

Assay potency is not an achieved human tissue concentration.

nutrient_topic

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

organism

Cell-free chemical assays

plain_language

Direct chemistry has a measured concentration requirement.

primary_references

[17576034] S-allylcysteine scavenges singlet oxygen and hypochlorous acid and protects LLC-PK(1) cells of potassium dichromate-induced toxicity. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17576034/ · DOI 10.1016/j.fct.2007.05.002

route

In vitro

tissue_or_cell_type

Reactive-species scavenging systems

S-allylcysteine: sulfur signaling, redox responses and cross-nutrient mechanisms (2026-09-20) · lines 68–75

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Reactive-species scavenging systems · source_derived_draft · unverified_draft

## s-allylcysteine-scavenging-peroxide Direct chemistry has a measured concentration requirement. SAC scavenged hydrogen peroxide in the tested chemical system; IC50 was 68 mM. Model: Reactive-species scavenging systems Limitations: Assay potency is not an achieved human tissue concentration. Evidence access: Primary abstract [17576034] S-allylcysteine scavenges singlet oxygen and hypochlorous acid and protects LLC-PK(1) cells of potassium dichromate-induced toxicity. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17576034/ · DOI 10.1016/j.fct.2007.05.002 Structured context: {"organism": "Cell-free chemical assays", "tissue_or_cell_type": "Reactive-species scavenging systems", "dose": "Assay-specific millimolar IC50 values", "duration": "Not specified in accessed abstract", "route": "In vitro", "experimental_comparison": "SAC concentration series versus corresponding reference scavengers", "acting_entity": "s-allylcysteine", "interpretation_status": "Source-derived research curation; not independent primary verification"}

experimental_model

CHO cells and cell-culture medium comparisons.

limitations

Culture autooxidation cannot be generalized to all tissues or used to dismiss every cell experiment.

nutrient_topic

EGCG collection; comparator and shared-pathway records retain their actual intervention. · Epigallocatechin-3-gallate (EGCG)

plain_language

EGCG can generate peroxide under some laboratory conditions.

primary_references

Different cytotoxic and clastogenic effects of epigallocatechin gallate in various cell-culture media due to variable rates of its oxidation in the culture medium. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17851114/ · DOI 10.1016/j.mrgentox.2007.07.009

EGCG: receptor signaling, metabolism, nutrient interactions and discovery questions (2026-09-18) · lines 332–338

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · CHO cells and cell-culture medium comparisons. · source_derived_draft · unverified_draft

## egcg-peroxide EGCG can generate peroxide under some laboratory conditions. EGCG-associated peroxide formation and CHO cytotoxicity differed substantially among seven culture media. Model: CHO cells and cell-culture medium comparisons. Limitations: Culture autooxidation cannot be generalized to all tissues or used to dismiss every cell experiment. Evidence access: primary abstract. Different cytotoxic and clastogenic effects of epigallocatechin gallate in various cell-culture media due to variable rates of its oxidation in the culture medium. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17851114/ · DOI 10.1016/j.mrgentox.2007.07.009

experimental_model

Animal selenium status and erythrocyte glutathione-peroxidase biochemistry.

limitations

This experiment-specific relationship does not establish a human dietary-deficiency threshold or supplementation benefit.

organism

Rat

Selenium: literature corrections and mechanism additions · lines 954–963

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Animal selenium status and erythrocyte glutathione-peroxidase biochemistry. · secondary_verified · secondary_verified

## gpx1-peroxide-reduction GPX1 uses glutathione to remove hydrogen peroxide. Classical GPX1 couples hydrogen-peroxide reduction to oxidation of reduced glutathione; water and glutathione disulfide are products. Experimental model: Animal selenium status and erythrocyte glutathione-peroxidase biochemistry. Organism: Rat Limitations: This experiment-specific relationship does not establish a human dietary-deficiency threshold or supplementation benefit. Primary reference: [Selenium: biochemical role as a component of glutathione peroxidase](https://pubmed.ncbi.nlm.nih.gov/4686466/)

cell_type

MCF-7 transfectants

experimental_model

GPX2 cDNA expression and enzyme assays

limitations

Expression model; not an intestinal clinical outcome.

organism

human

Selenium: literature corrections and mechanism additions · lines 642–652

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · GPX2 cDNA expression and enzyme assays · secondary_verified · secondary_verified

## gpx2-reduces-peroxide GPX2 can remove peroxide using glutathione. Expressed human GPX2 exhibited glutathione-dependent hydrogen-peroxide reduction. Organism: human Cell type: MCF-7 transfectants Experimental model: GPX2 cDNA expression and enzyme assays Limitations: Expression model; not an intestinal clinical outcome. Primary reference: [Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI](https://pubmed.ncbi.nlm.nih.gov/8428933/)

cell_type

plasma

experimental_model

Purified enzyme kinetics

limitations

Assay glutathione availability does not define every physiological electron donor.

organism

human

Selenium: literature corrections and mechanism additions · lines 678–688

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Purified enzyme kinetics · secondary_verified · secondary_verified

## gpx3-reduces-extracellular-peroxide GPX3 can remove peroxide outside cells. Purified human plasma glutathione peroxidase reduced hydrogen peroxide using glutathione. Organism: human Cell type: plasma Experimental model: Purified enzyme kinetics Limitations: Assay glutathione availability does not define every physiological electron donor. Primary reference: [Characterization of the major hydroperoxide-reducing activity of human plasma. Purification and properties of a selenium-dependent glutathione peroxidase.](https://www.sciencedirect.com/science/article/pii/S0021925818453926)

cell_type

cardiac mitochondria

experimental_model

Peroxide and redox measurements

limitations

Other mitochondrial peroxide defenses also contribute.

organism

mouse and guinea pig

Selenium: literature corrections and mechanism additions · lines 630–640

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Peroxide and redox measurements · secondary_verified · secondary_verified

## prdx3-reduces-mitochondrial-peroxide The relay ends in peroxide removal. PRDX3 consumes hydrogen peroxide, forming water within the mitochondrial thioredoxin circuit. Organism: mouse and guinea pig Cell type: cardiac mitochondria Experimental model: Peroxide and redox measurements Limitations: Other mitochondrial peroxide defenses also contribute. Primary reference: [Thioredoxin Reductase-2 Is Essential for Keeping Low Levels of H2O2 Emission from Isolated Heart Mitochondria](https://pubmed.ncbi.nlm.nih.gov/21832082/)

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_access

Primary abstract

experimental_model

Purified human MPO system and stimulated human neutrophils.

limitations

Taurine chloramine remains an oxidant; free taurine is not equivalent to every chloramine effect.

nutrient_topic

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

plain_language

An immune-cell oxidant reacts with taurine to make a different active molecule.

primary_references

Chlorination of taurine by human neutrophils. Evidence for hypochlorous acid generation. · 1982 · https://pubmed.ncbi.nlm.nih.gov/6286728/ · DOI 10.1172/jci110652

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 361–367

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Purified human MPO system and stimulated human neutrophils. · source_derived_draft · unverified_draft

## taurine-mpo-chlorination An immune-cell oxidant reacts with taurine to make a different active molecule. Purified myeloperoxidase plus hydrogen peroxide, chloride and taurine generated taurine chloramine; removing chloride or peroxide, or inhibiting MPO, blocked generation. Model: Purified human MPO system and stimulated human neutrophils. Limitations: Taurine chloramine remains an oxidant; free taurine is not equivalent to every chloramine effect. Evidence access: Primary abstract Chlorination of taurine by human neutrophils. Evidence for hypochlorous acid generation. · 1982 · https://pubmed.ncbi.nlm.nih.gov/6286728/ · DOI 10.1172/jci110652

dose

Eugenol with peroxidase and hydrogen peroxide

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Purified human MPO and activated human polymorphonuclear leukocytes

limitations

The reactive intermediate was inferred from chemistry; ordinary dietary exposure and organ-specific dose were not established.

nutrient_topic

Eugenol chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Eugenol

organism

Purified human MPO and activated human polymorphonuclear leukocytes

plain_language

Human myeloperoxidase with hydrogen peroxide oxidized eugenol toward a reactive intermediate consistent with a quinone methide.

primary_references

Metabolic activation of eugenol by myeloperoxidase and polymorphonuclear leukocytes. (1989). https://pubmed.ncbi.nlm.nih.gov/2562421/ DOI: 10.1021/tx00009a011

route

In vitro

tissue

Reactive-metabolite formation and protein binding

Eugenol: mechanism of action and interactions (2026-09-20) · lines 88–97

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Purified human MPO and activated human polymorphonuclear leukocytes · source_derived_draft · unverified_draft

## eugenol-mpo-activation Human myeloperoxidase with hydrogen peroxide oxidized eugenol toward a reactive intermediate consistent with a quinone methide. Model/species: Purified human MPO and activated human polymorphonuclear leukocytes Tissue/system: Reactive-metabolite formation and protein binding Exposure: Eugenol with peroxidase and hydrogen peroxide Route: In vitro Duration: Acute Limits: The reactive intermediate was inferred from chemistry; ordinary dietary exposure and organ-specific dose were not established. Primary reference: Metabolic activation of eugenol by myeloperoxidase and polymorphonuclear leukocytes. (1989). https://pubmed.ncbi.nlm.nih.gov/2562421/ DOI: 10.1021/tx00009a011 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_access

Primary abstract

experimental_model

PTP1B time-course experiments with catalase.

limitations

Catalase rescue supports peroxide involvement; it does not identify every species in living cells.

nutrient_topic

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

plain_language

An assay can generate a second inhibitor while it runs.

primary_references

Mechanism of inhibition of protein-tyrosine phosphatases by vanadate and pervanadate. · 1997 · https://pubmed.ncbi.nlm.nih.gov/8995372/ · DOI 10.1074/jbc.272.2.843

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 46–52

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · PTP1B time-course experiments with catalase. · source_derived_draft · unverified_draft

## vanadium-catalase-artifact An assay can generate a second inhibitor while it runs. Catalase blocked the slow time-dependent inactivation seen under some vanadate conditions, supporting an in-situ peroxide/pervanadate contribution. Model: PTP1B time-course experiments with catalase. Limitations: Catalase rescue supports peroxide involvement; it does not identify every species in living cells. Evidence access: Primary abstract Mechanism of inhibition of protein-tyrosine phosphatases by vanadate and pervanadate. · 1997 · https://pubmed.ncbi.nlm.nih.gov/8995372/ · DOI 10.1074/jbc.272.2.843

evidence_access

Primary abstract

experimental_model

Two cell lines with different susceptibilities; identities not provided in accessed abstract.

limitations

The proposed intracellular peroxovanadium sequence was not established as a universal mechanism.

nutrient_topic

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

plain_language

Available reducing or peroxide-removing capacity changed the toxicity response.

primary_references

Mechanisms of vanadate-induced cellular toxicity: role of cellular glutathione and NADPH. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12234491/ · DOI 10.1016/s0003-9861(02)00408-3

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 142–148

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Two cell lines with different susceptibilities; identities not provided in accessed abstract. · source_derived_draft · unverified_draft

## vanadium-gsh-cell-rescue Available reducing or peroxide-removing capacity changed the toxicity response. Glutathione and catalase reversed vanadate sensitivity in the susceptible cell line studied. Model: Two cell lines with different susceptibilities; identities not provided in accessed abstract. Limitations: The proposed intracellular peroxovanadium sequence was not established as a universal mechanism. Evidence access: Primary abstract Mechanisms of vanadate-induced cellular toxicity: role of cellular glutathione and NADPH. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12234491/ · DOI 10.1016/s0003-9861(02)00408-3

evidence_access

Primary abstract

experimental_model

Cell-free ESR spin trapping.

limitations

Chemical mechanism under specified reagents; not proof that vitamin C supplementation causes this injury in people.

nutrient_topic

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

plain_language

A reductant can enable pro-oxidant chemistry when peroxide is also present.

primary_references

One-electron reduction of vanadate by ascorbate and related free radical generation at physiological pH. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8051539/ · DOI 10.1016/0162-0134(94)85032-1

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 102–108

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free ESR spin trapping. · source_derived_draft · unverified_draft

## vanadium-peroxide-radicals A reductant can enable pro-oxidant chemistry when peroxide is also present. In phosphate/ascorbate mixtures with peroxide, reduced vanadium supported hydroxyl-radical generation; omitting phosphate sharply reduced the yield. Model: Cell-free ESR spin trapping. Limitations: Chemical mechanism under specified reagents; not proof that vitamin C supplementation causes this injury in people. Evidence access: Primary abstract One-electron reduction of vanadate by ascorbate and related free radical generation at physiological pH. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8051539/ · DOI 10.1016/0162-0134(94)85032-1

evidence_access

Primary abstract

experimental_model

Purified PTP1B kinetic and mass-spectrometric experiments.

limitations

Do not assign this irreversible oxidation to all vanadate exposures or dietary vanadium.

nutrient_topic

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

plain_language

The peroxide-containing species disables the enzyme through a different mechanism.

primary_references

Mechanism of inhibition of protein-tyrosine phosphatases by vanadate and pervanadate. · 1997 · https://pubmed.ncbi.nlm.nih.gov/8995372/ · DOI 10.1074/jbc.272.2.843

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 30–36

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified PTP1B kinetic and mass-spectrometric experiments. · source_derived_draft · unverified_draft

## vanadium-pervanadate-cysteine The peroxide-containing species disables the enzyme through a different mechanism. Pervanadate irreversibly inhibited PTP1B by oxidation of its catalytic cysteine, supported by mass spectrometry. Model: Purified PTP1B kinetic and mass-spectrometric experiments. Limitations: Do not assign this irreversible oxidation to all vanadate exposures or dietary vanadium. Evidence access: Primary abstract Mechanism of inhibition of protein-tyrosine phosphatases by vanadate and pervanadate. · 1997 · https://pubmed.ncbi.nlm.nih.gov/8995372/ · DOI 10.1074/jbc.272.2.843

evidence_access

Primary full text

experimental_model

Human HUVECs, 0.5 mM silicon preparation.

limitations

Expression is not measured catalytic flux or proof that silicon replaces established metal cofactors.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

An individual antioxidant or vascular enzyme was measured.

