Nutrient chapter

Iron

Elemental nutrient category; chemical oxidation state must be specified separately when measured.

146 recorded mechanisms · 24 availability situations · 21 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

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

Duodenal Cybrd1 expression induced ferric reductase activity in oocytes and cultured cells and localized to the enterocyte brush border.
Mouse duodenal cytochrome b / Cybrd1 → Intestinal ferric-to-ferrous iron reduction source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/11230685.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3ef2e0a58c59707a044f0507c68aa61988718dfc97611b6664705468a5efa32", "start_char": 0, "end_char": 824, "text_sha256": "e3ef2e0a58c59707a044f0507c68aa61988718dfc97611b6664705468a5efa32"}
experimental_model
Transporter/reductase discovery and expression assays
exposure
Cybrd1 expression and physiological modulation of iron absorption
limitations
Shows ferric reductase activity; not proof that this is the only reductase or universally indispensable in vivo.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mouse Cybrd1 expressed in Xenopus oocytes and cultured cells
plain_language
Before nonheme iron enters through the ferrous-iron transporter, an enzyme can help convert it to the required chemical form.
primary_references
[iron-p11230685] An iron-regulated ferric reductase associated with the absorption of dietary iron. (2001). https://pubmed.ncbi.nlm.nih.gov/11230685/ DOI: 10.1126/science.1057206
tissue_or_cell_type
Duodenal brush border and expression systems
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 381–392
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter/reductase discovery and expression assays · source_derived_draft · unverified_draft
### iron-dcytb-reduction Duodenal Cybrd1 expression induced ferric reductase activity in oocytes and cultured cells and localized to the enterocyte brush border. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Before nonheme iron enters through the ferrous-iron transporter, an enzyme can help convert it to the required chemical form. organism: Mouse Cybrd1 expressed in Xenopus oocytes and cultured cells tissue_or_cell_type: Duodenal brush border and expression systems experimental_model: Transporter/reductase discovery and expression assays limitations: Shows ferric reductase activity; not proof that this is the only reductase or universally indispensable in vivo. exposure: Cybrd1 expression and physiological modulation of iron absorption evidence_span: {"source_cache": "artifacts/iron-research/11230685.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3ef2e0a58c59707a044f0507c68aa61988718dfc97611b6664705468a5efa32", "start_char": 0, "end_char": 824, "text_sha256": "e3ef2e0a58c59707a044f0507c68aa61988718dfc97611b6664705468a5efa32"} [iron-p11230685] An iron-regulated ferric reductase associated with the absorption of dietary iron. (2001). https://pubmed.ncbi.nlm.nih.gov/11230685/ DOI: 10.1126/science.1057206
Complete structured claim and evidence
Rat DCT1/DMT1 mediated proton-coupled Fe(II) transport that depended on membrane potential.
Rat divalent metal transporter 1 / Slc11a2 → Ferrous iron source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/9242408.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0b5241ac49e6de4e273c91f36387357c9bd76ce602e44defffc3b8b42191fe52", "start_char": 0, "end_char": 1203, "text_sha256": "0b5241ac49e6de4e273c91f36387357c9bd76ce602e44defffc3b8b42191fe52"}
experimental_model
Cloning and functional expression of DCT1/DMT1
exposure
Metal-ion uptake, membrane potential and iron-deficient feeding
limitations
Original broad substrate profile; later substrate-specific studies and species differences must be retained. Competition in an assay is not a universal dietary interaction.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Rat transporter
plain_language
The uptake protein uses an electrochemical gradient to bring ferrous iron into cells.
primary_references
[iron-p9242408] Cloning and characterization of a mammalian proton-coupled metal-ion transporter. (1997). https://pubmed.ncbi.nlm.nih.gov/9242408/ DOI: 10.1038/41343
tissue_or_cell_type
Transport assay and duodenal expression
transport_effect
raises Proton-coupled and membrane-potential-dependent Fe(II) transport, which is inward.
transport_pool
the expressing cell Proton-coupled and membrane-potential-dependent Fe(II) transport, which is inward.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 394–405
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning and functional expression of DCT1/DMT1 · source_derived_draft · unverified_draft
### iron-dmt-proton-transport Rat DCT1/DMT1 mediated proton-coupled Fe(II) transport that depended on membrane potential. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The uptake protein uses an electrochemical gradient to bring ferrous iron into cells. organism: Rat transporter tissue_or_cell_type: Transport assay and duodenal expression experimental_model: Cloning and functional expression of DCT1/DMT1 limitations: Original broad substrate profile; later substrate-specific studies and species differences must be retained. Competition in an assay is not a universal dietary interaction. exposure: Metal-ion uptake, membrane potential and iron-deficient feeding evidence_span: {"source_cache": "artifacts/iron-research/9242408.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0b5241ac49e6de4e273c91f36387357c9bd76ce602e44defffc3b8b42191fe52", "start_char": 0, "end_char": 1203, "text_sha256": "0b5241ac49e6de4e273c91f36387357c9bd76ce602e44defffc3b8b42191fe52"} [iron-p9242408] Cloning and characterization of a mammalian proton-coupled metal-ion transporter. (1997). https://pubmed.ncbi.nlm.nih.gov/9242408/ DOI: 10.1038/41343
Complete structured claim and evidence
Recombinant copper-containing human hephaestin oxidized Fe(II), with an apparent substrate Km of 2.1 micromolar.
Human hephaestin / HEPH → Ferrous iron source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/16274220.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976", "start_char": 0, "end_char": 1880, "text_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976"}
experimental_model
Purified recombinant human hephaestin
exposure
Fe(II) substrate and apotransferrin assays
limitations
Soluble recombinant construct; average measured copper loading of 3.13 atoms is not a universal mature-protein stoichiometry.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human protein produced in baby hamster kidney cells
plain_language
A copper enzyme changes iron into the form needed for the next transport step.
primary_references
[copper-p16274220] Recombinant expression and functional characterization of human hephaestin: a multicopper oxidase with ferroxidase activity. (2005). https://pubmed.ncbi.nlm.nih.gov/16274220/ DOI: 10.1021/bi051559k
tissue_or_cell_type
Purified soluble hephaestin construct
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 767–778
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human hephaestin · source_derived_draft · unverified_draft
### copper-heph-ferroxidation Recombinant copper-containing human hephaestin oxidized Fe(II), with an apparent substrate Km of 2.1 micromolar. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A copper enzyme changes iron into the form needed for the next transport step. organism: Human protein produced in baby hamster kidney cells tissue_or_cell_type: Purified soluble hephaestin construct experimental_model: Purified recombinant human hephaestin limitations: Soluble recombinant construct; average measured copper loading of 3.13 atoms is not a universal mature-protein stoichiometry. exposure: Fe(II) substrate and apotransferrin assays evidence_span: {"source_cache": "artifacts/copper-research/16274220.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976", "start_char": 0, "end_char": 1880, "text_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976"} [copper-p16274220] Recombinant expression and functional characterization of human hephaestin: a multicopper oxidase with ferroxidase activity. (2005). https://pubmed.ncbi.nlm.nih.gov/16274220/ DOI: 10.1021/bi051559k
Complete structured claim and evidence
Hepcidin bound ferroportin in tissue-culture cells.
Hepcidin → Ferroportin / SLC40A1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/15514116.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "00a292f6693116798182b0f9418f2eb8466aa029f32905019416422002158c4a", "start_char": 0, "end_char": 758, "text_sha256": "00a292f6693116798182b0f9418f2eb8466aa029f32905019416422002158c4a"}
experimental_model
Hepcidin binding and cellular export experiments
exposure
Hepcidin exposure
limitations
Post-translational export regulation; no dose-response to dietary iron is inferred from the cell experiment.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Tissue-culture ferroportin systems
plain_language
The liver-derived control hormone acts directly on the iron-export protein.
primary_references
[iron-p15514116] Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. (2004). https://pubmed.ncbi.nlm.nih.gov/15514116/ DOI: 10.1126/science.1104742
tissue_or_cell_type
Plasma membrane
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 706–717
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hepcidin binding and cellular export experiments · source_derived_draft · unverified_draft
### iron-hepcidin-fpn-binding Hepcidin bound ferroportin in tissue-culture cells. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The liver-derived control hormone acts directly on the iron-export protein. organism: Tissue-culture ferroportin systems tissue_or_cell_type: Plasma membrane experimental_model: Hepcidin binding and cellular export experiments limitations: Post-translational export regulation; no dose-response to dietary iron is inferred from the cell experiment. exposure: Hepcidin exposure evidence_span: {"source_cache": "artifacts/iron-research/15514116.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "00a292f6693116798182b0f9418f2eb8466aa029f32905019416422002158c4a", "start_char": 0, "end_char": 758, "text_sha256": "00a292f6693116798182b0f9418f2eb8466aa029f32905019416422002158c4a"} [iron-p15514116] Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. (2004). https://pubmed.ncbi.nlm.nih.gov/15514116/ DOI: 10.1126/science.1104742
Complete structured claim and evidence
Hepcidin-induced ferroportin removal reduced cellular iron export.
Hepcidin → Cellular iron export source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/15514116.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "00a292f6693116798182b0f9418f2eb8466aa029f32905019416422002158c4a", "start_char": 0, "end_char": 758, "text_sha256": "00a292f6693116798182b0f9418f2eb8466aa029f32905019416422002158c4a"}
experimental_model
Hepcidin binding and cellular export experiments
exposure
Hepcidin exposure
limitations
Post-translational export regulation; no dose-response to dietary iron is inferred from the cell experiment.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Tissue-culture ferroportin systems
plain_language
Iron can be held inside cells instead of reaching the circulation.
primary_references
[iron-p15514116] Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. (2004). https://pubmed.ncbi.nlm.nih.gov/15514116/ DOI: 10.1126/science.1104742
tissue_or_cell_type
Plasma membrane
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 732–743
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hepcidin binding and cellular export experiments · source_derived_draft · unverified_draft
### iron-hepcidin-export Hepcidin-induced ferroportin removal reduced cellular iron export. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron can be held inside cells instead of reaching the circulation. organism: Tissue-culture ferroportin systems tissue_or_cell_type: Plasma membrane experimental_model: Hepcidin binding and cellular export experiments limitations: Post-translational export regulation; no dose-response to dietary iron is inferred from the cell experiment. exposure: Hepcidin exposure evidence_span: {"source_cache": "artifacts/iron-research/15514116.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "00a292f6693116798182b0f9418f2eb8466aa029f32905019416422002158c4a", "start_char": 0, "end_char": 758, "text_sha256": "00a292f6693116798182b0f9418f2eb8466aa029f32905019416422002158c4a"} [iron-p15514116] Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. (2004). https://pubmed.ncbi.nlm.nih.gov/15514116/ DOI: 10.1126/science.1104742
Complete structured claim and evidence
IL-6 induced hepcidin in the tested human liver-cell, mouse and volunteer systems.
IL6 → Hepcidin expression source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/15124018.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f2ed307ef57c255917685bb7bfb1f02f3a6481c732cc2ee41ad1f338e2a2a830", "start_char": 0, "end_char": 578, "text_sha256": "f2ed307ef57c255917685bb7bfb1f02f3a6481c732cc2ee41ad1f338e2a2a830"}
experimental_model
Human liver-cell, mouse and human-volunteer inflammation experiments
exposure
IL-6 and inflammatory stimulation
limitations
IL-6 dependence applies to the tested inflammatory models, not every possible inflammatory iron pathway.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Humans and mice
plain_language
Inflammation can turn up the hormone that restricts iron release.
primary_references
[iron-p15124018] IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. (2004). https://pubmed.ncbi.nlm.nih.gov/15124018/ DOI: 10.1172/jci20945
tissue_or_cell_type
Liver and circulation
trigger_kind
biomarker_context Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 875–886
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human liver-cell, mouse and human-volunteer inflammation experiments · source_derived_draft · unverified_draft
### iron-il6-hepcidin IL-6 induced hepcidin in the tested human liver-cell, mouse and volunteer systems. Condition category: biomarker_context nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Inflammation can turn up the hormone that restricts iron release. organism: Humans and mice tissue_or_cell_type: Liver and circulation experimental_model: Human liver-cell, mouse and human-volunteer inflammation experiments limitations: IL-6 dependence applies to the tested inflammatory models, not every possible inflammatory iron pathway. exposure: IL-6 and inflammatory stimulation evidence_span: {"source_cache": "artifacts/iron-research/15124018.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f2ed307ef57c255917685bb7bfb1f02f3a6481c732cc2ee41ad1f338e2a2a830", "start_char": 0, "end_char": 578, "text_sha256": "f2ed307ef57c255917685bb7bfb1f02f3a6481c732cc2ee41ad1f338e2a2a830"} [iron-p15124018] IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. (2004). https://pubmed.ncbi.nlm.nih.gov/15124018/ DOI: 10.1172/jci20945
Complete structured claim and evidence
The transferrin-cycle model supported by the binding experiments releases iron in acidified endosomes while apotransferrin remains receptor-bound.
Human serum transferrin / TF → Transferrin-dependent endosomal iron delivery to cytosol source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/6300903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852", "start_char": 0, "end_char": 906, "text_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852"}
experimental_model
Receptor binding at controlled pH and transferrin cycle analysis
exposure
Apotransferrin and diferric transferrin binding at acidic versus neutral pH
limitations
The indexed abstract does not identify the cell line; its experiments support a pH-dependent trafficking model, not direct measures of whole-body iron turnover.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Cultured-cell transferrin receptor system
plain_language
The carrier gives up its iron inside an acidic compartment but stays attached to its return transport.
primary_references
[iron-p6300903] pH and the recycling of transferrin during receptor-mediated endocytosis. (1983). https://pubmed.ncbi.nlm.nih.gov/6300903/ DOI: 10.1073/pnas.80.8.2258
tissue_or_cell_type
Cell surface and endosomal recycling model
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 420–431
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor binding at controlled pH and transferrin cycle analysis · source_derived_draft · unverified_draft
### iron-tf-acidic-release The transferrin-cycle model supported by the binding experiments releases iron in acidified endosomes while apotransferrin remains receptor-bound. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The carrier gives up its iron inside an acidic compartment but stays attached to its return transport. organism: Cultured-cell transferrin receptor system tissue_or_cell_type: Cell surface and endosomal recycling model experimental_model: Receptor binding at controlled pH and transferrin cycle analysis limitations: The indexed abstract does not identify the cell line; its experiments support a pH-dependent trafficking model, not direct measures of whole-body iron turnover. exposure: Apotransferrin and diferric transferrin binding at acidic versus neutral pH evidence_span: {"source_cache": "artifacts/iron-research/6300903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852", "start_char": 0, "end_char": 906, "text_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852"} [iron-p6300903] pH and the recycling of transferrin during receptor-mediated endocytosis. (1983). https://pubmed.ncbi.nlm.nih.gov/6300903/ DOI: 10.1073/pnas.80.8.2258
Complete structured claim and evidence
Mitoferrin function was required for mitochondrial iron assimilation and heme synthesis in the tested vertebrate erythroblasts.
Mouse mitoferrin-1 / Slc25a37 → Mitochondrial iron import source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/16511496.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cb2b06715c001133d1f1173d5084a2689170fa9a0e14f3b7b0a0cb5a7b6a5234", "start_char": 0, "end_char": 1533, "text_sha256": "cb2b06715c001133d1f1173d5084a2689170fa9a0e14f3b7b0a0cb5a7b6a5234"}
experimental_model
Zebrafish mutant, mouse stem-cell knockout and cross-species rescue
exposure
Mitoferrin loss and rescue
limitations
Species-specific loss/rescue evidence; no claim that plasma iron alone measures mitochondrial iron delivery.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Zebrafish, mice and yeast
plain_language
The final iron delivery step for heme synthesis is across the mitochondrial membrane.
primary_references
[iron-p16511496] Mitoferrin is essential for erythroid iron assimilation. (2006). https://pubmed.ncbi.nlm.nih.gov/16511496/ DOI: 10.1038/nature04512
tissue_or_cell_type
Developing erythroblasts and mitochondria
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 459–470
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Zebrafish mutant, mouse stem-cell knockout and cross-species rescue · source_derived_draft · unverified_draft
### iron-mitoferrin-import Mitoferrin function was required for mitochondrial iron assimilation and heme synthesis in the tested vertebrate erythroblasts. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The final iron delivery step for heme synthesis is across the mitochondrial membrane. organism: Zebrafish, mice and yeast tissue_or_cell_type: Developing erythroblasts and mitochondria experimental_model: Zebrafish mutant, mouse stem-cell knockout and cross-species rescue limitations: Species-specific loss/rescue evidence; no claim that plasma iron alone measures mitochondrial iron delivery. exposure: Mitoferrin loss and rescue evidence_span: {"source_cache": "artifacts/iron-research/16511496.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cb2b06715c001133d1f1173d5084a2689170fa9a0e14f3b7b0a0cb5a7b6a5234", "start_char": 0, "end_char": 1533, "text_sha256": "cb2b06715c001133d1f1173d5084a2689170fa9a0e14f3b7b0a0cb5a7b6a5234"} [iron-p16511496] Mitoferrin is essential for erythroid iron assimilation. (2006). https://pubmed.ncbi.nlm.nih.gov/16511496/ DOI: 10.1038/nature04512
Complete structured claim and evidence
Human ALAS2 uses PLP to condense glycine and succinyl-CoA into 5-aminolevulinate, releasing CoA and carbon dioxide.
Human erythroid aminolevulinate synthase 2 / ALAS2 → 5-Aminolevulinate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6 and glycine support the porphyrin precursor pathway upstream of iron insertion.
experimental_model
Purified recombinant human ALAS2; crystallography and kinetics
limitations
Iron insertion is a later ferrochelatase reaction, not an ALAS2 reaction.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
This B6-dependent step starts erythroid heme synthesis.
primary_references
[b6-alas2-2020] Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release (2020). https://www.nature.com/articles/s41467-020-16586-x DOI: 10.1038/s41467-020-16586-x
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 799–809
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human ALAS2; crystallography and kinetics · source_derived_draft · unverified_draft
### b6-met-alas2-ala Human ALAS2 uses PLP to condense glycine and succinyl-CoA into 5-aminolevulinate, releasing CoA and carbon dioxide. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This B6-dependent step starts erythroid heme synthesis. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human ALAS2; crystallography and kinetics limitations: Iron insertion is a later ferrochelatase reaction, not an ALAS2 reaction. cross_nutrient: B6 and glycine support the porphyrin precursor pathway upstream of iron insertion. [b6-alas2-2020] Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release (2020). https://www.nature.com/articles/s41467-020-16586-x DOI: 10.1038/s41467-020-16586-x
Complete structured claim and evidence
Human ferrochelatase inserts ferrous iron into protoporphyrin to form heme.
Human ferrochelatase / FECH → Protoporphyrin IX source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/11175906.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba1c88d4630f6f0ee7f70989705c81162a2f8651c066f46b3aac73988b8dfa11", "start_char": 0, "end_char": 770, "text_sha256": "ba1c88d4630f6f0ee7f70989705c81162a2f8651c066f46b3aac73988b8dfa11"}
experimental_model
Human ferrochelatase crystal structure
exposure
2.0 angstrom structure and biochemical catalytic interpretation
limitations
Purified enzyme; cluster structure is not a human dietary-iron threshold.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human enzyme
plain_language
The last step places an iron atom inside the finished heme ring.
primary_references
[iron-p11175906] The 2.0 A structure of human ferrochelatase, the terminal enzyme of heme biosynthesis. (2001). https://pubmed.ncbi.nlm.nih.gov/11175906/ DOI: 10.1038/84152
tissue_or_cell_type
Mitochondrial membrane-associated enzyme
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 511–522
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human ferrochelatase crystal structure · source_derived_draft · unverified_draft
### iron-fech-heme Human ferrochelatase inserts ferrous iron into protoporphyrin to form heme. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The last step places an iron atom inside the finished heme ring. organism: Human enzyme tissue_or_cell_type: Mitochondrial membrane-associated enzyme experimental_model: Human ferrochelatase crystal structure limitations: Purified enzyme; cluster structure is not a human dietary-iron threshold. exposure: 2.0 angstrom structure and biochemical catalytic interpretation evidence_span: {"source_cache": "artifacts/iron-research/11175906.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba1c88d4630f6f0ee7f70989705c81162a2f8651c066f46b3aac73988b8dfa11", "start_char": 0, "end_char": 770, "text_sha256": "ba1c88d4630f6f0ee7f70989705c81162a2f8651c066f46b3aac73988b8dfa11"} [iron-p11175906] The 2.0 A structure of human ferrochelatase, the terminal enzyme of heme biosynthesis. (2001). https://pubmed.ncbi.nlm.nih.gov/11175906/ DOI: 10.1038/84152
Complete structured claim and evidence
The NFS1-containing desulfurase complex structure resolved a solvent-exposed PLP cofactor and an unusual substrate-channel architecture.
Human cysteine desulfurase / NFS1 → PLP source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/28634302.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "82faf07d78311d063c1d990ebb922062650054be372fb324fa67020790c9fa04", "start_char": 0, "end_char": 1850, "text_sha256": "82faf07d78311d063c1d990ebb922062650054be372fb324fa67020790c9fa04"}
experimental_model
Crystallography, electron microscopy, kinetics and cell studies
exposure
SDA-complex structural analysis
limitations
Hybrid structural system: bacterial ACP must not be silently labeled human NDUFAB1. Direct dietary B6/B5 effects were not tested.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human NFS1/ISD11 with bacterial ACP in the recombinant structural complex
plain_language
The sulfur-supplying machinery for iron-sulfur clusters also uses a vitamin B6-derived cofactor.
primary_references
[iron-p28634302] Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions. (2017). https://pubmed.ncbi.nlm.nih.gov/28634302/ DOI: 10.1073/pnas.1702849114
tissue_or_cell_type
Mitochondrial Fe-S assembly machinery
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1148–1159
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystallography, electron microscopy, kinetics and cell studies · source_derived_draft · unverified_draft
### iron-nfs1-plp The NFS1-containing desulfurase complex structure resolved a solvent-exposed PLP cofactor and an unusual substrate-channel architecture. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The sulfur-supplying machinery for iron-sulfur clusters also uses a vitamin B6-derived cofactor. organism: Human NFS1/ISD11 with bacterial ACP in the recombinant structural complex tissue_or_cell_type: Mitochondrial Fe-S assembly machinery experimental_model: Crystallography, electron microscopy, kinetics and cell studies limitations: Hybrid structural system: bacterial ACP must not be silently labeled human NDUFAB1. Direct dietary B6/B5 effects were not tested. exposure: SDA-complex structural analysis evidence_span: {"source_cache": "artifacts/iron-research/28634302.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "82faf07d78311d063c1d990ebb922062650054be372fb324fa67020790c9fa04", "start_char": 0, "end_char": 1850, "text_sha256": "82faf07d78311d063c1d990ebb922062650054be372fb324fa67020790c9fa04"} [iron-p28634302] Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions. (2017). https://pubmed.ncbi.nlm.nih.gov/28634302/ DOI: 10.1073/pnas.1702849114
Complete structured claim and evidence
Ferric carboxymaltose increased biologically active FGF23 in the substudy; the mean within-person increase at the week-two peak was approximately 303%, versus 10% with ferumoxytol.
Ferric carboxymaltose → Circulating biologically active intact FGF23 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/30518682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257", "start_char": 0, "end_char": 2371, "text_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257"}
experimental_model
Double-blind randomized comparison with physiological substudy
exposure
One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up
limitations
Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
1997 adults with iron-deficiency anemia; 185 in substudy
plain_language
The treatment changed a hormone that controls phosphate handling.
primary_references
[iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
tissue_or_cell_type
Blood and renal phosphate handling
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 953–964
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized comparison with physiological substudy · source_derived_draft · unverified_draft
### iron-fcm-intact-fgf23 Ferric carboxymaltose increased biologically active FGF23 in the substudy; the mean within-person increase at the week-two peak was approximately 303%, versus 10% with ferumoxytol. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The treatment changed a hormone that controls phosphate handling. organism: 1997 adults with iron-deficiency anemia; 185 in substudy tissue_or_cell_type: Blood and renal phosphate handling experimental_model: Double-blind randomized comparison with physiological substudy limitations: Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow. exposure: One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up evidence_span: {"source_cache": "artifacts/iron-research/30518682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257", "start_char": 0, "end_char": 2371, "text_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257"} [iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
Complete structured claim and evidence
The original rat DCT1 expression assay also transported Mn(II), among other divalent metals.
Rat divalent metal transporter 1 / Slc11a2 → Mn2+ source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/9242408.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0b5241ac49e6de4e273c91f36387357c9bd76ce602e44defffc3b8b42191fe52", "start_char": 0, "end_char": 1203, "text_sha256": "0b5241ac49e6de4e273c91f36387357c9bd76ce602e44defffc3b8b42191fe52"}
experimental_model
Cloning and functional expression of DCT1/DMT1
exposure
Metal-ion uptake, membrane potential and iron-deficient feeding
limitations
Original broad substrate profile; later substrate-specific studies and species differences must be retained. Competition in an assay is not a universal dietary interaction.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Rat transporter
plain_language
Iron shares this transporter with other metals, making the transport setting important.
primary_references
[iron-p9242408] Cloning and characterization of a mammalian proton-coupled metal-ion transporter. (1997). https://pubmed.ncbi.nlm.nih.gov/9242408/ DOI: 10.1038/41343
tissue_or_cell_type
Transport assay and duodenal expression
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 407–418
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning and functional expression of DCT1/DMT1 · source_derived_draft · unverified_draft
### iron-dmt-other-metals The original rat DCT1 expression assay also transported Mn(II), among other divalent metals. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron shares this transporter with other metals, making the transport setting important. organism: Rat transporter tissue_or_cell_type: Transport assay and duodenal expression experimental_model: Cloning and functional expression of DCT1/DMT1 limitations: Original broad substrate profile; later substrate-specific studies and species differences must be retained. Competition in an assay is not a universal dietary interaction. exposure: Metal-ion uptake, membrane potential and iron-deficient feeding evidence_span: {"source_cache": "artifacts/iron-research/9242408.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0b5241ac49e6de4e273c91f36387357c9bd76ce602e44defffc3b8b42191fe52", "start_char": 0, "end_char": 1203, "text_sha256": "0b5241ac49e6de4e273c91f36387357c9bd76ce602e44defffc3b8b42191fe52"} [iron-p9242408] Cloning and characterization of a mammalian proton-coupled metal-ion transporter. (1997). https://pubmed.ncbi.nlm.nih.gov/9242408/ DOI: 10.1038/41343
Complete structured claim and evidence
Apotransferrin bound receptors at pH 5.4 but dissociated rapidly when pH was raised to 7.0.
Human transferrin receptor 1 / TFRC → Transferrin and transferrin-receptor recycling source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/6300903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852", "start_char": 0, "end_char": 906, "text_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852"}
experimental_model
Receptor binding at controlled pH and transferrin cycle analysis
exposure
Apotransferrin and diferric transferrin binding at acidic versus neutral pH
limitations
The indexed abstract does not identify the cell line; its experiments support a pH-dependent trafficking model, not direct measures of whole-body iron turnover.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Cultured-cell transferrin receptor system
plain_language
Returning to the neutral cell surface allows the empty carrier to detach.
primary_references
[iron-p6300903] pH and the recycling of transferrin during receptor-mediated endocytosis. (1983). https://pubmed.ncbi.nlm.nih.gov/6300903/ DOI: 10.1073/pnas.80.8.2258
tissue_or_cell_type
Cell surface and endosomal recycling model
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 433–444
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor binding at controlled pH and transferrin cycle analysis · source_derived_draft · unverified_draft
### iron-tf-recycling Apotransferrin bound receptors at pH 5.4 but dissociated rapidly when pH was raised to 7.0. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Returning to the neutral cell surface allows the empty carrier to detach. organism: Cultured-cell transferrin receptor system tissue_or_cell_type: Cell surface and endosomal recycling model experimental_model: Receptor binding at controlled pH and transferrin cycle analysis limitations: The indexed abstract does not identify the cell line; its experiments support a pH-dependent trafficking model, not direct measures of whole-body iron turnover. exposure: Apotransferrin and diferric transferrin binding at acidic versus neutral pH evidence_span: {"source_cache": "artifacts/iron-research/6300903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852", "start_char": 0, "end_char": 906, "text_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852"} [iron-p6300903] pH and the recycling of transferrin during receptor-mediated endocytosis. (1983). https://pubmed.ncbi.nlm.nih.gov/6300903/ DOI: 10.1073/pnas.80.8.2258
Complete structured claim and evidence
Steap3 colocalized with transferrin-cycle endosomes and promoted iron reduction and transferrin-dependent iron uptake.
Mouse metalloreductase Steap3 → Transferrin-dependent endosomal iron delivery to cytosol source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/16227996.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd6e35b6ea534163d0db76cbdec2fa6c3c2dd998b0a1f66d9f16479bcb87711b", "start_char": 0, "end_char": 1006, "text_sha256": "cd6e35b6ea534163d0db76cbdec2fa6c3c2dd998b0a1f66d9f16479bcb87711b"}
experimental_model
Positional cloning, overexpression and deficient-mouse experiments
exposure
Steap3 deficiency and overexpression
limitations
A dominant erythroid reduction pathway, not proof of equal dependence in every tissue.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mice and mouse Steap3 expression systems
plain_language
Iron released from transferrin needs another chemical reduction step before it can leave the endosome.
primary_references
[iron-p16227996] Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. (2005). https://pubmed.ncbi.nlm.nih.gov/16227996/ DOI: 10.1038/ng1658
tissue_or_cell_type
Erythroid endosomes
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 446–457
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Positional cloning, overexpression and deficient-mouse experiments · source_derived_draft · unverified_draft
### iron-steap-reduction Steap3 colocalized with transferrin-cycle endosomes and promoted iron reduction and transferrin-dependent iron uptake. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron released from transferrin needs another chemical reduction step before it can leave the endosome. organism: Mice and mouse Steap3 expression systems tissue_or_cell_type: Erythroid endosomes experimental_model: Positional cloning, overexpression and deficient-mouse experiments limitations: A dominant erythroid reduction pathway, not proof of equal dependence in every tissue. exposure: Steap3 deficiency and overexpression evidence_span: {"source_cache": "artifacts/iron-research/16227996.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd6e35b6ea534163d0db76cbdec2fa6c3c2dd998b0a1f66d9f16479bcb87711b", "start_char": 0, "end_char": 1006, "text_sha256": "cd6e35b6ea534163d0db76cbdec2fa6c3c2dd998b0a1f66d9f16479bcb87711b"} [iron-p16227996] Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. (2005). https://pubmed.ncbi.nlm.nih.gov/16227996/ DOI: 10.1038/ng1658
Complete structured claim and evidence
Mfrn-null mouse embryonic-stem-cell-derived erythroblasts arrested maturation and had severely impaired incorporation of iron-55 into heme.
Mouse mitoferrin-1 / Slc25a37 → Erythroid heme synthesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/16511496.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cb2b06715c001133d1f1173d5084a2689170fa9a0e14f3b7b0a0cb5a7b6a5234", "start_char": 0, "end_char": 1533, "text_sha256": "cb2b06715c001133d1f1173d5084a2689170fa9a0e14f3b7b0a0cb5a7b6a5234"}
experimental_model
Zebrafish mutant, mouse stem-cell knockout and cross-species rescue
exposure
Mitoferrin loss and rescue
limitations
Species-specific loss/rescue evidence; no claim that plasma iron alone measures mitochondrial iron delivery.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Zebrafish, mice and yeast
plain_language
Plenty of iron elsewhere would not replace this missing mitochondrial transport step.
primary_references
[iron-p16511496] Mitoferrin is essential for erythroid iron assimilation. (2006). https://pubmed.ncbi.nlm.nih.gov/16511496/ DOI: 10.1038/nature04512
tissue_or_cell_type
Developing erythroblasts and mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 472–483
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Zebrafish mutant, mouse stem-cell knockout and cross-species rescue · source_derived_draft · unverified_draft
### iron-mitoferrin-loss Mfrn-null mouse embryonic-stem-cell-derived erythroblasts arrested maturation and had severely impaired incorporation of iron-55 into heme. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Plenty of iron elsewhere would not replace this missing mitochondrial transport step. organism: Zebrafish, mice and yeast tissue_or_cell_type: Developing erythroblasts and mitochondria experimental_model: Zebrafish mutant, mouse stem-cell knockout and cross-species rescue limitations: Species-specific loss/rescue evidence; no claim that plasma iron alone measures mitochondrial iron delivery. exposure: Mitoferrin loss and rescue evidence_span: {"source_cache": "artifacts/iron-research/16511496.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cb2b06715c001133d1f1173d5084a2689170fa9a0e14f3b7b0a0cb5a7b6a5234", "start_char": 0, "end_char": 1533, "text_sha256": "cb2b06715c001133d1f1173d5084a2689170fa9a0e14f3b7b0a0cb5a7b6a5234"} [iron-p16511496] Mitoferrin is essential for erythroid iron assimilation. (2006). https://pubmed.ncbi.nlm.nih.gov/16511496/ DOI: 10.1038/nature04512
Complete structured claim and evidence
Abcb10 interacted with Mfrn1, enhanced its stability and promoted Mfrn1-dependent mitochondrial iron import.