primary_references

Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

Silica: soluble silicon, cellular transport and particle-specific 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 · Human HUVECs, 0.5 mM silicon preparation. · source_derived_draft · unverified_draft

## silica-endothelial-human-catalase An individual antioxidant or vascular enzyme was measured. Silicon-treated HUVECs increased catalase mRNA under the reported normal and peroxide conditions. Model: Human HUVECs, 0.5 mM silicon preparation. Limitations: Expression is not measured catalytic flux or proof that silicon replaces established metal cofactors. Evidence access: Primary full text Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

evidence_access

Primary full text

experimental_model

Human endothelial cultures; sodium-metasilicate-derived preparation.

limitations

Expression association does not establish direct activation or clinical angiogenesis.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

A distinct vascular regulator changed after exposure.

primary_references

Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

Silica: soluble silicon, cellular transport and particle-specific 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 · Human endothelial cultures; sodium-metasilicate-derived preparation. · source_derived_draft · unverified_draft

## silica-endothelial-marker-hif1a A distinct vascular regulator changed after exposure. The 0.5 mM silicon preparation increased HIF1A expression in HUVECs with or without the tested peroxide challenge. Model: Human endothelial cultures; sodium-metasilicate-derived preparation. Limitations: Expression association does not establish direct activation or clinical angiogenesis. Evidence access: Primary full text Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

evidence_access

Primary full text

experimental_model

Human endothelial cultures; sodium-metasilicate-derived preparation.

limitations

Expression association does not establish direct activation or clinical angiogenesis.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

A distinct vascular regulator changed after exposure.

primary_references

Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

Silica: soluble silicon, cellular transport and particle-specific 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 · Human endothelial cultures; sodium-metasilicate-derived preparation. · source_derived_draft · unverified_draft

## silica-endothelial-marker-human-kdr A distinct vascular regulator changed after exposure. The 0.5 mM silicon preparation increased VEGFR2 / KDR expression in HUVECs with or without the tested peroxide challenge. Model: Human endothelial cultures; sodium-metasilicate-derived preparation. Limitations: Expression association does not establish direct activation or clinical angiogenesis. Evidence access: Primary full text Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

evidence_access

Primary full text

experimental_model

Human endothelial cultures; sodium-metasilicate-derived preparation.

limitations

Expression association does not establish direct activation or clinical angiogenesis.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

A distinct vascular regulator changed after exposure.

primary_references

Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

Silica: soluble silicon, cellular transport and particle-specific 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 · Human endothelial cultures; sodium-metasilicate-derived preparation. · source_derived_draft · unverified_draft

## silica-endothelial-marker-human-vegfa A distinct vascular regulator changed after exposure. The 0.5 mM silicon preparation increased VEGFA expression in HUVECs with or without the tested peroxide challenge. Model: Human endothelial cultures; sodium-metasilicate-derived preparation. Limitations: Expression association does not establish direct activation or clinical angiogenesis. Evidence access: Primary full text Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

evidence_access

Primary full text

experimental_model

Human HUVECs, 0.5 mM silicon preparation.

limitations

Expression is not measured catalytic flux or proof that silicon replaces established metal cofactors.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

An individual antioxidant or vascular enzyme was measured.

primary_references

Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

Silica: soluble silicon, cellular transport and particle-specific 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 · Human HUVECs, 0.5 mM silicon preparation. · source_derived_draft · unverified_draft

## silica-endothelial-nos3 An individual antioxidant or vascular enzyme was measured. Silicon-treated HUVECs increased NOS3 mRNA under the reported normal and peroxide conditions. Model: Human HUVECs, 0.5 mM silicon preparation. Limitations: Expression is not measured catalytic flux or proof that silicon replaces established metal cofactors. Evidence access: Primary full text Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

evidence_access

Primary full text

experimental_model

Human HUVECs, 0.5 mM silicon preparation.

limitations

Expression is not measured catalytic flux or proof that silicon replaces established metal cofactors.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

An individual antioxidant or vascular enzyme was measured.

primary_references

Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

Silica: soluble silicon, cellular transport and particle-specific 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 · Human HUVECs, 0.5 mM silicon preparation. · source_derived_draft · unverified_draft

## silica-endothelial-sod1 An individual antioxidant or vascular enzyme was measured. Silicon-treated HUVECs increased SOD1 mRNA under the reported normal and peroxide conditions. Model: Human HUVECs, 0.5 mM silicon preparation. Limitations: Expression is not measured catalytic flux or proof that silicon replaces established metal cofactors. Evidence access: Primary full text Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

evidence_access

Primary full text

experimental_model

Sodium-metasilicate-derived medium; 0.6 mM H2O2 challenge.

limitations

Authors label exposure Si4+; this is not a measured pool of free aqueous Si4+. Supraphysiological culture exposure.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

Dissolved preparation altered the response to oxidative stress.

primary_references

Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

Silica: soluble silicon, cellular transport and particle-specific 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 · Sodium-metasilicate-derived medium; 0.6 mM H2O2 challenge. · source_derived_draft · unverified_draft

## silica-endothelial-survival Dissolved preparation altered the response to oxidative stress. A 0.5 mM silicon preparation improved HUVEC viability during hydrogen-peroxide exposure. Model: Sodium-metasilicate-derived medium; 0.6 mM H2O2 challenge. Limitations: Authors label exposure Si4+; this is not a measured pool of free aqueous Si4+. Supraphysiological culture exposure. Evidence access: Primary full text Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

evidence_access

Primary full text

experimental_model

Mouse muscle-cell culture, 24-hour challenge experiments.

limitations

Does not identify a direct antioxidant reaction or an in-vivo effective dose.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

Oxidative challenge changed the context in which protection was observed.

primary_references

Ionic Silicon Protects Oxidative Damage and Promotes Skeletal Muscle Cell Regeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33419056/ · DOI 10.3390/ijms22020497

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 328–334

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse muscle-cell culture, 24-hour challenge experiments. · source_derived_draft · unverified_draft

## silica-muscle-peroxide Oxidative challenge changed the context in which protection was observed. Silicon preparations at 0.1–2 mM attenuated peroxide-associated loss of viability and differentiation. Model: Mouse muscle-cell culture, 24-hour challenge experiments. Limitations: Does not identify a direct antioxidant reaction or an in-vivo effective dose. Evidence access: Primary full text Ionic Silicon Protects Oxidative Damage and Promotes Skeletal Muscle Cell Regeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33419056/ · DOI 10.3390/ijms22020497

evidence_span

{"source_cache": "artifacts/hbot-research/11023535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d", "start_char": 0, "end_char": 1576, "text_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d"}

experimental_model

Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement

exposure

100% oxygen at 2.5 ATA for three 20-minute periods

limitations

A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Human

plain_language

One exposure leaves the cells better able to survive the next oxidative hit.

primary_references

[hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

tissue_or_cell_type

Circulating lymphocytes

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 296–307

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement · source_derived_draft · unverified_draft

### hbot-adaptive-protection Blood taken 24 hours after treatment was significantly protected against DNA damage induced by hydrogen peroxide in vitro, while protection against gamma-irradiation was not significant. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: One exposure leaves the cells better able to survive the next oxidative hit. organism: Human tissue_or_cell_type: Circulating lymphocytes experimental_model: Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement limitations: A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron. exposure: 100% oxygen at 2.5 ATA for three 20-minute periods evidence_span: {"source_cache": "artifacts/hbot-research/11023535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d", "start_char": 0, "end_char": 1576, "text_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d"} [hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

evidence_span

{"source_cache": "artifacts/hbot-research/23770209.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1621131d902e359cb8c23a51c1d76596ddff036697818a1613e68b26095eed8a", "start_char": 0, "end_char": 1709, "text_sha256": "1621131d902e359cb8c23a51c1d76596ddff036697818a1613e68b26095eed8a"}

experimental_model

Differentiated HL-60 neutrophil-like cells across normoxia, hypoxia, hyperoxia, pressure alone and hyperbaric oxygen

exposure

97.9% oxygen at 2.4 ATA for 90 minutes, with hyperbaric normoxia as a pressure control

limitations

A cell-line model of the neutrophil with a pressure control. The authors report that both hyperoxia and pressure contributed, without a consistent pattern.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Human cell line

plain_language

The cells that kill bacteria did so more strongly after a session.

primary_references

[hbot-p23770209] Effects of hyperbaric oxygen treatment on antimicrobial function and apoptosis of differentiated HL-60 (neutrophil-like) cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23770209/ DOI: 10.1016/j.lfs.2013.06.003

tissue_or_cell_type

Neutrophil-like cells

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 1037–1048

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated HL-60 neutrophil-like cells across normoxia, hypoxia, hyperoxia, pressure alone and hyperbaric oxygen · source_derived_draft · unverified_draft

### hbot-respiratory-burst-increase A single 90-minute exposure increased the respiratory burst activity of neutrophil-like cells after exposure, and phagocytosis of Staphylococcus aureus was also increased. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The cells that kill bacteria did so more strongly after a session. organism: Human cell line tissue_or_cell_type: Neutrophil-like cells experimental_model: Differentiated HL-60 neutrophil-like cells across normoxia, hypoxia, hyperoxia, pressure alone and hyperbaric oxygen limitations: A cell-line model of the neutrophil with a pressure control. The authors report that both hyperoxia and pressure contributed, without a consistent pattern. exposure: 97.9% oxygen at 2.4 ATA for 90 minutes, with hyperbaric normoxia as a pressure control evidence_span: {"source_cache": "artifacts/hbot-research/23770209.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1621131d902e359cb8c23a51c1d76596ddff036697818a1613e68b26095eed8a", "start_char": 0, "end_char": 1709, "text_sha256": "1621131d902e359cb8c23a51c1d76596ddff036697818a1613e68b26095eed8a"} [hbot-p23770209] Effects of hyperbaric oxygen treatment on antimicrobial function and apoptosis of differentiated HL-60 (neutrophil-like) cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23770209/ DOI: 10.1016/j.lfs.2013.06.003

evidence_span

{"source_cache": "artifacts/hbot-research/6316150.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dc20323f9774c6c743e01f8bdbeedbc42b0ddac982f1e17d53a9591b87bf5379", "start_char": 0, "end_char": 867, "text_sha256": "dc20323f9774c6c743e01f8bdbeedbc42b0ddac982f1e17d53a9591b87bf5379"}

experimental_model

Refinement of the 2 angstrom crystal structure of copper, zinc superoxide dismutase with molecular surface analysis

exposure

Structural and mechanistic analysis of the active site

limitations

Structural chemistry. It explains why the enzyme needs its metals; it is not a statement about dietary copper or zinc.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Bovine enzyme structure

plain_language

The copper atom itself is what takes and gives back the electron.

primary_references

[hbot-p6316150] Structure and mechanism of copper, zinc superoxide dismutase. (1983). https://pubmed.ncbi.nlm.nih.gov/6316150/ DOI: 10.1038/306284a0

tissue_or_cell_type

Purified enzyme

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 491–502

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Refinement of the 2 angstrom crystal structure of copper, zinc superoxide dismutase with molecular surface analysis · source_derived_draft · unverified_draft

### hbot-sod1-copper-mechanism Copper, zinc superoxide dismutase catalyses the two-step dismutation of superoxide to molecular oxygen and hydrogen peroxide through alternate reduction and oxidation of the active-site copper, with a single complementary binding position for superoxide at the Cu(II) and the activity-important Arg141. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The copper atom itself is what takes and gives back the electron. organism: Bovine enzyme structure tissue_or_cell_type: Purified enzyme experimental_model: Refinement of the 2 angstrom crystal structure of copper, zinc superoxide dismutase with molecular surface analysis limitations: Structural chemistry. It explains why the enzyme needs its metals; it is not a statement about dietary copper or zinc. exposure: Structural and mechanistic analysis of the active site evidence_span: {"source_cache": "artifacts/hbot-research/6316150.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dc20323f9774c6c743e01f8bdbeedbc42b0ddac982f1e17d53a9591b87bf5379", "start_char": 0, "end_char": 867, "text_sha256": "dc20323f9774c6c743e01f8bdbeedbc42b0ddac982f1e17d53a9591b87bf5379"} [hbot-p6316150] Structure and mechanism of copper, zinc superoxide dismutase. (1983). https://pubmed.ncbi.nlm.nih.gov/6316150/ DOI: 10.1038/306284a0

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/hbot-research/10849437.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90", "start_char": 0, "end_char": 1374, "text_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90"}

experimental_model

Recombinant rat thioredoxin reductase with selenocysteine mutations expressed in E. coli

exposure

SeCys498 replaced by cysteine or serine, and a truncated protein lacking the C-terminal SeCys-Gly dipeptide

limitations

The truncated construct is described by the authors as the form expected in selenium deficiency, which is what links this enzyme chemistry to nutrient supply. It remains a recombinant model, not a measurement in a selenium-deficient animal.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Rat enzyme in a bacterial expression host

plain_language

Without selenium the enzyme can no longer destroy peroxide at all.

primary_references

[hbot-p10849437] Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations. (2000). https://pubmed.ncbi.nlm.nih.gov/10849437/ DOI: 10.1074/jbc.m000690200

tissue_or_cell_type

Purified enzyme

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 478–489

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant rat thioredoxin reductase with selenocysteine mutations expressed in E. coli · source_derived_draft · unverified_draft

### hbot-trxr-truncated-no-activity Whereas hydrogen peroxide was a substrate for the wild-type enzyme, all mutant enzymes, including the truncated form expected in selenium deficiency, lacked hydroperoxidase activity, so selenium is required for the catalytic activities of thioredoxin reductase. Condition category: nutrient_deficiency nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Without selenium the enzyme can no longer destroy peroxide at all. organism: Rat enzyme in a bacterial expression host tissue_or_cell_type: Purified enzyme experimental_model: Recombinant rat thioredoxin reductase with selenocysteine mutations expressed in E. coli limitations: The truncated construct is described by the authors as the form expected in selenium deficiency, which is what links this enzyme chemistry to nutrient supply. It remains a recombinant model, not a measurement in a selenium-deficient animal. exposure: SeCys498 replaced by cysteine or serine, and a truncated protein lacking the C-terminal SeCys-Gly dipeptide evidence_span: {"source_cache": "artifacts/hbot-research/10849437.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90", "start_char": 0, "end_char": 1374, "text_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90"} [hbot-p10849437] Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations. (2000). https://pubmed.ncbi.nlm.nih.gov/10849437/ DOI: 10.1074/jbc.m000690200

evidence_span

{"source_cache": "artifacts/chloride-research/9359420.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0", "start_char": 0, "end_char": 1700, "text_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0"}

experimental_model

Purified-enzyme substrate kinetics

exposure

100 mM chloride with varying thiocyanate

limitations

Product chemistry under assay conditions; not a recommendation to raise chloride or thiocyanate intake.

nutrient_topic

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

organism

Human neutrophil enzyme

plain_language

Immune chemistry can convert chloride into a reactive antimicrobial oxidant.

primary_references

[chloride-p9359420] Thiocyanate and chloride as competing substrates for myeloperoxidase. (1997). https://pubmed.ncbi.nlm.nih.gov/9359420/ DOI: 10.1042/bj3270487

tissue_or_cell_type

Myeloperoxidase reaction mixture

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 614–625

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

### chloride-mpo-hocl Myeloperoxidase used hydrogen peroxide to oxidize chloride to hypochlorous acid. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Immune chemistry can convert chloride into a reactive antimicrobial oxidant. organism: Human neutrophil enzyme tissue_or_cell_type: Myeloperoxidase reaction mixture experimental_model: Purified-enzyme substrate kinetics limitations: Product chemistry under assay conditions; not a recommendation to raise chloride or thiocyanate intake. exposure: 100 mM chloride with varying thiocyanate evidence_span: {"source_cache": "artifacts/chloride-research/9359420.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0", "start_char": 0, "end_char": 1700, "text_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0"} [chloride-p9359420] Thiocyanate and chloride as competing substrates for myeloperoxidase. (1997). https://pubmed.ncbi.nlm.nih.gov/9359420/ DOI: 10.1042/bj3270487

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Explains why B2-dependent GSH recycling and selenium-dependent GSH use are distinct requirements.

evidence_location

Abstract

experimental_model

Erythrocyte hemolyzates from selenium-deficient rats; glutathione addition during peroxide/ascorbate challenge and 75Se enzyme purification.

exposure

Selenium-deficient diet, then ex-vivo oxidant and glutathione exposure

limitations

Separate from FAD-dependent GSR recycling; neither riboflavin nor combined nutrient repletion was tested.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Rattus norvegicus

plain_language

Supplying glutathione did not replace the missing selenium-dependent enzyme activity.

primary_references

[rotruck1973] Selenium: biochemical role as a component of glutathione peroxidase. (1973). https://pubmed.ncbi.nlm.nih.gov/4686466/ DOI: 10.1126/science.179.4073.588

tissue_or_cell_type

Erythrocyte hemolyzates

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1472–1484

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Erythrocyte hemolyzates from selenium-deficient rats; glutathione addition during peroxide/ascorbate challenge and 75Se enzyme purification. · source_derived_draft · unverified_draft

### b2-redox-gsh-needs-selenium-peroxidase Added glutathione failed to protect hemoglobin during oxidant challenge of selenium-deficient rat hemolyzates with very low glutathione-peroxidase activity. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Supplying glutathione did not replace the missing selenium-dependent enzyme activity. organism: Rattus norvegicus tissue_or_cell_type: Erythrocyte hemolyzates experimental_model: Erythrocyte hemolyzates from selenium-deficient rats; glutathione addition during peroxide/ascorbate challenge and 75Se enzyme purification. limitations: Separate from FAD-dependent GSR recycling; neither riboflavin nor combined nutrient repletion was tested. exposure: Selenium-deficient diet, then ex-vivo oxidant and glutathione exposure cross_nutrient: Explains why B2-dependent GSH recycling and selenium-dependent GSH use are distinct requirements. evidence_location: Abstract [rotruck1973] Selenium: biochemical role as a component of glutathione peroxidase. (1973). https://pubmed.ncbi.nlm.nih.gov/4686466/ DOI: 10.1126/science.179.4073.588

experimental_model

Primary airway epithelial cultures and human oral-KI exposure; separate experimental arms.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Culture antiviral activity and human secretion measurements do not establish prevention or treatment of human infection.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

Changing the enzyme substrate changed antiviral activity.

primary_references

Enhancement of respiratory mucosal antiviral defenses by the oxidation of iodide. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21441383/ · DOI 10.1165/rcmb.2010-0329oc

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 72–78

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Primary airway epithelial cultures and human oral-KI exposure; separate experimental arms. · source_derived_draft · unverified_draft

## ki-air-adeno Changing the enzyme substrate changed antiviral activity. Replacing thiocyanate with iodide in the LPO/H2O2 system reduced adenovirus transduction. Model: Primary airway epithelial cultures and human oral-KI exposure; separate experimental arms. Limitations: Culture antiviral activity and human secretion measurements do not establish prevention or treatment of human infection. Evidence location: Primary abstract Enhancement of respiratory mucosal antiviral defenses by the oxidation of iodide. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21441383/ · DOI 10.1165/rcmb.2010-0329oc

experimental_model

Primary airway epithelial cultures and human oral-KI exposure; separate experimental arms.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Culture antiviral activity and human secretion measurements do not establish prevention or treatment of human infection.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

Iodide and thiocyanate were not interchangeable against these viruses.

primary_references

Enhancement of respiratory mucosal antiviral defenses by the oxidation of iodide. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21441383/ · DOI 10.1165/rcmb.2010-0329oc

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 80–86

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Primary airway epithelial cultures and human oral-KI exposure; separate experimental arms. · source_derived_draft · unverified_draft

## ki-air-rsv Iodide and thiocyanate were not interchangeable against these viruses. The LPO/iodide/H2O2 system reduced RSV titre; the tested thiocyanate system did not inactivate RSV or adenovirus. Model: Primary airway epithelial cultures and human oral-KI exposure; separate experimental arms. Limitations: Culture antiviral activity and human secretion measurements do not establish prevention or treatment of human infection. Evidence location: Primary abstract Enhancement of respiratory mucosal antiviral defenses by the oxidation of iodide. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21441383/ · DOI 10.1165/rcmb.2010-0329oc

experimental_model

Purified biochemical reaction; GSH measured by amperometric titration.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

No demonstration that ordinary KI intake depletes human glutathione.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

This iodine chemistry can consume glutathione in a test system.

primary_references

Free radical generation and coupled thiol oxidation by lactoperoxidase/SCN-/H2O2. · 1992 · https://pubmed.ncbi.nlm.nih.gov/1324202/ · DOI 10.1016/0891-5849(92)90014-8

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 248–254

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Purified biochemical reaction; GSH measured by amperometric titration. · source_derived_draft · unverified_draft

## ki-gsh This iodine chemistry can consume glutathione in a test system. Iodide substituted for thiocyanate in LPO/H2O2-dependent glutathione oxidation; chloride and bromide were ineffective substitutes. Model: Purified biochemical reaction; GSH measured by amperometric titration. Limitations: No demonstration that ordinary KI intake depletes human glutathione. Evidence location: Primary abstract Free radical generation and coupled thiol oxidation by lactoperoxidase/SCN-/H2O2. · 1992 · https://pubmed.ncbi.nlm.nih.gov/1324202/ · DOI 10.1016/0891-5849(92)90014-8

experimental_model

Purified LPO crystallography and activity assays; ammonium iodide supplied the anion, not KI.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Structural/biochemical model; enzyme species not assigned from abstract. Cofactor chemistry does not establish dietary iron responsiveness.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

Iron-containing heme positions peroxide in the enzyme.

primary_references

Structure of a ternary complex of lactoperoxidase with iodide and hydrogen peroxide at 1.77 Å resolution. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33882424/ · DOI 10.1016/j.jinorgbio.2021.111461

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 216–222

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Purified LPO crystallography and activity assays; ammonium iodide supplied the anion, not KI. · source_derived_draft · unverified_draft

## ki-lpo-heme Iron-containing heme positions peroxide in the enzyme. The LPO structure contains covalently attached heme; peroxide sits between its iron and distal His109. Model: Purified LPO crystallography and activity assays; ammonium iodide supplied the anion, not KI. Limitations: Structural/biochemical model; enzyme species not assigned from abstract. Cofactor chemistry does not establish dietary iron responsiveness. Evidence location: Primary abstract Structure of a ternary complex of lactoperoxidase with iodide and hydrogen peroxide at 1.77 Å resolution. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33882424/ · DOI 10.1016/j.jinorgbio.2021.111461

experimental_model

Purified LPO crystallography and activity assays; ammonium iodide supplied the anion, not KI.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Structural/biochemical model; enzyme species not assigned from abstract. Cofactor chemistry does not establish dietary iron responsiveness.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

The oxidized iodine product was observed structurally.

primary_references

Structural evidence of the oxidation of iodide ion into hyper-reactive hypoiodite ion by mammalian heme lactoperoxidase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34761444/ · DOI 10.1002/pro.4230

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 232–238

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Purified LPO crystallography and activity assays; ammonium iodide supplied the anion, not KI. · source_derived_draft · unverified_draft

## ki-lpo-product The oxidized iodine product was observed structurally. Peroxide-preincubated LPO exposed to iodide yielded a crystal complex containing hypoiodite in its substrate channel. Model: Purified LPO crystallography and activity assays; ammonium iodide supplied the anion, not KI. Limitations: Structural/biochemical model; enzyme species not assigned from abstract. Cofactor chemistry does not establish dietary iron responsiveness. Evidence location: Primary abstract Structural evidence of the oxidation of iodide ion into hyper-reactive hypoiodite ion by mammalian heme lactoperoxidase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34761444/ · DOI 10.1002/pro.4230

experimental_model

Purified LPO crystallography and activity assays; ammonium iodide supplied the anion, not KI.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Structural/biochemical model; enzyme species not assigned from abstract. Cofactor chemistry does not establish dietary iron responsiveness.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

Iodide can inhibit the enzyme under a different order of exposure.

primary_references

Structure of a ternary complex of lactoperoxidase with iodide and hydrogen peroxide at 1.77 Å resolution. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33882424/ · DOI 10.1016/j.jinorgbio.2021.111461

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 224–230

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Purified LPO crystallography and activity assays; ammonium iodide supplied the anion, not KI. · source_derived_draft · unverified_draft

## ki-lpo-substrate-block Iodide can inhibit the enzyme under a different order of exposure. Preincubating LPO with ammonium iodide decreased measured catalytic activity and stabilized a peroxide–iodide ternary complex. Model: Purified LPO crystallography and activity assays; ammonium iodide supplied the anion, not KI. Limitations: Structural/biochemical model; enzyme species not assigned from abstract. Cofactor chemistry does not establish dietary iron responsiveness. Evidence location: Primary abstract Structure of a ternary complex of lactoperoxidase with iodide and hydrogen peroxide at 1.77 Å resolution. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33882424/ · DOI 10.1016/j.jinorgbio.2021.111461

experimental_model

Cell-free LPO/H2O2 reactions with nicotinamide nucleotides.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Chemical oxidation is not evidence that supplementation drains niacin in vivo; the authors expected thiocyanate oxidation to predominate in milk/saliva.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

The NADH reaction did not simply regenerate normal NAD+.

primary_references

The oxidation of reduced nicotinamide nucleotides by hydrogen peroside in the presence of lactoperoxidase and thiocyanate, iodide or bromide. · 1970 · https://pubmed.ncbi.nlm.nih.gov/4317722/ · DOI 10.1042/bj1170791

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 256–262

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Cell-free LPO/H2O2 reactions with nicotinamide nucleotides. · source_derived_draft · unverified_draft

## ki-nadh The NADH reaction did not simply regenerate normal NAD+. LPO/H2O2/iodide oxidized NADH to a product chemically distinct from NAD+, unlike the thiocyanate and bromide systems. Model: Cell-free LPO/H2O2 reactions with nicotinamide nucleotides. Limitations: Chemical oxidation is not evidence that supplementation drains niacin in vivo; the authors expected thiocyanate oxidation to predominate in milk/saliva. Evidence location: Primary abstract The oxidation of reduced nicotinamide nucleotides by hydrogen peroside in the presence of lactoperoxidase and thiocyanate, iodide or bromide. · 1970 · https://pubmed.ncbi.nlm.nih.gov/4317722/ · DOI 10.1042/bj1170791

experimental_model

Cell-free LPO/H2O2 reactions with nicotinamide nucleotides.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Chemical oxidation is not evidence that supplementation drains niacin in vivo; the authors expected thiocyanate oxidation to predominate in milk/saliva.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

The chemistry also reaches the NADPH reducing pool.

primary_references

The oxidation of reduced nicotinamide nucleotides by hydrogen peroside in the presence of lactoperoxidase and thiocyanate, iodide or bromide. · 1970 · https://pubmed.ncbi.nlm.nih.gov/4317722/ · DOI 10.1042/bj1170791

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 264–270

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Cell-free LPO/H2O2 reactions with nicotinamide nucleotides. · source_derived_draft · unverified_draft

## ki-nadph The chemistry also reaches the NADPH reducing pool. NADPH was also oxidized under the LPO/H2O2/iodide conditions. Model: Cell-free LPO/H2O2 reactions with nicotinamide nucleotides. Limitations: Chemical oxidation is not evidence that supplementation drains niacin in vivo; the authors expected thiocyanate oxidation to predominate in milk/saliva. Evidence location: Primary abstract The oxidation of reduced nicotinamide nucleotides by hydrogen peroside in the presence of lactoperoxidase and thiocyanate, iodide or bromide. · 1970 · https://pubmed.ncbi.nlm.nih.gov/4317722/ · DOI 10.1042/bj1170791

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human cancer-cell genetic experiments; mixed polyamine comparisons.

limitations

Polyamine-class result; do not attribute all experiments to spermidine alone.

nutrient_topic

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

plain_language

Oxidative breakdown provides another route to lipid injury.

primary_references

Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38504107/ · DOI 10.1038/s41467-024-46776-w

trigger_kind

machinery_impairment Imported condition classification; unverified.