Mouse mitochondrial ABC transporter / Abcb10 → Mouse mitoferrin-1 / Slc25a37 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/19805291.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d513c833380932eae7a3667fae0e77d5bc7c03067c266e62438d8a63e3839955", "start_char": 0, "end_char": 1697, "text_sha256": "d513c833380932eae7a3667fae0e77d5bc7c03067c266e62438d8a63e3839955"}
experimental_model
Affinity purification, mass spectrometry and expression experiments
exposure
Abcb10/Mfrn1 expression during differentiation
limitations
Stabilization and transport were measured in cell systems, not supplementation experiments.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mouse erythroleukemia cells and heterologous COS7 cells
plain_language
An interacting protein helps keep the iron importer available.
primary_references
[iron-p19805291] Abcb10 physically interacts with mitoferrin-1 (Slc25a37) to enhance its stability and function in the erythroid mitochondria. (2009). https://pubmed.ncbi.nlm.nih.gov/19805291/ DOI: 10.1073/pnas.0904519106
tissue_or_cell_type
Mitochondrial inner membrane
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 485–496
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Affinity purification, mass spectrometry and expression experiments · source_derived_draft · unverified_draft
### iron-abcb10-mitoferrin Abcb10 interacted with Mfrn1, enhanced its stability and promoted Mfrn1-dependent mitochondrial iron import. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: An interacting protein helps keep the iron importer available. organism: Mouse erythroleukemia cells and heterologous COS7 cells tissue_or_cell_type: Mitochondrial inner membrane experimental_model: Affinity purification, mass spectrometry and expression experiments limitations: Stabilization and transport were measured in cell systems, not supplementation experiments. exposure: Abcb10/Mfrn1 expression during differentiation evidence_span: {"source_cache": "artifacts/iron-research/19805291.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d513c833380932eae7a3667fae0e77d5bc7c03067c266e62438d8a63e3839955", "start_char": 0, "end_char": 1697, "text_sha256": "d513c833380932eae7a3667fae0e77d5bc7c03067c266e62438d8a63e3839955"} [iron-p19805291] Abcb10 physically interacts with mitoferrin-1 (Slc25a37) to enhance its stability and function in the erythroid mitochondria. (2009). https://pubmed.ncbi.nlm.nih.gov/19805291/ DOI: 10.1073/pnas.0904519106
Complete structured claim and evidence
Fech interacted with both Mfrn1 and Abcb10 in the studied erythroid systems.
Mouse ferrochelatase / Fech → Mouse mitoferrin-1 / Slc25a37 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/20427704.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a4f3b1c37151557d4d888126ba888dd95391254c5e40d1c3576f0520eed7517c", "start_char": 0, "end_char": 1059, "text_sha256": "a4f3b1c37151557d4d888126ba888dd95391254c5e40d1c3576f0520eed7517c"}
experimental_model
Affinity purification and immunoprecipitation
exposure
Mfrn1, Abcb10 and Fech interaction analysis
limitations
Physical association supports coordination; direct substrate channeling was not separately proven.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mouse erythroleukemia cells and heterologous HEK293 expression
plain_language
Iron import and the final heme-synthesis enzyme can be physically organized together.
primary_references
[iron-p20427704] Ferrochelatase forms an oligomeric complex with mitoferrin-1 and Abcb10 for erythroid heme biosynthesis. (2010). https://pubmed.ncbi.nlm.nih.gov/20427704/ DOI: 10.1182/blood-2009-12-259614
tissue_or_cell_type
Mitochondrial heme-synthesis machinery
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 498–509
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Affinity purification and immunoprecipitation · source_derived_draft · unverified_draft
### iron-mitoferrin-fech-complex Fech interacted with both Mfrn1 and Abcb10 in the studied erythroid systems. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron import and the final heme-synthesis enzyme can be physically organized together. organism: Mouse erythroleukemia cells and heterologous HEK293 expression tissue_or_cell_type: Mitochondrial heme-synthesis machinery experimental_model: Affinity purification and immunoprecipitation limitations: Physical association supports coordination; direct substrate channeling was not separately proven. exposure: Mfrn1, Abcb10 and Fech interaction analysis evidence_span: {"source_cache": "artifacts/iron-research/20427704.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a4f3b1c37151557d4d888126ba888dd95391254c5e40d1c3576f0520eed7517c", "start_char": 0, "end_char": 1059, "text_sha256": "a4f3b1c37151557d4d888126ba888dd95391254c5e40d1c3576f0520eed7517c"} [iron-p20427704] Ferrochelatase forms an oligomeric complex with mitoferrin-1 and Abcb10 for erythroid heme biosynthesis. (2010). https://pubmed.ncbi.nlm.nih.gov/20427704/ DOI: 10.1182/blood-2009-12-259614
Complete structured claim and evidence
The human ferrochelatase homodimer contained two uniquely coordinated, nitric-oxide-sensitive [2Fe-2S] clusters.
Human ferrochelatase / FECH → [2Fe-2S] iron-sulfur cluster source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/11175906.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba1c88d4630f6f0ee7f70989705c81162a2f8651c066f46b3aac73988b8dfa11", "start_char": 0, "end_char": 770, "text_sha256": "ba1c88d4630f6f0ee7f70989705c81162a2f8651c066f46b3aac73988b8dfa11"}
experimental_model
Human ferrochelatase crystal structure
exposure
2.0 angstrom structure and biochemical catalytic interpretation
limitations
Purified enzyme; cluster structure is not a human dietary-iron threshold.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human enzyme
plain_language
The enzyme that inserts iron also carries its own iron-sulfur cofactors.
primary_references
[iron-p11175906] The 2.0 A structure of human ferrochelatase, the terminal enzyme of heme biosynthesis. (2001). https://pubmed.ncbi.nlm.nih.gov/11175906/ DOI: 10.1038/84152
tissue_or_cell_type
Mitochondrial membrane-associated enzyme
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 524–535
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human ferrochelatase crystal structure · source_derived_draft · unverified_draft
### iron-fech-clusters The human ferrochelatase homodimer contained two uniquely coordinated, nitric-oxide-sensitive [2Fe-2S] clusters. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme that inserts iron also carries its own iron-sulfur cofactors. organism: Human enzyme tissue_or_cell_type: Mitochondrial membrane-associated enzyme experimental_model: Human ferrochelatase crystal structure limitations: Purified enzyme; cluster structure is not a human dietary-iron threshold. exposure: 2.0 angstrom structure and biochemical catalytic interpretation evidence_span: {"source_cache": "artifacts/iron-research/11175906.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba1c88d4630f6f0ee7f70989705c81162a2f8651c066f46b3aac73988b8dfa11", "start_char": 0, "end_char": 770, "text_sha256": "ba1c88d4630f6f0ee7f70989705c81162a2f8651c066f46b3aac73988b8dfa11"} [iron-p11175906] The 2.0 A structure of human ferrochelatase, the terminal enzyme of heme biosynthesis. (2001). https://pubmed.ncbi.nlm.nih.gov/11175906/ DOI: 10.1038/84152
Complete structured claim and evidence
Oxyhemoglobin structures resolved hydrogen bonding between the oxygen ligand and distal histidine in both alpha and beta subunits.
Human adult hemoglobin A → Reversible oxygen binding by hemoglobin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/16765986.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "177ab81c08f82c99c81c69d1cb582e52216234e290066ae5aa380a887fb0e38c", "start_char": 0, "end_char": 1284, "text_sha256": "177ab81c08f82c99c81c69d1cb582e52216234e290066ae5aa380a887fb0e38c"}
experimental_model
High-resolution crystallographic comparison
exposure
1.25 angstrom structural refinement
limitations
Structural oxygen-ligand geometry, not a supplementation or oxygen-delivery clinical trial.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human hemoglobin A
plain_language
Hemoglobin holds oxygen at carefully organized heme sites so oxygen binding can be controlled.
primary_references
[iron-p16765986] 1.25 A resolution crystal structures of human haemoglobin in the oxy, deoxy and carbonmonoxy forms. (2006). https://pubmed.ncbi.nlm.nih.gov/16765986/ DOI: 10.1016/j.jmb.2006.05.036
tissue_or_cell_type
Purified oxy-, deoxy- and carbonmonoxyhemoglobin
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 537–548
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · High-resolution crystallographic comparison · source_derived_draft · unverified_draft
### iron-hemoglobin-oxygen-site Oxyhemoglobin structures resolved hydrogen bonding between the oxygen ligand and distal histidine in both alpha and beta subunits. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Hemoglobin holds oxygen at carefully organized heme sites so oxygen binding can be controlled. organism: Human hemoglobin A tissue_or_cell_type: Purified oxy-, deoxy- and carbonmonoxyhemoglobin experimental_model: High-resolution crystallographic comparison limitations: Structural oxygen-ligand geometry, not a supplementation or oxygen-delivery clinical trial. exposure: 1.25 angstrom structural refinement evidence_span: {"source_cache": "artifacts/iron-research/16765986.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "177ab81c08f82c99c81c69d1cb582e52216234e290066ae5aa380a887fb0e38c", "start_char": 0, "end_char": 1284, "text_sha256": "177ab81c08f82c99c81c69d1cb582e52216234e290066ae5aa380a887fb0e38c"} [iron-p16765986] 1.25 A resolution crystal structures of human haemoglobin in the oxy, deoxy and carbonmonoxy forms. (2006). https://pubmed.ncbi.nlm.nih.gov/16765986/ DOI: 10.1016/j.jmb.2006.05.036
Complete structured claim and evidence
Hrg1 localized to phagolysosomal membranes during erythrophagocytosis and transported heme toward the macrophage cytoplasm.
Mouse heme transporter HRG1 / Slc48a1 → Heme export from the macrophage phagolysosome source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/23395172.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9ffc7159cfb418fed987d6f3f9e34829861a8f4ede0fe564a2714ef0bc96968b", "start_char": 0, "end_char": 1074, "text_sha256": "9ffc7159cfb418fed987d6f3f9e34829861a8f4ede0fe564a2714ef0bc96968b"}
experimental_model
Macrophage depletion, localization and human variant assays
exposure
Hrg1 depletion and missense variants
limitations
Recycling pathway experiment; no estimate of dietary iron requirements is derived.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mouse macrophages and human HRG1 variants
plain_language
Macrophages must move heme out of the compartment where old red cells are broken down.
primary_references
[iron-p23395172] HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis. (2013). https://pubmed.ncbi.nlm.nih.gov/23395172/ DOI: 10.1016/j.cmet.2013.01.005
tissue_or_cell_type
Phagolysosomes during erythrophagocytosis
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 550–561
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Macrophage depletion, localization and human variant assays · source_derived_draft · unverified_draft
### iron-hrg1-recycling Hrg1 localized to phagolysosomal membranes during erythrophagocytosis and transported heme toward the macrophage cytoplasm. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Macrophages must move heme out of the compartment where old red cells are broken down. organism: Mouse macrophages and human HRG1 variants tissue_or_cell_type: Phagolysosomes during erythrophagocytosis experimental_model: Macrophage depletion, localization and human variant assays limitations: Recycling pathway experiment; no estimate of dietary iron requirements is derived. exposure: Hrg1 depletion and missense variants evidence_span: {"source_cache": "artifacts/iron-research/23395172.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9ffc7159cfb418fed987d6f3f9e34829861a8f4ede0fe564a2714ef0bc96968b", "start_char": 0, "end_char": 1074, "text_sha256": "9ffc7159cfb418fed987d6f3f9e34829861a8f4ede0fe564a2714ef0bc96968b"} [iron-p23395172] HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis. (2013). https://pubmed.ncbi.nlm.nih.gov/23395172/ DOI: 10.1016/j.cmet.2013.01.005
Complete structured claim and evidence
Hrg1 depletion attenuated heme transport from macrophage phagolysosomes.
Mouse heme transporter HRG1 / Slc48a1 → Heme export from the macrophage phagolysosome source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/23395172.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9ffc7159cfb418fed987d6f3f9e34829861a8f4ede0fe564a2714ef0bc96968b", "start_char": 0, "end_char": 1074, "text_sha256": "9ffc7159cfb418fed987d6f3f9e34829861a8f4ede0fe564a2714ef0bc96968b"}
experimental_model
Macrophage depletion, localization and human variant assays
exposure
Hrg1 depletion and missense variants
limitations
Recycling pathway experiment; no estimate of dietary iron requirements is derived.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mouse macrophages and human HRG1 variants
plain_language
A blocked recycling step can trap useful material inside a cellular compartment.
primary_references
[iron-p23395172] HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis. (2013). https://pubmed.ncbi.nlm.nih.gov/23395172/ DOI: 10.1016/j.cmet.2013.01.005
tissue_or_cell_type
Phagolysosomes during erythrophagocytosis
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 563–574
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Macrophage depletion, localization and human variant assays · source_derived_draft · unverified_draft
### iron-hrg1-loss Hrg1 depletion attenuated heme transport from macrophage phagolysosomes. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: A blocked recycling step can trap useful material inside a cellular compartment. organism: Mouse macrophages and human HRG1 variants tissue_or_cell_type: Phagolysosomes during erythrophagocytosis experimental_model: Macrophage depletion, localization and human variant assays limitations: Recycling pathway experiment; no estimate of dietary iron requirements is derived. exposure: Hrg1 depletion and missense variants evidence_span: {"source_cache": "artifacts/iron-research/23395172.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9ffc7159cfb418fed987d6f3f9e34829861a8f4ede0fe564a2714ef0bc96968b", "start_char": 0, "end_char": 1074, "text_sha256": "9ffc7159cfb418fed987d6f3f9e34829861a8f4ede0fe564a2714ef0bc96968b"} [iron-p23395172] HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis. (2013). https://pubmed.ncbi.nlm.nih.gov/23395172/ DOI: 10.1016/j.cmet.2013.01.005
Complete structured claim and evidence
Heme oxygenase oxidatively cleaves heme to biliverdin with release of iron and carbon monoxide.
Human heme oxygenase 1 / HMOX1 → Heme source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/15049686.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76bcb8ae12316350b1161f32c1633e2b5c752fcbf7e158940385b354ee3452d2", "start_char": 0, "end_char": 1167, "text_sha256": "76bcb8ae12316350b1161f32c1633e2b5c752fcbf7e158940385b354ee3452d2"}
experimental_model
Product-bound human HO-1 structure
exposure
Biliverdin-bound structure compared with heme-bound enzyme
limitations
Product release interpretation from structure; no in-vivo flux measurement.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human enzyme
plain_language
Breaking open heme makes its iron available for reuse.
primary_references
[iron-p15049686] Crystal structure of human heme oxygenase-1 in a complex with biliverdin. (2004). https://pubmed.ncbi.nlm.nih.gov/15049686/ DOI: 10.1021/bi035451l
tissue_or_cell_type
Purified heme oxygenase-1
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 576–587
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Product-bound human HO-1 structure · source_derived_draft · unverified_draft
### iron-heme-oxygenase Heme oxygenase oxidatively cleaves heme to biliverdin with release of iron and carbon monoxide. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Breaking open heme makes its iron available for reuse. organism: Human enzyme tissue_or_cell_type: Purified heme oxygenase-1 experimental_model: Product-bound human HO-1 structure limitations: Product release interpretation from structure; no in-vivo flux measurement. exposure: Biliverdin-bound structure compared with heme-bound enzyme evidence_span: {"source_cache": "artifacts/iron-research/15049686.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76bcb8ae12316350b1161f32c1633e2b5c752fcbf7e158940385b354ee3452d2", "start_char": 0, "end_char": 1167, "text_sha256": "76bcb8ae12316350b1161f32c1633e2b5c752fcbf7e158940385b354ee3452d2"} [iron-p15049686] Crystal structure of human heme oxygenase-1 in a complex with biliverdin. (2004). https://pubmed.ncbi.nlm.nih.gov/15049686/ DOI: 10.1021/bi035451l
Complete structured claim and evidence
PCBP1 bound iron and ferritin and facilitated iron loading into ferritin in vitro and in cellular systems.
Human poly(rC)-binding protein 1 / PCBP1 → Iron loading into cellular ferritin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/18511687.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8000e5c5f59dc72e9697d5aac77ce5070a1c92f6cada7e863088ec917684c68", "start_char": 0, "end_char": 703, "text_sha256": "d8000e5c5f59dc72e9697d5aac77ce5070a1c92f6cada7e863088ec917684c68"}
experimental_model
Yeast expression, in-vitro binding/loading and human-cell depletion
exposure
PCBP1 expression and depletion
limitations
Chaperone-mediated distribution is distinct from total cellular iron.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human PCBP1 and ferritin in yeast and human cells
plain_language
Iron has a delivery protein for safe storage, rather than simply drifting into every target.
primary_references
[iron-p18511687] A cytosolic iron chaperone that delivers iron to ferritin. (2008). https://pubmed.ncbi.nlm.nih.gov/18511687/ DOI: 10.1126/science.1157643
tissue_or_cell_type
Cytosol
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 589–600
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Yeast expression, in-vitro binding/loading and human-cell depletion · source_derived_draft · unverified_draft
### iron-pcbp-loads-ferritin PCBP1 bound iron and ferritin and facilitated iron loading into ferritin in vitro and in cellular systems. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron has a delivery protein for safe storage, rather than simply drifting into every target. organism: Human PCBP1 and ferritin in yeast and human cells tissue_or_cell_type: Cytosol experimental_model: Yeast expression, in-vitro binding/loading and human-cell depletion limitations: Chaperone-mediated distribution is distinct from total cellular iron. exposure: PCBP1 expression and depletion evidence_span: {"source_cache": "artifacts/iron-research/18511687.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8000e5c5f59dc72e9697d5aac77ce5070a1c92f6cada7e863088ec917684c68", "start_char": 0, "end_char": 703, "text_sha256": "d8000e5c5f59dc72e9697d5aac77ce5070a1c92f6cada7e863088ec917684c68"} [iron-p18511687] A cytosolic iron chaperone that delivers iron to ferritin. (2008). https://pubmed.ncbi.nlm.nih.gov/18511687/ DOI: 10.1126/science.1157643
Complete structured claim and evidence
PCBP1 depletion inhibited ferritin iron loading and increased cytosolic iron pools in human cells.
Human poly(rC)-binding protein 1 / PCBP1 → Cellular labile iron pool source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/18511687.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8000e5c5f59dc72e9697d5aac77ce5070a1c92f6cada7e863088ec917684c68", "start_char": 0, "end_char": 703, "text_sha256": "d8000e5c5f59dc72e9697d5aac77ce5070a1c92f6cada7e863088ec917684c68"}
experimental_model
Yeast expression, in-vitro binding/loading and human-cell depletion
exposure
PCBP1 expression and depletion
limitations
Chaperone-mediated distribution is distinct from total cellular iron.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human PCBP1 and ferritin in yeast and human cells
plain_language
Less iron in storage can coexist with more potentially reactive iron outside the store.
primary_references
[iron-p18511687] A cytosolic iron chaperone that delivers iron to ferritin. (2008). https://pubmed.ncbi.nlm.nih.gov/18511687/ DOI: 10.1126/science.1157643
tissue_or_cell_type
Cytosol
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 602–613
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Yeast expression, in-vitro binding/loading and human-cell depletion · source_derived_draft · unverified_draft
### iron-pcbp-depletion PCBP1 depletion inhibited ferritin iron loading and increased cytosolic iron pools in human cells. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less iron in storage can coexist with more potentially reactive iron outside the store. organism: Human PCBP1 and ferritin in yeast and human cells tissue_or_cell_type: Cytosol experimental_model: Yeast expression, in-vitro binding/loading and human-cell depletion limitations: Chaperone-mediated distribution is distinct from total cellular iron. exposure: PCBP1 expression and depletion evidence_span: {"source_cache": "artifacts/iron-research/18511687.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8000e5c5f59dc72e9697d5aac77ce5070a1c92f6cada7e863088ec917684c68", "start_char": 0, "end_char": 703, "text_sha256": "d8000e5c5f59dc72e9697d5aac77ce5070a1c92f6cada7e863088ec917684c68"} [iron-p18511687] A cytosolic iron chaperone that delivers iron to ferritin. (2008). https://pubmed.ncbi.nlm.nih.gov/18511687/ DOI: 10.1126/science.1157643
Complete structured claim and evidence
Human H-chain ferritin catalyzed Fe(II) oxidation; mutation of its proposed ferroxidase ligands Glu62 and His65 abolished most activity.
Ferritin heavy chain → Ferrous iron source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/8369307.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff", "start_char": 0, "end_char": 1709, "text_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff"}
experimental_model
Ferroxidase kinetics and site-directed mutants
exposure
Fe(II) oxidation by oxygen; H-chain mutations and zinc inhibition
limitations
In-vitro metal concentrations and H/L composition determine kinetics; this does not establish a dietary zinc effect on human iron stores.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human recombinant ferritin and human liver apoferritin
plain_language
Ferritin does chemical work to package iron, not just physical storage.
primary_references
[iron-p8369307] Ferroxidase kinetics of human liver apoferritin, recombinant H-chain apoferritin, and site-directed mutants. (1993). https://pubmed.ncbi.nlm.nih.gov/8369307/ DOI: 10.1021/bi00087a015
tissue_or_cell_type
Purified ferritin subunits/assemblies
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 615–626
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ferroxidase kinetics and site-directed mutants · source_derived_draft · unverified_draft
### iron-ferritin-h-oxidation Human H-chain ferritin catalyzed Fe(II) oxidation; mutation of its proposed ferroxidase ligands Glu62 and His65 abolished most activity. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Ferritin does chemical work to package iron, not just physical storage. organism: Human recombinant ferritin and human liver apoferritin tissue_or_cell_type: Purified ferritin subunits/assemblies experimental_model: Ferroxidase kinetics and site-directed mutants limitations: In-vitro metal concentrations and H/L composition determine kinetics; this does not establish a dietary zinc effect on human iron stores. exposure: Fe(II) oxidation by oxygen; H-chain mutations and zinc inhibition evidence_span: {"source_cache": "artifacts/iron-research/8369307.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff", "start_char": 0, "end_char": 1709, "text_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff"} [iron-p8369307] Ferroxidase kinetics of human liver apoferritin, recombinant H-chain apoferritin, and site-directed mutants. (1993). https://pubmed.ncbi.nlm.nih.gov/8369307/ DOI: 10.1021/bi00087a015
Complete structured claim and evidence
Recombinant human L-chain ferritin lacked ferroxidase activity, although H/L assembly composition altered whole-ferritin oxidation kinetics.
Human ferritin light chain / FTL → Ferritin ferroxidase activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/8369307.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff", "start_char": 0, "end_char": 1709, "text_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff"}
experimental_model
Ferroxidase kinetics and site-directed mutants
exposure
Fe(II) oxidation by oxygen; H-chain mutations and zinc inhibition
limitations
Purified recombinant subunits; H/L assembly kinetics do not establish a dietary zinc effect on human iron stores.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human recombinant ferritin and human liver apoferritin
plain_language
The heavy and light chains play different roles in the storage cage.
primary_references
[iron-p8369307] Ferroxidase kinetics of human liver apoferritin, recombinant H-chain apoferritin, and site-directed mutants. (1993). https://pubmed.ncbi.nlm.nih.gov/8369307/ DOI: 10.1021/bi00087a015
tissue_or_cell_type
Purified ferritin subunits/assemblies
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 628–639
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ferroxidase kinetics and site-directed mutants · source_derived_draft · unverified_draft
### iron-ferritin-l-distinction Recombinant human L-chain ferritin lacked ferroxidase activity, although H/L assembly composition altered whole-ferritin oxidation kinetics. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The heavy and light chains play different roles in the storage cage. organism: Human recombinant ferritin and human liver apoferritin tissue_or_cell_type: Purified ferritin subunits/assemblies experimental_model: Ferroxidase kinetics and site-directed mutants limitations: Purified recombinant subunits; H/L assembly kinetics do not establish a dietary zinc effect on human iron stores. exposure: Fe(II) oxidation by oxygen; H-chain mutations and zinc inhibition evidence_span: {"source_cache": "artifacts/iron-research/8369307.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff", "start_char": 0, "end_char": 1709, "text_sha256": "8ccc94b97da4dcc2557e2f8ce964949b4188cd6c7e54405f6d4268ea864697ff"} [iron-p8369307] Ferroxidase kinetics of human liver apoferritin, recombinant H-chain apoferritin, and site-directed mutants. (1993). https://pubmed.ncbi.nlm.nih.gov/8369307/ DOI: 10.1021/bi00087a015
Complete structured claim and evidence
NCOA4 associated with ferritin heavy/light chains and was required for their delivery to lysosomes.
Human nuclear receptor coactivator 4 / NCOA4 → Lysosomal delivery and degradation of ferritin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/24695223.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ff28f2795755fe6ec56b532f23bfdb66f3925ed0403c86ade859971ec1cc303a", "start_char": 0, "end_char": 1514, "text_sha256": "ff28f2795755fe6ec56b532f23bfdb66f3925ed0403c86ade859971ec1cc303a"}
experimental_model
Quantitative proteomics and selective-autophagy experiments
exposure
NCOA4 association and loss experiments
limitations
Ferritinophagy supplies intracellular iron; it is not equivalent to serum ferritin concentration.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human cultured cells
plain_language
A selective cargo receptor sends stored iron for release when cells need it.
primary_references
[iron-p24695223] Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. (2014). https://pubmed.ncbi.nlm.nih.gov/24695223/ DOI: 10.1038/nature13148
tissue_or_cell_type
Autophagosomes and lysosomes
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 641–652
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantitative proteomics and selective-autophagy experiments · source_derived_draft · unverified_draft
### iron-ncoa4-ferritin NCOA4 associated with ferritin heavy/light chains and was required for their delivery to lysosomes. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: A selective cargo receptor sends stored iron for release when cells need it. organism: Human cultured cells tissue_or_cell_type: Autophagosomes and lysosomes experimental_model: Quantitative proteomics and selective-autophagy experiments limitations: Ferritinophagy supplies intracellular iron; it is not equivalent to serum ferritin concentration. exposure: NCOA4 association and loss experiments evidence_span: {"source_cache": "artifacts/iron-research/24695223.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ff28f2795755fe6ec56b532f23bfdb66f3925ed0403c86ade859971ec1cc303a", "start_char": 0, "end_char": 1514, "text_sha256": "ff28f2795755fe6ec56b532f23bfdb66f3925ed0403c86ade859971ec1cc303a"} [iron-p24695223] Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. (2014). https://pubmed.ncbi.nlm.nih.gov/24695223/ DOI: 10.1038/nature13148
Complete structured claim and evidence
NCOA4-deficient cells could not degrade ferritin normally and had decreased bioavailable intracellular iron.
Human nuclear receptor coactivator 4 / NCOA4 → Cellular labile iron pool source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/24695223.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ff28f2795755fe6ec56b532f23bfdb66f3925ed0403c86ade859971ec1cc303a", "start_char": 0, "end_char": 1514, "text_sha256": "ff28f2795755fe6ec56b532f23bfdb66f3925ed0403c86ade859971ec1cc303a"}
experimental_model
Quantitative proteomics and selective-autophagy experiments
exposure
NCOA4 association and loss experiments
limitations
Ferritinophagy supplies intracellular iron; it is not equivalent to serum ferritin concentration.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human cultured cells
plain_language
The cell could have iron in a storage cage while still lacking usable iron.
primary_references
[iron-p24695223] Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. (2014). https://pubmed.ncbi.nlm.nih.gov/24695223/ DOI: 10.1038/nature13148
tissue_or_cell_type
Autophagosomes and lysosomes
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 654–665
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantitative proteomics and selective-autophagy experiments · source_derived_draft · unverified_draft
### iron-ncoa4-loss NCOA4-deficient cells could not degrade ferritin normally and had decreased bioavailable intracellular iron. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cell could have iron in a storage cage while still lacking usable iron. organism: Human cultured cells tissue_or_cell_type: Autophagosomes and lysosomes experimental_model: Quantitative proteomics and selective-autophagy experiments limitations: Ferritinophagy supplies intracellular iron; it is not equivalent to serum ferritin concentration. exposure: NCOA4 association and loss experiments evidence_span: {"source_cache": "artifacts/iron-research/24695223.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ff28f2795755fe6ec56b532f23bfdb66f3925ed0403c86ade859971ec1cc303a", "start_char": 0, "end_char": 1514, "text_sha256": "ff28f2795755fe6ec56b532f23bfdb66f3925ed0403c86ade859971ec1cc303a"} [iron-p24695223] Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. (2014). https://pubmed.ncbi.nlm.nih.gov/24695223/ DOI: 10.1038/nature13148
Complete structured claim and evidence
Manipulations of the IRE-binding protein Fe-S cluster reciprocally altered RNA-binding and aconitase activities.
Human cytosolic aconitase / iron regulatory protein 1 / ACO1 → Cellular iron-responsive RNA binding source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/1502165.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1fc2a7abe3fbac12a5196a163c8d6f21f5847bd89c049958dfb4055302a14a56", "start_char": 0, "end_char": 1583, "text_sha256": "1fc2a7abe3fbac12a5196a163c8d6f21f5847bd89c049958dfb4055302a14a56"}
experimental_model
Iron-sulfur manipulation and enzyme/RNA-binding assays
exposure
Iron and Fe-S cluster manipulation
limitations
IRP1/aconitase switch; no assertion that IRP2 has the same catalytic switch.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mammalian IRE-binding protein systems
plain_language
One protein can act as an enzyme or an iron-responsive RNA-binding regulator, depending on its cluster state.
primary_references
[iron-p1502165] Reciprocal control of RNA-binding and aconitase activity in the regulation of the iron-responsive element binding protein: role of the iron-sulfur cluster. (1992). https://pubmed.ncbi.nlm.nih.gov/1502165/ DOI: 10.1073/pnas.89.16.7536
tissue_or_cell_type
Purified/recombinant IRE-BP and cultured cells
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 667–678
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Iron-sulfur manipulation and enzyme/RNA-binding assays · source_derived_draft · unverified_draft
### iron-irp1-switch Manipulations of the IRE-binding protein Fe-S cluster reciprocally altered RNA-binding and aconitase activities. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: One protein can act as an enzyme or an iron-responsive RNA-binding regulator, depending on its cluster state. organism: Mammalian IRE-binding protein systems tissue_or_cell_type: Purified/recombinant IRE-BP and cultured cells experimental_model: Iron-sulfur manipulation and enzyme/RNA-binding assays limitations: IRP1/aconitase switch; no assertion that IRP2 has the same catalytic switch. exposure: Iron and Fe-S cluster manipulation evidence_span: {"source_cache": "artifacts/iron-research/1502165.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1fc2a7abe3fbac12a5196a163c8d6f21f5847bd89c049958dfb4055302a14a56", "start_char": 0, "end_char": 1583, "text_sha256": "1fc2a7abe3fbac12a5196a163c8d6f21f5847bd89c049958dfb4055302a14a56"} [iron-p1502165] Reciprocal control of RNA-binding and aconitase activity in the regulation of the iron-responsive element binding protein: role of the iron-sulfur cluster. (1992). https://pubmed.ncbi.nlm.nih.gov/1502165/ DOI: 10.1073/pnas.89.16.7536
Complete structured claim and evidence
A SKP1-CUL1-FBXL5 ligase complex associated with IRP2 and promoted its iron-dependent ubiquitination and degradation.
Human SKP1-CUL1-FBXL5 ubiquitin ligase complex → Human iron regulatory protein 2 / IREB2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/19762596.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9308ac435b303ee150d6c92a21c3d68731fed61f0894312026a8a19e57d5aac6", "start_char": 0, "end_char": 824, "text_sha256": "9308ac435b303ee150d6c92a21c3d68731fed61f0894312026a8a19e57d5aac6"}
experimental_model
Protein association, ubiquitination and degradation experiments
exposure
Iron and oxygen availability; FBXL5 stability
limitations
Cellular sensing mechanism, not a serum-iron diagnostic rule.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mammalian cellular systems
plain_language
When iron is available, an enzyme complex can remove a regulator that otherwise favors iron acquisition.
primary_references
[iron-p19762596] Control of iron homeostasis by an iron-regulated ubiquitin ligase. (2009). https://pubmed.ncbi.nlm.nih.gov/19762596/ DOI: 10.1126/science.1176333
tissue_or_cell_type
Cytosolic iron regulation
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 680–691
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein association, ubiquitination and degradation experiments · source_derived_draft · unverified_draft
### iron-fbxl5-irp2 A SKP1-CUL1-FBXL5 ligase complex associated with IRP2 and promoted its iron-dependent ubiquitination and degradation. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: When iron is available, an enzyme complex can remove a regulator that otherwise favors iron acquisition. organism: Mammalian cellular systems tissue_or_cell_type: Cytosolic iron regulation experimental_model: Protein association, ubiquitination and degradation experiments limitations: Cellular sensing mechanism, not a serum-iron diagnostic rule. exposure: Iron and oxygen availability; FBXL5 stability evidence_span: {"source_cache": "artifacts/iron-research/19762596.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9308ac435b303ee150d6c92a21c3d68731fed61f0894312026a8a19e57d5aac6", "start_char": 0, "end_char": 824, "text_sha256": "9308ac435b303ee150d6c92a21c3d68731fed61f0894312026a8a19e57d5aac6"} [iron-p19762596] Control of iron homeostasis by an iron-regulated ubiquitin ligase. (2009). https://pubmed.ncbi.nlm.nih.gov/19762596/ DOI: 10.1126/science.1176333
Complete structured claim and evidence
Iron or oxygen depletion triggered FBXL5 degradation through a process requiring its N-terminal hemerythrin-like iron-binding domain.
Iron → Human F-box and leucine-rich repeat protein 5 / FBXL5 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/19762596.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9308ac435b303ee150d6c92a21c3d68731fed61f0894312026a8a19e57d5aac6", "start_char": 0, "end_char": 824, "text_sha256": "9308ac435b303ee150d6c92a21c3d68731fed61f0894312026a8a19e57d5aac6"}
experimental_model
Protein association, ubiquitination and degradation experiments
exposure
Iron and oxygen availability; FBXL5 stability
limitations
Cellular sensing mechanism, not a serum-iron diagnostic rule.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mammalian cellular systems
plain_language
The control system responds to both iron and oxygen availability.
primary_references
[iron-p19762596] Control of iron homeostasis by an iron-regulated ubiquitin ligase. (2009). https://pubmed.ncbi.nlm.nih.gov/19762596/ DOI: 10.1126/science.1176333
tissue_or_cell_type
Cytosolic iron regulation
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 693–704
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein association, ubiquitination and degradation experiments · source_derived_draft · unverified_draft
### iron-fbxl5-iron-sensing Iron or oxygen depletion triggered FBXL5 degradation through a process requiring its N-terminal hemerythrin-like iron-binding domain. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The control system responds to both iron and oxygen availability. organism: Mammalian cellular systems tissue_or_cell_type: Cytosolic iron regulation experimental_model: Protein association, ubiquitination and degradation experiments limitations: Cellular sensing mechanism, not a serum-iron diagnostic rule. exposure: Iron and oxygen availability; FBXL5 stability evidence_span: {"source_cache": "artifacts/iron-research/19762596.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9308ac435b303ee150d6c92a21c3d68731fed61f0894312026a8a19e57d5aac6", "start_char": 0, "end_char": 824, "text_sha256": "9308ac435b303ee150d6c92a21c3d68731fed61f0894312026a8a19e57d5aac6"} [iron-p19762596] Control of iron homeostasis by an iron-regulated ubiquitin ligase. (2009). https://pubmed.ncbi.nlm.nih.gov/19762596/ DOI: 10.1126/science.1176333
Complete structured claim and evidence
Hepcidin binding induced ferroportin internalization and degradation.
Hepcidin → Cell-surface ferroportin abundance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/15514116.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "00a292f6693116798182b0f9418f2eb8466aa029f32905019416422002158c4a", "start_char": 0, "end_char": 758, "text_sha256": "00a292f6693116798182b0f9418f2eb8466aa029f32905019416422002158c4a"}
experimental_model
Hepcidin binding and cellular export experiments
exposure
Hepcidin exposure
limitations
Post-translational export regulation; no dose-response to dietary iron is inferred from the cell experiment.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Tissue-culture ferroportin systems
plain_language
The cell removes the exit route for iron from its surface.
primary_references
[iron-p15514116] Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. (2004). https://pubmed.ncbi.nlm.nih.gov/15514116/ DOI: 10.1126/science.1104742
tissue_or_cell_type
Plasma membrane
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 719–730
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hepcidin binding and cellular export experiments · source_derived_draft · unverified_draft
### iron-hepcidin-fpn-removal Hepcidin binding induced ferroportin internalization and degradation. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cell removes the exit route for iron from its surface. organism: Tissue-culture ferroportin systems tissue_or_cell_type: Plasma membrane experimental_model: Hepcidin binding and cellular export experiments limitations: Post-translational export regulation; no dose-response to dietary iron is inferred from the cell experiment. exposure: Hepcidin exposure evidence_span: {"source_cache": "artifacts/iron-research/15514116.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "00a292f6693116798182b0f9418f2eb8466aa029f32905019416422002158c4a", "start_char": 0, "end_char": 758, "text_sha256": "00a292f6693116798182b0f9418f2eb8466aa029f32905019416422002158c4a"} [iron-p15514116] Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. (2004). https://pubmed.ncbi.nlm.nih.gov/15514116/ DOI: 10.1126/science.1104742
Complete structured claim and evidence
Hepcidin occupied outward-open ferroportin and blocked its iron-efflux pathway.
Hepcidin → Ferroportin / SLC40A1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/32814342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8de67bc7ca2250cfab2f2cb71c2da16b4806c05cf5d4b6e648b191596b6e0da0", "start_char": 0, "end_char": 1365, "text_sha256": "8de67bc7ca2250cfab2f2cb71c2da16b4806c05cf5d4b6e648b191596b6e0da0"}
experimental_model
Cryo-EM in lipid nanodiscs and binding/transport analysis
exposure
Apo state, hepcidin and cobalt mimetic; iron-dependent affinity measurements
limitations
Metal sites include a cobalt-bound structural preparation; the degradation-selectivity model is an interpretation, not proof that only loaded molecules are ever degraded.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human ferroportin
plain_language
Hepcidin can physically block the exit channel as well as promote its removal.
primary_references
[iron-p32814342] Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms. (2020). https://pubmed.ncbi.nlm.nih.gov/32814342/ DOI: 10.1038/s41586-020-2668-z
tissue_or_cell_type
Purified membrane transporter
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 745–756
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM in lipid nanodiscs and binding/transport analysis · source_derived_draft · unverified_draft
### iron-hepcidin-plugs-fpn Hepcidin occupied outward-open ferroportin and blocked its iron-efflux pathway. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Hepcidin can physically block the exit channel as well as promote its removal. organism: Human ferroportin tissue_or_cell_type: Purified membrane transporter experimental_model: Cryo-EM in lipid nanodiscs and binding/transport analysis limitations: Metal sites include a cobalt-bound structural preparation; the degradation-selectivity model is an interpretation, not proof that only loaded molecules are ever degraded. exposure: Apo state, hepcidin and cobalt mimetic; iron-dependent affinity measurements evidence_span: {"source_cache": "artifacts/iron-research/32814342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8de67bc7ca2250cfab2f2cb71c2da16b4806c05cf5d4b6e648b191596b6e0da0", "start_char": 0, "end_char": 1365, "text_sha256": "8de67bc7ca2250cfab2f2cb71c2da16b4806c05cf5d4b6e648b191596b6e0da0"} [iron-p32814342] Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms. (2020). https://pubmed.ncbi.nlm.nih.gov/32814342/ DOI: 10.1038/s41586-020-2668-z
Complete structured claim and evidence
Iron increased hepcidin affinity for ferroportin approximately 80-fold in the measured binding system.
Ferrous iron → Ferroportin / SLC40A1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/32814342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8de67bc7ca2250cfab2f2cb71c2da16b4806c05cf5d4b6e648b191596b6e0da0", "start_char": 0, "end_char": 1365, "text_sha256": "8de67bc7ca2250cfab2f2cb71c2da16b4806c05cf5d4b6e648b191596b6e0da0"}
experimental_model
Cryo-EM in lipid nanodiscs and binding/transport analysis
exposure
Apo state, hepcidin and cobalt mimetic; iron-dependent affinity measurements
limitations
Metal sites include a cobalt-bound structural preparation; the degradation-selectivity model is an interpretation, not proof that only loaded molecules are ever degraded.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human ferroportin
plain_language
The exporter’s metal-loading state changes how strongly the regulator binds.
primary_references
[iron-p32814342] Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms. (2020). https://pubmed.ncbi.nlm.nih.gov/32814342/ DOI: 10.1038/s41586-020-2668-z
tissue_or_cell_type
Purified membrane transporter
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 758–769
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM in lipid nanodiscs and binding/transport analysis · source_derived_draft · unverified_draft
### iron-iron-hepcidin-affinity Iron increased hepcidin affinity for ferroportin approximately 80-fold in the measured binding system. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The exporter’s metal-loading state changes how strongly the regulator binds. organism: Human ferroportin tissue_or_cell_type: Purified membrane transporter experimental_model: Cryo-EM in lipid nanodiscs and binding/transport analysis limitations: Metal sites include a cobalt-bound structural preparation; the degradation-selectivity model is an interpretation, not proof that only loaded molecules are ever degraded. exposure: Apo state, hepcidin and cobalt mimetic; iron-dependent affinity measurements evidence_span: {"source_cache": "artifacts/iron-research/32814342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8de67bc7ca2250cfab2f2cb71c2da16b4806c05cf5d4b6e648b191596b6e0da0", "start_char": 0, "end_char": 1365, "text_sha256": "8de67bc7ca2250cfab2f2cb71c2da16b4806c05cf5d4b6e648b191596b6e0da0"} [iron-p32814342] Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms. (2020). https://pubmed.ncbi.nlm.nih.gov/32814342/ DOI: 10.1038/s41586-020-2668-z
Complete structured claim and evidence
The study demonstrated a physical interaction between BMP6 and soluble hemojuvelin fusion protein.
Bone morphogenetic protein 6 → Hemojuvelin / HFE2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/19252486.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f51b7e3f2c0882e3da19cc1f55c13f742c4cd47ca3db21bcc40be6263af76f2b", "start_char": 0, "end_char": 1168, "text_sha256": "f51b7e3f2c0882e3da19cc1f55c13f742c4cd47ca3db21bcc40be6263af76f2b"}
experimental_model
Ligand binding, antibody treatment and knockout studies
exposure
BMP6, BMP6 antibody, soluble HJV and Bmp6 deletion
limitations
Mouse causal regulation; the role of other BMP ligands is not excluded.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mice and biochemical HJV/BMP systems
plain_language
A ligand and its coreceptor form part of the signal controlling iron release.
primary_references
[iron-p19252486] BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. (2009). https://pubmed.ncbi.nlm.nih.gov/19252486/ DOI: 10.1038/ng.335
tissue_or_cell_type
Liver, blood and tissues
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 771–782
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ligand binding, antibody treatment and knockout studies · source_derived_draft · unverified_draft
### iron-bmp6-hemojuvelin The study demonstrated a physical interaction between BMP6 and soluble hemojuvelin fusion protein. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: A ligand and its coreceptor form part of the signal controlling iron release. organism: Mice and biochemical HJV/BMP systems tissue_or_cell_type: Liver, blood and tissues experimental_model: Ligand binding, antibody treatment and knockout studies limitations: Mouse causal regulation; the role of other BMP ligands is not excluded. exposure: BMP6, BMP6 antibody, soluble HJV and Bmp6 deletion evidence_span: {"source_cache": "artifacts/iron-research/19252486.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f51b7e3f2c0882e3da19cc1f55c13f742c4cd47ca3db21bcc40be6263af76f2b", "start_char": 0, "end_char": 1168, "text_sha256": "f51b7e3f2c0882e3da19cc1f55c13f742c4cd47ca3db21bcc40be6263af76f2b"} [iron-p19252486] BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. (2009). https://pubmed.ncbi.nlm.nih.gov/19252486/ DOI: 10.1038/ng.335
Complete structured claim and evidence
BMP6 increased hepcidin expression and reduced serum iron in mice.
Mouse bone morphogenetic protein 6 / Bmp6 → Hepcidin expression source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/19252486.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f51b7e3f2c0882e3da19cc1f55c13f742c4cd47ca3db21bcc40be6263af76f2b", "start_char": 0, "end_char": 1168, "text_sha256": "f51b7e3f2c0882e3da19cc1f55c13f742c4cd47ca3db21bcc40be6263af76f2b"}
experimental_model
Ligand binding, antibody treatment and knockout studies
exposure
BMP6, BMP6 antibody, soluble HJV and Bmp6 deletion
limitations
Mouse causal regulation; the role of other BMP ligands is not excluded.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mice and biochemical HJV/BMP systems
plain_language
This signaling pathway tells the body to restrict iron entry into the circulation.
primary_references
[iron-p19252486] BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. (2009). https://pubmed.ncbi.nlm.nih.gov/19252486/ DOI: 10.1038/ng.335
tissue_or_cell_type
Liver, blood and tissues
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 784–795
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ligand binding, antibody treatment and knockout studies · source_derived_draft · unverified_draft
### iron-bmp6-hepcidin BMP6 increased hepcidin expression and reduced serum iron in mice. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: This signaling pathway tells the body to restrict iron entry into the circulation. organism: Mice and biochemical HJV/BMP systems tissue_or_cell_type: Liver, blood and tissues experimental_model: Ligand binding, antibody treatment and knockout studies limitations: Mouse causal regulation; the role of other BMP ligands is not excluded. exposure: BMP6, BMP6 antibody, soluble HJV and Bmp6 deletion evidence_span: {"source_cache": "artifacts/iron-research/19252486.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f51b7e3f2c0882e3da19cc1f55c13f742c4cd47ca3db21bcc40be6263af76f2b", "start_char": 0, "end_char": 1168, "text_sha256": "f51b7e3f2c0882e3da19cc1f55c13f742c4cd47ca3db21bcc40be6263af76f2b"} [iron-p19252486] BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. (2009). https://pubmed.ncbi.nlm.nih.gov/19252486/ DOI: 10.1038/ng.335
Complete structured claim and evidence
Bmp6-null mice had reduced hepcidin expression and tissue iron overload.
Mouse bone morphogenetic protein 6 / Bmp6 → Systemic tissue iron overload source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/19252486.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f51b7e3f2c0882e3da19cc1f55c13f742c4cd47ca3db21bcc40be6263af76f2b", "start_char": 0, "end_char": 1168, "text_sha256": "f51b7e3f2c0882e3da19cc1f55c13f742c4cd47ca3db21bcc40be6263af76f2b"}
experimental_model
Ligand binding, antibody treatment and knockout studies
exposure
BMP6, BMP6 antibody, soluble HJV and Bmp6 deletion
limitations
Mouse causal regulation; the role of other BMP ligands is not excluded.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mice and biochemical HJV/BMP systems
plain_language
An iron-control defect can produce excess stores despite the element being essential.
primary_references
[iron-p19252486] BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. (2009). https://pubmed.ncbi.nlm.nih.gov/19252486/ DOI: 10.1038/ng.335
tissue_or_cell_type
Liver, blood and tissues
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 797–808
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ligand binding, antibody treatment and knockout studies · source_derived_draft · unverified_draft
### iron-bmp6-overload Bmp6-null mice had reduced hepcidin expression and tissue iron overload. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: An iron-control defect can produce excess stores despite the element being essential. organism: Mice and biochemical HJV/BMP systems tissue_or_cell_type: Liver, blood and tissues experimental_model: Ligand binding, antibody treatment and knockout studies limitations: Mouse causal regulation; the role of other BMP ligands is not excluded. exposure: BMP6, BMP6 antibody, soluble HJV and Bmp6 deletion evidence_span: {"source_cache": "artifacts/iron-research/19252486.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f51b7e3f2c0882e3da19cc1f55c13f742c4cd47ca3db21bcc40be6263af76f2b", "start_char": 0, "end_char": 1168, "text_sha256": "f51b7e3f2c0882e3da19cc1f55c13f742c4cd47ca3db21bcc40be6263af76f2b"} [iron-p19252486] BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. (2009). https://pubmed.ncbi.nlm.nih.gov/19252486/ DOI: 10.1038/ng.335
Complete structured claim and evidence
Erythroblasts produced erythroferrone in response to erythropoietin.
Mouse erythropoietin / Epo → Mouse erythroferrone / Erfe source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/24880340.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e290e3082fe90ef8ef538ec8d5151082e3d38672abfba19731ea158957fcc54", "start_char": 0, "end_char": 738, "text_sha256": "1e290e3082fe90ef8ef538ec8d5151082e3d38672abfba19731ea158957fcc54"}
experimental_model
Hemorrhage, erythropoietin response and gene deletion
exposure
Blood loss, EPO stimulation and Erfe deletion; thalassemia model
limitations
Stress erythropoiesis and mouse overload mechanisms; the author correction (PMID 32107478; https://doi.org/10.1038/s41588-019-0548-y) corrects swapped human FAM132B and HPRT primer labels in Supplementary Table 2.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mice
plain_language
Red-cell production sends a hormonal request for more available iron.
primary_references
[iron-p24880340] Identification of erythroferrone as an erythroid regulator of iron metabolism. (2014). https://pubmed.ncbi.nlm.nih.gov/24880340/ DOI: 10.1038/ng.2996
tissue_or_cell_type
Erythroblasts and hepatic iron regulation
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 810–821
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hemorrhage, erythropoietin response and gene deletion · source_derived_draft · unverified_draft
### iron-epo-erfe Erythroblasts produced erythroferrone in response to erythropoietin. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Red-cell production sends a hormonal request for more available iron. organism: Mice tissue_or_cell_type: Erythroblasts and hepatic iron regulation experimental_model: Hemorrhage, erythropoietin response and gene deletion limitations: Stress erythropoiesis and mouse overload mechanisms; the author correction (PMID 32107478; https://doi.org/10.1038/s41588-019-0548-y) corrects swapped human FAM132B and HPRT primer labels in Supplementary Table 2. exposure: Blood loss, EPO stimulation and Erfe deletion; thalassemia model evidence_span: {"source_cache": "artifacts/iron-research/24880340.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e290e3082fe90ef8ef538ec8d5151082e3d38672abfba19731ea158957fcc54", "start_char": 0, "end_char": 738, "text_sha256": "1e290e3082fe90ef8ef538ec8d5151082e3d38672abfba19731ea158957fcc54"} [iron-p24880340] Identification of erythroferrone as an erythroid regulator of iron metabolism. (2014). https://pubmed.ncbi.nlm.nih.gov/24880340/ DOI: 10.1038/ng.2996
Complete structured claim and evidence
Erythroferrone mediated hepcidin suppression during stress erythropoiesis.
Mouse erythroferrone / Erfe → Hepcidin expression source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/24880340.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e290e3082fe90ef8ef538ec8d5151082e3d38672abfba19731ea158957fcc54", "start_char": 0, "end_char": 738, "text_sha256": "1e290e3082fe90ef8ef538ec8d5151082e3d38672abfba19731ea158957fcc54"}
experimental_model
Hemorrhage, erythropoietin response and gene deletion
exposure
Blood loss, EPO stimulation and Erfe deletion; thalassemia model
limitations
Stress erythropoiesis and mouse overload mechanisms; the author correction (PMID 32107478; https://doi.org/10.1038/s41588-019-0548-y) corrects swapped human FAM132B and HPRT primer labels in Supplementary Table 2.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mice
plain_language
The request relaxes the hormone-controlled restriction on iron supply.
primary_references
[iron-p24880340] Identification of erythroferrone as an erythroid regulator of iron metabolism. (2014). https://pubmed.ncbi.nlm.nih.gov/24880340/ DOI: 10.1038/ng.2996
tissue_or_cell_type
Erythroblasts and hepatic iron regulation
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 823–834
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hemorrhage, erythropoietin response and gene deletion · source_derived_draft · unverified_draft
### iron-erfe-hepcidin Erythroferrone mediated hepcidin suppression during stress erythropoiesis. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The request relaxes the hormone-controlled restriction on iron supply. organism: Mice tissue_or_cell_type: Erythroblasts and hepatic iron regulation experimental_model: Hemorrhage, erythropoietin response and gene deletion limitations: Stress erythropoiesis and mouse overload mechanisms; the author correction (PMID 32107478; https://doi.org/10.1038/s41588-019-0548-y) corrects swapped human FAM132B and HPRT primer labels in Supplementary Table 2. exposure: Blood loss, EPO stimulation and Erfe deletion; thalassemia model evidence_span: {"source_cache": "artifacts/iron-research/24880340.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e290e3082fe90ef8ef538ec8d5151082e3d38672abfba19731ea158957fcc54", "start_char": 0, "end_char": 738, "text_sha256": "1e290e3082fe90ef8ef538ec8d5151082e3d38672abfba19731ea158957fcc54"} [iron-p24880340] Identification of erythroferrone as an erythroid regulator of iron metabolism. (2014). https://pubmed.ncbi.nlm.nih.gov/24880340/ DOI: 10.1038/ng.2996
Complete structured claim and evidence
ERFE-deficient mice failed to suppress hepcidin rapidly after hemorrhage and recovered more slowly from blood loss.
Mouse erythroferrone / Erfe → Recovery of erythropoiesis after blood loss source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/24880340.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e290e3082fe90ef8ef538ec8d5151082e3d38672abfba19731ea158957fcc54", "start_char": 0, "end_char": 738, "text_sha256": "1e290e3082fe90ef8ef538ec8d5151082e3d38672abfba19731ea158957fcc54"}
experimental_model
Hemorrhage, erythropoietin response and gene deletion
exposure
Blood loss, EPO stimulation and Erfe deletion; thalassemia model
limitations
Stress erythropoiesis and mouse overload mechanisms; the author correction (PMID 32107478; https://doi.org/10.1038/s41588-019-0548-y) corrects swapped human FAM132B and HPRT primer labels in Supplementary Table 2.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mice
plain_language
The response to blood loss depended on mobilizing stored and absorbed iron.
primary_references
[iron-p24880340] Identification of erythroferrone as an erythroid regulator of iron metabolism. (2014). https://pubmed.ncbi.nlm.nih.gov/24880340/ DOI: 10.1038/ng.2996
tissue_or_cell_type
Erythroblasts and hepatic iron regulation
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 836–847
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hemorrhage, erythropoietin response and gene deletion · source_derived_draft · unverified_draft
### iron-erfe-loss ERFE-deficient mice failed to suppress hepcidin rapidly after hemorrhage and recovered more slowly from blood loss. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response to blood loss depended on mobilizing stored and absorbed iron. organism: Mice tissue_or_cell_type: Erythroblasts and hepatic iron regulation experimental_model: Hemorrhage, erythropoietin response and gene deletion limitations: Stress erythropoiesis and mouse overload mechanisms; the author correction (PMID 32107478; https://doi.org/10.1038/s41588-019-0548-y) corrects swapped human FAM132B and HPRT primer labels in Supplementary Table 2. exposure: Blood loss, EPO stimulation and Erfe deletion; thalassemia model evidence_span: {"source_cache": "artifacts/iron-research/24880340.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e290e3082fe90ef8ef538ec8d5151082e3d38672abfba19731ea158957fcc54", "start_char": 0, "end_char": 738, "text_sha256": "1e290e3082fe90ef8ef538ec8d5151082e3d38672abfba19731ea158957fcc54"} [iron-p24880340] Identification of erythroferrone as an erythroid regulator of iron metabolism. (2014). https://pubmed.ncbi.nlm.nih.gov/24880340/ DOI: 10.1038/ng.2996
Complete structured claim and evidence
Intestinal HIF-2alpha directly regulated DMT1 transcription and was required for iron balance; HIF-1alpha was not required for iron absorption in this study.
Mouse hypoxia-inducible factor 2 alpha / Epas1 → Mouse DMT1 (Slc11a2) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/19352007.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "623fedcdd407c02879254b087510cff95b61336f7605c2430f51ab75ac550040", "start_char": 0, "end_char": 1411, "text_sha256": "623fedcdd407c02879254b087510cff95b61336f7605c2430f51ab75ac550040"}
experimental_model
Conditional intestinal Hif1a/Hif2a knockout
exposure
Separate Hif1a versus Hif2a deletion
limitations
HIF isoforms were not interchangeable in this mouse experiment.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mice
plain_language
The intestine uses a particular oxygen-responsive transcription factor to adjust its iron uptake machinery.
primary_references
[iron-p19352007] HIF-2alpha, but not HIF-1alpha, promotes iron absorption in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19352007/ DOI: 10.1172/jci38499
tissue_or_cell_type
Duodenal epithelium and systemic iron
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 849–860
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conditional intestinal Hif1a/Hif2a knockout · source_derived_draft · unverified_draft
### iron-hif2-dmt1 Intestinal HIF-2alpha directly regulated DMT1 transcription and was required for iron balance; HIF-1alpha was not required for iron absorption in this study. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The intestine uses a particular oxygen-responsive transcription factor to adjust its iron uptake machinery. organism: Mice tissue_or_cell_type: Duodenal epithelium and systemic iron experimental_model: Conditional intestinal Hif1a/Hif2a knockout limitations: HIF isoforms were not interchangeable in this mouse experiment. exposure: Separate Hif1a versus Hif2a deletion evidence_span: {"source_cache": "artifacts/iron-research/19352007.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "623fedcdd407c02879254b087510cff95b61336f7605c2430f51ab75ac550040", "start_char": 0, "end_char": 1411, "text_sha256": "623fedcdd407c02879254b087510cff95b61336f7605c2430f51ab75ac550040"} [iron-p19352007] HIF-2alpha, but not HIF-1alpha, promotes iron absorption in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19352007/ DOI: 10.1172/jci38499
Complete structured claim and evidence
Intestinal Hif2a deletion lowered serum and liver iron and markedly reduced liver hepcidin expression.
Mouse hypoxia-inducible factor 2 alpha / Epas1 → Serum iron concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/19352007.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "623fedcdd407c02879254b087510cff95b61336f7605c2430f51ab75ac550040", "start_char": 0, "end_char": 1411, "text_sha256": "623fedcdd407c02879254b087510cff95b61336f7605c2430f51ab75ac550040"}
experimental_model
Conditional intestinal Hif1a/Hif2a knockout
exposure
Separate Hif1a versus Hif2a deletion
limitations
HIF isoforms were not interchangeable in this mouse experiment.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mice
plain_language
A hormonal attempt to increase iron availability did not replace the missing intestinal regulator.
primary_references
[iron-p19352007] HIF-2alpha, but not HIF-1alpha, promotes iron absorption in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19352007/ DOI: 10.1172/jci38499
tissue_or_cell_type
Duodenal epithelium and systemic iron
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 862–873
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conditional intestinal Hif1a/Hif2a knockout · source_derived_draft · unverified_draft
### iron-hif2-loss Intestinal Hif2a deletion lowered serum and liver iron and markedly reduced liver hepcidin expression. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: A hormonal attempt to increase iron availability did not replace the missing intestinal regulator. organism: Mice tissue_or_cell_type: Duodenal epithelium and systemic iron experimental_model: Conditional intestinal Hif1a/Hif2a knockout limitations: HIF isoforms were not interchangeable in this mouse experiment. exposure: Separate Hif1a versus Hif2a deletion evidence_span: {"source_cache": "artifacts/iron-research/19352007.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "623fedcdd407c02879254b087510cff95b61336f7605c2430f51ab75ac550040", "start_char": 0, "end_char": 1411, "text_sha256": "623fedcdd407c02879254b087510cff95b61336f7605c2430f51ab75ac550040"} [iron-p19352007] HIF-2alpha, but not HIF-1alpha, promotes iron absorption in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19352007/ DOI: 10.1172/jci38499
Complete structured claim and evidence
The IL-6–hepcidin axis mediated inflammation-associated hypoferremia in the studied systems.
Hepcidin → Serum iron concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/15124018.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f2ed307ef57c255917685bb7bfb1f02f3a6481c732cc2ee41ad1f338e2a2a830", "start_char": 0, "end_char": 578, "text_sha256": "f2ed307ef57c255917685bb7bfb1f02f3a6481c732cc2ee41ad1f338e2a2a830"}
experimental_model
Human liver-cell, mouse and human-volunteer inflammation experiments
exposure
IL-6 and inflammatory stimulation
limitations
IL-6 dependence applies to the tested inflammatory models, not every possible inflammatory iron pathway.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Humans and mice
plain_language
Low blood iron during inflammation is a distribution response, not by itself proof of low total-body stores.
primary_references
[iron-p15124018] IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. (2004). https://pubmed.ncbi.nlm.nih.gov/15124018/ DOI: 10.1172/jci20945
tissue_or_cell_type
Liver and circulation
trigger_kind
biomarker_context Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 888–899
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human liver-cell, mouse and human-volunteer inflammation experiments · source_derived_draft · unverified_draft
### iron-inflammatory-low-serum The IL-6–hepcidin axis mediated inflammation-associated hypoferremia in the studied systems. Condition category: biomarker_context nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low blood iron during inflammation is a distribution response, not by itself proof of low total-body stores. organism: Humans and mice tissue_or_cell_type: Liver and circulation experimental_model: Human liver-cell, mouse and human-volunteer inflammation experiments limitations: IL-6 dependence applies to the tested inflammatory models, not every possible inflammatory iron pathway. exposure: IL-6 and inflammatory stimulation evidence_span: {"source_cache": "artifacts/iron-research/15124018.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f2ed307ef57c255917685bb7bfb1f02f3a6481c732cc2ee41ad1f338e2a2a830", "start_char": 0, "end_char": 578, "text_sha256": "f2ed307ef57c255917685bb7bfb1f02f3a6481c732cc2ee41ad1f338e2a2a830"} [iron-p15124018] IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. (2004). https://pubmed.ncbi.nlm.nih.gov/15124018/ DOI: 10.1172/jci20945
Complete structured claim and evidence
Iron-deficiency anemia independently reduced thyroid peroxidase activity after accounting for food restriction in the rat experiment.
Iron → Thyroid peroxidase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/12097675.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "26b7a5ddb0985abdb2325c7ecd505c46f02604bd4d35f68ed0c9ad67113a148e", "start_char": 0, "end_char": 1527, "text_sha256": "26b7a5ddb0985abdb2325c7ecd505c46f02604bd4d35f68ed0c9ad67113a148e"}
experimental_model
Controlled iron-deficient diets with pair-fed controls
exposure
Four weeks of graded iron restriction; separate food-restriction controls
limitations
Food restriction also reduced TPO; the iron effect was separately estimated. No human serum threshold or automatic iodine-treatment failure rule.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
84 male weanling rats
plain_language
Iodine supply is only part of thyroid-hormone synthesis; its working enzyme also depends on iron-containing heme.
primary_references
[iron-p12097675] Iron deficiency anemia reduces thyroid peroxidase activity in rats. (2002). https://pubmed.ncbi.nlm.nih.gov/12097675/ DOI: 10.1093/jn/132.7.1951
tissue_or_cell_type
Thyroid and blood
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 901–912
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled iron-deficient diets with pair-fed controls · source_derived_draft · unverified_draft
### iron-iron-tpo-deficiency Iron-deficiency anemia independently reduced thyroid peroxidase activity after accounting for food restriction in the rat experiment. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iodine supply is only part of thyroid-hormone synthesis; its working enzyme also depends on iron-containing heme. organism: 84 male weanling rats tissue_or_cell_type: Thyroid and blood experimental_model: Controlled iron-deficient diets with pair-fed controls limitations: Food restriction also reduced TPO; the iron effect was separately estimated. No human serum threshold or automatic iodine-treatment failure rule. exposure: Four weeks of graded iron restriction; separate food-restriction controls evidence_span: {"source_cache": "artifacts/iron-research/12097675.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "26b7a5ddb0985abdb2325c7ecd505c46f02604bd4d35f68ed0c9ad67113a148e", "start_char": 0, "end_char": 1527, "text_sha256": "26b7a5ddb0985abdb2325c7ecd505c46f02604bd4d35f68ed0c9ad67113a148e"} [iron-p12097675] Iron deficiency anemia reduces thyroid peroxidase activity in rats. (2002). https://pubmed.ncbi.nlm.nih.gov/12097675/ DOI: 10.1093/jn/132.7.1951
Complete structured claim and evidence
Very-high-iron feeding caused low serum/tissue copper, reduced circulating ceruloplasmin activity, anemia and cardiac hypertrophy in the studied rats.
Iron → Anemia in copper-deficient rats source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/27537180.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59f2a83f1bffcacfed0df109f3690413aa2e6f08be6ad400817c5cbe2165e523", "start_char": 0, "end_char": 1840, "text_sha256": "59f2a83f1bffcacfed0df109f3690413aa2e6f08be6ad400817c5cbe2165e523"}
experimental_model
Five-week factorial iron/copper feeding
exposure
Approximately 8800, 80 or 11 ppm iron crossed with approximately 183, 8 or 0.9 ppm copper
limitations
Very high experimental iron exposure; not an estimate of human supplement risk at ordinary intake. Copper restoration did not normalize every iron measure.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Weanling male Sprague-Dawley rats
plain_language
Anemia developed despite abundant iron because another part of iron handling became deficient.
primary_references
[iron-p27537180] High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats. (2016). https://pubmed.ncbi.nlm.nih.gov/27537180/ DOI: 10.1371/journal.pone.0161033
tissue_or_cell_type
Systemic copper and iron status
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 914–925
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-week factorial iron/copper feeding · source_derived_draft · unverified_draft
### iron-high-iron-copper-deficiency Very-high-iron feeding caused low serum/tissue copper, reduced circulating ceruloplasmin activity, anemia and cardiac hypertrophy in the studied rats. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Anemia developed despite abundant iron because another part of iron handling became deficient. organism: Weanling male Sprague-Dawley rats tissue_or_cell_type: Systemic copper and iron status experimental_model: Five-week factorial iron/copper feeding limitations: Very high experimental iron exposure; not an estimate of human supplement risk at ordinary intake. Copper restoration did not normalize every iron measure. exposure: Approximately 8800, 80 or 11 ppm iron crossed with approximately 183, 8 or 0.9 ppm copper evidence_span: {"source_cache": "artifacts/iron-research/27537180.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59f2a83f1bffcacfed0df109f3690413aa2e6f08be6ad400817c5cbe2165e523", "start_char": 0, "end_char": 1840, "text_sha256": "59f2a83f1bffcacfed0df109f3690413aa2e6f08be6ad400817c5cbe2165e523"} [iron-p27537180] High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats. (2016). https://pubmed.ncbi.nlm.nih.gov/27537180/ DOI: 10.1371/journal.pone.0161033
Complete structured claim and evidence
Additional copper prevented the reported growth, cardiac and anemia disturbances under high-iron feeding, but increased hepatic nonheme iron loading.