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 534–540

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell genetic experiments; mixed polyamine comparisons. · source_derived_draft · unverified_draft

## spermidine-oxidase-ferroptosis Oxidative breakdown provides another route to lipid injury. PAOX/SMOX knockout reduced polyamine-associated sensitization to ferroptosis in A549 and HT1080 cells. Model: Human cancer-cell genetic experiments; mixed polyamine comparisons. Limitations: Polyamine-class result; do not attribute all experiments to spermidine alone. Evidence access: Primary full text Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38504107/ · DOI 10.1038/s41467-024-46776-w

evidence_access

Primary full text

experimental_model

Serum comparisons and cultured cancer cells.

limitations

Do not mistake serum-generated oxidants for direct intracellular target engagement.

nutrient_topic

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

plain_language

The culture medium can transform the compound before cells respond.

primary_references

Oxidative degradation of polyamines by serum supplement causes cytotoxicity on cultured cells. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29991686/ · DOI 10.1038/s41598-018-28648-8

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 486–492

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Serum comparisons and cultured cancer cells. · source_derived_draft · unverified_draft

## spermidine-serum-peroxide The culture medium can transform the compound before cells respond. Added spermidine generated hydrogen peroxide in several animal-serum-containing media but not the tested human-serum medium. Model: Serum comparisons and cultured cancer cells. Limitations: Do not mistake serum-generated oxidants for direct intracellular target engagement. Evidence access: Primary full text Oxidative degradation of polyamines by serum supplement causes cytotoxicity on cultured cells. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29991686/ · DOI 10.1038/s41598-018-28648-8

evidence_access

Primary abstract

experimental_model

Human ERO1A structural and biochemical study.

limitations

Protein-residue oxidation is separate from free cystine reduction; dietary cysteine effects were not tested.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

Cysteines already incorporated into proteins are joined and rearranged during folding.

primary_references

Crystal structures of human Ero1α reveal the mechanisms of regulated and targeted oxidation of PDI. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20834232/ · DOI 10.1038/emboj.2010.222

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 484–490

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human ERO1A structural and biochemical study. · source_derived_draft · unverified_draft

## l-cysteine-ero1-pdi-targeting Cysteines already incorporated into proteins are joined and rearranged during folding. Human ERO1A targets PDI through contacts with its b-prime substrate-binding domain, supporting the disulfide-forming pathway for protein folding. Model: Human ERO1A structural and biochemical study. Limitations: Protein-residue oxidation is separate from free cystine reduction; dietary cysteine effects were not tested. Evidence access: Primary abstract Crystal structures of human Ero1α reveal the mechanisms of regulated and targeted oxidation of PDI. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20834232/ · DOI 10.1038/emboj.2010.222

cross_nutrient

false

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/2841932.json", "json_field": "abstractText", "text_sha256": "00e19301656f8e8fdb9a047cfa29daf1c66f9a73c84d6c450ff805a6d8b497eb", "text_characters": 1113, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

Dog thyroid slices with iodide, stimulatory probes and methimazole

exposure

Iodide exposure in dog thyroid slices stimulated by thyrotropin, carbamylcholine or intracellular-signaling probes; concentrations not given in abstract. Methimazole coexposure.

limitations

Pharmacological probe supports oxidation dependence; the inhibitory iodinated species was not identified.

nutrient_topic

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

organism

Canis lupus familiaris

plain_language

Preventing iodide oxidation blocked this feedback effect in thyroid tissue.

primary_references

[iodine-syn-block1988] Inhibition by iodide of iodide binding to proteins: the "Wolff-Chaikoff" effect is caused by inhibition of H2O2 generation. (1988). https://pubmed.ncbi.nlm.nih.gov/2841932/ DOI: 10.1016/0006-291x(88)90279-3

tissue_or_cell_type

Thyroid slices

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 814–826

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dog thyroid slices with iodide, stimulatory probes and methimazole · source_derived_draft · unverified_draft

### iodine-syn-acute-block-oxidation Methimazole suppressed the inhibitory effects of iodide on stimulated H2O2 generation in dog thyroid slices. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Preventing iodide oxidation blocked this feedback effect in thyroid tissue. organism: Canis lupus familiaris tissue_or_cell_type: Thyroid slices experimental_model: Dog thyroid slices with iodide, stimulatory probes and methimazole limitations: Pharmacological probe supports oxidation dependence; the inhibitory iodinated species was not identified. exposure: Iodide exposure in dog thyroid slices stimulated by thyrotropin, carbamylcholine or intracellular-signaling probes; concentrations not given in abstract. Methimazole coexposure. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/2841932.json", "json_field": "abstractText", "text_sha256": "00e19301656f8e8fdb9a047cfa29daf1c66f9a73c84d6c450ff805a6d8b497eb", "text_characters": 1113, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-block1988] Inhibition by iodide of iodide binding to proteins: the "Wolff-Chaikoff" effect is caused by inhibition of H2O2 generation. (1988). https://pubmed.ncbi.nlm.nih.gov/2841932/ DOI: 10.1016/0006-291x(88)90279-3

cross_nutrient

false

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/2841932.json", "json_field": "abstractText", "text_sha256": "00e19301656f8e8fdb9a047cfa29daf1c66f9a73c84d6c450ff805a6d8b497eb", "text_characters": 1113, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

Dog thyroid slices with iodide, stimulatory probes and methimazole

exposure

Iodide exposure in dog thyroid slices stimulated by thyrotropin, carbamylcholine or intracellular-signaling probes; concentrations not given in abstract.

limitations

Ex-vivo dog tissue; does not identify human DUOX2 as a directly bound molecular target.

nutrient_topic

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

organism

Canis lupus familiaris

plain_language

Excess iodide can suppress the peroxide supply required for its own incorporation.

primary_references

[iodine-syn-block1988] Inhibition by iodide of iodide binding to proteins: the "Wolff-Chaikoff" effect is caused by inhibition of H2O2 generation. (1988). https://pubmed.ncbi.nlm.nih.gov/2841932/ DOI: 10.1016/0006-291x(88)90279-3

tissue_or_cell_type

Thyroid slices

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 800–812

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dog thyroid slices with iodide, stimulatory probes and methimazole · source_derived_draft · unverified_draft

### iodine-syn-acute-peroxide-block Iodide inhibited stimulated H2O2 generation in dog thyroid slices, including responses to probes acting downstream of receptor activation. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Excess iodide can suppress the peroxide supply required for its own incorporation. organism: Canis lupus familiaris tissue_or_cell_type: Thyroid slices experimental_model: Dog thyroid slices with iodide, stimulatory probes and methimazole limitations: Ex-vivo dog tissue; does not identify human DUOX2 as a directly bound molecular target. exposure: Iodide exposure in dog thyroid slices stimulated by thyrotropin, carbamylcholine or intracellular-signaling probes; concentrations not given in abstract. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/2841932.json", "json_field": "abstractText", "text_sha256": "00e19301656f8e8fdb9a047cfa29daf1c66f9a73c84d6c450ff805a6d8b497eb", "text_characters": 1113, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-block1988] Inhibition by iodide of iodide binding to proteins: the "Wolff-Chaikoff" effect is caused by inhibition of H2O2 generation. (1988). https://pubmed.ncbi.nlm.nih.gov/2841932/ DOI: 10.1016/0006-291x(88)90279-3

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/12110737.json", "json_field": "abstractText", "text_sha256": "a0fa87eb7c584eb2b54cdc1de43ef65dd31bb4b7300f06c5b9ff4a8f703a151e", "text_characters": 1953, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

Sequencing of nine newborn-screened patients with iodide-organification defects and their relatives

exposure

Inherited DUOX2 truncation; no imposed dietary iodine restriction.

limitations

Small selected genetic series; no universal genotype-to-prognosis rule.

nutrient_topic

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

organism

Homo sapiens

plain_language

A broken peroxide generator can prevent iodine from being incorporated into thyroid proteins.

primary_references

[iodine-syn-duox2002] Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism. (2002). https://pubmed.ncbi.nlm.nih.gov/12110737/ DOI: 10.1056/nejmoa012752

tissue_or_cell_type

Thyroid

trigger_kind

machinery_impairment Imported condition classification; unverified.

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 520–532

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sequencing of nine newborn-screened patients with iodide-organification defects and their relatives · source_derived_draft · unverified_draft

### iodine-syn-duox2-organification A homozygous truncating DUOX2 mutation accompanied a complete iodide-organification defect in the severe permanent case in the 2002 series. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A broken peroxide generator can prevent iodine from being incorporated into thyroid proteins. organism: Homo sapiens tissue_or_cell_type: Thyroid experimental_model: Sequencing of nine newborn-screened patients with iodide-organification defects and their relatives limitations: Small selected genetic series; no universal genotype-to-prognosis rule. exposure: Inherited DUOX2 truncation; no imposed dietary iodine restriction. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/12110737.json", "json_field": "abstractText", "text_sha256": "a0fa87eb7c584eb2b54cdc1de43ef65dd31bb4b7300f06c5b9ff4a8f703a151e", "text_characters": 1953, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-duox2002] Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism. (2002). https://pubmed.ncbi.nlm.nih.gov/12110737/ DOI: 10.1056/nejmoa012752

cross_nutrient

true

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/32025030.txt", "start_char": 37661, "end_char": 38631, "text_sha256": "edbab2cbd62ebd263ef59f543f10aad3692d3a3983ef5abad904e697ea34ca04", "text_characters": 970, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants

exposure

Extended Data Fig.6c: 0.1 micromolar TG, 1 mM KI, glucose/glucose oxidase peroxide supply, 10 minutes at 37 C; TPO added at fivefold the LPO concentration to compensate for approximately 20% heme occupancy; T4 measured after Pronase digestion.

limitations

This identifies the TPO-containing assay arm; most TG mutagenesis experiments used LPO. The measured T4 was liberated by assay proteolysis after formation on TG.

nutrient_topic

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

organism

Homo sapiens TG and TPO; HEK293T TG expression and insect-cell TPO expression

plain_language

Human TPO can drive hormone formation on human thyroglobulin.

primary_references

[iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4

tissue_or_cell_type

Purified-protein reconstitution

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 842–854

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants · source_derived_draft · unverified_draft

### iodine-syn-human-tpo-t4-synthesis Recombinant human TPO catalyzed T4 formation from recombinant human TG in the direct TPO-versus-lactoperoxidase comparison. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human TPO can drive hormone formation on human thyroglobulin. organism: Homo sapiens TG and TPO; HEK293T TG expression and insect-cell TPO expression tissue_or_cell_type: Purified-protein reconstitution experimental_model: Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants limitations: This identifies the TPO-containing assay arm; most TG mutagenesis experiments used LPO. The measured T4 was liberated by assay proteolysis after formation on TG. exposure: Extended Data Fig.6c: 0.1 micromolar TG, 1 mM KI, glucose/glucose oxidase peroxide supply, 10 minutes at 37 C; TPO added at fivefold the LPO concentration to compensate for approximately 20% heme occupancy; T4 measured after Pronase digestion. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/32025030.txt", "start_char": 37661, "end_char": 38631, "text_sha256": "edbab2cbd62ebd263ef59f543f10aad3692d3a3983ef5abad904e697ea34ca04", "text_characters": 970, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4

cross_nutrient

false

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/32025030.txt", "start_char": 37603, "end_char": 38323, "text_sha256": "dfd7b409d46dbfe4e78cf481b6074477d36d70e14b5731f95a6b99ef0c43b33a", "text_characters": 720, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants

exposure

0.1 micromolar human TG, 1 mM KI, 24 mM glucose, 2 micrograms/mL glucose oxidase and 3 micrograms/mL lactoperoxidase; 10 minutes at 37 C followed by approximately 2.5 micrograms/mL Pronase and T4 ELISA. Most assays used lactoperoxidase after comparison with human TPO.

limitations

Artificial reaction with lactoperoxidase in most assays; not an intake-response curve.

nutrient_topic

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

organism

Homo sapiens TG expressed in HEK293T cells

plain_language

Iodide supplies the iodine needed to build T4 on thyroglobulin.

primary_references

[iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4

tissue_or_cell_type

Purified-protein reaction

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 618–630

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants · source_derived_draft · unverified_draft

### iodine-syn-tg-iodide-required Recombinant human TG produced a T4 signal after in-vitro iodination and proteolysis, whereas omission of iodide prevented the reaction. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iodide supplies the iodine needed to build T4 on thyroglobulin. organism: Homo sapiens TG expressed in HEK293T cells tissue_or_cell_type: Purified-protein reaction experimental_model: Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants limitations: Artificial reaction with lactoperoxidase in most assays; not an intake-response curve. exposure: 0.1 micromolar human TG, 1 mM KI, 24 mM glucose, 2 micrograms/mL glucose oxidase and 3 micrograms/mL lactoperoxidase; 10 minutes at 37 C followed by approximately 2.5 micrograms/mL Pronase and T4 ELISA. Most assays used lactoperoxidase after comparison with human TPO. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/32025030.txt", "start_char": 37603, "end_char": 38323, "text_sha256": "dfd7b409d46dbfe4e78cf481b6074477d36d70e14b5731f95a6b99ef0c43b33a", "text_characters": 720, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4

cross_nutrient

false

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/6706940.json", "json_field": "abstractText", "text_sha256": "e7d184d64b66b0dc89f61c511688c79ffc9785b20233e7746ef4c97de351c78c", "text_characters": 1442, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

Purified hog thyroid peroxidase with hog thyroglobulin; steady-state and stopped-flow kinetics

exposure

Purified hog TPO; native TG with 1.0% iodine and further-iodinated TG with 1.2% iodine; reagent concentrations not stated in abstract.

limitations

Reaction measures TG iodination, not free iodotyrosine recycling. The proposed iodinium intermediate is a model, not imported as an established mechanism.

nutrient_topic

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

organism

Sus scrofa

plain_language

TPO attaches iodine to tyrosine residues within the TG protein.

primary_references

[iodine-syn-tpo-iodination1984] Iodination and oxidation of thyroglobulin catalyzed by thyroid peroxidase. (1984). https://pubmed.ncbi.nlm.nih.gov/6706940/ DOI: 10.1016/s0021-9258(17)43667-2

tissue_or_cell_type

Purified thyroid enzyme and protein substrate

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 828–840

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified hog thyroid peroxidase with hog thyroglobulin; steady-state and stopped-flow kinetics · source_derived_draft · unverified_draft