Copper → Anemia in copper-deficient rats source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/27537180.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59f2a83f1bffcacfed0df109f3690413aa2e6f08be6ad400817c5cbe2165e523", "start_char": 0, "end_char": 1840, "text_sha256": "59f2a83f1bffcacfed0df109f3690413aa2e6f08be6ad400817c5cbe2165e523"}
experimental_model
Five-week factorial iron/copper feeding
exposure
Approximately 8800, 80 or 11 ppm iron crossed with approximately 183, 8 or 0.9 ppm copper
limitations
Very high experimental iron exposure; not an estimate of human supplement risk at ordinary intake. Copper restoration did not normalize every iron measure.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Weanling male Sprague-Dawley rats
plain_language
Correcting the copper-related problem did not mean the excess-iron problem had disappeared.
primary_references
[iron-p27537180] High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats. (2016). https://pubmed.ncbi.nlm.nih.gov/27537180/ DOI: 10.1371/journal.pone.0161033
tissue_or_cell_type
Systemic copper and iron status
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 927–938
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-week factorial iron/copper feeding · source_derived_draft · unverified_draft
### iron-copper-rescue-tradeoff Additional copper prevented the reported growth, cardiac and anemia disturbances under high-iron feeding, but increased hepatic nonheme iron loading. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Correcting the copper-related problem did not mean the excess-iron problem had disappeared. organism: Weanling male Sprague-Dawley rats tissue_or_cell_type: Systemic copper and iron status experimental_model: Five-week factorial iron/copper feeding limitations: Very high experimental iron exposure; not an estimate of human supplement risk at ordinary intake. Copper restoration did not normalize every iron measure. exposure: Approximately 8800, 80 or 11 ppm iron crossed with approximately 183, 8 or 0.9 ppm copper evidence_span: {"source_cache": "artifacts/iron-research/27537180.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59f2a83f1bffcacfed0df109f3690413aa2e6f08be6ad400817c5cbe2165e523", "start_char": 0, "end_char": 1840, "text_sha256": "59f2a83f1bffcacfed0df109f3690413aa2e6f08be6ad400817c5cbe2165e523"} [iron-p27537180] High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats. (2016). https://pubmed.ncbi.nlm.nih.gov/27537180/ DOI: 10.1371/journal.pone.0161033
Complete structured claim and evidence
Phosphate below 2.0 mg/dL occurred in 50.8% with ferric carboxymaltose versus 0.9% with ferumoxytol; low phosphate persisted at five weeks in 29.1% versus none.
Ferric carboxymaltose → Hypophosphatemia after intravenous iron source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/30518682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257", "start_char": 0, "end_char": 2371, "text_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257"}
experimental_model
Double-blind randomized comparison with physiological substudy
exposure
One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up
limitations
Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
1997 adults with iron-deficiency anemia; 185 in substudy
plain_language
The phosphate risk depended strongly on the iron formulation.
primary_references
[iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
tissue_or_cell_type
Blood and renal phosphate handling
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 940–951
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized comparison with physiological substudy · source_derived_draft · unverified_draft
### iron-fcm-phosphate-frequency Phosphate below 2.0 mg/dL occurred in 50.8% with ferric carboxymaltose versus 0.9% with ferumoxytol; low phosphate persisted at five weeks in 29.1% versus none. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The phosphate risk depended strongly on the iron formulation. organism: 1997 adults with iron-deficiency anemia; 185 in substudy tissue_or_cell_type: Blood and renal phosphate handling experimental_model: Double-blind randomized comparison with physiological substudy limitations: Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow. exposure: One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up evidence_span: {"source_cache": "artifacts/iron-research/30518682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257", "start_char": 0, "end_char": 2371, "text_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257"} [iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
Complete structured claim and evidence
The rise in active FGF23 was associated with increased renal phosphate wasting and hypophosphatemia.
Circulating biologically active intact FGF23 → Renal phosphate wasting source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/30518682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257", "start_char": 0, "end_char": 2371, "text_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257"}
experimental_model
Double-blind randomized comparison with physiological substudy
exposure
One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up
limitations
Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
1997 adults with iron-deficiency anemia; 185 in substudy
plain_language
More phosphate was being lost through the kidneys as the hormone rose.
primary_references
[iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
tissue_or_cell_type
Blood and renal phosphate handling
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 966–977
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized comparison with physiological substudy · source_derived_draft · unverified_draft
### iron-fgf23-phosphate-loss The rise in active FGF23 was associated with increased renal phosphate wasting and hypophosphatemia. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: More phosphate was being lost through the kidneys as the hormone rose. organism: 1997 adults with iron-deficiency anemia; 185 in substudy tissue_or_cell_type: Blood and renal phosphate handling experimental_model: Double-blind randomized comparison with physiological substudy limitations: Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow. exposure: One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up evidence_span: {"source_cache": "artifacts/iron-research/30518682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257", "start_char": 0, "end_char": 2371, "text_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257"} [iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
Complete structured claim and evidence
The FGF23 rise was associated with lower calcitriol and serum calcium and higher PTH concentrations.
Circulating biologically active intact FGF23 → Circulating calcitriol concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/30518682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257", "start_char": 0, "end_char": 2371, "text_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257"}
experimental_model
Double-blind randomized comparison with physiological substudy
exposure
One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up
limitations
Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
1997 adults with iron-deficiency anemia; 185 in substudy
plain_language
The phosphate disturbance connected to active vitamin D and calcium-regulating hormones.
primary_references
[iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
tissue_or_cell_type
Blood and renal phosphate handling
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 979–990
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized comparison with physiological substudy · source_derived_draft · unverified_draft
### iron-fgf23-vitamin-d-calcium The FGF23 rise was associated with lower calcitriol and serum calcium and higher PTH concentrations. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The phosphate disturbance connected to active vitamin D and calcium-regulating hormones. organism: 1997 adults with iron-deficiency anemia; 185 in substudy tissue_or_cell_type: Blood and renal phosphate handling experimental_model: Double-blind randomized comparison with physiological substudy limitations: Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow. exposure: One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up evidence_span: {"source_cache": "artifacts/iron-research/30518682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257", "start_char": 0, "end_char": 2371, "text_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257"} [iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
Complete structured claim and evidence
Hypophosphatemia occurred in 7.9% versus 75.0% in trial A and 8.1% versus 73.7% in trial B with derisomaltose versus carboxymaltose.
Ferric derisomaltose / iron isomaltoside → Hypophosphatemia after intravenous iron source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/32016310.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "883aac76c40012cb98ac88924e33b33f4985d356302929b8b26931c1869e2f0a", "start_char": 0, "end_char": 2731, "text_sha256": "883aac76c40012cb98ac88924e33b33f4985d356302929b8b26931c1869e2f0a"}
experimental_model
Two open-label randomized trials
exposure
Ferric derisomaltose 1000 mg once versus ferric carboxymaltose 750 mg twice; 35 days
limitations
Formulation and total regimen differed; no fracture endpoint or identical risk in all populations is inferred.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
245 adults, predominantly women, without reduced kidney function
plain_language
A second pair of trials also found that iron formulations differed in their phosphate effects.
primary_references
[iron-p32016310] Effects of Iron Isomaltoside vs Ferric Carboxymaltose on Hypophosphatemia in Iron-Deficiency Anemia: Two Randomized Clinical Trials. (2020). https://pubmed.ncbi.nlm.nih.gov/32016310/ DOI: 10.1001/jama.2019.22450
tissue_or_cell_type
Serum phosphate
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 992–1003
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two open-label randomized trials · source_derived_draft · unverified_draft
### iron-fdi-fcm-comparison Hypophosphatemia occurred in 7.9% versus 75.0% in trial A and 8.1% versus 73.7% in trial B with derisomaltose versus carboxymaltose. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second pair of trials also found that iron formulations differed in their phosphate effects. organism: 245 adults, predominantly women, without reduced kidney function tissue_or_cell_type: Serum phosphate experimental_model: Two open-label randomized trials limitations: Formulation and total regimen differed; no fracture endpoint or identical risk in all populations is inferred. exposure: Ferric derisomaltose 1000 mg once versus ferric carboxymaltose 750 mg twice; 35 days evidence_span: {"source_cache": "artifacts/iron-research/32016310.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "883aac76c40012cb98ac88924e33b33f4985d356302929b8b26931c1869e2f0a", "start_char": 0, "end_char": 2731, "text_sha256": "883aac76c40012cb98ac88924e33b33f4985d356302929b8b26931c1869e2f0a"} [iron-p32016310] Effects of Iron Isomaltoside vs Ferric Carboxymaltose on Hypophosphatemia in Iron-Deficiency Anemia: Two Randomized Clinical Trials. (2020). https://pubmed.ncbi.nlm.nih.gov/32016310/ DOI: 10.1001/jama.2019.22450
Complete structured claim and evidence
Iron absorption was significantly higher when tea was consumed one hour after the meal than when consumed simultaneously (P=0.046).
Nonheme dietary iron → Nonheme iron absorption source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/29046302.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a01f467e543b56e182ef6acfe15ca9d65474590ef9490bc698f864765588366", "start_char": 0, "end_char": 1971, "text_sha256": "3a01f467e543b56e182ef6acfe15ca9d65474590ef9490bc698f864765588366"}
experimental_model
Three-period stable-isotope meal experiment
exposure
Labeled porridge with water, simultaneous tea or tea one hour later
limitations
Acute fractional absorption endpoint; not a long-term anemia trial or proof that all tea preparations have equal effects.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
12 iron-replete nonanemic women
plain_language
The timing of a meal inhibitor changed how much iron was absorbed.
primary_references
[iron-p29046302] A 1-h time interval between a meal containing iron and consumption of tea attenuates the inhibitory effects on iron absorption: a controlled trial in a cohort of healthy UK women using a stable iron isotope. (2017). https://pubmed.ncbi.nlm.nih.gov/29046302/ DOI: 10.3945/ajcn.117.161364
tissue_or_cell_type
Intestinal nonheme iron absorption
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1005–1016
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three-period stable-isotope meal experiment · source_derived_draft · unverified_draft
### iron-tea-timing Iron absorption was significantly higher when tea was consumed one hour after the meal than when consumed simultaneously (P=0.046). Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The timing of a meal inhibitor changed how much iron was absorbed. organism: 12 iron-replete nonanemic women tissue_or_cell_type: Intestinal nonheme iron absorption experimental_model: Three-period stable-isotope meal experiment limitations: Acute fractional absorption endpoint; not a long-term anemia trial or proof that all tea preparations have equal effects. exposure: Labeled porridge with water, simultaneous tea or tea one hour later evidence_span: {"source_cache": "artifacts/iron-research/29046302.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a01f467e543b56e182ef6acfe15ca9d65474590ef9490bc698f864765588366", "start_char": 0, "end_char": 1971, "text_sha256": "3a01f467e543b56e182ef6acfe15ca9d65474590ef9490bc698f864765588366"} [iron-p29046302] A 1-h time interval between a meal containing iron and consumption of tea attenuates the inhibitory effects on iron absorption: a controlled trial in a cohort of healthy UK women using a stable iron isotope. (2017). https://pubmed.ncbi.nlm.nih.gov/29046302/ DOI: 10.3945/ajcn.117.161364
Complete structured claim and evidence
Germline TMPRSS6 mutations caused iron-deficiency anemia refractory to oral iron therapy in the studied families.
Human matriptase-2 / TMPRSS6 → Microcytic anemia refractory to oral iron in genetic iron-handling disorders source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/18408718.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "26d5ec56d21c4675127615cc14ef1b167eef0d8c5e2fe7d69a5b316f4e06011e", "start_char": 0, "end_char": 468, "text_sha256": "26d5ec56d21c4675127615cc14ef1b167eef0d8c5e2fe7d69a5b316f4e06011e"}
experimental_model
Family genetic investigation
exposure
Germline TMPRSS6 variants
limitations
Rare inherited disorder; not an explanation for every failure of oral iron.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Humans with refractory iron-deficiency anemia
plain_language
The problem can be the body’s control of iron availability, rather than simply too little iron supplied.
primary_references
[iron-p18408718] Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). (2008). https://pubmed.ncbi.nlm.nih.gov/18408718/ DOI: 10.1038/ng.130
tissue_or_cell_type
Systemic iron regulation
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1018–1029
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Family genetic investigation · source_derived_draft · unverified_draft
### iron-tmprss6-irida Germline TMPRSS6 mutations caused iron-deficiency anemia refractory to oral iron therapy in the studied families. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The problem can be the body’s control of iron availability, rather than simply too little iron supplied. organism: Humans with refractory iron-deficiency anemia tissue_or_cell_type: Systemic iron regulation experimental_model: Family genetic investigation limitations: Rare inherited disorder; not an explanation for every failure of oral iron. exposure: Germline TMPRSS6 variants evidence_span: {"source_cache": "artifacts/iron-research/18408718.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "26d5ec56d21c4675127615cc14ef1b167eef0d8c5e2fe7d69a5b316f4e06011e", "start_char": 0, "end_char": 468, "text_sha256": "26d5ec56d21c4675127615cc14ef1b167eef0d8c5e2fe7d69a5b316f4e06011e"} [iron-p18408718] Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). (2008). https://pubmed.ncbi.nlm.nih.gov/18408718/ DOI: 10.1038/ng.130
Complete structured claim and evidence
The patient had microcytic anemia from birth and progressive liver iron overload with compound-heterozygous DMT1 mutations.
Human divalent metal transporter 1 / SLC11A2 → Microcytic anemia refractory to oral iron in genetic iron-handling disorders source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/16439678.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ec63a88b5bebf3aecdfdea088979b051141b6ce89ceec92b66d219b99b6512c2", "start_char": 0, "end_char": 1003, "text_sha256": "ec63a88b5bebf3aecdfdea088979b051141b6ce89ceec92b66d219b99b6512c2"}
experimental_model
Human case with compound-heterozygous DMT1 variants
exposure
SLC11A2 V114 deletion and G212V variants
limitations
Rare genetic syndrome; ferritin is not a universal quantitative proxy for liver iron in this setting.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human patient, compared with two prior cases
plain_language
Having iron in the liver did not ensure that developing red cells could use it.
primary_references
[iron-p16439678] Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload. (2006). https://pubmed.ncbi.nlm.nih.gov/16439678/ DOI: 10.1182/blood-2005-10-4269
tissue_or_cell_type
Red-cell indices, liver and blood markers
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1031–1042
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human case with compound-heterozygous DMT1 variants · source_derived_draft · unverified_draft
### iron-human-dmt1-defect The patient had microcytic anemia from birth and progressive liver iron overload with compound-heterozygous DMT1 mutations. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Having iron in the liver did not ensure that developing red cells could use it. organism: Human patient, compared with two prior cases tissue_or_cell_type: Red-cell indices, liver and blood markers experimental_model: Human case with compound-heterozygous DMT1 variants limitations: Rare genetic syndrome; ferritin is not a universal quantitative proxy for liver iron in this setting. exposure: SLC11A2 V114 deletion and G212V variants evidence_span: {"source_cache": "artifacts/iron-research/16439678.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ec63a88b5bebf3aecdfdea088979b051141b6ce89ceec92b66d219b99b6512c2", "start_char": 0, "end_char": 1003, "text_sha256": "ec63a88b5bebf3aecdfdea088979b051141b6ce89ceec92b66d219b99b6512c2"} [iron-p16439678] Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload. (2006). https://pubmed.ncbi.nlm.nih.gov/16439678/ DOI: 10.1182/blood-2005-10-4269
Complete structured claim and evidence
The reported DMT1-deficiency syndrome included liver iron overload despite normal to moderately elevated serum ferritin.
Human divalent metal transporter 1 / SLC11A2 → Serum ferritin concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/16439678.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ec63a88b5bebf3aecdfdea088979b051141b6ce89ceec92b66d219b99b6512c2", "start_char": 0, "end_char": 1003, "text_sha256": "ec63a88b5bebf3aecdfdea088979b051141b6ce89ceec92b66d219b99b6512c2"}
experimental_model
Human case with compound-heterozygous DMT1 variants
exposure
SLC11A2 V114 deletion and G212V variants
limitations
Rare genetic syndrome; ferritin is not a universal quantitative proxy for liver iron in this setting.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human patient, compared with two prior cases
plain_language
A storage marker could understate tissue loading in this specific genetic disorder.
primary_references
[iron-p16439678] Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload. (2006). https://pubmed.ncbi.nlm.nih.gov/16439678/ DOI: 10.1182/blood-2005-10-4269
tissue_or_cell_type
Red-cell indices, liver and blood markers
trigger_kind
biomarker_context Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1044–1055
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human case with compound-heterozygous DMT1 variants · source_derived_draft · unverified_draft
### iron-human-dmt1-ferritin The reported DMT1-deficiency syndrome included liver iron overload despite normal to moderately elevated serum ferritin. Condition category: biomarker_context nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: A storage marker could understate tissue loading in this specific genetic disorder. organism: Human patient, compared with two prior cases tissue_or_cell_type: Red-cell indices, liver and blood markers experimental_model: Human case with compound-heterozygous DMT1 variants limitations: Rare genetic syndrome; ferritin is not a universal quantitative proxy for liver iron in this setting. exposure: SLC11A2 V114 deletion and G212V variants evidence_span: {"source_cache": "artifacts/iron-research/16439678.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ec63a88b5bebf3aecdfdea088979b051141b6ce89ceec92b66d219b99b6512c2", "start_char": 0, "end_char": 1003, "text_sha256": "ec63a88b5bebf3aecdfdea088979b051141b6ce89ceec92b66d219b99b6512c2"} [iron-p16439678] Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload. (2006). https://pubmed.ncbi.nlm.nih.gov/16439678/ DOI: 10.1182/blood-2005-10-4269
Complete structured claim and evidence
Cybrd1 deletion had little or no effect on mouse body iron stores even during iron deficiency, implying alternative reduction routes.
Mouse duodenal cytochrome b / Cybrd1 → Blood iron-status markers source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/15961514.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "82665d0951ddf0b58240697d40ec2390474e6799bbeba29f132e57f562e5782d", "start_char": 0, "end_char": 621, "text_sha256": "82665d0951ddf0b58240697d40ec2390474e6799bbeba29f132e57f562e5782d"}
experimental_model
Gene inactivation and iron-status measurements
exposure
Normal and iron-deficient conditions
limitations
A mouse compensation result; it does not negate Cybrd1 ferric-reductase activity or prove dispensability in humans.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Cybrd1-null mice
plain_language
A real enzyme function does not mean that losing that enzyme always removes every route to iron absorption.
primary_references
[iron-p15961514] Cybrd1 (duodenal cytochrome b) is not necessary for dietary iron absorption in mice. (2005). https://pubmed.ncbi.nlm.nih.gov/15961514/ DOI: 10.1182/blood-2005-02-0716
tissue_or_cell_type
Whole-body and tissue iron stores
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1057–1068
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene inactivation and iron-status measurements · source_derived_draft · unverified_draft
### iron-dcytb-compensation Cybrd1 deletion had little or no effect on mouse body iron stores even during iron deficiency, implying alternative reduction routes. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: A real enzyme function does not mean that losing that enzyme always removes every route to iron absorption. organism: Cybrd1-null mice tissue_or_cell_type: Whole-body and tissue iron stores experimental_model: Gene inactivation and iron-status measurements limitations: A mouse compensation result; it does not negate Cybrd1 ferric-reductase activity or prove dispensability in humans. exposure: Normal and iron-deficient conditions evidence_span: {"source_cache": "artifacts/iron-research/15961514.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "82665d0951ddf0b58240697d40ec2390474e6799bbeba29f132e57f562e5782d", "start_char": 0, "end_char": 621, "text_sha256": "82665d0951ddf0b58240697d40ec2390474e6799bbeba29f132e57f562e5782d"} [iron-p15961514] Cybrd1 (duodenal cytochrome b) is not necessary for dietary iron absorption in mice. (2005). https://pubmed.ncbi.nlm.nih.gov/15961514/ DOI: 10.1182/blood-2005-02-0716
Complete structured claim and evidence
Ferrochelatase protein abundance increased in patient-derived cells, while its catalytic activity was drastically reduced.
Human mitochondrial glutaredoxin 5 / GLRX5 → Ferrochelatase catalytic activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/30660387.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e", "start_char": 0, "end_char": 1625, "text_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e"}
experimental_model
Patient-derived cell biochemistry and variant structural analysis
exposure
Compound-heterozygous GLRX5 variants
limitations
One patient; reduced succinyl-CoA contribution to ALAS2 dysfunction was proposed, not definitively isolated.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human GLRX5-deficient patient
plain_language
More enzyme protein did not mean more working enzyme.
primary_references
[iron-p30660387] GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia. (2019). https://pubmed.ncbi.nlm.nih.gov/30660387/ DOI: 10.1016/j.ymgme.2018.12.012
tissue_or_cell_type
Lymphoblastoid and CD34-positive cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1070–1081
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient-derived cell biochemistry and variant structural analysis · source_derived_draft · unverified_draft
### iron-glrx5-fech Ferrochelatase protein abundance increased in patient-derived cells, while its catalytic activity was drastically reduced. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: More enzyme protein did not mean more working enzyme. organism: Human GLRX5-deficient patient tissue_or_cell_type: Lymphoblastoid and CD34-positive cells experimental_model: Patient-derived cell biochemistry and variant structural analysis limitations: One patient; reduced succinyl-CoA contribution to ALAS2 dysfunction was proposed, not definitively isolated. exposure: Compound-heterozygous GLRX5 variants evidence_span: {"source_cache": "artifacts/iron-research/30660387.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e", "start_char": 0, "end_char": 1625, "text_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e"} [iron-p30660387] GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia. (2019). https://pubmed.ncbi.nlm.nih.gov/30660387/ DOI: 10.1016/j.ymgme.2018.12.012
Complete structured claim and evidence
ALAS2 activity was altered in the GLRX5-deficient cells; a problem in succinyl-CoA supply was proposed as a contributor.
Human mitochondrial glutaredoxin 5 / GLRX5 → Human erythroid aminolevulinate synthase 2 / ALAS2 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/30660387.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e", "start_char": 0, "end_char": 1625, "text_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e"}
experimental_model
Patient-derived cell biochemistry and variant structural analysis
exposure
Compound-heterozygous GLRX5 variants
limitations
One patient; reduced succinyl-CoA contribution to ALAS2 dysfunction was proposed, not definitively isolated.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human GLRX5-deficient patient
plain_language
A mitochondrial assembly defect may also limit the starting materials used early in heme synthesis.
primary_references
[iron-p30660387] GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia. (2019). https://pubmed.ncbi.nlm.nih.gov/30660387/ DOI: 10.1016/j.ymgme.2018.12.012
tissue_or_cell_type
Lymphoblastoid and CD34-positive cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1083–1094
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient-derived cell biochemistry and variant structural analysis · source_derived_draft · unverified_draft
### iron-glrx5-alas2 ALAS2 activity was altered in the GLRX5-deficient cells; a problem in succinyl-CoA supply was proposed as a contributor. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: A mitochondrial assembly defect may also limit the starting materials used early in heme synthesis. organism: Human GLRX5-deficient patient tissue_or_cell_type: Lymphoblastoid and CD34-positive cells experimental_model: Patient-derived cell biochemistry and variant structural analysis limitations: One patient; reduced succinyl-CoA contribution to ALAS2 dysfunction was proposed, not definitively isolated. exposure: Compound-heterozygous GLRX5 variants evidence_span: {"source_cache": "artifacts/iron-research/30660387.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e", "start_char": 0, "end_char": 1625, "text_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e"} [iron-p30660387] GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia. (2019). https://pubmed.ncbi.nlm.nih.gov/30660387/ DOI: 10.1016/j.ymgme.2018.12.012
Complete structured claim and evidence
Patient-derived cells showed reduced glutathione and aconitase activity, damaged/depleted mitochondrial DNA, lower complex I/IV activities and lower ATP content.
Human mitochondrial glutaredoxin 5 / GLRX5 → ATP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/30660387.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e", "start_char": 0, "end_char": 1625, "text_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e"}
experimental_model
Patient-derived cell biochemistry and variant structural analysis
exposure
Compound-heterozygous GLRX5 variants
limitations
One patient; reduced succinyl-CoA contribution to ALAS2 dysfunction was proposed, not definitively isolated.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human GLRX5-deficient patient
plain_language
The defect extended beyond red-cell pigment to mitochondrial energy handling.
primary_references
[iron-p30660387] GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia. (2019). https://pubmed.ncbi.nlm.nih.gov/30660387/ DOI: 10.1016/j.ymgme.2018.12.012
tissue_or_cell_type
Lymphoblastoid and CD34-positive cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1096–1107
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient-derived cell biochemistry and variant structural analysis · source_derived_draft · unverified_draft
### iron-glrx5-energy Patient-derived cells showed reduced glutathione and aconitase activity, damaged/depleted mitochondrial DNA, lower complex I/IV activities and lower ATP content. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The defect extended beyond red-cell pigment to mitochondrial energy handling. organism: Human GLRX5-deficient patient tissue_or_cell_type: Lymphoblastoid and CD34-positive cells experimental_model: Patient-derived cell biochemistry and variant structural analysis limitations: One patient; reduced succinyl-CoA contribution to ALAS2 dysfunction was proposed, not definitively isolated. exposure: Compound-heterozygous GLRX5 variants evidence_span: {"source_cache": "artifacts/iron-research/30660387.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e", "start_char": 0, "end_char": 1625, "text_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e"} [iron-p30660387] GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia. (2019). https://pubmed.ncbi.nlm.nih.gov/30660387/ DOI: 10.1016/j.ymgme.2018.12.012
Complete structured claim and evidence
When intracellular heme declined, HRI inhibited translation initiation and restrained both alpha- and beta-globin synthesis in erythroid precursors.
Mouse heme-regulated eIF2 alpha kinase HRI / Eif2ak1 → Globin protein synthesis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/11726526.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6182d43925454a0208a74bed0b7da46736b9ff456509b215aa87e3051fe92eb3", "start_char": 0, "end_char": 1056, "text_sha256": "6182d43925454a0208a74bed0b7da46736b9ff456509b215aa87e3051fe92eb3"}
experimental_model
Targeted gene disruption with iron-deficient feeding
exposure
Hri deletion crossed with iron deficiency
limitations
Combined gene-loss and nutritional stress; the unusual knockout anemia pattern is not the standard description of ordinary iron deficiency.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mice
plain_language
Cells normally slow globin production when there is not enough heme to assemble hemoglobin.
primary_references
[iron-p11726526] Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency. (2001). https://pubmed.ncbi.nlm.nih.gov/11726526/ DOI: 10.1093/emboj/20.23.6909
tissue_or_cell_type
Erythroid precursors and red cells
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1109–1120
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted gene disruption with iron-deficient feeding · source_derived_draft · unverified_draft
### iron-hri-translation When intracellular heme declined, HRI inhibited translation initiation and restrained both alpha- and beta-globin synthesis in erythroid precursors. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cells normally slow globin production when there is not enough heme to assemble hemoglobin. organism: Mice tissue_or_cell_type: Erythroid precursors and red cells experimental_model: Targeted gene disruption with iron-deficient feeding limitations: Combined gene-loss and nutritional stress; the unusual knockout anemia pattern is not the standard description of ordinary iron deficiency. exposure: Hri deletion crossed with iron deficiency evidence_span: {"source_cache": "artifacts/iron-research/11726526.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6182d43925454a0208a74bed0b7da46736b9ff456509b215aa87e3051fe92eb3", "start_char": 0, "end_char": 1056, "text_sha256": "6182d43925454a0208a74bed0b7da46736b9ff456509b215aa87e3051fe92eb3"} [iron-p11726526] Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency. (2001). https://pubmed.ncbi.nlm.nih.gov/11726526/ DOI: 10.1093/emboj/20.23.6909
Complete structured claim and evidence
Iron-deficient Hri-null mice accumulated globin aggregates lacking heme within red cells and their precursors.
Mouse heme-regulated eIF2 alpha kinase HRI / Eif2ak1 → Aggregation of globin lacking heme source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/11726526.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6182d43925454a0208a74bed0b7da46736b9ff456509b215aa87e3051fe92eb3", "start_char": 0, "end_char": 1056, "text_sha256": "6182d43925454a0208a74bed0b7da46736b9ff456509b215aa87e3051fe92eb3"}
experimental_model
Targeted gene disruption with iron-deficient feeding
exposure
Hri deletion crossed with iron deficiency
limitations
Combined gene-loss and nutritional stress; the unusual knockout anemia pattern is not the standard description of ordinary iron deficiency.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mice
plain_language
Without the protective brake, cells kept making protein they could not safely assemble.
primary_references
[iron-p11726526] Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency. (2001). https://pubmed.ncbi.nlm.nih.gov/11726526/ DOI: 10.1093/emboj/20.23.6909
tissue_or_cell_type
Erythroid precursors and red cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1122–1133
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted gene disruption with iron-deficient feeding · source_derived_draft · unverified_draft
### iron-hri-globin-aggregation Iron-deficient Hri-null mice accumulated globin aggregates lacking heme within red cells and their precursors. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Without the protective brake, cells kept making protein they could not safely assemble. organism: Mice tissue_or_cell_type: Erythroid precursors and red cells experimental_model: Targeted gene disruption with iron-deficient feeding limitations: Combined gene-loss and nutritional stress; the unusual knockout anemia pattern is not the standard description of ordinary iron deficiency. exposure: Hri deletion crossed with iron deficiency evidence_span: {"source_cache": "artifacts/iron-research/11726526.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6182d43925454a0208a74bed0b7da46736b9ff456509b215aa87e3051fe92eb3", "start_char": 0, "end_char": 1056, "text_sha256": "6182d43925454a0208a74bed0b7da46736b9ff456509b215aa87e3051fe92eb3"} [iron-p11726526] Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency. (2001). https://pubmed.ncbi.nlm.nih.gov/11726526/ DOI: 10.1093/emboj/20.23.6909
Complete structured claim and evidence
Hri-null mice under iron deficiency had accelerated erythroid apoptosis and reduced red-cell counts.
Mouse heme-regulated eIF2 alpha kinase HRI / Eif2ak1 → Survival of erythroid precursor cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/11726526.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6182d43925454a0208a74bed0b7da46736b9ff456509b215aa87e3051fe92eb3", "start_char": 0, "end_char": 1056, "text_sha256": "6182d43925454a0208a74bed0b7da46736b9ff456509b215aa87e3051fe92eb3"}
experimental_model
Targeted gene disruption with iron-deficient feeding
exposure
Hri deletion crossed with iron deficiency
limitations
Combined gene-loss and nutritional stress; the unusual knockout anemia pattern is not the standard description of ordinary iron deficiency.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Mice
plain_language
The failed adaptation damaged the cells meant to carry oxygen.
primary_references
[iron-p11726526] Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency. (2001). https://pubmed.ncbi.nlm.nih.gov/11726526/ DOI: 10.1093/emboj/20.23.6909
tissue_or_cell_type
Erythroid precursors and red cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1135–1146
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted gene disruption with iron-deficient feeding · source_derived_draft · unverified_draft
### iron-hri-survival Hri-null mice under iron deficiency had accelerated erythroid apoptosis and reduced red-cell counts. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The failed adaptation damaged the cells meant to carry oxygen. organism: Mice tissue_or_cell_type: Erythroid precursors and red cells experimental_model: Targeted gene disruption with iron-deficient feeding limitations: Combined gene-loss and nutritional stress; the unusual knockout anemia pattern is not the standard description of ordinary iron deficiency. exposure: Hri deletion crossed with iron deficiency evidence_span: {"source_cache": "artifacts/iron-research/11726526.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6182d43925454a0208a74bed0b7da46736b9ff456509b215aa87e3051fe92eb3", "start_char": 0, "end_char": 1056, "text_sha256": "6182d43925454a0208a74bed0b7da46736b9ff456509b215aa87e3051fe92eb3"} [iron-p11726526] Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency. (2001). https://pubmed.ncbi.nlm.nih.gov/11726526/ DOI: 10.1093/emboj/20.23.6909
Complete structured claim and evidence
The NFS1–ISD11–ACP core associates with ISCU, frataxin and ferredoxin to support Fe-S cluster biosynthesis.
Human cysteine desulfurase / NFS1 → Iron-sulfur cluster biosynthesis and assembly source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/28634302.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "82faf07d78311d063c1d990ebb922062650054be372fb324fa67020790c9fa04", "start_char": 0, "end_char": 1850, "text_sha256": "82faf07d78311d063c1d990ebb922062650054be372fb324fa67020790c9fa04"}
experimental_model
Crystallography, electron microscopy, kinetics and cell studies
exposure
SDA-complex structural analysis
limitations
Hybrid structural system: bacterial ACP must not be silently labeled human NDUFAB1. Direct dietary B6/B5 effects were not tested.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human NFS1/ISD11 with bacterial ACP in the recombinant structural complex
plain_language
Iron needs an assembly system and a sulfur supply before it becomes a working iron-sulfur cofactor.
primary_references
[iron-p28634302] Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions. (2017). https://pubmed.ncbi.nlm.nih.gov/28634302/ DOI: 10.1073/pnas.1702849114
tissue_or_cell_type
Mitochondrial Fe-S assembly machinery
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1161–1172
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystallography, electron microscopy, kinetics and cell studies · source_derived_draft · unverified_draft
### iron-sda-assembly The NFS1–ISD11–ACP core associates with ISCU, frataxin and ferredoxin to support Fe-S cluster biosynthesis. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron needs an assembly system and a sulfur supply before it becomes a working iron-sulfur cofactor. organism: Human NFS1/ISD11 with bacterial ACP in the recombinant structural complex tissue_or_cell_type: Mitochondrial Fe-S assembly machinery experimental_model: Crystallography, electron microscopy, kinetics and cell studies limitations: Hybrid structural system: bacterial ACP must not be silently labeled human NDUFAB1. Direct dietary B6/B5 effects were not tested. exposure: SDA-complex structural analysis evidence_span: {"source_cache": "artifacts/iron-research/28634302.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "82faf07d78311d063c1d990ebb922062650054be372fb324fa67020790c9fa04", "start_char": 0, "end_char": 1850, "text_sha256": "82faf07d78311d063c1d990ebb922062650054be372fb324fa67020790c9fa04"} [iron-p28634302] Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions. (2017). https://pubmed.ncbi.nlm.nih.gov/28634302/ DOI: 10.1073/pnas.1702849114
Complete structured claim and evidence
Human RRM2 radical-center tyrosine mutations abolished the detectable stable radical and ribonucleotide-reductase activity in the tested assays.
Human ribonucleotide reductase small subunit RRM2 → Deoxyribonucleotide synthesis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/16373698.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc", "start_char": 0, "end_char": 1165, "text_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc"}
experimental_model
Mutagenesis, EPR and catalytic assays
exposure
Conserved tyrosine mutations around the diiron center
limitations
Purified enzyme mechanisms; no recommendation to increase dietary iron for DNA synthesis.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human RRM2 and RRM2B proteins
plain_language
DNA building-block synthesis needs a functioning iron/radical enzyme system.
primary_references
[iron-p16373698] A dityrosyl-diiron radical cofactor center is essential for human ribonucleotide reductases. (2005). https://pubmed.ncbi.nlm.nih.gov/16373698/ DOI: 10.1158/1535-7163.mct-05-0273
tissue_or_cell_type
Ribonucleotide reductase small subunits
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1174–1185
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mutagenesis, EPR and catalytic assays · source_derived_draft · unverified_draft
### iron-rrm2-iron-radical Human RRM2 radical-center tyrosine mutations abolished the detectable stable radical and ribonucleotide-reductase activity in the tested assays. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: DNA building-block synthesis needs a functioning iron/radical enzyme system. organism: Human RRM2 and RRM2B proteins tissue_or_cell_type: Ribonucleotide reductase small subunits experimental_model: Mutagenesis, EPR and catalytic assays limitations: Purified enzyme mechanisms; no recommendation to increase dietary iron for DNA synthesis. exposure: Conserved tyrosine mutations around the diiron center evidence_span: {"source_cache": "artifacts/iron-research/16373698.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc", "start_char": 0, "end_char": 1165, "text_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc"} [iron-p16373698] A dityrosyl-diiron radical cofactor center is essential for human ribonucleotide reductases. (2005). https://pubmed.ncbi.nlm.nih.gov/16373698/ DOI: 10.1158/1535-7163.mct-05-0273
Complete structured claim and evidence
The corresponding conserved-tyrosine perturbation also disabled the radical and catalytic activity of the human p53R2/RRM2B system.
Human p53-inducible ribonucleotide reductase small subunit / RRM2B → Deoxyribonucleotide synthesis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/16373698.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc", "start_char": 0, "end_char": 1165, "text_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc"}
experimental_model
Mutagenesis, EPR and catalytic assays
exposure
Conserved tyrosine mutations around the diiron center
limitations
Purified enzyme mechanisms; no recommendation to increase dietary iron for DNA synthesis.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human RRM2 and RRM2B proteins
plain_language
The related small subunit is recorded separately so its role is not lost inside a generic enzyme label.
primary_references
[iron-p16373698] A dityrosyl-diiron radical cofactor center is essential for human ribonucleotide reductases. (2005). https://pubmed.ncbi.nlm.nih.gov/16373698/ DOI: 10.1158/1535-7163.mct-05-0273
tissue_or_cell_type
Ribonucleotide reductase small subunits
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1187–1198
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mutagenesis, EPR and catalytic assays · source_derived_draft · unverified_draft
### iron-rrm2b-iron-radical The corresponding conserved-tyrosine perturbation also disabled the radical and catalytic activity of the human p53R2/RRM2B system. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The related small subunit is recorded separately so its role is not lost inside a generic enzyme label. organism: Human RRM2 and RRM2B proteins tissue_or_cell_type: Ribonucleotide reductase small subunits experimental_model: Mutagenesis, EPR and catalytic assays limitations: Purified enzyme mechanisms; no recommendation to increase dietary iron for DNA synthesis. exposure: Conserved tyrosine mutations around the diiron center evidence_span: {"source_cache": "artifacts/iron-research/16373698.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc", "start_char": 0, "end_char": 1165, "text_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc"} [iron-p16373698] A dityrosyl-diiron radical cofactor center is essential for human ribonucleotide reductases. (2005). https://pubmed.ncbi.nlm.nih.gov/16373698/ DOI: 10.1158/1535-7163.mct-05-0273
Complete structured claim and evidence
Intracellular iron chelation removed the ribonucleotide-reductase tyrosyl radical, with depletion and regeneration kinetics depending on the chelator.
Cellular labile iron pool → Ribonucleotide reductase tyrosyl radical cofactor source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/8702762.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ceb70db961d5ae6f975c9edf1df28c495811a38189831240b8e3e61530b3a7f0", "start_char": 0, "end_char": 1525, "text_sha256": "ceb70db961d5ae6f975c9edf1df28c495811a38189831240b8e3e61530b3a7f0"}
experimental_model
Intracellular chelation with simultaneous EPR measurements
exposure
Hydroxypyridinone versus desferrioxamine chelation and washout
limitations
Pharmacological cell experiment; radical loss is not a direct clinical measure of nutritional iron deficiency.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human leukemia K562 cells
plain_language
Iron locked away by a chelator was not equally available to maintain the DNA-synthesis enzyme.
primary_references
[iron-p8702762] The relationship of intracellular iron chelation to the inhibition and regeneration of human ribonucleotide reductase. (1996). https://pubmed.ncbi.nlm.nih.gov/8702762/ DOI: 10.1074/jbc.271.34.20291
tissue_or_cell_type
Intracellular iron pool and ribonucleotide reductase
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1200–1211
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intracellular chelation with simultaneous EPR measurements · source_derived_draft · unverified_draft
### iron-chelation-rr Intracellular iron chelation removed the ribonucleotide-reductase tyrosyl radical, with depletion and regeneration kinetics depending on the chelator. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron locked away by a chelator was not equally available to maintain the DNA-synthesis enzyme. organism: Human leukemia K562 cells tissue_or_cell_type: Intracellular iron pool and ribonucleotide reductase experimental_model: Intracellular chelation with simultaneous EPR measurements limitations: Pharmacological cell experiment; radical loss is not a direct clinical measure of nutritional iron deficiency. exposure: Hydroxypyridinone versus desferrioxamine chelation and washout evidence_span: {"source_cache": "artifacts/iron-research/8702762.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ceb70db961d5ae6f975c9edf1df28c495811a38189831240b8e3e61530b3a7f0", "start_char": 0, "end_char": 1525, "text_sha256": "ceb70db961d5ae6f975c9edf1df28c495811a38189831240b8e3e61530b3a7f0"} [iron-p8702762] The relationship of intracellular iron chelation to the inhibition and regeneration of human ribonucleotide reductase. (1996). https://pubmed.ncbi.nlm.nih.gov/8702762/ DOI: 10.1074/jbc.271.34.20291
Complete structured claim and evidence
A major HFE missense alteration was homozygous in 83% of 178 hereditary-hemochromatosis patients in the discovery cohort.
Human homeostatic iron regulator / HFE → Systemic tissue iron overload source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/8696333.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "812dfc62980bb4a17920e9eb490a2d1abc529b468c0531ffd59011713a60a15a", "start_char": 0, "end_char": 921, "text_sha256": "812dfc62980bb4a17920e9eb490a2d1abc529b468c0531ffd59011713a60a15a"}
experimental_model
Linkage disequilibrium and human genetic association
exposure
HFE discovery and missense variants
limitations
Historical selected population; 83% is not penetrance or a current general-population risk estimate.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
178 hereditary-hemochromatosis patients in the reported cohort
plain_language
The body’s iron-control machinery can be defective even when dietary supply is ordinary.
primary_references
[iron-p8696333] A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. (1996). https://pubmed.ncbi.nlm.nih.gov/8696333/ DOI: 10.1038/ng0896-399
tissue_or_cell_type
Genetic iron-overload phenotype
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1213–1224
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Linkage disequilibrium and human genetic association · source_derived_draft · unverified_draft
### iron-hfe-association A major HFE missense alteration was homozygous in 83% of 178 hereditary-hemochromatosis patients in the discovery cohort. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The body’s iron-control machinery can be defective even when dietary supply is ordinary. organism: 178 hereditary-hemochromatosis patients in the reported cohort tissue_or_cell_type: Genetic iron-overload phenotype experimental_model: Linkage disequilibrium and human genetic association limitations: Historical selected population; 83% is not penetrance or a current general-population risk estimate. exposure: HFE discovery and missense variants evidence_span: {"source_cache": "artifacts/iron-research/8696333.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "812dfc62980bb4a17920e9eb490a2d1abc529b468c0531ffd59011713a60a15a", "start_char": 0, "end_char": 921, "text_sha256": "812dfc62980bb4a17920e9eb490a2d1abc529b468c0531ffd59011713a60a15a"} [iron-p8696333] A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. (1996). https://pubmed.ncbi.nlm.nih.gov/8696333/ DOI: 10.1038/ng0896-399
Complete structured claim and evidence
Erastin-induced ferroptosis depended on intracellular iron and was distinct from apoptosis, necrosis and autophagy in the study.
Cellular labile iron pool → Ferroptosis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/22632970.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0137d17ae5942c8904ece05ab6513f4fad588149ed0d7167e49f01a63b36cb0", "start_char": 0, "end_char": 1089, "text_sha256": "c0137d17ae5942c8904ece05ab6513f4fad588149ed0d7167e49f01a63b36cb0"}
experimental_model
Chemical and genetic characterization of nonapoptotic cell death
exposure
Erastin and ferrostatin-1 experiments
limitations
Experimental ferroptosis; dietary iron is not equated with a cancer-cell-death drug exposure.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Cancer-cell systems and rat brain slices
plain_language
Usable iron is essential, but under particular conditions it also enables oxidative cell death.
primary_references
[iron-p22632970] Ferroptosis: an iron-dependent form of nonapoptotic cell death. (2012). https://pubmed.ncbi.nlm.nih.gov/22632970/ DOI: 10.1016/j.cell.2012.03.042
tissue_or_cell_type
Cellular iron, cystine transport and oxidative injury
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1226–1237
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemical and genetic characterization of nonapoptotic cell death · source_derived_draft · unverified_draft
### iron-iron-ferroptosis Erastin-induced ferroptosis depended on intracellular iron and was distinct from apoptosis, necrosis and autophagy in the study. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Usable iron is essential, but under particular conditions it also enables oxidative cell death. organism: Cancer-cell systems and rat brain slices tissue_or_cell_type: Cellular iron, cystine transport and oxidative injury experimental_model: Chemical and genetic characterization of nonapoptotic cell death limitations: Experimental ferroptosis; dietary iron is not equated with a cancer-cell-death drug exposure. exposure: Erastin and ferrostatin-1 experiments evidence_span: {"source_cache": "artifacts/iron-research/22632970.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0137d17ae5942c8904ece05ab6513f4fad588149ed0d7167e49f01a63b36cb0", "start_char": 0, "end_char": 1089, "text_sha256": "c0137d17ae5942c8904ece05ab6513f4fad588149ed0d7167e49f01a63b36cb0"} [iron-p22632970] Ferroptosis: an iron-dependent form of nonapoptotic cell death. (2012). https://pubmed.ncbi.nlm.nih.gov/22632970/ DOI: 10.1016/j.cell.2012.03.042
Complete structured claim and evidence
Erastin inhibited cystine uptake through system xc-minus, weakening antioxidant defenses before iron-dependent oxidative death.
Erastin → cystine uptake source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/22632970.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0137d17ae5942c8904ece05ab6513f4fad588149ed0d7167e49f01a63b36cb0", "start_char": 0, "end_char": 1089, "text_sha256": "c0137d17ae5942c8904ece05ab6513f4fad588149ed0d7167e49f01a63b36cb0"}
experimental_model
Chemical and genetic characterization of nonapoptotic cell death
exposure
Erastin and ferrostatin-1 experiments
limitations
Experimental ferroptosis; dietary iron is not equated with a cancer-cell-death drug exposure.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Cancer-cell systems and rat brain slices
plain_language
The death pathway connected iron with the supply of material needed for glutathione.
primary_references
[iron-p22632970] Ferroptosis: an iron-dependent form of nonapoptotic cell death. (2012). https://pubmed.ncbi.nlm.nih.gov/22632970/ DOI: 10.1016/j.cell.2012.03.042
tissue_or_cell_type
Cellular iron, cystine transport and oxidative injury
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1239–1250
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemical and genetic characterization of nonapoptotic cell death · source_derived_draft · unverified_draft
### iron-cystine-ferroptosis Erastin inhibited cystine uptake through system xc-minus, weakening antioxidant defenses before iron-dependent oxidative death. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The death pathway connected iron with the supply of material needed for glutathione. organism: Cancer-cell systems and rat brain slices tissue_or_cell_type: Cellular iron, cystine transport and oxidative injury experimental_model: Chemical and genetic characterization of nonapoptotic cell death limitations: Experimental ferroptosis; dietary iron is not equated with a cancer-cell-death drug exposure. exposure: Erastin and ferrostatin-1 experiments evidence_span: {"source_cache": "artifacts/iron-research/22632970.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0137d17ae5942c8904ece05ab6513f4fad588149ed0d7167e49f01a63b36cb0", "start_char": 0, "end_char": 1089, "text_sha256": "c0137d17ae5942c8904ece05ab6513f4fad588149ed0d7167e49f01a63b36cb0"} [iron-p22632970] Ferroptosis: an iron-dependent form of nonapoptotic cell death. (2012). https://pubmed.ncbi.nlm.nih.gov/22632970/ DOI: 10.1016/j.cell.2012.03.042
Complete structured claim and evidence
Glutathione depletion in response to one class of ferroptosis inducers inactivated glutathione peroxidases, while another class directly inhibited GPX4.
GSH → GPX4 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/24439385.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703", "start_char": 0, "end_char": 957, "text_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703"}
experimental_model
Metabolomics, chemoproteomics, perturbation and cancer-cell sensitivity profiling
exposure
Two classes of ferroptosis-inducing compounds
limitations
Preclinical drug-response mechanism; selenium or vitamin E supplementation is not established as a universal treatment.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human cancer-cell lines and mouse xenografts
plain_language
Losing the antioxidant substrate and directly blocking its enzyme are different routes into the same vulnerability.
primary_references
[iron-p24439385] Regulation of ferroptotic cancer cell death by GPX4. (2014). https://pubmed.ncbi.nlm.nih.gov/24439385/ DOI: 10.1016/j.cell.2013.12.010
tissue_or_cell_type
Glutathione/GPX4 antioxidant system
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1252–1263
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolomics, chemoproteomics, perturbation and cancer-cell sensitivity profiling · source_derived_draft · unverified_draft
### iron-gsh-gpx-loss Glutathione depletion in response to one class of ferroptosis inducers inactivated glutathione peroxidases, while another class directly inhibited GPX4. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Losing the antioxidant substrate and directly blocking its enzyme are different routes into the same vulnerability. organism: Human cancer-cell lines and mouse xenografts tissue_or_cell_type: Glutathione/GPX4 antioxidant system experimental_model: Metabolomics, chemoproteomics, perturbation and cancer-cell sensitivity profiling limitations: Preclinical drug-response mechanism; selenium or vitamin E supplementation is not established as a universal treatment. exposure: Two classes of ferroptosis-inducing compounds evidence_span: {"source_cache": "artifacts/iron-research/24439385.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703", "start_char": 0, "end_char": 957, "text_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703"} [iron-p24439385] Regulation of ferroptotic cancer cell death by GPX4. (2014). https://pubmed.ncbi.nlm.nih.gov/24439385/ DOI: 10.1016/j.cell.2013.12.010
Complete structured claim and evidence
GPX4 overexpression or knockdown altered lethality of all 12 tested ferroptosis inducers, but not 11 compounds with other lethal mechanisms.
GPX4 → Ferroptosis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/24439385.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703", "start_char": 0, "end_char": 957, "text_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703"}
experimental_model
Metabolomics, chemoproteomics, perturbation and cancer-cell sensitivity profiling
exposure
Two classes of ferroptosis-inducing compounds
limitations
Preclinical drug-response mechanism; selenium or vitamin E supplementation is not established as a universal treatment.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human cancer-cell lines and mouse xenografts
plain_language
The protective enzyme specifically controlled this iron-linked death pathway in the tested cells.
primary_references
[iron-p24439385] Regulation of ferroptotic cancer cell death by GPX4. (2014). https://pubmed.ncbi.nlm.nih.gov/24439385/ DOI: 10.1016/j.cell.2013.12.010
tissue_or_cell_type
Glutathione/GPX4 antioxidant system
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1265–1276
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolomics, chemoproteomics, perturbation and cancer-cell sensitivity profiling · source_derived_draft · unverified_draft
### iron-gpx4-ferroptosis GPX4 overexpression or knockdown altered lethality of all 12 tested ferroptosis inducers, but not 11 compounds with other lethal mechanisms. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The protective enzyme specifically controlled this iron-linked death pathway in the tested cells. organism: Human cancer-cell lines and mouse xenografts tissue_or_cell_type: Glutathione/GPX4 antioxidant system experimental_model: Metabolomics, chemoproteomics, perturbation and cancer-cell sensitivity profiling limitations: Preclinical drug-response mechanism; selenium or vitamin E supplementation is not established as a universal treatment. exposure: Two classes of ferroptosis-inducing compounds evidence_span: {"source_cache": "artifacts/iron-research/24439385.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703", "start_char": 0, "end_char": 957, "text_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703"} [iron-p24439385] Regulation of ferroptotic cancer cell death by GPX4. (2014). https://pubmed.ncbi.nlm.nih.gov/24439385/ DOI: 10.1016/j.cell.2013.12.010
Complete structured claim and evidence
Doses of at least 60 mg raised hepcidin at 24 hours and reduced fractional absorption of subsequent iron by 35–45%.
Ferrous sulfate → Circulating hepcidin concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/26289639.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "67eb8d47c0df5398c03a2a73fdd7698efc0467e85db72cfdcc829fab72b90096", "start_char": 0, "end_char": 1708, "text_sha256": "67eb8d47c0df5398c03a2a73fdd7698efc0467e85db72cfdcc829fab72b90096"}
experimental_model
Stable-isotope dose studies
exposure
40–240 mg oral labeled ferrous sulfate; successive or twice-daily doses
limitations
Short-term fractional absorption is not equivalent to long-term hemoglobin recovery; dose values describe the experiment.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
54 nonanemic iron-depleted young women
plain_language
An iron dose can temporarily make the next dose harder to absorb.
primary_references
[iron-p26289639] Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. (2015). https://pubmed.ncbi.nlm.nih.gov/26289639/ DOI: 10.1182/blood-2015-05-642223
tissue_or_cell_type
Iron absorption and circulating hepcidin
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1278–1289
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope dose studies · source_derived_draft · unverified_draft
### iron-oral-iron-hepcidin Doses of at least 60 mg raised hepcidin at 24 hours and reduced fractional absorption of subsequent iron by 35–45%. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: An iron dose can temporarily make the next dose harder to absorb. organism: 54 nonanemic iron-depleted young women tissue_or_cell_type: Iron absorption and circulating hepcidin experimental_model: Stable-isotope dose studies limitations: Short-term fractional absorption is not equivalent to long-term hemoglobin recovery; dose values describe the experiment. exposure: 40–240 mg oral labeled ferrous sulfate; successive or twice-daily doses evidence_span: {"source_cache": "artifacts/iron-research/26289639.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "67eb8d47c0df5398c03a2a73fdd7698efc0467e85db72cfdcc829fab72b90096", "start_char": 0, "end_char": 1708, "text_sha256": "67eb8d47c0df5398c03a2a73fdd7698efc0467e85db72cfdcc829fab72b90096"} [iron-p26289639] Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. (2015). https://pubmed.ncbi.nlm.nih.gov/26289639/ DOI: 10.1182/blood-2015-05-642223
Complete structured claim and evidence
Increasing the dose from 40 to 240 mg reduced fractional absorption but increased the absolute amount absorbed from 6.7 to 18.1 mg.
Ferrous sulfate → Nonheme iron absorption source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/26289639.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "67eb8d47c0df5398c03a2a73fdd7698efc0467e85db72cfdcc829fab72b90096", "start_char": 0, "end_char": 1708, "text_sha256": "67eb8d47c0df5398c03a2a73fdd7698efc0467e85db72cfdcc829fab72b90096"}
experimental_model
Stable-isotope dose studies
exposure
40–240 mg oral labeled ferrous sulfate; successive or twice-daily doses
limitations
Short-term fractional absorption is not equivalent to long-term hemoglobin recovery; dose values describe the experiment.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
54 nonanemic iron-depleted young women
plain_language
A smaller absorbed percentage can still represent more milligrams; the two measurements should not be confused.
primary_references
[iron-p26289639] Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. (2015). https://pubmed.ncbi.nlm.nih.gov/26289639/ DOI: 10.1182/blood-2015-05-642223
tissue_or_cell_type
Iron absorption and circulating hepcidin
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1291–1302
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope dose studies · source_derived_draft · unverified_draft
### iron-fraction-versus-amount Increasing the dose from 40 to 240 mg reduced fractional absorption but increased the absolute amount absorbed from 6.7 to 18.1 mg. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: A smaller absorbed percentage can still represent more milligrams; the two measurements should not be confused. organism: 54 nonanemic iron-depleted young women tissue_or_cell_type: Iron absorption and circulating hepcidin experimental_model: Stable-isotope dose studies limitations: Short-term fractional absorption is not equivalent to long-term hemoglobin recovery; dose values describe the experiment. exposure: 40–240 mg oral labeled ferrous sulfate; successive or twice-daily doses evidence_span: {"source_cache": "artifacts/iron-research/26289639.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "67eb8d47c0df5398c03a2a73fdd7698efc0467e85db72cfdcc829fab72b90096", "start_char": 0, "end_char": 1708, "text_sha256": "67eb8d47c0df5398c03a2a73fdd7698efc0467e85db72cfdcc829fab72b90096"} [iron-p26289639] Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. (2015). https://pubmed.ncbi.nlm.nih.gov/26289639/ DOI: 10.1182/blood-2015-05-642223
Complete structured claim and evidence
Fractional iron absorption on the initial and alternate-day doses was 40–50% higher than on the consecutive-day dose.
Ferrous sulfate → Nonheme iron absorption source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/31413088.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8b12cbd03fa44886ae6bf6bd4d58db7bbbf21dad0461eef9b63d3c7da25c542c", "start_char": 0, "end_char": 2483, "text_sha256": "8b12cbd03fa44886ae6bf6bd4d58db7bbbf21dad0461eef9b63d3c7da25c542c"}
experimental_model
Stable-isotope crossover absorption study
exposure
100 or 200 mg ferrous sulfate on consecutive and alternate days
limitations
Absorption trial, not a universal dosing directive; the indexed abstract contains implausible units for baseline hemoglobin/ferritin, which are not reproduced as clinical thresholds.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
19 women with iron-deficiency anemia
plain_language
Spacing changed absorption in this trial, but the study alone does not decide every patient’s regimen.
primary_references
[iron-p31413088] Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women. (2020). https://pubmed.ncbi.nlm.nih.gov/31413088/ DOI: 10.3324/haematol.2019.220830
tissue_or_cell_type
Oral absorption and hepcidin
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1304–1315
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope crossover absorption study · source_derived_draft · unverified_draft
### iron-alternate-absorption Fractional iron absorption on the initial and alternate-day doses was 40–50% higher than on the consecutive-day dose. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Spacing changed absorption in this trial, but the study alone does not decide every patient’s regimen. organism: 19 women with iron-deficiency anemia tissue_or_cell_type: Oral absorption and hepcidin experimental_model: Stable-isotope crossover absorption study limitations: Absorption trial, not a universal dosing directive; the indexed abstract contains implausible units for baseline hemoglobin/ferritin, which are not reproduced as clinical thresholds. exposure: 100 or 200 mg ferrous sulfate on consecutive and alternate days evidence_span: {"source_cache": "artifacts/iron-research/31413088.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8b12cbd03fa44886ae6bf6bd4d58db7bbbf21dad0461eef9b63d3c7da25c542c", "start_char": 0, "end_char": 2483, "text_sha256": "8b12cbd03fa44886ae6bf6bd4d58db7bbbf21dad0461eef9b63d3c7da25c542c"} [iron-p31413088] Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women. (2020). https://pubmed.ncbi.nlm.nih.gov/31413088/ DOI: 10.3324/haematol.2019.220830
Complete structured claim and evidence
Fatigue scores decreased 47.7% with iron versus 28.8% with placebo; the between-group difference was significant (P=0.02).
Ferrous sulfate → Self-reported fatigue severity source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/22777991.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d8d360cee2d71d5cf1d7b19bbd5c740164d24c16daf98fe4519551573f8fb75", "start_char": 0, "end_char": 1708, "text_sha256": "7d8d360cee2d71d5cf1d7b19bbd5c740164d24c16daf98fe4519551573f8fb75"}
experimental_model
Randomized placebo-controlled 12-week trial
exposure
Ferritin below 50 micrograms/L, hemoglobin above 12 g/dL; 80 mg elemental iron/day versus placebo
limitations
Trial inclusion criteria are not a universal deficiency threshold. No significant improvement in depression, anxiety or overall quality of life.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
198 nonanemic menstruating women with fatigue
plain_language
Normal-range hemoglobin did not exclude an iron-responsive fatigue outcome in this selected group.
primary_references
[iron-p22777991] Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/22777991/ DOI: 10.1503/cmaj.110950
tissue_or_cell_type
Reported symptoms and blood markers
trigger_kind
biomarker_context Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1317–1328
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled 12-week trial · source_derived_draft · unverified_draft
### iron-nonanemic-fatigue Fatigue scores decreased 47.7% with iron versus 28.8% with placebo; the between-group difference was significant (P=0.02). Condition category: biomarker_context nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Normal-range hemoglobin did not exclude an iron-responsive fatigue outcome in this selected group. organism: 198 nonanemic menstruating women with fatigue tissue_or_cell_type: Reported symptoms and blood markers experimental_model: Randomized placebo-controlled 12-week trial limitations: Trial inclusion criteria are not a universal deficiency threshold. No significant improvement in depression, anxiety or overall quality of life. exposure: Ferritin below 50 micrograms/L, hemoglobin above 12 g/dL; 80 mg elemental iron/day versus placebo evidence_span: {"source_cache": "artifacts/iron-research/22777991.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d8d360cee2d71d5cf1d7b19bbd5c740164d24c16daf98fe4519551573f8fb75", "start_char": 0, "end_char": 1708, "text_sha256": "7d8d360cee2d71d5cf1d7b19bbd5c740164d24c16daf98fe4519551573f8fb75"} [iron-p22777991] Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/22777991/ DOI: 10.1503/cmaj.110950
Complete structured claim and evidence
Adjusting ferritin for inflammation increased estimated depleted-store prevalence by 7–25 median percentage points in children and 2–8 points in women, depending on the method.
Serum ferritin concentration → Population estimate of depleted iron stores source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/28615259.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "482315ae02220062888b95687924e871f354ca9edb9fda6303c415799ce9cd4e", "start_char": 0, "end_char": 2373, "text_sha256": "482315ae02220062888b95687924e871f354ca9edb9fda6303c415799ce9cd4e"}
experimental_model
Cross-sectional analysis of population surveys
exposure
Inflammation-adjustment comparisons in BRINDA surveys
limitations
Population prevalence estimation; the correction methods are not an individual diagnostic formula.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
27865 preschool children and 24844 women of reproductive age
plain_language
A seemingly reassuring ferritin result can be influenced by inflammation; this study analyzed populations rather than diagnosing individuals.
primary_references
[iron-p28615259] Adjusting ferritin concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. (2017). https://pubmed.ncbi.nlm.nih.gov/28615259/ DOI: 10.3945/ajcn.116.141762
tissue_or_cell_type
Ferritin, CRP and alpha-1-acid glycoprotein
trigger_kind
biomarker_context Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1330–1341
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cross-sectional analysis of population surveys · source_derived_draft · unverified_draft
### iron-ferritin-inflammation Adjusting ferritin for inflammation increased estimated depleted-store prevalence by 7–25 median percentage points in children and 2–8 points in women, depending on the method. Condition category: biomarker_context nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: A seemingly reassuring ferritin result can be influenced by inflammation; this study analyzed populations rather than diagnosing individuals. organism: 27865 preschool children and 24844 women of reproductive age tissue_or_cell_type: Ferritin, CRP and alpha-1-acid glycoprotein experimental_model: Cross-sectional analysis of population surveys limitations: Population prevalence estimation; the correction methods are not an individual diagnostic formula. exposure: Inflammation-adjustment comparisons in BRINDA surveys evidence_span: {"source_cache": "artifacts/iron-research/28615259.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "482315ae02220062888b95687924e871f354ca9edb9fda6303c415799ce9cd4e", "start_char": 0, "end_char": 2373, "text_sha256": "482315ae02220062888b95687924e871f354ca9edb9fda6303c415799ce9cd4e"} [iron-p28615259] Adjusting ferritin concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. (2017). https://pubmed.ncbi.nlm.nih.gov/28615259/ DOI: 10.3945/ajcn.116.141762
Complete structured claim and evidence
Ascorbate enhanced ferric-NTA iron uptake; ascorbate oxidase and Fe(II) chelators inhibited the enhancement, supporting a required Fe(III)-to-Fe(II) reduction step in this cell model.
L-Ascorbate → Caco-2 apical iron uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin C changes availability of iron for uptake; not proof that all iron absorption requires added vitamin C.
experimental_model
Differentiated human Caco-2 monolayers; apical ferric nitrilotriacetate and transepithelial transport assays.
exposure
Apical 10 micromolar Fe(III) as 1 Fe:2 NTA, varied ascorbic acid, ascorbate oxidase and Fe(II) chelators.
limitations
Chelator/oxidase interventions support redox dependence; the experiment does not identify every human intestinal transport step.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Homo sapiens
plain_language
Changing iron’s chemical state helped the intestinal-model cells acquire it.
primary_references
[c-han1995] Reduction of Fe(III) is required for uptake of nonheme iron by Caco-2 cells (1995). https://pubmed.ncbi.nlm.nih.gov/7738689/ DOI: 10.1093/jn/125.5.1291
tissue_or_cell_type
Human Caco-2 apical cell surface and culture medium
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1554–1565
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated human Caco-2 monolayers; apical ferric nitrilotriacetate and transepithelial transport assays. · source_derived_draft · unverified_draft
### c-iron-ferric-reduction-uptake Ascorbate enhanced ferric-NTA iron uptake; ascorbate oxidase and Fe(II) chelators inhibited the enhancement, supporting a required Fe(III)-to-Fe(II) reduction step in this cell model. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing iron’s chemical state helped the intestinal-model cells acquire it. organism: Homo sapiens tissue_or_cell_type: Human Caco-2 apical cell surface and culture medium experimental_model: Differentiated human Caco-2 monolayers; apical ferric nitrilotriacetate and transepithelial transport assays. limitations: Chelator/oxidase interventions support redox dependence; the experiment does not identify every human intestinal transport step. exposure: Apical 10 micromolar Fe(III) as 1 Fe:2 NTA, varied ascorbic acid, ascorbate oxidase and Fe(II) chelators. cross_nutrient: Vitamin C changes availability of iron for uptake; not proof that all iron absorption requires added vitamin C. [c-han1995] Reduction of Fe(III) is required for uptake of nonheme iron by Caco-2 cells (1995). https://pubmed.ncbi.nlm.nih.gov/7738689/ DOI: 10.1093/jn/125.5.1291
Complete structured claim and evidence
Apical ascorbic acid at 100 and 1000 micromolar increased apical-to-basolateral iron transport 5.6-fold and 30-fold, respectively, in the ferric-NTA system.