### iodine-syn-tpo-protein-iodination Purified hog TPO catalyzed iodine incorporation into hog thyroglobulin in kinetic assays of protein iodination. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: TPO attaches iodine to tyrosine residues within the TG protein. organism: Sus scrofa tissue_or_cell_type: Purified thyroid enzyme and protein substrate experimental_model: Purified hog thyroid peroxidase with hog thyroglobulin; steady-state and stopped-flow kinetics limitations: Reaction measures TG iodination, not free iodotyrosine recycling. The proposed iodinium intermediate is a model, not imported as an established mechanism. exposure: Purified hog TPO; native TG with 1.0% iodine and further-iodinated TG with 1.2% iodine; reagent concentrations not stated in abstract. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/6706940.json", "json_field": "abstractText", "text_sha256": "e7d184d64b66b0dc89f61c511688c79ffc9785b20233e7746ef4c97de351c78c", "text_characters": 1442, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tpo-iodination1984] Iodination and oxidation of thyroglobulin catalyzed by thyroid peroxidase. (1984). https://pubmed.ncbi.nlm.nih.gov/6706940/ DOI: 10.1016/s0021-9258(17)43667-2

evidence_access

Primary abstract

experimental_model

Human-cell GLS2/p53 and oxidative-stress experiments.

limitations

Cysteine, glycine and synthesis machinery remain necessary; glutamate is not established as the universal limiting substrate.

nutrient_topic

L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate

plain_language

The same supply route fed antioxidant chemistry as well as energy metabolism.

primary_references

Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20378837/ · DOI 10.1073/pnas.1001006107

L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 226–232

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human-cell GLS2/p53 and oxidative-stress experiments. · source_derived_draft · unverified_draft

## glutamate-gls2-gsh The same supply route fed antioxidant chemistry as well as energy metabolism. Increasing GLS2 supported higher reduced-glutathione levels, lower reactive oxygen species and protection from peroxide-induced apoptosis in the reported cell experiments. Model: Human-cell GLS2/p53 and oxidative-stress experiments. Limitations: Cysteine, glycine and synthesis machinery remain necessary; glutamate is not established as the universal limiting substrate. Evidence access: Primary abstract Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20378837/ · DOI 10.1073/pnas.1001006107

cross_nutrient

Iron misincorporation competes with normal Mn cofactor chemistry; iron-loaded SOD2 is not functional replacement.

experimental_model

Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments

exposure

Enzyme metal substitution; low Mn:Fe cell media; altered mouse diets

limitations

Iron-loading experiments and overexpression cell models; no human prevalence or dietary threshold inferred.

nutrient_topic

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

organism

Homo sapiens; Mus musculus

plain_language

Iron in the SOD2 site can change what the enzyme does.

primary_references

[mn-enz-29398562] Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. (2018). https://pubmed.ncbi.nlm.nih.gov/29398562/ DOI: 10.1016/j.chembiol.2018.01.007

tissue_or_cell_type

Purified enzyme, cultured cells and mouse liver

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 495–506

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments · source_derived_draft · unverified_draft

### mn-enz-sod2-iron-peroxidase Iron incorporation into SOD2 generated a form that used hydrogen peroxide for prooxidant peroxidase chemistry in the reported biochemical and cell experiments. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron in the SOD2 site can change what the enzyme does. organism: Homo sapiens; Mus musculus tissue_or_cell_type: Purified enzyme, cultured cells and mouse liver experimental_model: Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments limitations: Iron-loading experiments and overexpression cell models; no human prevalence or dietary threshold inferred. exposure: Enzyme metal substitution; low Mn:Fe cell media; altered mouse diets cross_nutrient: Iron misincorporation competes with normal Mn cofactor chemistry; iron-loaded SOD2 is not functional replacement. [mn-enz-29398562] Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. (2018). https://pubmed.ncbi.nlm.nih.gov/29398562/ DOI: 10.1016/j.chembiol.2018.01.007

experimental_model

Redox-controlled neutron structures of human SOD2

exposure

Redox-controlled Mn(III) and Mn(II) crystals

limitations

Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established.

nutrient_topic

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

organism

Homo sapiens

plain_language

SOD2 removes superoxide; it produces hydrogen peroxide that requires further handling.

primary_references

[mn-enz-33824320] Direct detection of coupled proton and electron transfers in human manganese superoxide dismutase. (2021). https://pubmed.ncbi.nlm.nih.gov/33824320/ DOI: 10.1038/s41467-021-22290-1

tissue_or_cell_type

Purified enzyme; mitochondrial-matrix protein

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 446–456

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Redox-controlled neutron structures of human SOD2 · source_derived_draft · unverified_draft

### mn-enz-sod2-superoxide Human SOD2 uses a Mn(III)/Mn(II) cycle to convert superoxide into oxygen and hydrogen peroxide. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: SOD2 removes superoxide; it produces hydrogen peroxide that requires further handling. organism: Homo sapiens tissue_or_cell_type: Purified enzyme; mitochondrial-matrix protein experimental_model: Redox-controlled neutron structures of human SOD2 limitations: Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established. exposure: Redox-controlled Mn(III) and Mn(II) crystals [mn-enz-33824320] Direct detection of coupled proton and electron transfers in human manganese superoxide dismutase. (2021). https://pubmed.ncbi.nlm.nih.gov/33824320/ DOI: 10.1038/s41467-021-22290-1

experimental_model

LOXL2 assay development with extracellular matrix; family-level reaction context.

limitations

This is a reaction-class record; not every hydroxylysine site is an accessible LOX substrate.

organism

Mammalian cells/tissues and recombinant LOXL2; see study methods

plain_language

Hydroxylated lysines provide a different aldehyde starting point for cross-links.

primary_references

[lox-assay-2021] An in situ activity assay for lysyl oxidases (2021). https://pubmed.ncbi.nlm.nih.gov/34226627/

tissue_or_cell_type

Not specified as a whole tissue; see experimental model.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 477–485

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · LOXL2 assay development with extracellular matrix; family-level reaction context. · source_derived_draft · unverified_draft

### lox-hydroxylysine-oxidation Lysyl-oxidase activity can convert collagen hydroxylysine side chains to hydroxyallysine. Plain language: Hydroxylated lysines provide a different aldehyde starting point for cross-links. Condition category: normal organism: Mammalian cells/tissues and recombinant LOXL2; see study methods tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: LOXL2 assay development with extracellular matrix; family-level reaction context. limitations: This is a reaction-class record; not every hydroxylysine site is an accessible LOX substrate. [lox-assay-2021] An in situ activity assay for lysyl oxidases (2021). https://pubmed.ncbi.nlm.nih.gov/34226627/

experimental_model

LOXL2 assay development and total-family activity detection in cultured cells and tissue.

limitations

Substrate sites and enzyme-family members differ; peroxide production alone does not establish systemic oxidative injury.

organism

Mammalian cells/tissues and recombinant LOXL2; see study methods

plain_language

An enzyme creates reactive attachment sites used in matrix cross-linking.

primary_references

[lox-assay-2021] An in situ activity assay for lysyl oxidases (2021). https://pubmed.ncbi.nlm.nih.gov/34226627/

tissue_or_cell_type

Not specified as a whole tissue; see experimental model.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 467–475

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · LOXL2 assay development and total-family activity detection in cultured cells and tissue. · source_derived_draft · unverified_draft

### lox-peptidyl-lysine-oxidation Lysyl oxidase converts suitable peptidyl lysines to allysine, producing ammonia and hydrogen peroxide. Plain language: An enzyme creates reactive attachment sites used in matrix cross-linking. Condition category: normal organism: Mammalian cells/tissues and recombinant LOXL2; see study methods tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: LOXL2 assay development and total-family activity detection in cultured cells and tissue. limitations: Substrate sites and enzyme-family members differ; peroxide production alone does not establish systemic oxidative injury. [lox-assay-2021] An in situ activity assay for lysyl oxidases (2021). https://pubmed.ncbi.nlm.nih.gov/34226627/

dose

Indicaxanthin compared with Trolox and vitamin C; exact concentrations not in accessed abstract

duration

Spectrophotometric kinetic assay

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Cell-free haemoglobin redox preparation

limitations

A haemoglobin intermediate was reduced; dietary iron chelation and human treatment efficacy were not established.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Cell-free haemoglobin redox preparation

plain_language

Indicaxanthin reduced the perferryl-haemoglobin intermediate in the spectrophotometric reaction system.

primary_references

Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16984002/ DOI: 10.1080/10715760600554228

route

In vitro addition

tissue

Met-Hb/peroxide reaction mixture

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 52–61

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Cell-free haemoglobin redox preparation · source_derived_draft · unverified_draft

## indicaxanthin-perferryl-hb Indicaxanthin reduced the perferryl-haemoglobin intermediate in the spectrophotometric reaction system. Model/species: Cell-free haemoglobin redox preparation Tissue: Met-Hb/peroxide reaction mixture Exposure: Indicaxanthin compared with Trolox and vitamin C; exact concentrations not in accessed abstract Route: In vitro addition Duration: Spectrophotometric kinetic assay Limits: A haemoglobin intermediate was reduced; dietary iron chelation and human treatment efficacy were not established. Primary reference: Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16984002/ DOI: 10.1080/10715760600554228 Access: Primary PubMed abstract.

dose

Micromolar substrates; concentration-dependent chlorination assays

duration

Rapid kinetic measurements at 25 degrees C; pH 7.0 and pH 5.0

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

Purified human myeloperoxidase; cell-free chemistry

limitations

MPO substrates can stimulate or inhibit chlorination depending on conditions; not a universal MPO inhibitor.

nutrient_topic

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

organism

Purified human myeloperoxidase; cell-free chemistry

plain_language

Betanin stimulated or inhibited MPO chlorination at neutral pH depending on concentration; at pH 5 only inhibition was observed.

primary_references

Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid. (2005). https://pubmed.ncbi.nlm.nih.gov/15913556/ DOI: 10.1016/j.bbrc.2005.05.031

route

In vitro reagent addition

tissue

MPO redox cycle and HOCl solution

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 137–145

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Purified human myeloperoxidase; cell-free chemistry · source_derived_draft · unverified_draft

## betalains-betanin-chlorination Betanin stimulated or inhibited MPO chlorination at neutral pH depending on concentration; at pH 5 only inhibition was observed. Model/species: Purified human myeloperoxidase; cell-free chemistry Tissue: MPO redox cycle and HOCl solution Exposure: Micromolar substrates; concentration-dependent chlorination assays Route: In vitro reagent addition Duration: Rapid kinetic measurements at 25 degrees C; pH 7.0 and pH 5.0 Limits: MPO substrates can stimulate or inhibit chlorination depending on conditions; not a universal MPO inhibitor. Primary reference: Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid. (2005). https://pubmed.ncbi.nlm.nih.gov/15913556/ DOI: 10.1016/j.bbrc.2005.05.031

dose

Micromolar substrates; concentration-dependent chlorination assays

duration

Rapid kinetic measurements at 25 degrees C; pH 7.0 and pH 5.0

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

Purified human myeloperoxidase; cell-free chemistry

limitations

MPO substrates can stimulate or inhibit chlorination depending on conditions; not a universal MPO inhibitor.

nutrient_topic

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

organism

Purified human myeloperoxidase; cell-free chemistry

plain_language

Indicaxanthin stimulated or inhibited MPO chlorination at neutral pH depending on concentration; at pH 5 only inhibition was observed.

primary_references

Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid. (2005). https://pubmed.ncbi.nlm.nih.gov/15913556/ DOI: 10.1016/j.bbrc.2005.05.031

route

In vitro reagent addition

tissue

MPO redox cycle and HOCl solution

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 177–185

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Purified human myeloperoxidase; cell-free chemistry · source_derived_draft · unverified_draft

## betalains-indicaxanthin-chlorination Indicaxanthin stimulated or inhibited MPO chlorination at neutral pH depending on concentration; at pH 5 only inhibition was observed. Model/species: Purified human myeloperoxidase; cell-free chemistry Tissue: MPO redox cycle and HOCl solution Exposure: Micromolar substrates; concentration-dependent chlorination assays Route: In vitro reagent addition Duration: Rapid kinetic measurements at 25 degrees C; pH 7.0 and pH 5.0 Limits: MPO substrates can stimulate or inhibit chlorination depending on conditions; not a universal MPO inhibitor. Primary reference: Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid. (2005). https://pubmed.ncbi.nlm.nih.gov/15913556/ DOI: 10.1016/j.bbrc.2005.05.031

dose

Individual pigments 1-100 micromolar; LPS inflammatory stimulation or hydrogen peroxide oxidative challenge

duration

Not specified in accessed primary abstract

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

Mouse RAW 264.7 macrophages

limitations

Mouse-cell results are separate from human intestinal assays. Pro-oxidant effects under peroxide challenge do not imply every dietary exposure is harmful. Context difference from intestinal anti-inflammatory findings; not a contradiction or a universal pigment property.

nutrient_topic

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

organism

Mouse RAW 264.7 macrophages

plain_language

Indicaxanthin increased ROS beyond the hydrogen-peroxide-challenged level in RAW 264.7 cells.

primary_references

Differential Effects of Betacyanin and Betaxanthin Pigments on Oxidative Stress and Inflammatory Response in Murine Macrophages. (2023). https://pubmed.ncbi.nlm.nih.gov/37203590/ DOI: 10.1002/mnfr.202200583

route

In vitro exposure

tissue

Macrophages

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 437–445

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Mouse RAW 264.7 macrophages · source_derived_draft · unverified_draft