L-Ascorbic acid → Caco-2 transepithelial iron flux source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Direct vitamin C/iron transport experiment.
experimental_model
Differentiated human Caco-2 monolayers; apical ferric nitrilotriacetate and transepithelial transport assays.
exposure
Apical 10 micromolar Fe(III) as 1 Fe:2 NTA, varied ascorbic acid, ascorbate oxidase and Fe(II) chelators.
limitations
Culture concentrations and ligand system cannot be converted into a human absorption percentage.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Homo sapiens
plain_language
More iron crossed the model cell layer under those experimental conditions.
primary_references
[c-han1995] Reduction of Fe(III) is required for uptake of nonheme iron by Caco-2 cells (1995). https://pubmed.ncbi.nlm.nih.gov/7738689/ DOI: 10.1093/jn/125.5.1291
tissue_or_cell_type
Human Caco-2 monolayers
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1567–1578
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated human Caco-2 monolayers; apical ferric nitrilotriacetate and transepithelial transport assays. · source_derived_draft · unverified_draft
### c-iron-transepithelial-flux Apical ascorbic acid at 100 and 1000 micromolar increased apical-to-basolateral iron transport 5.6-fold and 30-fold, respectively, in the ferric-NTA system. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: More iron crossed the model cell layer under those experimental conditions. organism: Homo sapiens tissue_or_cell_type: Human Caco-2 monolayers experimental_model: Differentiated human Caco-2 monolayers; apical ferric nitrilotriacetate and transepithelial transport assays. limitations: Culture concentrations and ligand system cannot be converted into a human absorption percentage. exposure: Apical 10 micromolar Fe(III) as 1 Fe:2 NTA, varied ascorbic acid, ascorbate oxidase and Fe(II) chelators. cross_nutrient: Direct vitamin C/iron transport experiment. [c-han1995] Reduction of Fe(III) is required for uptake of nonheme iron by Caco-2 cells (1995). https://pubmed.ncbi.nlm.nih.gov/7738689/ DOI: 10.1093/jn/125.5.1291
Complete structured claim and evidence
Added ascorbic acid significantly counteracted the inhibition of radiolabeled nonheme iron absorption caused by sodium phytate in wheat-roll meals.
L-Ascorbic acid → Nonheme iron absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Meal composition modifies the vitamin C/iron interaction.
experimental_model
Human alternate-day paired radiolabeled wheat-roll experiments.
exposure
Seven sodium phytate levels spanning 2–250 mg expressed as phytate phosphorus, with and without ascorbic acid; 55Fe/59Fe labels. Exact C dose and participant count are not extracted from the abstract.
limitations
Single-meal tracer result; does not prove full cancellation of inhibition or long-term correction of anemia.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Homo sapiens
plain_language
Vitamin C helped offset an iron-absorption inhibitor in the tested meals.
primary_references
[c-hallberg1989] Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate (1989). https://pubmed.ncbi.nlm.nih.gov/2911999/ DOI: 10.1093/ajcn/49.1.140
tissue_or_cell_type
Human blood or whole-person endpoints
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1580–1591
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human alternate-day paired radiolabeled wheat-roll experiments. · source_derived_draft · unverified_draft
### c-phytate-iron-inhibition-counteraction Added ascorbic acid significantly counteracted the inhibition of radiolabeled nonheme iron absorption caused by sodium phytate in wheat-roll meals. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C helped offset an iron-absorption inhibitor in the tested meals. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Human alternate-day paired radiolabeled wheat-roll experiments. limitations: Single-meal tracer result; does not prove full cancellation of inhibition or long-term correction of anemia. exposure: Seven sodium phytate levels spanning 2–250 mg expressed as phytate phosphorus, with and without ascorbic acid; 55Fe/59Fe labels. Exact C dose and participant count are not extracted from the abstract. cross_nutrient: Meal composition modifies the vitamin C/iron interaction. [c-hallberg1989] Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate (1989). https://pubmed.ncbi.nlm.nih.gov/2911999/ DOI: 10.1093/ajcn/49.1.140
Complete structured claim and evidence
Hemoglobin increased 2.00 g/dL with iron plus C versus 1.84 with iron alone at two weeks; difference 0.16 (95% CI -0.03 to 0.35), within the prespecified 1-g/dL equivalence margin.
L-Ascorbic acid → Blood hemoglobin concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Separates chemical absorption support from added clinical benefit during iron replacement.
experimental_model
Single-center open-label randomized equivalence trial: 440 adults with iron-deficiency anemia, 426 women.
exposure
Ferrous succinate 100 mg/tablet with or without vitamin C 200 mg every eight hours, three months; taken half an hour after meals. Tablet mass is not relabeled as elemental iron.
limitations
Equivalence is margin-dependent and does not mean numerical identity; no direct isotope absorption or intracellular mechanism was measured.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Homo sapiens
plain_language
Adding vitamin C did not provide a clinically distinct early hemoglobin response under the trial’s equivalence definition.
primary_references
[c-li2020] The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial (2020). https://pubmed.ncbi.nlm.nih.gov/33136134/ DOI: 10.1001/jamanetworkopen.2020.23644
tissue_or_cell_type
Human blood or whole-person endpoints
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1619–1630
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-center open-label randomized equivalence trial: 440 adults with iron-deficiency anemia, 426 women. · source_derived_draft · unverified_draft
### c-iron-treatment-hemoglobin-equivalence Hemoglobin increased 2.00 g/dL with iron plus C versus 1.84 with iron alone at two weeks; difference 0.16 (95% CI -0.03 to 0.35), within the prespecified 1-g/dL equivalence margin. Condition category: nutrient_deficiency nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding vitamin C did not provide a clinically distinct early hemoglobin response under the trial’s equivalence definition. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Single-center open-label randomized equivalence trial: 440 adults with iron-deficiency anemia, 426 women. limitations: Equivalence is margin-dependent and does not mean numerical identity; no direct isotope absorption or intracellular mechanism was measured. exposure: Ferrous succinate 100 mg/tablet with or without vitamin C 200 mg every eight hours, three months; taken half an hour after meals. Tablet mass is not relabeled as elemental iron. cross_nutrient: Separates chemical absorption support from added clinical benefit during iron replacement. [c-li2020] The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial (2020). https://pubmed.ncbi.nlm.nih.gov/33136134/ DOI: 10.1001/jamanetworkopen.2020.23644
Complete structured claim and evidence
Eight-week ferritin increases were 35.75 versus 34.48 ng/mL; between-group difference 1.27 (95% CI -0.70 to 3.24; P=0.21).
L-Ascorbic acid → Serum ferritin concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Vitamin C/iron clinical outcome recorded separately from the uptake reaction.
experimental_model
Single-center open-label randomized equivalence trial: 440 adults with iron-deficiency anemia, 426 women.
exposure
Ferrous succinate 100 mg/tablet with or without vitamin C 200 mg every eight hours, three months; taken half an hour after meals. Tablet mass is not relabeled as elemental iron.
limitations
Ferritin is a biomarker; no proof that iron absorption was identical at every meal.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Homo sapiens
plain_language
The added vitamin C did not significantly improve the measured iron-storage response.
primary_references
[c-li2020] The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial (2020). https://pubmed.ncbi.nlm.nih.gov/33136134/ DOI: 10.1001/jamanetworkopen.2020.23644
tissue_or_cell_type
Human blood or whole-person endpoints
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1632–1643
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-center open-label randomized equivalence trial: 440 adults with iron-deficiency anemia, 426 women. · source_derived_draft · unverified_draft
### c-iron-treatment-ferritin-null Eight-week ferritin increases were 35.75 versus 34.48 ng/mL; between-group difference 1.27 (95% CI -0.70 to 3.24; P=0.21). Condition category: nutrient_deficiency nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The added vitamin C did not significantly improve the measured iron-storage response. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Single-center open-label randomized equivalence trial: 440 adults with iron-deficiency anemia, 426 women. limitations: Ferritin is a biomarker; no proof that iron absorption was identical at every meal. exposure: Ferrous succinate 100 mg/tablet with or without vitamin C 200 mg every eight hours, three months; taken half an hour after meals. Tablet mass is not relabeled as elemental iron. cross_nutrient: Vitamin C/iron clinical outcome recorded separately from the uptake reaction. [c-li2020] The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial (2020). https://pubmed.ncbi.nlm.nih.gov/33136134/ DOI: 10.1001/jamanetworkopen.2020.23644
Complete structured claim and evidence
Copper-deficient rats had enterocyte hephaestin protein at about 35% of copper-adequate controls.
Copper → Rat enterocyte hephaestin protein abundance source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/15623839.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac", "start_char": 0, "end_char": 1613, "text_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac"}
experimental_model
Controlled copper-deficient versus adequate diets with radiolabeled iron
exposure
Less than 0.3 versus 5 mg copper/kg diet; male and female weanlings
limitations
Animal depletion regimens are not human thresholds. Iron redistribution differed by sex.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Rat
plain_language
Copper shortage reduced part of the intestine’s iron-processing machinery.
primary_references
[copper-p15623839] Dietary copper deficiency reduces iron absorption and duodenal enterocyte hephaestin protein in male and female rats. (2005). https://pubmed.ncbi.nlm.nih.gov/15623839/ DOI: 10.1093/jn/135.1.92
tissue_or_cell_type
Duodenal enterocytes and whole-body iron
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 858–869
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled copper-deficient versus adequate diets with radiolabeled iron · source_derived_draft · unverified_draft
### copper-cud-hephaestin Copper-deficient rats had enterocyte hephaestin protein at about 35% of copper-adequate controls. Condition category: nutrient_deficiency nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper shortage reduced part of the intestine’s iron-processing machinery. organism: Rat tissue_or_cell_type: Duodenal enterocytes and whole-body iron experimental_model: Controlled copper-deficient versus adequate diets with radiolabeled iron limitations: Animal depletion regimens are not human thresholds. Iron redistribution differed by sex. exposure: Less than 0.3 versus 5 mg copper/kg diet; male and female weanlings evidence_span: {"source_cache": "artifacts/copper-research/15623839.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac", "start_char": 0, "end_char": 1613, "text_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac"} [copper-p15623839] Dietary copper deficiency reduces iron absorption and duodenal enterocyte hephaestin protein in male and female rats. (2005). https://pubmed.ncbi.nlm.nih.gov/15623839/ DOI: 10.1093/jn/135.1.92
Complete structured claim and evidence
Copper-deficient male and female rats absorbed about 60% and 70%, respectively, of the iron absorbed by copper-adequate controls.
Copper → Rat intestinal iron absorption source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/15623839.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac", "start_char": 0, "end_char": 1613, "text_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac"}
experimental_model
Controlled copper-deficient versus adequate diets with radiolabeled iron
exposure
Less than 0.3 versus 5 mg copper/kg diet; male and female weanlings
limitations
Animal depletion regimens are not human thresholds. Iron redistribution differed by sex.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Rat
plain_language
Adding iron alone does not describe the copper-dependent processing step.
primary_references
[copper-p15623839] Dietary copper deficiency reduces iron absorption and duodenal enterocyte hephaestin protein in male and female rats. (2005). https://pubmed.ncbi.nlm.nih.gov/15623839/ DOI: 10.1093/jn/135.1.92
tissue_or_cell_type
Duodenal enterocytes and whole-body iron
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 871–882
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled copper-deficient versus adequate diets with radiolabeled iron · source_derived_draft · unverified_draft
### copper-cud-iron-absorption Copper-deficient male and female rats absorbed about 60% and 70%, respectively, of the iron absorbed by copper-adequate controls. Condition category: nutrient_deficiency nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding iron alone does not describe the copper-dependent processing step. organism: Rat tissue_or_cell_type: Duodenal enterocytes and whole-body iron experimental_model: Controlled copper-deficient versus adequate diets with radiolabeled iron limitations: Animal depletion regimens are not human thresholds. Iron redistribution differed by sex. exposure: Less than 0.3 versus 5 mg copper/kg diet; male and female weanlings evidence_span: {"source_cache": "artifacts/copper-research/15623839.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac", "start_char": 0, "end_char": 1613, "text_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac"} [copper-p15623839] Dietary copper deficiency reduces iron absorption and duodenal enterocyte hephaestin protein in male and female rats. (2005). https://pubmed.ncbi.nlm.nih.gov/15623839/ DOI: 10.1093/jn/135.1.92
Complete structured claim and evidence
Cp-null mice had impaired iron release from hepatocytes and reticuloendothelial cells, while measured iron absorption and plasma turnover were comparable to controls.
Mouse ceruloplasmin Cp → Mouse release of stored iron from hepatocytes and reticuloendothelial cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/10485908.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2feaccc19bf8f4480643a918de9300a6c224935b47c24e251d96050599e3b067", "start_char": 0, "end_char": 1368, "text_sha256": "2feaccc19bf8f4480643a918de9300a6c224935b47c24e251d96050599e3b067"}
experimental_model
Ceruloplasmin gene disruption and ferrokinetics
exposure
Cp knockout followed through one year
limitations
Genetic ceruloplasmin absence differs from dietary copper shortage; normal intestinal absorption in this experiment does not imply all copper-deficient states absorb iron normally.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
The main defect was moving stored iron out of cells.
primary_references
[copper-p10485908] Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. (1999). https://pubmed.ncbi.nlm.nih.gov/10485908/ DOI: 10.1073/pnas.96.19.10812
tissue_or_cell_type
Liver, spleen and reticuloendothelial cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 793–804
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ceruloplasmin gene disruption and ferrokinetics · source_derived_draft · unverified_draft
### copper-cp-iron-mobilization Cp-null mice had impaired iron release from hepatocytes and reticuloendothelial cells, while measured iron absorption and plasma turnover were comparable to controls. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The main defect was moving stored iron out of cells. organism: Mouse tissue_or_cell_type: Liver, spleen and reticuloendothelial cells experimental_model: Ceruloplasmin gene disruption and ferrokinetics limitations: Genetic ceruloplasmin absence differs from dietary copper shortage; normal intestinal absorption in this experiment does not imply all copper-deficient states absorb iron normally. exposure: Cp knockout followed through one year evidence_span: {"source_cache": "artifacts/copper-research/10485908.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2feaccc19bf8f4480643a918de9300a6c224935b47c24e251d96050599e3b067", "start_char": 0, "end_char": 1368, "text_sha256": "2feaccc19bf8f4480643a918de9300a6c224935b47c24e251d96050599e3b067"} [copper-p10485908] Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. (1999). https://pubmed.ncbi.nlm.nih.gov/10485908/ DOI: 10.1073/pnas.96.19.10812
Complete structured claim and evidence
Whole-body Heph/Cp double-knockout mice developed severe anemia and low serum iron despite iron-loaded tissues.
Mouse hephaestin Heph → Mouse circulating iron availability source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/30182051.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72", "start_char": 0, "end_char": 1882, "text_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72"}
experimental_model
Whole-body and intestine-specific Heph/Cp double-knockout mice
exposure
Combined or tissue-specific deletion; oral iron tracer
limitations
Double knockouts differ from low dietary copper. Detectable iron absorption remained, so these enzymes are not an absolute all-or-none gate for every absorption route.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
The body had iron, but much of it was in the wrong places.
primary_references
[copper-p30182051] Severe Iron Metabolism Defects in Mice With Double Knockout of the Multicopper Ferroxidases Hephaestin and Ceruloplasmin. (2018). https://pubmed.ncbi.nlm.nih.gov/30182051/ DOI: 10.1016/j.jcmgh.2018.06.006
tissue_or_cell_type
Intestine, liver, heart, pancreas and blood
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 819–830
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-body and intestine-specific Heph/Cp double-knockout mice · source_derived_draft · unverified_draft
### copper-heph-cp-low-blood-iron Whole-body Heph/Cp double-knockout mice developed severe anemia and low serum iron despite iron-loaded tissues. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The body had iron, but much of it was in the wrong places. organism: Mouse tissue_or_cell_type: Intestine, liver, heart, pancreas and blood experimental_model: Whole-body and intestine-specific Heph/Cp double-knockout mice limitations: Double knockouts differ from low dietary copper. Detectable iron absorption remained, so these enzymes are not an absolute all-or-none gate for every absorption route. exposure: Combined or tissue-specific deletion; oral iron tracer evidence_span: {"source_cache": "artifacts/copper-research/30182051.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72", "start_char": 0, "end_char": 1882, "text_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72"} [copper-p30182051] Severe Iron Metabolism Defects in Mice With Double Knockout of the Multicopper Ferroxidases Hephaestin and Ceruloplasmin. (2018). https://pubmed.ncbi.nlm.nih.gov/30182051/ DOI: 10.1016/j.jcmgh.2018.06.006
Complete structured claim and evidence
Both Heph/Cp double-knockout models still absorbed oral iron tracer, but retained an abnormally high fraction in the liver.
Mouse hephaestin Heph → Mouse intestinal iron absorption source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/30182051.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72", "start_char": 0, "end_char": 1882, "text_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72"}
experimental_model
Whole-body and intestine-specific Heph/Cp double-knockout mice
exposure
Combined or tissue-specific deletion; oral iron tracer
limitations
Double knockouts differ from low dietary copper. Detectable iron absorption remained, so these enzymes are not an absolute all-or-none gate for every absorption route.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
Absorption and useful distribution are different steps.
primary_references
[copper-p30182051] Severe Iron Metabolism Defects in Mice With Double Knockout of the Multicopper Ferroxidases Hephaestin and Ceruloplasmin. (2018). https://pubmed.ncbi.nlm.nih.gov/30182051/ DOI: 10.1016/j.jcmgh.2018.06.006
tissue_or_cell_type
Intestine, liver, heart, pancreas and blood
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 845–856
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-body and intestine-specific Heph/Cp double-knockout mice · source_derived_draft · unverified_draft
### copper-heph-cp-residual-absorption Both Heph/Cp double-knockout models still absorbed oral iron tracer, but retained an abnormally high fraction in the liver. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Absorption and useful distribution are different steps. organism: Mouse tissue_or_cell_type: Intestine, liver, heart, pancreas and blood experimental_model: Whole-body and intestine-specific Heph/Cp double-knockout mice limitations: Double knockouts differ from low dietary copper. Detectable iron absorption remained, so these enzymes are not an absolute all-or-none gate for every absorption route. exposure: Combined or tissue-specific deletion; oral iron tracer evidence_span: {"source_cache": "artifacts/copper-research/30182051.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72", "start_char": 0, "end_char": 1882, "text_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72"} [copper-p30182051] Severe Iron Metabolism Defects in Mice With Double Knockout of the Multicopper Ferroxidases Hephaestin and Ceruloplasmin. (2018). https://pubmed.ncbi.nlm.nih.gov/30182051/ DOI: 10.1016/j.jcmgh.2018.06.006
Complete structured claim and evidence
Ceruloplasmin copper incorporation was cooperative, and its final conformational state required occupation of all six copper-binding sites in the tested system.
Human ceruloplasmin / CP → Copper-loaded human holoceruloplasmin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/12351628.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4492680e4d410b1e32f77dea6aa0c26b2303b26d4fadfef25a350338ac365de3", "start_char": 0, "end_char": 1541, "text_sha256": "4492680e4d410b1e32f77dea6aa0c26b2303b26d4fadfef25a350338ac365de3"}
experimental_model
Human ceruloplasmin expression, radiocopper labeling and in-vitro loading
exposure
Wild-type and copper-site mutants including G631R
limitations
The final conformation required six occupied sites in these assays; no hierarchy was apparent. Do not confuse this structural requirement with circulating protein concentration.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human protein expressed in Chinese hamster ovary cells
plain_language
The protein needs coordinated metal loading to reach its mature form.
primary_references
[copper-p12351628] Mechanisms of copper incorporation into human ceruloplasmin. (2002). https://pubmed.ncbi.nlm.nih.gov/12351628/ DOI: 10.1074/jbc.m206246200
tissue_or_cell_type
Secretory protein biosynthesis
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1053–1064
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human ceruloplasmin expression, radiocopper labeling and in-vitro loading · source_derived_draft · unverified_draft
### copper-cp-six-site-loading Ceruloplasmin copper incorporation was cooperative, and its final conformational state required occupation of all six copper-binding sites in the tested system. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The protein needs coordinated metal loading to reach its mature form. organism: Human protein expressed in Chinese hamster ovary cells tissue_or_cell_type: Secretory protein biosynthesis experimental_model: Human ceruloplasmin expression, radiocopper labeling and in-vitro loading limitations: The final conformation required six occupied sites in these assays; no hierarchy was apparent. Do not confuse this structural requirement with circulating protein concentration. exposure: Wild-type and copper-site mutants including G631R evidence_span: {"source_cache": "artifacts/copper-research/12351628.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4492680e4d410b1e32f77dea6aa0c26b2303b26d4fadfef25a350338ac365de3", "start_char": 0, "end_char": 1541, "text_sha256": "4492680e4d410b1e32f77dea6aa0c26b2303b26d4fadfef25a350338ac365de3"} [copper-p12351628] Mechanisms of copper incorporation into human ceruloplasmin. (2002). https://pubmed.ncbi.nlm.nih.gov/12351628/ DOI: 10.1074/jbc.m206246200
Complete structured claim and evidence
The human ALAS2 structure positions PLP at the catalytic dimer interface with its covalent attachment to Lys391.
PLP → Human erythroid aminolevulinate synthase 2 / ALAS2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6-dependent production of precursors for iron-containing heme.
experimental_model
Purified recombinant human ALAS2; crystallography and kinetics
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Active B6 is bound inside the erythroid heme-precursor enzyme.
primary_references
[b6-alas2-2020] Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release (2020). https://www.nature.com/articles/s41467-020-16586-x DOI: 10.1038/s41467-020-16586-x
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 787–797
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human ALAS2; crystallography and kinetics · source_derived_draft · unverified_draft
### b6-met-alas2-plp The human ALAS2 structure positions PLP at the catalytic dimer interface with its covalent attachment to Lys391. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Active B6 is bound inside the erythroid heme-precursor enzyme. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human ALAS2; crystallography and kinetics limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. cross_nutrient: B6-dependent production of precursors for iron-containing heme. [b6-alas2-2020] Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release (2020). https://www.nature.com/articles/s41467-020-16586-x DOI: 10.1038/s41467-020-16586-x
Complete structured claim and evidence
ALAS2 Arg452Cys showed reduced PLP affinity and altered succinyl-CoA kinetics despite retained SUCLA2 binding.
Human ALAS2 Arg452Cys variant → PLP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Genetic impairment of a B6-dependent enzyme in an iron/heme disorder.
experimental_model
Human XLSA variants; recombinant enzyme kinetics and SUCLA2 affinity assays
limitations
Variant-specific in-vitro kinetics do not predict all clinical responses.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
An inherited heme-synthesis defect can impair B6 cofactor use.
primary_references
[b6-alas2-2012] X-linked Sideroblastic Anemia Due to Carboxyl-terminal ALAS2 Mutations That Cause Loss of Binding to the beta-Subunit of Succinyl-CoA Synthetase (SUCLA2) (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3436539/ DOI: 10.1074/jbc.M111.306423
tissue_or_cell_type
Purified recombinant protein; no intact tissue
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 811–821
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human XLSA variants; recombinant enzyme kinetics and SUCLA2 affinity assays · source_derived_draft · unverified_draft
### b6-met-alas2-r452c ALAS2 Arg452Cys showed reduced PLP affinity and altered succinyl-CoA kinetics despite retained SUCLA2 binding. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: An inherited heme-synthesis defect can impair B6 cofactor use. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Human XLSA variants; recombinant enzyme kinetics and SUCLA2 affinity assays limitations: Variant-specific in-vitro kinetics do not predict all clinical responses. cross_nutrient: Genetic impairment of a B6-dependent enzyme in an iron/heme disorder. [b6-alas2-2012] X-linked Sideroblastic Anemia Due to Carboxyl-terminal ALAS2 Mutations That Cause Loss of Binding to the beta-Subunit of Succinyl-CoA Synthetase (SUCLA2) (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3436539/ DOI: 10.1074/jbc.M111.306423
Complete structured claim and evidence
In two patients with induced B2 deficiency, parenteral iron did not trigger reticulocytosis, whereas subsequent riboflavin did.
Iron → Erythroid cell production source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Documented failure of iron response in a specific induced B2-deficiency setting.
experimental_model
Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group.
exposure
Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics.
limitations
Two cases within a six-person cancer/galactoflavin experiment; cannot generalize this to every anemia or infer a modern treatment regimen.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
More iron did not restore new red-cell production while usable B2 was severely limited in these cases.
primary_references
[b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921
tissue_or_cell_type
Circulating reticulocytes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1814–1825
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. · source_derived_draft · unverified_draft
### b2-induced-iron-response-failure In two patients with induced B2 deficiency, parenteral iron did not trigger reticulocytosis, whereas subsequent riboflavin did. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: More iron did not restore new red-cell production while usable B2 was severely limited in these cases. organism: Homo sapiens tissue_or_cell_type: Circulating reticulocytes experimental_model: Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. limitations: Two cases within a six-person cancer/galactoflavin experiment; cannot generalize this to every anemia or infer a modern treatment regimen. exposure: Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics. cross_nutrient: Documented failure of iron response in a specific induced B2-deficiency setting. [b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921
Complete structured claim and evidence
Riboflavin supplementation improved B2 status and hemoglobin in deficient Gambian men; low plasma ferritin did not change.
Riboflavin (vitamin B2) → Blood hemoglobin concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B2 and iron supply can constrain different parts of erythropoiesis.
experimental_model
Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption.
exposure
Oral riboflavin versus no riboflavin; 3.38 mg 58Fe test dose before and after intervention; treatment dose not inferred from accessed abstract.
limitations
Controlled study in anemic deficient men; the specific marrow or mobilization mechanism was inferred, not directly established.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Hemoglobin improved even though the measured storage marker stayed low.
primary_references
[b2-fairweather1992] Riboflavin deficiency and iron absorption in adult Gambian men (1992). https://pubmed.ncbi.nlm.nih.gov/1590670/ DOI: 10.1159/000177696
tissue_or_cell_type
Human clinical setting
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1578–1589
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption. · source_derived_draft · unverified_draft
### b2-gambia-hemoglobin Riboflavin supplementation improved B2 status and hemoglobin in deficient Gambian men; low plasma ferritin did not change. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Hemoglobin improved even though the measured storage marker stayed low. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption. limitations: Controlled study in anemic deficient men; the specific marrow or mobilization mechanism was inferred, not directly established. exposure: Oral riboflavin versus no riboflavin; 3.38 mg 58Fe test dose before and after intervention; treatment dose not inferred from accessed abstract. cross_nutrient: B2 and iron supply can constrain different parts of erythropoiesis. [b2-fairweather1992] Riboflavin deficiency and iron absorption in adult Gambian men (1992). https://pubmed.ncbi.nlm.nih.gov/1590670/ DOI: 10.1159/000177696
Complete structured claim and evidence
Stable-isotope iron absorption varied widely within and between Gambian participants and showed no measurable change after riboflavin.
Riboflavin (vitamin B2) → Nonheme iron absorption source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Iron-use improvement is distinct from intestinal absorption.
experimental_model
Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption.
exposure
Oral riboflavin versus no riboflavin; 3.38 mg 58Fe test dose before and after intervention; treatment dose not inferred from accessed abstract.
limitations
Measurement variability and study size limit exclusion of smaller effects; rat intestinal findings need separate model labels.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
This human study does not support a blanket claim that B2 always raises iron absorption.
primary_references
[b2-fairweather1992] Riboflavin deficiency and iron absorption in adult Gambian men (1992). https://pubmed.ncbi.nlm.nih.gov/1590670/ DOI: 10.1159/000177696
tissue_or_cell_type
Human clinical setting
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1591–1602
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption. · source_derived_draft · unverified_draft
### b2-gambia-iron-absorption Stable-isotope iron absorption varied widely within and between Gambian participants and showed no measurable change after riboflavin. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This human study does not support a blanket claim that B2 always raises iron absorption. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption. limitations: Measurement variability and study size limit exclusion of smaller effects; rat intestinal findings need separate model labels. exposure: Oral riboflavin versus no riboflavin; 3.38 mg 58Fe test dose before and after intervention; treatment dose not inferred from accessed abstract. cross_nutrient: Iron-use improvement is distinct from intestinal absorption. [b2-fairweather1992] Riboflavin deficiency and iron absorption in adult Gambian men (1992). https://pubmed.ncbi.nlm.nih.gov/1590670/ DOI: 10.1159/000177696
Complete structured claim and evidence
Riboflavin-deficient rats transferred less intragastrically administered 59Fe to plasma than age- or weight-matched controls.
Riboflavin (vitamin B2) → Nonheme iron absorption source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B2 status changed systemic appearance of administered iron.
evidence_location
Abstract
experimental_model
Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles.
exposure
Dietary riboflavin deficiency plus intragastric 59Fe
limitations
Rat tracer experiment; does not establish an identical human absorption response.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Rattus norvegicus
plain_language
Less of the administered iron reached the blood.
primary_references
[butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/
tissue_or_cell_type
Intestine and plasma
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1416–1428
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. · source_derived_draft · unverified_draft
### b2-rat-enteral-iron-transfer Riboflavin-deficient rats transferred less intragastrically administered 59Fe to plasma than age- or weight-matched controls. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less of the administered iron reached the blood. organism: Rattus norvegicus tissue_or_cell_type: Intestine and plasma experimental_model: Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. limitations: Rat tracer experiment; does not establish an identical human absorption response. exposure: Dietary riboflavin deficiency plus intragastric 59Fe cross_nutrient: B2 status changed systemic appearance of administered iron. evidence_location: Abstract [butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/
Complete structured claim and evidence
After intraperitoneal 59Fe, riboflavin-deficient rats lost about twice as much endogenous tracer in feces as weight-matched controls.
Riboflavin (vitamin B2) → Endogenous fecal iron loss source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B2 status affected post-absorption iron retention in rats.
evidence_location
Abstract
experimental_model
Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing.
exposure
Dietary riboflavin deficiency plus intraperitoneal tracer
limitations
The proposed enterocyte-turnover mechanism is supported indirectly; this is not measurement of unabsorbed oral iron.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Rattus norvegicus
plain_language
Deficiency increased loss of iron already inside the body.
primary_references
[powers1993] A proposed intestinal mechanism for the effect of riboflavin deficiency on iron loss in the rat. (1993). https://pubmed.ncbi.nlm.nih.gov/8490008/ DOI: 10.1079/bjn19930055
tissue_or_cell_type
Gastrointestinal tract and feces
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1458–1470
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing. · source_derived_draft · unverified_draft
### b2-rat-endogenous-iron-loss After intraperitoneal 59Fe, riboflavin-deficient rats lost about twice as much endogenous tracer in feces as weight-matched controls. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Deficiency increased loss of iron already inside the body. organism: Rattus norvegicus tissue_or_cell_type: Gastrointestinal tract and feces experimental_model: Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing. limitations: The proposed enterocyte-turnover mechanism is supported indirectly; this is not measurement of unabsorbed oral iron. exposure: Dietary riboflavin deficiency plus intraperitoneal tracer cross_nutrient: B2 status affected post-absorption iron retention in rats. evidence_location: Abstract [powers1993] A proposed intestinal mechanism for the effect of riboflavin deficiency on iron loss in the rat. (1993). https://pubmed.ncbi.nlm.nih.gov/8490008/ DOI: 10.1079/bjn19930055
Complete structured claim and evidence
The authors proposed that ineffective erythropoiesis during cobalamin deficiency reduces iron use by erythroblasts, helping explain the before/after iron results.
Vitamin B12 (cobalamins) → Iron utilization by erythroblasts source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Specific candidate mechanism connecting B12 function to iron utilization.
experimental_model
Before/after series of 75 patients diagnosed with cobalamin deficiency.
exposure
Blood counts and iron-status measurements before and after cobalamin therapy; regimen is not extracted from the abstract.
limitations
Proposed explanation, not a directly measured isotope flux or demonstrated cellular mediator in this study.
nutrient_topic
Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
organism
Homo sapiens
plain_language
If red-cell production is impaired, available iron and productive iron use need not move together.
primary_references
[b12-solmaz2015] Cobalamin deficiency can mask depleted body iron reserves (2015). https://pubmed.ncbi.nlm.nih.gov/25825568/ DOI: 10.1007/s12288-014-0417-x
tissue_or_cell_type
Human blood or whole-person endpoints
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1611–1622
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Before/after series of 75 patients diagnosed with cobalamin deficiency. · source_derived_draft · unverified_draft
### b12-ineffective-erythropoiesis-iron-hypothesis The authors proposed that ineffective erythropoiesis during cobalamin deficiency reduces iron use by erythroblasts, helping explain the before/after iron results. Condition category: nutrient_deficiency nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: If red-cell production is impaired, available iron and productive iron use need not move together. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Before/after series of 75 patients diagnosed with cobalamin deficiency. limitations: Proposed explanation, not a directly measured isotope flux or demonstrated cellular mediator in this study. exposure: Blood counts and iron-status measurements before and after cobalamin therapy; regimen is not extracted from the abstract. cross_nutrient: Specific candidate mechanism connecting B12 function to iron utilization. [b12-solmaz2015] Cobalamin deficiency can mask depleted body iron reserves (2015). https://pubmed.ncbi.nlm.nih.gov/25825568/ DOI: 10.1007/s12288-014-0417-x
Complete structured claim and evidence
Iron deficiency was identified in 7 of 75 patients before cobalamin therapy and 37 of 75 afterward.