## betalains-indicaxanthin-mouse-prooxidant Indicaxanthin increased ROS beyond the hydrogen-peroxide-challenged level in RAW 264.7 cells. Model/species: Mouse RAW 264.7 macrophages Tissue: Macrophages Exposure: Individual pigments 1-100 micromolar; LPS inflammatory stimulation or hydrogen peroxide oxidative challenge Route: In vitro exposure Duration: Not specified in accessed primary abstract Limits: Mouse-cell results are separate from human intestinal assays. Pro-oxidant effects under peroxide challenge do not imply every dietary exposure is harmful. Context difference from intestinal anti-inflammatory findings; not a contradiction or a universal pigment property. Primary reference: Differential Effects of Betacyanin and Betaxanthin Pigments on Oxidative Stress and Inflammatory Response in Murine Macrophages. (2023). https://pubmed.ncbi.nlm.nih.gov/37203590/ DOI: 10.1002/mnfr.202200583

dose

Individual pigments 1-100 micromolar; LPS inflammatory stimulation or hydrogen peroxide oxidative challenge

duration

Not specified in accessed primary abstract

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

Mouse RAW 264.7 macrophages

limitations

Mouse-cell results are separate from human intestinal assays. Pro-oxidant effects under peroxide challenge do not imply every dietary exposure is harmful. Context difference from intestinal anti-inflammatory findings; not a contradiction or a universal pigment property.

nutrient_topic

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

organism

Mouse RAW 264.7 macrophages

plain_language

Vulgaxanthin-i increased ROS beyond the hydrogen-peroxide-challenged level in RAW 264.7 cells.

primary_references

Differential Effects of Betacyanin and Betaxanthin Pigments on Oxidative Stress and Inflammatory Response in Murine Macrophages. (2023). https://pubmed.ncbi.nlm.nih.gov/37203590/ DOI: 10.1002/mnfr.202200583

route

In vitro exposure

tissue

Macrophages

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 447–455

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Mouse RAW 264.7 macrophages · source_derived_draft · unverified_draft

## betalains-vulgaxanthin-i-mouse-prooxidant Vulgaxanthin-i increased ROS beyond the hydrogen-peroxide-challenged level in RAW 264.7 cells. Model/species: Mouse RAW 264.7 macrophages Tissue: Macrophages Exposure: Individual pigments 1-100 micromolar; LPS inflammatory stimulation or hydrogen peroxide oxidative challenge Route: In vitro exposure Duration: Not specified in accessed primary abstract Limits: Mouse-cell results are separate from human intestinal assays. Pro-oxidant effects under peroxide challenge do not imply every dietary exposure is harmful. Context difference from intestinal anti-inflammatory findings; not a contradiction or a universal pigment property. Primary reference: Differential Effects of Betacyanin and Betaxanthin Pigments on Oxidative Stress and Inflammatory Response in Murine Macrophages. (2023). https://pubmed.ncbi.nlm.nih.gov/37203590/ DOI: 10.1002/mnfr.202200583

cross_nutrient

true

evidence_location

Figure 6C

experimental_model

Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; total-cell aconitase activity assay and adenoviral catalase rescue

exposure

15 pmol ascorbate/cell (approximately 8 mM), 1 h; catalase rescue 50-MOI vector transduction 36 h before treatment.

limitations

Short pharmacological culture exposure; dose per cell, medium and density alter toxicity. Enzyme activity loss is consistent with Fe-S damage but does not directly trace individual iron atoms leaving a cluster. Total assay does not resolve cytosolic ACO1 from mitochondrial ACO2.

nutrient_topic

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

organism

Homo sapiens

plain_language

High-concentration vitamin C impaired an iron-sulfur enzyme in these cancer cells, and removing peroxide protected its activity.

primary_references

[c-reg-schoenfeld] O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. (2017). https://pubmed.ncbi.nlm.nih.gov/28366679/ DOI: 10.1016/j.ccell.2017.02.018

tissue_or_cell_type

NSCLC cell cultures

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1327–1339

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; total-cell aconitase activity assay and adenoviral catalase rescue · source_derived_draft · unverified_draft

### c-reg-aconitase-inactivation Pharmacological ascorbate decreased total cellular aconitase activity in NSCLC cultures; catalase overexpression prevented this activity loss, implicating peroxide-dependent injury to the Fe-S enzyme system. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: High-concentration vitamin C impaired an iron-sulfur enzyme in these cancer cells, and removing peroxide protected its activity. organism: Homo sapiens tissue_or_cell_type: NSCLC cell cultures experimental_model: Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; total-cell aconitase activity assay and adenoviral catalase rescue limitations: Short pharmacological culture exposure; dose per cell, medium and density alter toxicity. Enzyme activity loss is consistent with Fe-S damage but does not directly trace individual iron atoms leaving a cluster. Total assay does not resolve cytosolic ACO1 from mitochondrial ACO2. exposure: 15 pmol ascorbate/cell (approximately 8 mM), 1 h; catalase rescue 50-MOI vector transduction 36 h before treatment. cross_nutrient: true evidence_location: Figure 6C [c-reg-schoenfeld] O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. (2017). https://pubmed.ncbi.nlm.nih.gov/28366679/ DOI: 10.1016/j.ccell.2017.02.018

cross_nutrient

false

evidence_location

Figure 3A

experimental_model

Human JLP-119 Burkitt lymphoma culture; 1-h exposure, washing, Hoechst/propidium iodide cell-death assessment after 18–22 h

exposure

Fresh L-ascorbic acid neutralized to pH 7.0; 2 mM extracellular ascorbate for 1 h; cells 2.5 × 10^5/mL in serum-containing culture medium. Catalase 100 µg/mL preincubated 30 min.

limitations

Primary paper identifies catalase but does not specify species in the inspected Methods; the source species should not be inferred. Pharmacological in-vitro exposure; medium chemistry and peroxide clearance differ from intact tissues. No dietary or clinical anticancer inference.

nutrient_topic

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

organism

Homo sapiens cells; experimental catalase preparation

plain_language

Breaking down peroxide outside the cells prevented the vitamin C-associated killing.

primary_references

[c-reg-chen] Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. (2005). https://pubmed.ncbi.nlm.nih.gov/16157892/ DOI: 10.1073/pnas.0506390102

tissue_or_cell_type

Burkitt lymphoma cells

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1243–1255

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human JLP-119 Burkitt lymphoma culture; 1-h exposure, washing, Hoechst/propidium iodide cell-death assessment after 18–22 h · source_derived_draft · unverified_draft

### c-reg-catalase-protects-lymphoma Extracellular catalase prevented JLP-119 cell death after 2 mM ascorbate, supporting peroxide as a required mediator in this culture experiment. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Breaking down peroxide outside the cells prevented the vitamin C-associated killing. organism: Homo sapiens cells; experimental catalase preparation tissue_or_cell_type: Burkitt lymphoma cells experimental_model: Human JLP-119 Burkitt lymphoma culture; 1-h exposure, washing, Hoechst/propidium iodide cell-death assessment after 18–22 h limitations: Primary paper identifies catalase but does not specify species in the inspected Methods; the source species should not be inferred. Pharmacological in-vitro exposure; medium chemistry and peroxide clearance differ from intact tissues. No dietary or clinical anticancer inference. exposure: Fresh L-ascorbic acid neutralized to pH 7.0; 2 mM extracellular ascorbate for 1 h; cells 2.5 × 10^5/mL in serum-containing culture medium. Catalase 100 µg/mL preincubated 30 min. cross_nutrient: false evidence_location: Figure 3A [c-reg-chen] Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. (2005). https://pubmed.ncbi.nlm.nih.gov/16157892/ DOI: 10.1073/pnas.0506390102

cross_nutrient

true

evidence_location

Figure 6D

experimental_model

Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; isolated lysate respiratory-enzyme activity assays

exposure

15 pmol/cell (approximately 8 mM) ascorbate for 1 h before activity assays.

limitations

Short pharmacological culture exposure; dose per cell, medium and density alter toxicity. Enzyme activity loss is consistent with Fe-S damage but does not directly trace individual iron atoms leaving a cluster. This pattern supports but does not by itself prove direct cluster oxidation; no organism-level mitochondrial benefit or harm claimed.

nutrient_topic

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

organism

Homo sapiens

plain_language

This high-concentration exposure impaired respiratory complex I in the studied cancer cells.

primary_references

[c-reg-schoenfeld] O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. (2017). https://pubmed.ncbi.nlm.nih.gov/28366679/ DOI: 10.1016/j.ccell.2017.02.018

tissue_or_cell_type

NSCLC cell cultures

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1341–1353

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; isolated lysate respiratory-enzyme activity assays · source_derived_draft · unverified_draft

### c-reg-complex-i-inactivation After 15 pmol/cell (approximately 8 mM) ascorbate for 1 h, NSCLC lysates showed reduced respiratory-complex I activity while the separately assayed complex IV activity was retained, consistent with vulnerability of Fe-S-containing machinery. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: This high-concentration exposure impaired respiratory complex I in the studied cancer cells. organism: Homo sapiens tissue_or_cell_type: NSCLC cell cultures experimental_model: Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; isolated lysate respiratory-enzyme activity assays limitations: Short pharmacological culture exposure; dose per cell, medium and density alter toxicity. Enzyme activity loss is consistent with Fe-S damage but does not directly trace individual iron atoms leaving a cluster. This pattern supports but does not by itself prove direct cluster oxidation; no organism-level mitochondrial benefit or harm claimed. exposure: 15 pmol/cell (approximately 8 mM) ascorbate for 1 h before activity assays. cross_nutrient: true evidence_location: Figure 6D [c-reg-schoenfeld] O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. (2017). https://pubmed.ncbi.nlm.nih.gov/28366679/ DOI: 10.1016/j.ccell.2017.02.018

cross_nutrient

true

evidence_location

Figure 6D

experimental_model

Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; isolated lysate respiratory-enzyme activity assays

exposure

15 pmol/cell (approximately 8 mM) ascorbate for 1 h before activity assays.

limitations

Short pharmacological culture exposure; dose per cell, medium and density alter toxicity. Enzyme activity loss is consistent with Fe-S damage but does not directly trace individual iron atoms leaving a cluster. This pattern supports but does not by itself prove direct cluster oxidation; no organism-level mitochondrial benefit or harm claimed.

nutrient_topic

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

organism

Homo sapiens

plain_language

The exposure also impaired respiratory complex II, which participates in respiration and the citric acid cycle.

primary_references

[c-reg-schoenfeld] O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. (2017). https://pubmed.ncbi.nlm.nih.gov/28366679/ DOI: 10.1016/j.ccell.2017.02.018

tissue_or_cell_type

NSCLC cell cultures

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1383–1395

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; isolated lysate respiratory-enzyme activity assays · source_derived_draft · unverified_draft

### c-reg-complex-ii-inactivation The same pharmacological ascorbate exposure reduced NSCLC respiratory-complex II activity, extending the observed impairment to a second Fe-S-containing respiratory complex; complex IV activity was retained. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The exposure also impaired respiratory complex II, which participates in respiration and the citric acid cycle. organism: Homo sapiens tissue_or_cell_type: NSCLC cell cultures experimental_model: Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; isolated lysate respiratory-enzyme activity assays limitations: Short pharmacological culture exposure; dose per cell, medium and density alter toxicity. Enzyme activity loss is consistent with Fe-S damage but does not directly trace individual iron atoms leaving a cluster. This pattern supports but does not by itself prove direct cluster oxidation; no organism-level mitochondrial benefit or harm claimed. exposure: 15 pmol/cell (approximately 8 mM) ascorbate for 1 h before activity assays. cross_nutrient: true evidence_location: Figure 6D [c-reg-schoenfeld] O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. (2017). https://pubmed.ncbi.nlm.nih.gov/28366679/ DOI: 10.1016/j.ccell.2017.02.018

cross_nutrient

false

evidence_location

Figure 5C; Methods RBC mixtures

experimental_model

Human JLP-119 Burkitt lymphoma culture; 1-h exposure, washing, Hoechst/propidium iodide cell-death assessment after 18–22 h with added human red blood cells

exposure

Fresh L-ascorbic acid neutralized to pH 7.0; 2 mM extracellular ascorbate for 1 h; cells 2.5 × 10^5/mL in serum-containing culture medium. Reconstituted 25% or 50% hematocrit; lymphoma cells recovered before later assessment.

limitations

Pharmacological in-vitro exposure; medium chemistry and peroxide clearance differ from intact tissues. No dietary or clinical anticancer inference. Protective blood-cell mixture is not proof that all extravascular compartments are equally protected.

nutrient_topic

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

organism

Homo sapiens

plain_language

Red blood cells removed the damaging chemistry sufficiently to protect the lymphoma cells in this mixture.

primary_references

[c-reg-chen] Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. (2005). https://pubmed.ncbi.nlm.nih.gov/16157892/ DOI: 10.1073/pnas.0506390102

tissue_or_cell_type

Lymphoma/erythrocyte coculture

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1271–1283

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human JLP-119 Burkitt lymphoma culture; 1-h exposure, washing, Hoechst/propidium iodide cell-death assessment after 18–22 h with added human red blood cells · source_derived_draft · unverified_draft

### c-reg-erythrocytes-protect-lymphoma Adding human erythrocytes at 25% or 50% hematocrit protected JLP-119 lymphoma cells from the 2 mM ascorbate challenge, demonstrating that blood-cell clearance can change an otherwise cytotoxic culture exposure. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Red blood cells removed the damaging chemistry sufficiently to protect the lymphoma cells in this mixture. organism: Homo sapiens tissue_or_cell_type: Lymphoma/erythrocyte coculture experimental_model: Human JLP-119 Burkitt lymphoma culture; 1-h exposure, washing, Hoechst/propidium iodide cell-death assessment after 18–22 h with added human red blood cells limitations: Pharmacological in-vitro exposure; medium chemistry and peroxide clearance differ from intact tissues. No dietary or clinical anticancer inference. Protective blood-cell mixture is not proof that all extravascular compartments are equally protected. exposure: Fresh L-ascorbic acid neutralized to pH 7.0; 2 mM extracellular ascorbate for 1 h; cells 2.5 × 10^5/mL in serum-containing culture medium. Reconstituted 25% or 50% hematocrit; lymphoma cells recovered before later assessment. cross_nutrient: false evidence_location: Figure 5C; Methods RBC mixtures [c-reg-chen] Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. (2005). https://pubmed.ncbi.nlm.nih.gov/16157892/ DOI: 10.1073/pnas.0506390102

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 2a–b; Oximetry Methods

experimental_model

Cell-free medium oximetry; peroxide inferred from catalase-triggered oxygen release

exposure

5 mM ascorbate ±5 µM FAC iron; oxygen trace and 600 U catalase addition after about 15 min.

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. The endpoint measures net peroxide and does not separately determine every elementary redox rate.

nutrient_topic

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

organism

Cell-free bovine-serum-containing medium

plain_language

Iron sped up vitamin C oxidation while also helping remove the peroxide produced.

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

RPMI-1640 +10% FCS

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1299–1311

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free medium oximetry; peroxide inferred from catalase-triggered oxygen release · source_derived_draft · unverified_draft

### c-reg-extracellular-iron-peroxide-removal In RPMI/FCS exposed to 5 mM ascorbate, added 5 µM FAC iron accelerated oxygen consumption/ascorbate oxidation but reduced detectable peroxide accumulation, showing that faster oxidation need not yield a larger steady peroxide pool. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron sped up vitamin C oxidation while also helping remove the peroxide produced. organism: Cell-free bovine-serum-containing medium tissue_or_cell_type: RPMI-1640 +10% FCS experimental_model: Cell-free medium oximetry; peroxide inferred from catalase-triggered oxygen release 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. The endpoint measures net peroxide and does not separately determine every elementary redox rate. exposure: 5 mM ascorbate ±5 µM FAC iron; oxygen trace and 600 U catalase addition after about 15 min. cross_nutrient: true evidence_location: Figure 2a–b; Oximetry 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 3a–c; Results discussing failed EPR spin trapping

experimental_model

Biochemical extracellular protein-oxidation assay and intracellular thiol-sensitive RSSR EPR assay

exposure

5 mM ascorbate ±5 µM FAC iron for 2 h in RPMI-1640 +10% FCS; additional 30 µM iron experiment gave similar results. Thiols assayed using 100 µM RSSR probe.

limitations

Observed protein oxidation supports but does not directly prove the proposed hydroxyl-radical buffering mechanism. FAC speciation and medium composition limit tissue extrapolation.

nutrient_topic

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

organism

Homo sapiens LNCaP/PC-3 cells; bovine-serum-containing extracellular medium

plain_language

Extra iron shifted more oxidation onto proteins in the culture liquid while protecting the cells. The proposed short-lived radical intermediate could not be directly measured.

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 cancer-cell cultures and their extracellular RPMI/FCS medium

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1313–1325

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical extracellular protein-oxidation assay and intracellular thiol-sensitive RSSR EPR assay · source_derived_draft · unverified_draft

### c-reg-extracellular-protein-oxidation Adding iron to pharmacological ascorbate increased measured extracellular protein oxidation about threefold in the RPMI/FCS experiment while preserving intracellular thiols. The authors interpreted this as extracellular interception of Fenton-derived oxidants; direct hydroxyl-radical spin trapping was unsuccessful because ascorbate reduced the spin adducts. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra iron shifted more oxidation onto proteins in the culture liquid while protecting the cells. The proposed short-lived radical intermediate could not be directly measured. organism: Homo sapiens LNCaP/PC-3 cells; bovine-serum-containing extracellular medium tissue_or_cell_type: Prostate cancer-cell cultures and their extracellular RPMI/FCS medium experimental_model: Biochemical extracellular protein-oxidation assay and intracellular thiol-sensitive RSSR EPR assay limitations: Observed protein oxidation supports but does not directly prove the proposed hydroxyl-radical buffering mechanism. FAC speciation and medium composition limit tissue extrapolation. exposure: 5 mM ascorbate ±5 µM FAC iron for 2 h in RPMI-1640 +10% FCS; additional 30 µM iron experiment gave similar results. Thiols assayed using 100 µM RSSR probe. cross_nutrient: true evidence_location: Figure 3a–c; Results discussing failed EPR spin trapping [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

false

evidence_location

Figure 2D–E

experimental_model

Human JLP-119 Burkitt lymphoma culture; 1-h exposure, washing, Hoechst/propidium iodide cell-death assessment after 18–22 h

exposure

Fresh L-ascorbic acid neutralized to pH 7.0; 2 mM extracellular ascorbate for 1 h; cells 2.5 × 10^5/mL in serum-containing culture medium.

limitations

Pharmacological in-vitro exposure; medium chemistry and peroxide clearance differ from intact tissues. No dietary or clinical anticancer inference. This conclusion is specific to this line and loading protocol.

nutrient_topic

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

organism

Homo sapiens

plain_language

The killing depended on vitamin C outside these lymphoma cells, not merely on having vitamin C inside them.

primary_references

[c-reg-chen] Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. (2005). https://pubmed.ncbi.nlm.nih.gov/16157892/ DOI: 10.1073/pnas.0506390102

tissue_or_cell_type

Burkitt lymphoma cells

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1229–1241

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human JLP-119 Burkitt lymphoma culture; 1-h exposure, washing, Hoechst/propidium iodide cell-death assessment after 18–22 h · source_derived_draft · unverified_draft

### c-reg-lymphoma-extracellular-ascorbate JLP-119 lymphoma cells died after extracellular ascorbate exposure even when previously loaded to about 3 mM intracellular ascorbate; matched loading through dehydroascorbic acid did not reproduce the extracellular-ascorbate death effect. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The killing depended on vitamin C outside these lymphoma cells, not merely on having vitamin C inside them. organism: Homo sapiens tissue_or_cell_type: Burkitt lymphoma cells experimental_model: Human JLP-119 Burkitt lymphoma culture; 1-h exposure, washing, Hoechst/propidium iodide cell-death assessment after 18–22 h limitations: Pharmacological in-vitro exposure; medium chemistry and peroxide clearance differ from intact tissues. No dietary or clinical anticancer inference. This conclusion is specific to this line and loading protocol. exposure: Fresh L-ascorbic acid neutralized to pH 7.0; 2 mM extracellular ascorbate for 1 h; cells 2.5 × 10^5/mL in serum-containing culture medium. cross_nutrient: false evidence_location: Figure 2D–E [c-reg-chen] Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. (2005). https://pubmed.ncbi.nlm.nih.gov/16157892/ DOI: 10.1073/pnas.0506390102

cross_nutrient

false

evidence_location

Figure 4A–C

experimental_model

Cell-free medium; catalase-dependent oxygen-electrode peroxide assay and EPR

exposure

0.2–2 mM ascorbate over 1 h; 2 mM ascorbate with 0.5–10% FBS in serum-dependence experiment.

limitations

Pharmacological in-vitro exposure; medium chemistry and peroxide clearance differ from intact tissues. No dietary or clinical anticancer inference. Net accumulation reflects both production and removal; ascorbate can interfere with routine peroxidase assays.

nutrient_topic

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

organism

Cell-free; bovine serum-containing medium

plain_language

The culture liquid itself could turn high-concentration vitamin C into peroxide.

primary_references

[c-reg-chen] Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. (2005). https://pubmed.ncbi.nlm.nih.gov/16157892/ DOI: 10.1073/pnas.0506390102

tissue_or_cell_type

Extracellular assay medium

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1257–1269

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free medium; catalase-dependent oxygen-electrode peroxide assay and EPR · source_derived_draft · unverified_draft

### c-reg-medium-peroxide-generation Ascorbate produced peroxide in cell culture medium without requiring cells; accumulation depended on ascorbate concentration, time and serum fraction, and tracked ascorbyl radical detected by EPR. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The culture liquid itself could turn high-concentration vitamin C into peroxide. organism: Cell-free; bovine serum-containing medium tissue_or_cell_type: Extracellular assay medium experimental_model: Cell-free medium; catalase-dependent oxygen-electrode peroxide assay and EPR limitations: Pharmacological in-vitro exposure; medium chemistry and peroxide clearance differ from intact tissues. No dietary or clinical anticancer inference. Net accumulation reflects both production and removal; ascorbate can interfere with routine peroxidase assays. exposure: 0.2–2 mM ascorbate over 1 h; 2 mM ascorbate with 0.5–10% FBS in serum-dependence experiment. cross_nutrient: false evidence_location: Figure 4A–C [c-reg-chen] Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. (2005). https://pubmed.ncbi.nlm.nih.gov/16157892/ DOI: 10.1073/pnas.0506390102

evidence_span

{"source_cache": "artifacts/molybdenum-research/37713777.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "30e93ea24784120403bef1dfe72cf46411f1af88946b9cc1cba3d4c45a367bf9", "start_char": 0, "end_char": 1655, "text_sha256": "30e93ea24784120403bef1dfe72cf46411f1af88946b9cc1cba3d4c45a367bf9"}

experimental_model

Recombinant human XDH variants with urate, superoxide and NO assays

exposure

Xanthine, oxygen and inorganic nitrite assays

limitations

The 2023 Fig. 6E corrigendum corrects a displayed panel; authors state data and conclusions are unchanged. Enzyme activity is not a clinical benefit or dietary response.

nutrient_topic

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

organism

Homo sapiens protein

plain_language

The enzyme can generate oxidants as well as carry out purine breakdown.

primary_references

[mo-p37713777] Natural mutations of human XDH promote the nitrite (NO2-)-reductase capacity of xanthine oxidoreductase: A novel mechanism to promote redox health? (2023). https://pubmed.ncbi.nlm.nih.gov/37713777/ DOI: 10.1016/j.redox.2023.102864

tissue_or_cell_type

Purified human enzyme

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 781–792

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human XDH variants with urate, superoxide and NO assays · source_derived_draft · unverified_draft

### mo-xor-oxygen In its oxidase activity, XOR can generate superoxide and hydrogen peroxide rather than exclusively transferring electrons to NAD+. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme can generate oxidants as well as carry out purine breakdown. organism: Homo sapiens protein tissue_or_cell_type: Purified human enzyme experimental_model: Recombinant human XDH variants with urate, superoxide and NO assays limitations: The 2023 Fig. 6E corrigendum corrects a displayed panel; authors state data and conclusions are unchanged. Enzyme activity is not a clinical benefit or dietary response. exposure: Xanthine, oxygen and inorganic nitrite assays evidence_span: {"source_cache": "artifacts/molybdenum-research/37713777.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "30e93ea24784120403bef1dfe72cf46411f1af88946b9cc1cba3d4c45a367bf9", "start_char": 0, "end_char": 1655, "text_sha256": "30e93ea24784120403bef1dfe72cf46411f1af88946b9cc1cba3d4c45a367bf9"} [mo-p37713777] Natural mutations of human XDH promote the nitrite (NO2-)-reductase capacity of xanthine oxidoreductase: A novel mechanism to promote redox health? (2023). https://pubmed.ncbi.nlm.nih.gov/37713777/ DOI: 10.1016/j.redox.2023.102864

availability_state

biomarker_context Imported condition classification; unverified.

cross_nutrient

false

experimental_model

Historical clinical series of 50 premature infants aged 6–8 weeks

exposure

Blood vitamin E and hydrogen-peroxide hemolysis were assessed; oral vitamin E 10 mg/day was administered.

limitations

Historical feeding conditions and infant ages; an ex vivo hemolysis assay is not a universal explanation for anemia of prematurity. Formulation not specified in the abstract. The reported concentration is specific to this study, not a universal cellular adequacy threshold.

nutrient_topic

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

organism

Homo sapiens

plain_language

In this infant study, a low vitamin E reading accompanied fragile red cells in a peroxide test.

primary_references

[e-clin-lo1973] Vitamin E and haemolytic anaemia in premature infants. (1973). https://pubmed.ncbi.nlm.nih.gov/4739911/ DOI: 10.1136/adc.48.5.360

tissue_or_cell_type

Blood and erythrocytes

trigger_kind

biomarker_context Imported condition classification; unverified.

Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1193–1204

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical clinical series of 50 premature infants aged 6–8 weeks · source_derived_draft · unverified_draft

### e-clin-infant-peroxide-association In the historical premature-infant series, blood vitamin E below 0.6 mg/100 mL was associated with greater hydrogen-peroxide-induced erythrocyte hemolysis. Condition category: biomarker_context nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this infant study, a low vitamin E reading accompanied fragile red cells in a peroxide test. organism: Homo sapiens tissue_or_cell_type: Blood and erythrocytes experimental_model: Historical clinical series of 50 premature infants aged 6–8 weeks limitations: Historical feeding conditions and infant ages; an ex vivo hemolysis assay is not a universal explanation for anemia of prematurity. Formulation not specified in the abstract. The reported concentration is specific to this study, not a universal cellular adequacy threshold. exposure: Blood vitamin E and hydrogen-peroxide hemolysis were assessed; oral vitamin E 10 mg/day was administered. cross_nutrient: false [e-clin-lo1973] Vitamin E and haemolytic anaemia in premature infants. (1973). https://pubmed.ncbi.nlm.nih.gov/4739911/ DOI: 10.1136/adc.48.5.360

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

false

experimental_model

Historical clinical series of 50 premature infants aged 6–8 weeks

exposure

Blood vitamin E and hydrogen-peroxide hemolysis were assessed; oral vitamin E 10 mg/day was administered.

limitations

Historical feeding conditions and infant ages; an ex vivo hemolysis assay is not a universal explanation for anemia of prematurity. Formulation not specified in the abstract.

nutrient_topic

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

organism

Homo sapiens

plain_language

Restoring vitamin E reduced red-cell fragility in the tested infants.

primary_references

[e-clin-lo1973] Vitamin E and haemolytic anaemia in premature infants. (1973). https://pubmed.ncbi.nlm.nih.gov/4739911/ DOI: 10.1136/adc.48.5.360

tissue_or_cell_type

Blood and erythrocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1206–1217

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical clinical series of 50 premature infants aged 6–8 weeks · source_derived_draft · unverified_draft

### e-clin-infant-peroxide-repletion Peroxide hemolysis normalized within days of oral vitamin E administration and rising blood vitamin E in the premature-infant series. Condition category: nutrient_deficiency nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring vitamin E reduced red-cell fragility in the tested infants. organism: Homo sapiens tissue_or_cell_type: Blood and erythrocytes experimental_model: Historical clinical series of 50 premature infants aged 6–8 weeks limitations: Historical feeding conditions and infant ages; an ex vivo hemolysis assay is not a universal explanation for anemia of prematurity. Formulation not specified in the abstract. exposure: Blood vitamin E and hydrogen-peroxide hemolysis were assessed; oral vitamin E 10 mg/day was administered. cross_nutrient: false [e-clin-lo1973] Vitamin E and haemolytic anaemia in premature infants. (1973). https://pubmed.ncbi.nlm.nih.gov/4739911/ DOI: 10.1136/adc.48.5.360

cross_nutrient

true

experimental_model

Recombinant HIS-tagged human PKC alpha biochemical assay with iron and peroxide

exposure

15 ng dialyzed PKC alpha; 45 µM FeCl2; 1 or 10 mM H2O2 activation for 2 min, stopped with 9 mM DTT; no PS or calcium cofactors.