Vitamin B12 (cobalamins) → Iron deficiency classification source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Retains the iron/B12 interaction without claiming either nutrient universally replaces the other.
experimental_model
Before/after series of 75 patients diagnosed with cobalamin deficiency.
exposure
Blood counts and iron-status measurements before and after cobalamin therapy; regimen is not extracted from the abstract.
limitations
A diagnostic reclassification is not proof of newly caused iron depletion.
nutrient_topic
Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
organism
Homo sapiens
plain_language
An accompanying iron shortage could become easier to recognize during recovery.
primary_references
[b12-solmaz2015] Cobalamin deficiency can mask depleted body iron reserves (2015). https://pubmed.ncbi.nlm.nih.gov/25825568/ DOI: 10.1007/s12288-014-0417-x
tissue_or_cell_type
Human blood or whole-person endpoints
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1598–1609
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Before/after series of 75 patients diagnosed with cobalamin deficiency. · source_derived_draft · unverified_draft
### b12-repletion-iron-deficiency-detection Iron deficiency was identified in 7 of 75 patients before cobalamin therapy and 37 of 75 afterward. Condition category: nutrient_deficiency nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: An accompanying iron shortage could become easier to recognize during recovery. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Before/after series of 75 patients diagnosed with cobalamin deficiency. limitations: A diagnostic reclassification is not proof of newly caused iron depletion. exposure: Blood counts and iron-status measurements before and after cobalamin therapy; regimen is not extracted from the abstract. cross_nutrient: Retains the iron/B12 interaction without claiming either nutrient universally replaces the other. [b12-solmaz2015] Cobalamin deficiency can mask depleted body iron reserves (2015). https://pubmed.ncbi.nlm.nih.gov/25825568/ DOI: 10.1007/s12288-014-0417-x
Complete structured claim and evidence
After cobalamin therapy, mean serum iron fell from 126.4 to 59.1 micrograms/dL, ferritin from 192.5 to 44.9 ng/mL and transferrin saturation from 47.2% to 17.5%.
Vitamin B12 (cobalamins) → Serum iron concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B12-associated ineffective blood-cell production can complicate iron-status interpretation.
experimental_model
Before/after series of 75 patients diagnosed with cobalamin deficiency.
exposure
Blood counts and iron-status measurements before and after cobalamin therapy; regimen is not extracted from the abstract.
limitations
Before/after observations cannot isolate iron utilization from all other changes.
nutrient_topic
Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
organism
Homo sapiens
plain_language
Restoring B12 changed how the blood iron results looked.
primary_references
[b12-solmaz2015] Cobalamin deficiency can mask depleted body iron reserves (2015). https://pubmed.ncbi.nlm.nih.gov/25825568/ DOI: 10.1007/s12288-014-0417-x
tissue_or_cell_type
Human blood or whole-person endpoints
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1585–1596
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Before/after series of 75 patients diagnosed with cobalamin deficiency. · source_derived_draft · unverified_draft
### b12-repletion-iron-readouts After cobalamin therapy, mean serum iron fell from 126.4 to 59.1 micrograms/dL, ferritin from 192.5 to 44.9 ng/mL and transferrin saturation from 47.2% to 17.5%. Condition category: nutrient_deficiency nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring B12 changed how the blood iron results looked. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Before/after series of 75 patients diagnosed with cobalamin deficiency. limitations: Before/after observations cannot isolate iron utilization from all other changes. exposure: Blood counts and iron-status measurements before and after cobalamin therapy; regimen is not extracted from the abstract. cross_nutrient: B12-associated ineffective blood-cell production can complicate iron-status interpretation. [b12-solmaz2015] Cobalamin deficiency can mask depleted body iron reserves (2015). https://pubmed.ncbi.nlm.nih.gov/25825568/ DOI: 10.1007/s12288-014-0417-x
Complete structured claim and evidence
Vitamin A-deficient rats had more splenic iron but lower serum iron and transferrin saturation.
Vitamin A → Splenic iron storage source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Vitamin A deficiency -> iron distribution.
experimental_model
Controlled rat dietary groups.
limitations
Erythrophagocytosis is a proposed explanation, not a fully isolated causal sequence.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Rattus norvegicus
plain_language
Iron could be retained in one tissue while circulating availability fell.
primary_references
[va-cunha2014] Vitamin A deficiency modulates iron metabolism via ineffective erythropoiesis (2014). https://pubmed.ncbi.nlm.nih.gov/24998947/ DOI: 10.1016/j.jnutbio.2014.05.005
tissue_or_cell_type
Spleen and serum
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1743–1753
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled rat dietary groups. · source_derived_draft · unverified_draft
### va-deficiency-iron-sequestration Vitamin A-deficient rats had more splenic iron but lower serum iron and transferrin saturation. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron could be retained in one tissue while circulating availability fell. organism: Rattus norvegicus tissue_or_cell_type: Spleen and serum experimental_model: Controlled rat dietary groups. limitations: Erythrophagocytosis is a proposed explanation, not a fully isolated causal sequence. cross_nutrient: Vitamin A deficiency -> iron distribution. [va-cunha2014] Vitamin A deficiency modulates iron metabolism via ineffective erythropoiesis (2014). https://pubmed.ncbi.nlm.nih.gov/24998947/ DOI: 10.1016/j.jnutbio.2014.05.005
Complete structured claim and evidence
Vitamin A deficiency reduced intestinal Fpn1 transcripts in the same rat study.
Vitamin A → SLC40A1 mRNA source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Intestinal mRNA assay.
limitations
Does not quantify ferroportin membrane protein or iron-export flux.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Rattus norvegicus
plain_language
Expression of an iron-export component changed alongside systemic signals.
primary_references
[va-cunha2016] Vitamin A deficiency modulates iron metabolism independent of hemojuvelin (Hfe2) and bone morphogenetic protein 6 (Bmp6) transcript levels (2016). https://pubmed.ncbi.nlm.nih.gov/27551308/ DOI: 10.1186/s12263-016-0519-4
tissue_or_cell_type
Small intestine
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1778–1787
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intestinal mRNA assay. · source_derived_draft · unverified_draft
### va-deficiency-ferroportin-transcript Vitamin A deficiency reduced intestinal Fpn1 transcripts in the same rat study. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Expression of an iron-export component changed alongside systemic signals. organism: Rattus norvegicus tissue_or_cell_type: Small intestine experimental_model: Intestinal mRNA assay. limitations: Does not quantify ferroportin membrane protein or iron-export flux. [va-cunha2016] Vitamin A deficiency modulates iron metabolism independent of hemojuvelin (Hfe2) and bone morphogenetic protein 6 (Bmp6) transcript levels (2016). https://pubmed.ncbi.nlm.nih.gov/27551308/ DOI: 10.1186/s12263-016-0519-4
Complete structured claim and evidence
Combined vitamin A and iron produced the largest hemoglobin response in the factorial pregnancy trial.
Vitamin A → Blood hemoglobin concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Vitamin A/iron -> hemoglobin response.
experimental_model
Eight-week randomized trial.
limitations
Combined benefit does not prove a biochemical synergy or specify the cellular mediator.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Homo sapiens
plain_language
Correcting more than one shortage improved the measured response in this population.
primary_references
[va-suharno1993] Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia (1993). https://pubmed.ncbi.nlm.nih.gov/7901636/ DOI: 10.1016/0140-6736(93)92246-p
tissue_or_cell_type
Blood
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1448–1458
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Eight-week randomized trial. · source_derived_draft · unverified_draft
### va-iron-combined-hemoglobin Combined vitamin A and iron produced the largest hemoglobin response in the factorial pregnancy trial. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Correcting more than one shortage improved the measured response in this population. organism: Homo sapiens tissue_or_cell_type: Blood experimental_model: Eight-week randomized trial. limitations: Combined benefit does not prove a biochemical synergy or specify the cellular mediator. cross_nutrient: Vitamin A/iron -> hemoglobin response. [va-suharno1993] Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia (1993). https://pubmed.ncbi.nlm.nih.gov/7901636/ DOI: 10.1016/0140-6736(93)92246-p
Complete structured claim and evidence
Vitamin A and beta-carotene increased labelled nonheme iron absorption from tested cereal meals.
Vitamin A → Nonheme iron absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin A/carotene -> iron absorption; contested.
experimental_model
Six human cereal-meal studies.
limitations
Not consistently replicated; the claimed iron-complex mechanism was proposed rather than structurally demonstrated.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Homo sapiens
plain_language
This study found that the meal additives made more iron available.
primary_references
[va-garciacasal1998] Vitamin A and beta-carotene can improve nonheme iron absorption from rice, wheat and corn by humans (1998). https://pubmed.ncbi.nlm.nih.gov/9482776/ DOI: 10.1093/jn/128.3.646
tissue_or_cell_type
Intestinal absorption
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1542–1552
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six human cereal-meal studies. · source_derived_draft · unverified_draft
### va-iron-absorption-positive1998 Vitamin A and beta-carotene increased labelled nonheme iron absorption from tested cereal meals. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: This study found that the meal additives made more iron available. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Six human cereal-meal studies. limitations: Not consistently replicated; the claimed iron-complex mechanism was proposed rather than structurally demonstrated. cross_nutrient: Vitamin A/carotene -> iron absorption; contested. [va-garciacasal1998] Vitamin A and beta-carotene can improve nonheme iron absorption from rice, wheat and corn by humans (1998). https://pubmed.ncbi.nlm.nih.gov/9482776/ DOI: 10.1093/jn/128.3.646
Complete structured claim and evidence
Five isotope studies did not confirm enhanced iron absorption after adding retinyl palmitate to corn-bread meals.
All-trans-retinyl palmitate → Nonheme iron absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin A/iron absorption replication disagreement.
experimental_model
Water/coffee meal conditions; stable and radioisotope methods.
limitations
Possible effect modification by poor vitamin A status remained unresolved; beta-carotene was not directly retested.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Homo sapiens
plain_language
Follow-up experiments did not reproduce the earlier positive result.
primary_references
[va-walczyk2003] No enhancing effect of vitamin A on iron absorption in humans (2003). https://pubmed.ncbi.nlm.nih.gov/12499334/ DOI: 10.1093/ajcn/77.1.144
tissue_or_cell_type
Intestinal absorption
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1566–1576
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Water/coffee meal conditions; stable and radioisotope methods. · source_derived_draft · unverified_draft
### va-iron-absorption-no-enhancement2003 Five isotope studies did not confirm enhanced iron absorption after adding retinyl palmitate to corn-bread meals. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Follow-up experiments did not reproduce the earlier positive result. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Water/coffee meal conditions; stable and radioisotope methods. limitations: Possible effect modification by poor vitamin A status remained unresolved; beta-carotene was not directly retested. cross_nutrient: Vitamin A/iron absorption replication disagreement. [va-walczyk2003] No enhancing effect of vitamin A on iron absorption in humans (2003). https://pubmed.ncbi.nlm.nih.gov/12499334/ DOI: 10.1093/ajcn/77.1.144
Complete structured claim and evidence
FeSO4 restored chelator-inhibited RPE65 isomerohydrolase activity in bovine microsomes and recombinant assays; ferric salts did not.
Ferrous iron → RPE65 retinoid isomerohydrolase source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Iron availability at RPE65 enables formation of the cis-retinoid visual-cycle intermediate.
experimental_model
Chelation and metal rescue
limitations
This is enzyme-cofactor evidence, not a human iron-deficiency threshold.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Bos taurus; recombinant RPE65 in human 293A cells
plain_language
Ferrous iron is required for this vitamin A recycling enzyme.
primary_references
[moiseyev-2006] RPE65 is an iron(II)-dependent isomerohydrolase in the retinoid visual cycle (2006). https://pubmed.ncbi.nlm.nih.gov/16319067/ DOI: 10.1074/jbc.M508903200
tissue_or_cell_type
RPE microsomes and cultured-cell preparations
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 677–687
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chelation and metal rescue · source_derived_draft · unverified_draft
### a-vision-rpe65-iron FeSO4 restored chelator-inhibited RPE65 isomerohydrolase activity in bovine microsomes and recombinant assays; ferric salts did not. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Ferrous iron is required for this vitamin A recycling enzyme. organism: Bos taurus; recombinant RPE65 in human 293A cells tissue_or_cell_type: RPE microsomes and cultured-cell preparations experimental_model: Chelation and metal rescue limitations: This is enzyme-cofactor evidence, not a human iron-deficiency threshold. cross_nutrient: Iron availability at RPE65 enables formation of the cis-retinoid visual-cycle intermediate. [moiseyev-2006] RPE65 is an iron(II)-dependent isomerohydrolase in the retinoid visual cycle (2006). https://pubmed.ncbi.nlm.nih.gov/16319067/ DOI: 10.1074/jbc.M508903200
Complete structured claim and evidence
Substitution of conserved histidines or Glu405 in mouse BCO1 abolished cleavage and reduced protein-bound iron.
Beta-carotene oxygenase 1 / BCO1 → Iron source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Links enzyme-bound iron to vitamin A precursor processing.
evidence_location
Abstract
experimental_model
Site-directed mutant mouse BCO1; cleavage assays and protein-bound iron spectroscopy.
exposure
Individual alanine substitutions at conserved catalytic-site residues.
limitations
Coordination inferred from mutagenesis and iron measurements, not a dietary iron trial.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Mus musculus recombinant protein
outcome
Substitution of conserved histidines or Glu405 in mouse BCO1 abolished cleavage and reduced protein-bound iron.
plain_language
An intact iron-binding environment is necessary for this enzyme to work.
primary_references
[va-poliakov-2005] Key role of conserved histidines in recombinant mouse beta-carotene 15,15'-monooxygenase-1 activity (2005). https://pubmed.ncbi.nlm.nih.gov/15951442/ DOI: 10.1074/jbc.M500409200
tissue_or_cell_type
Cell-free protein
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 217–230
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutant mouse BCO1; cleavage assays and protein-bound iron spectroscopy. · source_derived_draft · unverified_draft
### va-bco1-iron-binding-machinery Substitution of conserved histidines or Glu405 in mouse BCO1 abolished cleavage and reduced protein-bound iron. Condition category: machinery_impairment nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: An intact iron-binding environment is necessary for this enzyme to work. organism: Mus musculus recombinant protein tissue_or_cell_type: Cell-free protein experimental_model: Site-directed mutant mouse BCO1; cleavage assays and protein-bound iron spectroscopy. limitations: Coordination inferred from mutagenesis and iron measurements, not a dietary iron trial. exposure: Individual alanine substitutions at conserved catalytic-site residues. outcome: Substitution of conserved histidines or Glu405 in mouse BCO1 abolished cleavage and reduced protein-bound iron. evidence_location: Abstract cross_nutrient: Links enzyme-bound iron to vitamin A precursor processing. [va-poliakov-2005] Key role of conserved histidines in recombinant mouse beta-carotene 15,15'-monooxygenase-1 activity (2005). https://pubmed.ncbi.nlm.nih.gov/15951442/ DOI: 10.1074/jbc.M500409200
Complete structured claim and evidence
Added calcium reduced nonheme-iron absorption in the studied meals.
Calcium → Nonheme iron absorption source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human isotope meal experiments.
limitations
Meal processing/phytate and direct effects both occurred; no specific molecular transporter was identified and long-term iron deficiency was not demonstrated.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
Calcium can reduce iron absorbed from a particular meal.
primary_references
[cal-clin-hallberg1991] Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans (1991). https://pubmed.ncbi.nlm.nih.gov/1984335/ DOI: 10.1093/ajcn/53.1.112
tissue_or_cell_type
Human clinical or absorption endpoint
Calcium: mechanism-first literature curation (2026-09-17) · lines 1412–1421
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human isotope meal experiments. · source_derived_draft · unverified_draft
### cal-meal-nonheme-iron Added calcium reduced nonheme-iron absorption in the studied meals. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium can reduce iron absorbed from a particular meal. organism: Homo sapiens tissue_or_cell_type: Human clinical or absorption endpoint experimental_model: Human isotope meal experiments. limitations: Meal processing/phytate and direct effects both occurred; no specific molecular transporter was identified and long-term iron deficiency was not demonstrated. [cal-clin-hallberg1991] Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans (1991). https://pubmed.ncbi.nlm.nih.gov/1984335/ DOI: 10.1093/ajcn/53.1.112
Complete structured claim and evidence
Calcium also reduced heme-iron absorption in the meal experiments.
Calcium → Heme iron absorption source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human isotope meal experiments with heme substrate.
limitations
A shared mucosal mechanism was proposed, not directly localized to a named protein.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
The acute interaction was not limited to nonheme iron.
primary_references
[cal-clin-hallberg1991] Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans (1991). https://pubmed.ncbi.nlm.nih.gov/1984335/ DOI: 10.1093/ajcn/53.1.112
tissue_or_cell_type
Human clinical or absorption endpoint
Calcium: mechanism-first literature curation (2026-09-17) · lines 1423–1432
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human isotope meal experiments with heme substrate. · source_derived_draft · unverified_draft
### cal-meal-heme-iron Calcium also reduced heme-iron absorption in the meal experiments. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The acute interaction was not limited to nonheme iron. organism: Homo sapiens tissue_or_cell_type: Human clinical or absorption endpoint experimental_model: Human isotope meal experiments with heme substrate. limitations: A shared mucosal mechanism was proposed, not directly localized to a named protein. [cal-clin-hallberg1991] Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans (1991). https://pubmed.ncbi.nlm.nih.gov/1984335/ DOI: 10.1093/ajcn/53.1.112
Complete structured claim and evidence
One year of calcium supplementation did not significantly alter measured iron-status markers in adolescent girls.
Calcium → Blood iron-status markers source_derived_draftungraded
Experimental context and source evidence
experimental_model
113 girls, randomized double-blind placebo-controlled trial.
exposure
500 mg calcium/day with evening meal for one year; reported marker comparisons were nonsignificant.
limitations
Does not establish absence of effect in iron-deficient people; hemoglobin, ferritin and soluble transferrin receptor are distinct endpoints.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
No significant worsening of iron markers was found after a year of supplementation in these girls.
primary_references
[cal-clin-molgaard2005] Long-term calcium supplementation does not affect the iron status of 12-14-y-old girls (2005). https://pubmed.ncbi.nlm.nih.gov/16002806/ DOI: 10.1093/ajcn.82.1.98
tissue_or_cell_type
Human clinical or absorption endpoint
Calcium: mechanism-first literature curation (2026-09-17) · lines 1434–1444
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 113 girls, randomized double-blind placebo-controlled trial. · source_derived_draft · unverified_draft
### cal-iron-status-longterm One year of calcium supplementation did not significantly alter measured iron-status markers in adolescent girls. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: No significant worsening of iron markers was found after a year of supplementation in these girls. organism: Homo sapiens tissue_or_cell_type: Human clinical or absorption endpoint experimental_model: 113 girls, randomized double-blind placebo-controlled trial. limitations: Does not establish absence of effect in iron-deficient people; hemoglobin, ferritin and soluble transferrin receptor are distinct endpoints. exposure: 500 mg calcium/day with evening meal for one year; reported marker comparisons were nonsignificant. [cal-clin-molgaard2005] Long-term calcium supplementation does not affect the iron status of 12-14-y-old girls (2005). https://pubmed.ncbi.nlm.nih.gov/16002806/ DOI: 10.1093/ajcn.82.1.98
Complete structured claim and evidence
Fasting-water zinc absorption was 59%, 58% and 34% at ferrous Fe:Zn molar ratios of 1:1, 2.5:1 and 25:1 respectively; inhibition was significant at the highest ratio.
Ferrous iron → Intestinal zinc absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc(II) ion (absorbed_nutrient_ion); Iron (coadministered_nutrient); L-Ascorbate (coadministered_ligand)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044}
experimental_model
Human 65Zn tracer study with whole-body counting after two weeks
exposure
Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons.
limitations
Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
The high iron-to-zinc ratio reduced zinc uptake in the fasting solution.
primary_references
[zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411
tissue_or_cell_type
Intestinal absorption
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1226–1239
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 65Zn tracer study with whole-body counting after two weeks · source_derived_draft · unverified_draft
### zn-clin-iron-fasting Fasting-water zinc absorption was 59%, 58% and 34% at ferrous Fe:Zn molar ratios of 1:1, 2.5:1 and 25:1 respectively; inhibition was significant at the highest ratio. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The high iron-to-zinc ratio reduced zinc uptake in the fasting solution. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Human 65Zn tracer study with whole-body counting after two weeks limitations: Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows. exposure: Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons. cross_nutrient: Zinc(II) ion (absorbed_nutrient_ion); Iron (coadministered_nutrient); L-Ascorbate (coadministered_ligand) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044} [zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411
Complete structured claim and evidence
When the corresponding iron-to-zinc ratios were administered with a meal, zinc absorption was 25%, 23% and 22%, without the inhibitory iron effect detected in fasting water. Two weeks of iron preloading also did not alter zinc absorption from water.
Ferrous iron → Intestinal zinc absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc(II) ion (absorbed_nutrient_ion); Iron (dietary_context)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044}
experimental_model
Human 65Zn tracer study with whole-body counting after two weeks
exposure
Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons.
limitations
Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
The fasting-solution result did not carry over to the tested meal.
primary_references
[zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411
tissue_or_cell_type
Intestinal absorption
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1241–1254
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 65Zn tracer study with whole-body counting after two weeks · source_derived_draft · unverified_draft
### zn-clin-iron-meal When the corresponding iron-to-zinc ratios were administered with a meal, zinc absorption was 25%, 23% and 22%, without the inhibitory iron effect detected in fasting water. Two weeks of iron preloading also did not alter zinc absorption from water. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The fasting-solution result did not carry over to the tested meal. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Human 65Zn tracer study with whole-body counting after two weeks limitations: Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows. exposure: Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons. cross_nutrient: Zinc(II) ion (absorbed_nutrient_ion); Iron (dietary_context) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044} [zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411
Complete structured claim and evidence
Mn(II) inhibited mouse ZIP14-mediated Fe(II) uptake in Xenopus oocytes.
Mn2+ → Cellular iron uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Mouse ZIP14 in RNA-injected Xenopus laevis oocytes
exposure
Radiolabeled Fe(II) uptake with added Mn(II).
limitations
Measured competition is assay-specific and does not establish dietary antagonism or ferric-iron transport.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mouse protein in Xenopus laevis oocytes
plain_language
Manganese reduced ferrous iron entry through ZIP14 in the assay.
primary_references
[mn-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
tissue_or_cell_type
Oocyte plasma membrane
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 292–303
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse ZIP14 in RNA-injected Xenopus laevis oocytes · source_derived_draft · unverified_draft
### mn-trans-zip14-mn-inhibits-fe Mn(II) inhibited mouse ZIP14-mediated Fe(II) uptake in Xenopus oocytes. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Manganese reduced ferrous iron entry through ZIP14 in the assay. organism: Mouse protein in Xenopus laevis oocytes tissue_or_cell_type: Oocyte plasma membrane experimental_model: Mouse ZIP14 in RNA-injected Xenopus laevis oocytes limitations: Measured competition is assay-specific and does not establish dietary antagonism or ferric-iron transport. exposure: Radiolabeled Fe(II) uptake with added Mn(II). cross_nutrient: true [mn-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
Complete structured claim and evidence
Fe(II) inhibited mouse ZIP14-mediated Mn(II) uptake in Xenopus oocytes under the tested competition conditions.
Ferrous iron → Cellular manganese uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Mouse ZIP14 in RNA-injected Xenopus laevis oocytes
exposure
2 micromolar radiolabeled Mn(II) with candidate inhibitor metal at 20 micromolar and 1 mM L-ascorbic acid; Figure 9B.
limitations
A tenfold molar competitor in a heterologous system is not a dietary competition threshold.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mouse protein in Xenopus laevis oocytes
plain_language
Fe(II) competed with manganese entry through ZIP14 in this assay.
primary_references
[mn-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
tissue_or_cell_type
Oocyte plasma membrane
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 305–316
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse ZIP14 in RNA-injected Xenopus laevis oocytes · source_derived_draft · unverified_draft
### mn-trans-zip14-fe-inhibits-mn Fe(II) inhibited mouse ZIP14-mediated Mn(II) uptake in Xenopus oocytes under the tested competition conditions. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Fe(II) competed with manganese entry through ZIP14 in this assay. organism: Mouse protein in Xenopus laevis oocytes tissue_or_cell_type: Oocyte plasma membrane experimental_model: Mouse ZIP14 in RNA-injected Xenopus laevis oocytes limitations: A tenfold molar competitor in a heterologous system is not a dietary competition threshold. exposure: 2 micromolar radiolabeled Mn(II) with candidate inhibitor metal at 20 micromolar and 1 mM L-ascorbic acid; Figure 9B. cross_nutrient: true [mn-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
Complete structured claim and evidence
Iron added to the wheat-bread test meal did not significantly change manganese absorption.
Iron → Intestinal manganese absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Manganese (measured_nutrient)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/davidsson1991.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "start_char": 0, "end_char": 912, "text_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "text_characters": 912}
experimental_model
Paired radiotracer test-meal study in adults
exposure
Human milk, infant formula and wheat bread used as adult test meals; individual mineral and dietary-component additions.
limitations
These were adult experiments even when milk or infant formula was the matrix. Added amounts were not independently verified from the indexed abstract; no universal interaction or spacing rule follows.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
An iron interaction was not detected in every meal.
primary_references
[mn-clin-davidsson1991] The effect of individual dietary components on manganese absorption in humans. (1991). https://pubmed.ncbi.nlm.nih.gov/1957822/ DOI: 10.1093/ajcn/54.6.1065
tissue_or_cell_type
Intestinal absorption
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1034–1046
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired radiotracer test-meal study in adults · source_derived_draft · unverified_draft
### mn-clin-meal-iron Iron added to the wheat-bread test meal did not significantly change manganese absorption. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: An iron interaction was not detected in every meal. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Paired radiotracer test-meal study in adults limitations: These were adult experiments even when milk or infant formula was the matrix. Added amounts were not independently verified from the indexed abstract; no universal interaction or spacing rule follows. exposure: Human milk, infant formula and wheat bread used as adult test meals; individual mineral and dietary-component additions. cross_nutrient: Manganese (measured_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/davidsson1991.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "start_char": 0, "end_char": 912, "text_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "text_characters": 912} [mn-clin-davidsson1991] The effect of individual dietary components on manganese absorption in humans. (1991). https://pubmed.ncbi.nlm.nih.gov/1957822/ DOI: 10.1093/ajcn/54.6.1065
Complete structured claim and evidence
Iron incorporation into SOD2 generated a form that used hydrogen peroxide for prooxidant peroxidase chemistry in the reported biochemical and cell experiments.
Iron-loaded human SOD2 → Iron-loaded SOD2 peroxidase activity source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
After four weeks on the iron-enriched diet, nearly 80% of isolated mouse liver Sod2 was iron-loaded.
Iron → Iron-loaded mouse Sod2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Iron excess altered occupancy of a Mn enzyme.
experimental_model
Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments
exposure
Five-week-old male C57BL/6J mice; 2700 ppm Fe and 150 ppm Mn versus control 275 ppm Fe and 150 ppm Mn, four weeks.
limitations
Experimental iron excess, not iron deficiency or a human oral-dose equivalence.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
A high-iron mouse diet shifted Sod2 toward iron loading.
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
Liver Sod2
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 521–532
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-mouse-high-fe-iron-sod2 After four weeks on the iron-enriched diet, nearly 80% of isolated mouse liver Sod2 was iron-loaded. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: A high-iron mouse diet shifted Sod2 toward iron loading. organism: Mus musculus tissue_or_cell_type: Liver Sod2 experimental_model: Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments limitations: Experimental iron excess, not iron deficiency or a human oral-dose equivalence. exposure: Five-week-old male C57BL/6J mice; 2700 ppm Fe and 150 ppm Mn versus control 275 ppm Fe and 150 ppm Mn, four weeks. cross_nutrient: Iron excess altered occupancy of a Mn enzyme. [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
Complete structured claim and evidence
Mean thyroid-volume reduction at 40 weeks was 38% with dual iron–iodine salt versus 18% with iodine-only salt (P<0.01).
Iron → Thyroid volume source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Primary indexed abstract.
experimental_model
Nine-month randomized double-blind controlled trial in 377 goitrous children aged 6–15 with high anemia prevalence
exposure
Iodized salt 25 micrograms iodine/g versus dual-fortified salt with the same iodine plus 1 mg iron/g as microencapsulated ferrous sulfate; 40-week measurements.
limitations
Clinical intervention and thyroid endpoints do not identify the exact iron-dependent step. Iodized-salt-only participants also improved. Related publications from this cohort are not independent trials.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
Adding iron improved the response to the same amount of iodine in this trial.
primary_references
[iod-clin-zimmer2002] Addition of microencapsulated iron to iodized salt improves the efficacy of iodine in goitrous, iron-deficient children: a randomized, double-blind, controlled trial. (2002). https://pubmed.ncbi.nlm.nih.gov/12457449/ DOI: 10.1530/eje.0.1470747
tissue_or_cell_type
Thyroid volume, circulating thyroxine and iron indices
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1230–1242
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine-month randomized double-blind controlled trial in 377 goitrous children aged 6–15 with high anemia prevalence · source_derived_draft · unverified_draft
### iod-clin-dual-salt-volume Mean thyroid-volume reduction at 40 weeks was 38% with dual iron–iodine salt versus 18% with iodine-only salt (P<0.01). Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding iron improved the response to the same amount of iodine in this trial. organism: Homo sapiens tissue_or_cell_type: Thyroid volume, circulating thyroxine and iron indices experimental_model: Nine-month randomized double-blind controlled trial in 377 goitrous children aged 6–15 with high anemia prevalence limitations: Clinical intervention and thyroid endpoints do not identify the exact iron-dependent step. Iodized-salt-only participants also improved. Related publications from this cohort are not independent trials. exposure: Iodized salt 25 micrograms iodine/g versus dual-fortified salt with the same iodine plus 1 mg iron/g as microencapsulated ferrous sulfate; 40-week measurements. cross_nutrient: true evidence_location: Primary indexed abstract. [iod-clin-zimmer2002] Addition of microencapsulated iron to iodized salt improves the efficacy of iodine in goitrous, iron-deficient children: a randomized, double-blind, controlled trial. (2002). https://pubmed.ncbi.nlm.nih.gov/12457449/ DOI: 10.1530/eje.0.1470747
Complete structured claim and evidence
Serum thyroxine was higher with dual-fortified salt than with iodized salt alone (P<0.05), with lower reported hypothyroidism and goiter prevalence (P<0.01).
Iron → Serum total thyroxine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Primary indexed abstract.
experimental_model
Nine-month randomized double-blind controlled trial in 377 goitrous children aged 6–15 with high anemia prevalence
exposure
Iodized salt 25 micrograms iodine/g versus dual-fortified salt with the same iodine plus 1 mg iron/g as microencapsulated ferrous sulfate; 40-week measurements.
limitations
Clinical intervention and thyroid endpoints do not identify the exact iron-dependent step. Iodized-salt-only participants also improved. Related publications from this cohort are not independent trials. The abstract does not provide the exact between-group thyroxine effect size. The two iron trials have distinct populations and endpoints; their hormone results are not declared a contradiction.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
This iron–iodine trial also found a hormone response.
primary_references
[iod-clin-zimmer2002] Addition of microencapsulated iron to iodized salt improves the efficacy of iodine in goitrous, iron-deficient children: a randomized, double-blind, controlled trial. (2002). https://pubmed.ncbi.nlm.nih.gov/12457449/ DOI: 10.1530/eje.0.1470747
tissue_or_cell_type
Thyroid volume, circulating thyroxine and iron indices
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1244–1256
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine-month randomized double-blind controlled trial in 377 goitrous children aged 6–15 with high anemia prevalence · source_derived_draft · unverified_draft
### iod-clin-dual-salt-thyroxine Serum thyroxine was higher with dual-fortified salt than with iodized salt alone (P<0.05), with lower reported hypothyroidism and goiter prevalence (P<0.01). Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This iron–iodine trial also found a hormone response. organism: Homo sapiens tissue_or_cell_type: Thyroid volume, circulating thyroxine and iron indices experimental_model: Nine-month randomized double-blind controlled trial in 377 goitrous children aged 6–15 with high anemia prevalence limitations: Clinical intervention and thyroid endpoints do not identify the exact iron-dependent step. Iodized-salt-only participants also improved. Related publications from this cohort are not independent trials. The abstract does not provide the exact between-group thyroxine effect size. The two iron trials have distinct populations and endpoints; their hormone results are not declared a contradiction. exposure: Iodized salt 25 micrograms iodine/g versus dual-fortified salt with the same iodine plus 1 mg iron/g as microencapsulated ferrous sulfate; 40-week measurements. cross_nutrient: true evidence_location: Primary indexed abstract. [iod-clin-zimmer2002] Addition of microencapsulated iron to iodized salt improves the efficacy of iodine in goitrous, iron-deficient children: a randomized, double-blind, controlled trial. (2002). https://pubmed.ncbi.nlm.nih.gov/12457449/ DOI: 10.1530/eje.0.1470747
Complete structured claim and evidence
Cryo-EM structures of the human TPO extracellular domain resolve heme at the peroxidase active site.