limitations

Millimolar peroxide in a cell-free reaction is not normal intracellular exposure. This is distinct from cofactor-dependent gamma activation.

nutrient_topic

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

organism

Homo sapiens

plain_language

Both natural tocopherols reduced oxidative activation of this kinase, with alpha active at a lower tested concentration.

primary_references

[mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. (2012). https://pubmed.ncbi.nlm.nih.gov/21933153/ DOI: 10.1042/bj20111318

tissue_or_cell_type

Cell-free enzyme

Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 959–970

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant HIS-tagged human PKC alpha biochemical assay with iron and peroxide · source_derived_draft · unverified_draft

### e-sig-alpha-pkc-oxidative RRR-alpha-tocopherol at 0.01 µM inhibited peroxide/iron-induced activation of recombinant PKC alpha; gamma-tocopherol required 0.1 µM for significant inhibition in the same assay. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Both natural tocopherols reduced oxidative activation of this kinase, with alpha active at a lower tested concentration. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Recombinant HIS-tagged human PKC alpha biochemical assay with iron and peroxide limitations: Millimolar peroxide in a cell-free reaction is not normal intracellular exposure. This is distinct from cofactor-dependent gamma activation. exposure: 15 ng dialyzed PKC alpha; 45 µM FeCl2; 1 or 10 mM H2O2 activation for 2 min, stopped with 9 mM DTT; no PS or calcium cofactors. cross_nutrient: true [mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. (2012). https://pubmed.ncbi.nlm.nih.gov/21933153/ DOI: 10.1042/bj20111318

cross_nutrient

false

evidence_location

Figure 4a–b

experimental_model

Oxidant challenge during laser-wound assay

exposure

200 µM racemic alpha-tocopherol (96% pure), 24 h; 1 mM H2O2 during injury.

limitations

Oxidant and loading concentrations are experimental; no specific fusion protein target was identified.

nutrient_topic

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

organism

African green monkey-derived cell line

plain_language

Vitamin E loading protected the repair response against this oxidant challenge.

primary_references

[ver-howard2011] Promotion of plasma membrane repair by vitamin E. (2011). https://pubmed.ncbi.nlm.nih.gov/22186893/ DOI: 10.1038/ncomms1594

tissue_or_cell_type

BS-C-1 kidney epithelial cells

Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 690–702

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oxidant challenge during laser-wound assay · source_derived_draft · unverified_draft

### ver-oxidant-challenged-repair Pretreatment of BS-C-1 cells with 200 µM alpha-tocopherol for 24 hours prevented the membrane-repair defect caused by 1 mM hydrogen peroxide during laser injury. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E loading protected the repair response against this oxidant challenge. organism: African green monkey-derived cell line tissue_or_cell_type: BS-C-1 kidney epithelial cells experimental_model: Oxidant challenge during laser-wound assay limitations: Oxidant and loading concentrations are experimental; no specific fusion protein target was identified. exposure: 200 µM racemic alpha-tocopherol (96% pure), 24 h; 1 mM H2O2 during injury. cross_nutrient: false evidence_location: Figure 4a–b [ver-howard2011] Promotion of plasma membrane repair by vitamin E. (2011). https://pubmed.ncbi.nlm.nih.gov/22186893/ DOI: 10.1038/ncomms1594

evidence_span

{"source_cache": "artifacts/nasunin-research/10962130.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61b195a6eff14c25cfc341069c7cafb8fe4d0b374aa294b3d28e0e48bbed7c16", "start_char": 0, "end_char": 1706, "text_sha256": "61b195a6eff14c25cfc341069c7cafb8fe4d0b374aa294b3d28e0e48bbed7c16"}

experimental_model

DMPO-competition ESR assay and peroxide challenge

exposure

Variable DMPO concentrations; nasunin below 50 micromolar in homogenate experiments

limitations

Related investigators and overlapping numerical results with the 1998 report; not independent replication. Ferrous-chelation interpretation is distinct from the earlier Fe(III) stoichiometry experiment.

nutrient_topic

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

organism

Cell-free reaction and rat brain homogenate

plain_language

Preventing a radical from forming differs from catching it afterward.

primary_references

[nasunin-p10962130] Antioxidant activity of nasunin, an anthocyanin in eggplant peels. (2000). https://pubmed.ncbi.nlm.nih.gov/10962130/ DOI: 10.1016/s0300-483x(00)00202-x

tissue_or_cell_type

Fenton chemistry and lipid-peroxidation markers

Nasunin: identity, redox chemistry and nutrient connections (2026-09-17) · lines 575–586

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · DMPO-competition ESR assay and peroxide challenge · source_derived_draft · unverified_draft

### nasunin-fenton-prevention Changing DMPO concentration did not change the inhibition midpoint, supporting prevention of radical generation through iron chelation rather than direct hydroxyl-radical trapping. Condition category: normal nutrient_topic: Nasunin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Preventing a radical from forming differs from catching it afterward. organism: Cell-free reaction and rat brain homogenate tissue_or_cell_type: Fenton chemistry and lipid-peroxidation markers experimental_model: DMPO-competition ESR assay and peroxide challenge limitations: Related investigators and overlapping numerical results with the 1998 report; not independent replication. Ferrous-chelation interpretation is distinct from the earlier Fe(III) stoichiometry experiment. exposure: Variable DMPO concentrations; nasunin below 50 micromolar in homogenate experiments evidence_span: {"source_cache": "artifacts/nasunin-research/10962130.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61b195a6eff14c25cfc341069c7cafb8fe4d0b374aa294b3d28e0e48bbed7c16", "start_char": 0, "end_char": 1706, "text_sha256": "61b195a6eff14c25cfc341069c7cafb8fe4d0b374aa294b3d28e0e48bbed7c16"} [nasunin-p10962130] Antioxidant activity of nasunin, an anthocyanin in eggplant peels. (2000). https://pubmed.ncbi.nlm.nih.gov/10962130/ DOI: 10.1016/s0300-483x(00)00202-x

evidence_span

{"source_cache": "artifacts/nasunin-research/10962130.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61b195a6eff14c25cfc341069c7cafb8fe4d0b374aa294b3d28e0e48bbed7c16", "start_char": 0, "end_char": 1706, "text_sha256": "61b195a6eff14c25cfc341069c7cafb8fe4d0b374aa294b3d28e0e48bbed7c16"}

experimental_model

DMPO-competition ESR assay and peroxide challenge

exposure

Variable DMPO concentrations; nasunin below 50 micromolar in homogenate experiments

limitations

Related investigators and overlapping numerical results with the 1998 report; not independent replication. Ferrous-chelation interpretation is distinct from the earlier Fe(III) stoichiometry experiment.

nutrient_topic

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

organism

Cell-free reaction and rat brain homogenate

plain_language

This is a biochemical protection result, not a brain-treatment trial.

primary_references

[nasunin-p10962130] Antioxidant activity of nasunin, an anthocyanin in eggplant peels. (2000). https://pubmed.ncbi.nlm.nih.gov/10962130/ DOI: 10.1016/s0300-483x(00)00202-x

tissue_or_cell_type

Fenton chemistry and lipid-peroxidation markers

Nasunin: identity, redox chemistry and nutrient connections (2026-09-17) · lines 588–599

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · DMPO-competition ESR assay and peroxide challenge · source_derived_draft · unverified_draft

### nasunin-peroxide-lipid-protection Nasunin below 50 micromolar reduced peroxide-induced lipid-peroxidation readouts in rat brain homogenates. Condition category: normal nutrient_topic: Nasunin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This is a biochemical protection result, not a brain-treatment trial. organism: Cell-free reaction and rat brain homogenate tissue_or_cell_type: Fenton chemistry and lipid-peroxidation markers experimental_model: DMPO-competition ESR assay and peroxide challenge limitations: Related investigators and overlapping numerical results with the 1998 report; not independent replication. Ferrous-chelation interpretation is distinct from the earlier Fe(III) stoichiometry experiment. exposure: Variable DMPO concentrations; nasunin below 50 micromolar in homogenate experiments evidence_span: {"source_cache": "artifacts/nasunin-research/10962130.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61b195a6eff14c25cfc341069c7cafb8fe4d0b374aa294b3d28e0e48bbed7c16", "start_char": 0, "end_char": 1706, "text_sha256": "61b195a6eff14c25cfc341069c7cafb8fe4d0b374aa294b3d28e0e48bbed7c16"} [nasunin-p10962130] Antioxidant activity of nasunin, an anthocyanin in eggplant peels. (2000). https://pubmed.ncbi.nlm.nih.gov/10962130/ DOI: 10.1016/s0300-483x(00)00202-x

experimental_model

CHO-cell experiments.

limitations

Rescue implicates peroxide in this setting; it does not establish oral catalase or antioxidant combinations as treatment.

nutrient_topic

EGCG collection; comparator and shared-pathway records retain their actual intervention. · Epigallocatechin-3-gallate (EGCG)

plain_language

Removing peroxide reduced the observed cell injury.

primary_references

Different cytotoxic and clastogenic effects of epigallocatechin gallate in various cell-culture media due to variable rates of its oxidation in the culture medium. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17851114/ · DOI 10.1016/j.mrgentox.2007.07.009

EGCG: receptor signaling, metabolism, nutrient interactions and discovery questions (2026-09-18) · lines 340–346

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · CHO-cell experiments. · source_derived_draft · unverified_draft

## egcg-catalase Removing peroxide reduced the observed cell injury. Added catalase substantially reduced EGCG cytotoxicity in the culture comparison. Model: CHO-cell experiments. Limitations: Rescue implicates peroxide in this setting; it does not establish oral catalase or antioxidant combinations as treatment. Evidence access: primary abstract. Different cytotoxic and clastogenic effects of epigallocatechin gallate in various cell-culture media due to variable rates of its oxidation in the culture medium. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17851114/ · DOI 10.1016/j.mrgentox.2007.07.009

cross_nutrient

false

evidence_location

Full text line 115; Fig. 2C

experimental_model

Oxidant washout in HEK293 cells stably overexpressing Pank1beta

exposure

500 micromolar H2O2 for 60 minutes, then recovery in complete growth medium.

limitations

The removal mechanism was not identified; engineered high-CoA cells are not ordinary circulating blood cells. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

The CoA modification receded when the oxidative exposure ended.

primary_references

[b5-met-coalation2017] Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells. (2017). https://pubmed.ncbi.nlm.nih.gov/28341808/ DOI: 10.1042/bcj20170129

tissue_or_cell_type

Engineered HEK293 cultures

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1061–1073

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oxidant washout in HEK293 cells stably overexpressing Pank1beta · source_derived_draft · unverified_draft

### b5-met-coalation-reversal After removal of hydrogen peroxide from HEK293/Pank1beta cultures, induced protein CoAlation declined within 5 minutes and returned to baseline within 90 minutes. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The CoA modification receded when the oxidative exposure ended. organism: Homo sapiens tissue_or_cell_type: Engineered HEK293 cultures experimental_model: Oxidant washout in HEK293 cells stably overexpressing Pank1beta limitations: The removal mechanism was not identified; engineered high-CoA cells are not ordinary circulating blood cells. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: 500 micromolar H2O2 for 60 minutes, then recovery in complete growth medium. cross_nutrient: false evidence_location: Full text line 115; Fig. 2C [b5-met-coalation2017] Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells. (2017). https://pubmed.ncbi.nlm.nih.gov/28341808/ DOI: 10.1042/bcj20170129

evidence_span

{"source_cache": "artifacts/phosphorus-research/42247296.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76", "start_char": 0, "end_char": 1041, "text_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76"}

experimental_model

Osteosarcoma-cell signaling with in-vivo tumor experiments

exposure

Elevated phosphate challenges and receptor activation experiments

limitations

New 2026 mechanism in tumor models; blood-Pi/tumor-growth association is not proof that dietary phosphorus causes human cancer. No specific transporter or oxidized residue number is invented from the abstract.

nutrient_topic

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

organism

Osteosarcoma cellular and animal systems; precise species not fully resolved from abstract

plain_language

Mitochondrial phosphate handling fed a redox signal in these tumor models.

primary_references

[phosphorus-p42247296] Unconventional activation of the proto-oncogene FGFR1 by extracellular phosphate via H2O2-mediated kinase oxidation. (2026). https://pubmed.ncbi.nlm.nih.gov/42247296/ DOI: 10.1016/j.celrep.2026.117504

tissue_or_cell_type

Plasma-membrane/mitochondrial phosphate handling and FGFR1 signaling

Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 867–878

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Osteosarcoma-cell signaling with in-vivo tumor experiments · source_derived_draft · unverified_draft

### phosphorus-pi-mito-peroxide The study linked phosphate entry into mitochondria to increased hydrogen-peroxide production in the FGFR1 activation pathway. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mitochondrial phosphate handling fed a redox signal in these tumor models. organism: Osteosarcoma cellular and animal systems; precise species not fully resolved from abstract tissue_or_cell_type: Plasma-membrane/mitochondrial phosphate handling and FGFR1 signaling experimental_model: Osteosarcoma-cell signaling with in-vivo tumor experiments limitations: New 2026 mechanism in tumor models; blood-Pi/tumor-growth association is not proof that dietary phosphorus causes human cancer. No specific transporter or oxidized residue number is invented from the abstract. exposure: Elevated phosphate challenges and receptor activation experiments evidence_span: {"source_cache": "artifacts/phosphorus-research/42247296.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76", "start_char": 0, "end_char": 1041, "text_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76"} [phosphorus-p42247296] Unconventional activation of the proto-oncogene FGFR1 by extracellular phosphate via H2O2-mediated kinase oxidation. (2026). https://pubmed.ncbi.nlm.nih.gov/42247296/ DOI: 10.1016/j.celrep.2026.117504