Human TPO ectodomain residues 1–839 → Heme source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/36537574.txt", "start_char": 17835, "end_char": 18855, "text_sha256": "6771d21482631bf712dfa882f1d08e4f40e02507211c65a60c7ef47f0d02e5d4", "text_characters": 1020, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Cryo-EM of recombinant human TPO extracellular domain with antibody fragments
exposure
Human TPO residues 1–839 expressed in High Five insect cells and bound to 2G4 or 4F5 antibody fragments.
limitations
A structural observation; no selenium catalytic requirement or dietary iron dose is demonstrated.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens protein; Trichoplusia ni expression cells
plain_language
TPO contains an iron-bearing heme group at its catalytic center.
primary_references
[iodine-syn-tpo2023] Cryo-electron microscopy structures of human thyroid peroxidase (TPO) in complex with TPO antibodies. (2023). https://pubmed.ncbi.nlm.nih.gov/36537574/ DOI: 10.1530/jme-22-0149
tissue_or_cell_type
Purified extracellular-domain antibody complexes
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 604–616
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM of recombinant human TPO extracellular domain with antibody fragments · source_derived_draft · unverified_draft
### iodine-syn-tpo-heme-structure Cryo-EM structures of the human TPO extracellular domain resolve heme at the peroxidase active site. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: TPO contains an iron-bearing heme group at its catalytic center. organism: Homo sapiens protein; Trichoplusia ni expression cells tissue_or_cell_type: Purified extracellular-domain antibody complexes experimental_model: Cryo-EM of recombinant human TPO extracellular domain with antibody fragments limitations: A structural observation; no selenium catalytic requirement or dietary iron dose is demonstrated. exposure: Human TPO residues 1–839 expressed in High Five insect cells and bound to 2G4 or 4F5 antibody fragments. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/36537574.txt", "start_char": 17835, "end_char": 18855, "text_sha256": "6771d21482631bf712dfa882f1d08e4f40e02507211c65a60c7ef47f0d02e5d4", "text_characters": 1020, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tpo2023] Cryo-electron microscopy structures of human thyroid peroxidase (TPO) in complex with TPO antibodies. (2023). https://pubmed.ncbi.nlm.nih.gov/36537574/ DOI: 10.1530/jme-22-0149
Complete structured claim and evidence
In the recombinant hybrid NFS1–ISD11–ACP structure, the phosphopantetheine-linked acyl group of E. coli ACP occupies the hydrophobic core of human ISD11.
Escherichia coli acylated phosphopantetheinyl-AcpP → Human ISD11 / LYRM4 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Abstract; primary Results: Identification of the ACP–Lipid–ISD11 Motif
experimental_model
Hybrid recombinant human NFS1–ISD11 plus native E. coli ACP; X-ray/EM structure
exposure
Coexpression and structural analysis; no nutrient restriction.
limitations
This is not an all-human ACP structure. The bound PLP and acyl-ACP show cofactor coexistence; dietary B6/B5 dependency or repletion was not tested. 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 proteins; Escherichia coli ACP
plain_language
The CoA-derived carrier arm holds a fatty-acid chain that helps form the iron–sulfur complex interface.
primary_references
[b5-met-cory2017] Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions. (2017). https://pubmed.ncbi.nlm.nih.gov/28634302/ DOI: 10.1073/pnas.1702849114
tissue_or_cell_type
Purified recombinant Fe–S assembly subcomplex
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 935–947
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hybrid recombinant human NFS1–ISD11 plus native E. coli ACP; X-ray/EM structure · source_derived_draft · unverified_draft
### b5-met-acyl-acp-isd11-interface In the recombinant hybrid NFS1–ISD11–ACP structure, the phosphopantetheine-linked acyl group of E. coli ACP occupies the hydrophobic core of human ISD11. 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-derived carrier arm holds a fatty-acid chain that helps form the iron–sulfur complex interface. organism: Homo sapiens proteins; Escherichia coli ACP tissue_or_cell_type: Purified recombinant Fe–S assembly subcomplex experimental_model: Hybrid recombinant human NFS1–ISD11 plus native E. coli ACP; X-ray/EM structure limitations: This is not an all-human ACP structure. The bound PLP and acyl-ACP show cofactor coexistence; dietary B6/B5 dependency or repletion was not tested. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Coexpression and structural analysis; no nutrient restriction. cross_nutrient: true evidence_location: Abstract; primary Results: Identification of the ACP–Lipid–ISD11 Motif [b5-met-cory2017] Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions. (2017). https://pubmed.ncbi.nlm.nih.gov/28634302/ DOI: 10.1073/pnas.1702849114
Complete structured claim and evidence
Ndufab1 siRNA in mouse C2C12 myoblasts reduced mitochondrial Nfs1, Isd11 and Iscu2 protein abundance.
Mouse mitochondrial acyl carrier protein / Ndufab1 → Mouse cysteine desulfurase / Nfs1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Full text line 117; Fig. 3C
experimental_model
Pooled Ndufab1 siRNA versus scrambled control
exposure
Ndufab1-targeting siRNA; immunoblot of isolated mitochondria.
limitations
The mammalian intact Nfs1–Isd11 complex could not be resolved by the authors with BN-PAGE; the direct mammalian result is subunit abundance. 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
Mus musculus
plain_language
The iron–sulfur machinery also became less stable after carrier depletion in mouse muscle cells.
primary_references
[b5-met-acp2016] The mitochondrial acyl carrier protein (ACP) coordinates mitochondrial fatty acid synthesis with iron sulfur cluster biogenesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27540631/ DOI: 10.7554/elife.17828
tissue_or_cell_type
C2C12 myoblast mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 921–933
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pooled Ndufab1 siRNA versus scrambled control · source_derived_draft · unverified_draft
### b5-met-mouse-acp-isu-stability Ndufab1 siRNA in mouse C2C12 myoblasts reduced mitochondrial Nfs1, Isd11 and Iscu2 protein abundance. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The iron–sulfur machinery also became less stable after carrier depletion in mouse muscle cells. organism: Mus musculus tissue_or_cell_type: C2C12 myoblast mitochondria experimental_model: Pooled Ndufab1 siRNA versus scrambled control limitations: The mammalian intact Nfs1–Isd11 complex could not be resolved by the authors with BN-PAGE; the direct mammalian result is subunit abundance. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Ndufab1-targeting siRNA; immunoblot of isolated mitochondria. cross_nutrient: true evidence_location: Full text line 117; Fig. 3C [b5-met-acp2016] The mitochondrial acyl carrier protein (ACP) coordinates mitochondrial fatty acid synthesis with iron sulfur cluster biogenesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27540631/ DOI: 10.7554/elife.17828
Complete structured claim and evidence
The yeast Acp1 S82A variant, which cannot carry phosphopantetheine at that site, only modestly restored Nfs1–Isd11 abundance in Acp1-depleted cells, unlike wild-type Acp1.
Saccharomyces cerevisiae Acp1 S82A variant → Saccharomyces cerevisiae Nfs1–Isd11 complex source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Full text line 151; Fig. 4A–B
experimental_model
Wild-type versus S82A rescue of conditional yeast ACP1 depletion
exposure
Plasmid expression; 18 hours of 10 micrograms/mL doxycycline suppression.
limitations
S82A retained viability and some aconitase rescue. The study did not directly prove identical folding of apo and holo carrier proteins. 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
Saccharomyces cerevisiae
plain_language
The protein without its CoA-derived arm retained some function, but failed to restore normal complex stability.
primary_references
[b5-met-acp2016] The mitochondrial acyl carrier protein (ACP) coordinates mitochondrial fatty acid synthesis with iron sulfur cluster biogenesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27540631/ DOI: 10.7554/elife.17828
tissue_or_cell_type
Mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 893–905
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type versus S82A rescue of conditional yeast ACP1 depletion · source_derived_draft · unverified_draft
### b5-met-yeast-acp-s82a-partial The yeast Acp1 S82A variant, which cannot carry phosphopantetheine at that site, only modestly restored Nfs1–Isd11 abundance in Acp1-depleted cells, unlike wild-type Acp1. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The protein without its CoA-derived arm retained some function, but failed to restore normal complex stability. organism: Saccharomyces cerevisiae tissue_or_cell_type: Mitochondria experimental_model: Wild-type versus S82A rescue of conditional yeast ACP1 depletion limitations: S82A retained viability and some aconitase rescue. The study did not directly prove identical folding of apo and holo carrier proteins. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Plasmid expression; 18 hours of 10 micrograms/mL doxycycline suppression. cross_nutrient: true evidence_location: Full text line 151; Fig. 4A–B [b5-met-acp2016] The mitochondrial acyl carrier protein (ACP) coordinates mitochondrial fatty acid synthesis with iron sulfur cluster biogenesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27540631/ DOI: 10.7554/elife.17828
Complete structured claim and evidence
LIAS has distinct radical-SAM and auxiliary [4Fe-4S] clusters; the latter supplies sulfur during lipoyl synthesis.
Lipoic acid synthetase / LIAS → [4Fe-4S] iron-sulfur cluster source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"}
experimental_model
Purified human LIAS turnover and cluster-transfer assays
exposure
LIAS with candidate iron-sulfur cluster donors
limitations
Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human recombinant proteins
plain_language
Two iron-sulfur clusters perform different jobs in the same enzyme.
primary_references
[ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
tissue_or_cell_type
Mitochondrial lipoyl synthesis machinery
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 299–310
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human LIAS turnover and cluster-transfer assays · source_derived_draft · unverified_draft
### ala-lias-two-clusters LIAS has distinct radical-SAM and auxiliary [4Fe-4S] clusters; the latter supplies sulfur during lipoyl synthesis. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two iron-sulfur clusters perform different jobs in the same enzyme. organism: Human recombinant proteins tissue_or_cell_type: Mitochondrial lipoyl synthesis machinery experimental_model: Purified human LIAS turnover and cluster-transfer assays limitations: Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells. exposure: LIAS with candidate iron-sulfur cluster donors evidence_span: {"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"} [ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
Complete structured claim and evidence
[2Fe-2S]-loaded human ISCU and ISCA2 reconstituted catalytically active human LIAS in vitro.
Human ISCU → Lipoic acid synthetase / LIAS source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/33562493.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4261f63098ce640cc87368d3f23f294441fdfa2a3f9b271086821fc1196bb3ac", "start_char": 0, "end_char": 1544, "text_sha256": "4261f63098ce640cc87368d3f23f294441fdfa2a3f9b271086821fc1196bb3ac"}
experimental_model
Recombinant human LIAS cluster reconstitution, EPR and LC-MS
exposure
[2Fe-2S]-loaded ISCU or ISCA2 donors
limitations
In vitro donor capacity does not establish a unique physiological donor or exclude other routes.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human proteins
plain_language
These carrier proteins can help rebuild active enzyme under assay conditions.
primary_references
[ala-p33562493] Characterization and Reconstitution of Human Lipoyl Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered Mechanism of Cluster Assembly. (2021). https://pubmed.ncbi.nlm.nih.gov/33562493/ DOI: 10.3390/ijms22041598
tissue_or_cell_type
Two LIAS iron-sulfur sites
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 390–401
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human LIAS cluster reconstitution, EPR and LC-MS · source_derived_draft · unverified_draft
### ala-iscu-isca2-reconstitution [2Fe-2S]-loaded human ISCU and ISCA2 reconstituted catalytically active human LIAS in vitro. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: These carrier proteins can help rebuild active enzyme under assay conditions. organism: Human proteins tissue_or_cell_type: Two LIAS iron-sulfur sites experimental_model: Recombinant human LIAS cluster reconstitution, EPR and LC-MS limitations: In vitro donor capacity does not establish a unique physiological donor or exclude other routes. exposure: [2Fe-2S]-loaded ISCU or ISCA2 donors evidence_span: {"source_cache": "artifacts/ala-research/33562493.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4261f63098ce640cc87368d3f23f294441fdfa2a3f9b271086821fc1196bb3ac", "start_char": 0, "end_char": 1544, "text_sha256": "4261f63098ce640cc87368d3f23f294441fdfa2a3f9b271086821fc1196bb3ac"} [ala-p33562493] Characterization and Reconstitution of Human Lipoyl Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered Mechanism of Cluster Assembly. (2021). https://pubmed.ncbi.nlm.nih.gov/33562493/ DOI: 10.3390/ijms22041598
Complete structured claim and evidence
Human complex II structure and EPR resolved SDHB-associated [2Fe-2S], [4Fe-4S] and [3Fe-4S] redox centers adjacent to its SDHA FAD system.
Human succinate dehydrogenase iron-sulfur subunit / SDHB → [4Fe-4S] iron-sulfur cluster source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-derived FAD and iron-containing redox centers cooperate within one respiratory complex.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 2, "char_start": 0, "char_end": 1105, "evidence_access": "full-text"}]
experimental_model
Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays.
exposure
No nutrient intervention; structural or biochemical characterization.
limitations
Structural co-dependence does not show that B2 corrects iron deficiency or that iron supplementation improves this reaction.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Complex II couples a B2-derived flavin with separate iron-sulfur centers.
primary_references
[du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120
tissue_or_cell_type
HEK293F-derived purified complex II
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 649–661
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. · source_derived_draft · unverified_draft
### b2-met-human-sdhb-iron-sulfur Human complex II structure and EPR resolved SDHB-associated [2Fe-2S], [4Fe-4S] and [3Fe-4S] redox centers adjacent to its SDHA FAD system. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Complex II couples a B2-derived flavin with separate iron-sulfur centers. organism: Homo sapiens tissue_or_cell_type: HEK293F-derived purified complex II experimental_model: Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. limitations: Structural co-dependence does not show that B2 corrects iron deficiency or that iron supplementation improves this reaction. exposure: No nutrient intervention; structural or biochemical characterization. cross_nutrient: B2-derived FAD and iron-containing redox centers cooperate within one respiratory complex. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 2, "char_start": 0, "char_end": 1105, "evidence_access": "full-text"}] [du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120
Complete structured claim and evidence
BBOX1 hydroxylates gamma-butyrobetaine to L-carnitine using oxygen, 2-oxoglutarate and ferrous iron.
gamma-Butyrobetaine → L-Carnitine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human cDNA expression and human tissue activity assays
limitations
Do not generalize full carnitine-synthesis capacity to every tissue.
organism
Homo sapiens
plain_language
BBOX1 completes carnitine synthesis.
primary_references
[vaz1998] Carnitine biosynthesis: identification of the cDNA encoding human gamma-butyrobetaine hydroxylase (1998). https://pubmed.ncbi.nlm.nih.gov/9753662/ DOI: 10.1006/bbrc.1998.9343 [rebouche1980] Tissue distribution of carnitine biosynthetic enzymes in man (1980). https://pubmed.ncbi.nlm.nih.gov/6770910/ DOI: 10.1016/0304-4165(80)90133-6
tissue_or_cell_type
Kidney, liver and brain; abundance differs
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 207–216
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cDNA expression and human tissue activity assays · source_derived_draft · unverified_draft
### bbox1-carnitine-formation BBOX1 hydroxylates gamma-butyrobetaine to L-carnitine using oxygen, 2-oxoglutarate and ferrous iron. Plain language: BBOX1 completes carnitine synthesis. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Kidney, liver and brain; abundance differs experimental_model: Human cDNA expression and human tissue activity assays limitations: Do not generalize full carnitine-synthesis capacity to every tissue. [vaz1998] Carnitine biosynthesis: identification of the cDNA encoding human gamma-butyrobetaine hydroxylase (1998). https://pubmed.ncbi.nlm.nih.gov/9753662/ DOI: 10.1006/bbrc.1998.9343 [rebouche1980] Tissue distribution of carnitine biosynthetic enzymes in man (1980). https://pubmed.ncbi.nlm.nih.gov/6770910/ DOI: 10.1016/0304-4165(80)90133-6
Complete structured claim and evidence
After 2-oxoglutarate-associated inactivation of chick prolyl hydroxylase, ascorbate decreased its ferric EPR signal and partly restored activity, supporting reduction of enzyme-bound Fe(III).
L-Ascorbate → Chick collagen prolyl 4-hydroxylase with oxidized enzyme-bound iron source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.
experimental_model
Purified chick collagen prolyl hydroxylase, EPR and activity measurements
exposure
400 micromolar 2-oxoglutarate; enzyme inactivation within 1 minute without ascorbate; 30-second EPR incubation at 37 C.
limitations
Protein-bound redox chemistry; no claim that serum iron or dietary iron supplementation predicts this state.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Gallus gallus
plain_language
Vitamin C can restore the iron inside an inactive collagen enzyme to a working redox state.
primary_references
[dejong1982] Prolyl 4-hydroxylase activity in relation to the oxidation state of enzyme-bound iron. The role of ascorbate in peptidyl proline hydroxylation. (1982). https://pubmed.ncbi.nlm.nih.gov/6285984/ DOI: 10.1016/0167-4838(82)90162-5
tissue_or_cell_type
Chick embryo enzyme preparation
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 624–635
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified chick collagen prolyl hydroxylase, EPR and activity measurements · source_derived_draft · unverified_draft
### vc-enzyme-bound-iron-reactivation After 2-oxoglutarate-associated inactivation of chick prolyl hydroxylase, ascorbate decreased its ferric EPR signal and partly restored activity, supporting reduction of enzyme-bound Fe(III). Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C can restore the iron inside an inactive collagen enzyme to a working redox state. organism: Gallus gallus tissue_or_cell_type: Chick embryo enzyme preparation experimental_model: Purified chick collagen prolyl hydroxylase, EPR and activity measurements limitations: Protein-bound redox chemistry; no claim that serum iron or dietary iron supplementation predicts this state. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: 400 micromolar 2-oxoglutarate; enzyme inactivation within 1 minute without ascorbate; 30-second EPR incubation at 37 C. [dejong1982] Prolyl 4-hydroxylase activity in relation to the oxidation state of enzyme-bound iron. The role of ascorbate in peptidyl proline hydroxylation. (1982). https://pubmed.ncbi.nlm.nih.gov/6285984/ DOI: 10.1016/0167-4838(82)90162-5
Complete structured claim and evidence
Ascorbate restored murine TET1-CD activity with ferric iron or under pH 8.0 conditions that rapidly oxidized Fe(II); iron-redox measurements support provision of reduced iron as the rescue mechanism.
L-Ascorbate → Mouse Tet1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Figure 1D–E; Figure S1A–C
experimental_model
Recombinant murine TET1 catalytic domain expressed in E. coli; methylated 86-mer DNA ELISA assay
exposure
1.5 µM TET1-CD, 0.5 µM DNA, 1 mM 2-oxoglutarate, 10 or 100 µM iron; sodium L-ascorbate 1 mM; pH 6.8 versus pH 8.0.
limitations
This does not directly measure free iron inside cells or establish a dietary iron/ascorbate requirement.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Mus musculus protein expressed in Escherichia coli
plain_language
Vitamin C helped restore the usable iron needed by this isolated DNA-modifying enzyme.
primary_references
[c-reg-hore] Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms. (2016). https://pubmed.ncbi.nlm.nih.gov/27729528/ DOI: 10.1073/pnas.1608679113
tissue_or_cell_type
Cell-free
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1019–1031
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant murine TET1 catalytic domain expressed in E. coli; methylated 86-mer DNA ELISA assay · source_derived_draft · unverified_draft
### c-reg-tet-iron-reduction-rescue Ascorbate restored murine TET1-CD activity with ferric iron or under pH 8.0 conditions that rapidly oxidized Fe(II); iron-redox measurements support provision of reduced iron as the rescue mechanism. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C helped restore the usable iron needed by this isolated DNA-modifying enzyme. organism: Mus musculus protein expressed in Escherichia coli tissue_or_cell_type: Cell-free experimental_model: Recombinant murine TET1 catalytic domain expressed in E. coli; methylated 86-mer DNA ELISA assay limitations: This does not directly measure free iron inside cells or establish a dietary iron/ascorbate requirement. exposure: 1.5 µM TET1-CD, 0.5 µM DNA, 1 mM 2-oxoglutarate, 10 or 100 µM iron; sodium L-ascorbate 1 mM; pH 6.8 versus pH 8.0. cross_nutrient: true evidence_location: Figure 1D–E; Figure S1A–C [c-reg-hore] Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms. (2016). https://pubmed.ncbi.nlm.nih.gov/27729528/ DOI: 10.1073/pnas.1608679113
Complete structured claim and evidence
Crystallography and metal characterization identified iron in the active site of human HAAO, with spectroscopic behavior consistent with the ferrous preparation before air oxidation.
Ferrous iron → Human 3-hydroxyanthranilate 3,4-dioxygenase / HAAO source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Nonheme iron participates in a downstream tryptophan/niacin pathway enzyme; nutritional iron restriction was not tested.
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/haao2017.paragraphs.txt", "locator": "Normalized full-text paragraphs 33–33 (0-based)", "start_char": 22514, "end_char": 24337, "file_sha256": "d02386a59595104ccae2e62943e69030930da86ec005769b469f2001e31a6eb5", "text_sha256": "4c47aa3f5cdc1fd3c776752c345f1d60e4833d0e3b7e8227c574ae086c3b1783"}
experimental_model
Purified human HAAO metal-containing crystal structures and ICP-MS/XRF/EPR characterization
exposure
Biochemical or structural assay; no dietary intervention
limitations
Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
A second iron-containing enzyme acts farther along the tryptophan route.
primary_references
[b3-pre-haao2017] Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site. (2017). https://pubmed.ncbi.nlm.nih.gov/28375145/ DOI: 10.1107/s2059798317002029
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 507–519
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human HAAO metal-containing crystal structures and ICP-MS/XRF/EPR characterization · source_derived_draft · unverified_draft
### b3-pre-haao-iron Crystallography and metal characterization identified iron in the active site of human HAAO, with spectroscopic behavior consistent with the ferrous preparation before air oxidation. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second iron-containing enzyme acts farther along the tryptophan route. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human HAAO metal-containing crystal structures and ICP-MS/XRF/EPR characterization limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention cross_nutrient: Nonheme iron participates in a downstream tryptophan/niacin pathway enzyme; nutritional iron restriction was not tested. evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/haao2017.paragraphs.txt", "locator": "Normalized full-text paragraphs 33–33 (0-based)", "start_char": 22514, "end_char": 24337, "file_sha256": "d02386a59595104ccae2e62943e69030930da86ec005769b469f2001e31a6eb5", "text_sha256": "4c47aa3f5cdc1fd3c776752c345f1d60e4833d0e3b7e8227c574ae086c3b1783"} [b3-pre-haao2017] Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site. (2017). https://pubmed.ncbi.nlm.nih.gov/28375145/ DOI: 10.1107/s2059798317002029
Complete structured claim and evidence
In the human TDO2 substrate complex, molecular oxygen was coordinated to the heme iron next to the L-tryptophan substrate.
Heme → Human tryptophan 2,3-dioxygenase / TDO2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Heme iron participates in a tryptophan-to-niacin upstream enzyme; the structure does not establish a dietary iron threshold.
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/tdo2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 7–7 (0-based)", "start_char": 5512, "end_char": 7250, "file_sha256": "3f91886745b8ff9fb808232c839dd346b03605dd025d5fa682a3de4f81338ec5", "text_sha256": "057137936657c739cdef730f5d10b930ec40af5e09f0ed4e2abbd813f26db9f0"}
experimental_model
Purified human TDO2 crystallography and spectroscopy; substrate/product complexes
exposure
Biochemical or structural assay; no dietary intervention
limitations
Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Iron held in heme positions oxygen for this precursor reaction.
primary_references
[b3-pre-tdo2016] Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase. (2016). https://pubmed.ncbi.nlm.nih.gov/27762317/ DOI: 10.1038/srep35169
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 493–505
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human TDO2 crystallography and spectroscopy; substrate/product complexes · source_derived_draft · unverified_draft
### b3-pre-tdo-heme-oxygen In the human TDO2 substrate complex, molecular oxygen was coordinated to the heme iron next to the L-tryptophan substrate. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron held in heme positions oxygen for this precursor reaction. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human TDO2 crystallography and spectroscopy; substrate/product complexes limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention cross_nutrient: Heme iron participates in a tryptophan-to-niacin upstream enzyme; the structure does not establish a dietary iron threshold. evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/tdo2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 7–7 (0-based)", "start_char": 5512, "end_char": 7250, "file_sha256": "3f91886745b8ff9fb808232c839dd346b03605dd025d5fa682a3de4f81338ec5", "text_sha256": "057137936657c739cdef730f5d10b930ec40af5e09f0ed4e2abbd813f26db9f0"} [b3-pre-tdo2016] Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase. (2016). https://pubmed.ncbi.nlm.nih.gov/27762317/ DOI: 10.1038/srep35169
Complete structured claim and evidence
SUOX sulfite oxidation depends on Moco at the catalytic site and a separate heme cofactor.
Molybdenum cofactor / Moco → Human sulfite oxidase / SUOX source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/molybdenum-research/31127934.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de", "start_char": 0, "end_char": 1649, "text_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de"}
experimental_model
Human SUOX Gly362Ser patient fibroblasts and recombinant enzyme maturation assays
exposure
G362S versus WT protein; Moco reconstitution and molybdate supplementation in culture
limitations
One genotype; in-vitro molybdate rescue is not demonstrated clinical treatment for all SUOX defects.
nutrient_topic
Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum
organism
Homo sapiens
plain_language
Molybdenum and iron-containing heme perform different jobs within this enzyme.
primary_references
[mo-p31127934] Impaired mitochondrial maturation of sulfite oxidase in a patient with severe sulfite oxidase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/31127934/ DOI: 10.1093/hmg/ddz109
tissue_or_cell_type
Mitochondrial intermembrane space; patient fibroblasts
Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 599–610
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SUOX Gly362Ser patient fibroblasts and recombinant enzyme maturation assays · source_derived_draft · unverified_draft
### mo-suox-cofactors SUOX sulfite oxidation depends on Moco at the catalytic site and a separate heme cofactor. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Molybdenum and iron-containing heme perform different jobs within this enzyme. organism: Homo sapiens tissue_or_cell_type: Mitochondrial intermembrane space; patient fibroblasts experimental_model: Human SUOX Gly362Ser patient fibroblasts and recombinant enzyme maturation assays limitations: One genotype; in-vitro molybdate rescue is not demonstrated clinical treatment for all SUOX defects. exposure: G362S versus WT protein; Moco reconstitution and molybdate supplementation in culture evidence_span: {"source_cache": "artifacts/molybdenum-research/31127934.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de", "start_char": 0, "end_char": 1649, "text_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de"} [mo-p31127934] Impaired mitochondrial maturation of sulfite oxidase in a patient with severe sulfite oxidase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/31127934/ DOI: 10.1093/hmg/ddz109
Complete structured claim and evidence
The human CYP2R1-D3 structure contained heme, with the vitamin D3 side chain directed toward this catalytic prosthetic group.
Human vitamin D 25-hydroxylase / CYP2R1 → Heme source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract and structure PDB 3C6G.
experimental_model
Purified human enzyme crystallography
exposure
CYP2R1-D3 crystal complex; PDB 3C6G.
limitations
A structural iron requirement is not evidence that iron supplements increase vitamin D activation in iron-replete people.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Homo sapiens protein
plain_language
D3 activation uses an iron-containing heme enzyme.
primary_references
[strushkevich2008] Structural analysis of CYP2R1 in complex with vitamin D3. (2008). https://pubmed.ncbi.nlm.nih.gov/18511070/ DOI: 10.1016/j.jmb.2008.03.065
tissue_or_cell_type
CYP2R1 active site
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 377–390
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human enzyme crystallography · source_derived_draft · unverified_draft
### vd-act-cyp2r1-heme The human CYP2R1-D3 structure contained heme, with the vitamin D3 side chain directed toward this catalytic prosthetic group. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: D3 activation uses an iron-containing heme enzyme. organism: Homo sapiens protein tissue_or_cell_type: CYP2R1 active site experimental_model: Purified human enzyme crystallography limitations: A structural iron requirement is not evidence that iron supplements increase vitamin D activation in iron-replete people. exposure: CYP2R1-D3 crystal complex; PDB 3C6G. cross_nutrient: true evidence_location: Primary abstract and structure PDB 3C6G. nutrient: Vitamin D2 and D3 [strushkevich2008] Structural analysis of CYP2R1 in complex with vitamin D3. (2008). https://pubmed.ncbi.nlm.nih.gov/18511070/ DOI: 10.1016/j.jmb.2008.03.065
Complete structured claim and evidence
At a physiological vitamin E-to-phospholipid ratio, inhibition of iron-dependent lipid peroxidation in rat liver microsomes and dispersed microsomal lipids was observed only when PHGPX (GPX4) and glutathione were also present.
Alpha-tocopherol → Lipid peroxidation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Microsomes and Triton-dispersed lipid micelles
exposure
Iron-dependent peroxidation; physiological vitamin E:phospholipid ratio as reported in abstract.
limitations
Exact concentrations are not available in the inspected abstract. Model-specific dependence does not imply every membrane requires added GPX4 to show E protection.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Rattus norvegicus
plain_language
Vitamin E protection depended on peroxide removal by the GPX4/glutathione system in these preparations.
primary_references
[ver-maiorino1989] Microsomal lipid peroxidation: effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase. (1989). https://pubmed.ncbi.nlm.nih.gov/2586229/ DOI: 10.1007/bf02535211
tissue_or_cell_type
Liver microsomal lipids
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 592–604
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomes and Triton-dispersed lipid micelles · source_derived_draft · unverified_draft
### ver-gpx4-gsh-tocopherol-cooperation At a physiological vitamin E-to-phospholipid ratio, inhibition of iron-dependent lipid peroxidation in rat liver microsomes and dispersed microsomal lipids was observed only when PHGPX (GPX4) and glutathione were also present. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E protection depended on peroxide removal by the GPX4/glutathione system in these preparations. organism: Rattus norvegicus tissue_or_cell_type: Liver microsomal lipids experimental_model: Microsomes and Triton-dispersed lipid micelles limitations: Exact concentrations are not available in the inspected abstract. Model-specific dependence does not imply every membrane requires added GPX4 to show E protection. exposure: Iron-dependent peroxidation; physiological vitamin E:phospholipid ratio as reported in abstract. cross_nutrient: true evidence_location: Primary abstract [ver-maiorino1989] Microsomal lipid peroxidation: effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase. (1989). https://pubmed.ncbi.nlm.nih.gov/2586229/ DOI: 10.1007/bf02535211
Complete structured claim and evidence
Iron chelation arrested DELE1 import and stabilized full-length DELE1 at the mitochondrial surface.
Deferoxamine → Full-length human DELE1 retained at mitochondrial surface during iron chelation source_derived_draftungraded
Experimental context and source evidence
access_level
selected_indexed_full_text_passages
evidence_cache
artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3
experimental_model
Human cultured cells
exposure
Pharmacological DFO; panel-specific dose/time unresolved
limitations
Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium.
organism
Human cultured cells; mouse xenograft host only for colonization endpoint
plain_language
Iron chelation arrested DELE1 import and stabilized full-length DELE1 at the mitochondrial surface.
primary_locator
https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Results: DELE1 on mitochondrial surface activates HRI; Figures 5–6
primary_references
https://doi.org/10.1016/j.molcel.2023.05.031
DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signaling · lines 55–64
Targeted primary-literature curation; selected indexed full-text passages, 2026-09-20. · supports · Human cultured cells · source_derived_draft · unverified_draft
Iron chelation arrested DELE1 import and stabilized full-length DELE1 at the mitochondrial surface. primary_references: https://doi.org/10.1016/j.molcel.2023.05.031 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Results: DELE1 on mitochondrial surface activates HRI; Figures 5–6 evidence_cache: artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3 access_level: selected_indexed_full_text_passages experimental_model: Human cultured cells organism: Human cultured cells; mouse xenograft host only for colonization endpoint exposure: Pharmacological DFO; panel-specific dose/time unresolved limitations: Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium. plain_language: Iron chelation arrested DELE1 import and stabilized full-length DELE1 at the mitochondrial surface.
Complete structured claim and evidence
Surface-retained DELE1 engaged HRI during iron deficiency.
Full-length human DELE1 retained at mitochondrial surface during iron chelation → Human HRI / EIF2AK1 source_derived_draftungraded
Experimental context and source evidence
access_level
selected_indexed_full_text_passages
evidence_cache
artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3
experimental_model
Human cultured cells
exposure
Iron chelation; panel-specific dose/time unresolved
limitations
Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium.
organism
Human cultured cells; mouse xenograft host only for colonization endpoint
plain_language
Surface-retained DELE1 engaged HRI during iron deficiency.
primary_locator
https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figures 5–6; TPR accessibility experiments
primary_references
https://doi.org/10.1016/j.molcel.2023.05.031
DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signaling · lines 67–76
Targeted primary-literature curation; selected indexed full-text passages, 2026-09-20. · supports · Human cultured cells · source_derived_draft · unverified_draft
Surface-retained DELE1 engaged HRI during iron deficiency. primary_references: https://doi.org/10.1016/j.molcel.2023.05.031 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figures 5–6; TPR accessibility experiments evidence_cache: artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3 access_level: selected_indexed_full_text_passages experimental_model: Human cultured cells organism: Human cultured cells; mouse xenograft host only for colonization endpoint exposure: Iron chelation; panel-specific dose/time unresolved limitations: Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium. plain_language: Surface-retained DELE1 engaged HRI during iron deficiency.
Complete structured claim and evidence
HRI knockdown suppressed iron-chelator-induced ISR activation.
HRI knockdown in human cultured cells → Human activating transcription factor 4 / ATF4 source_derived_draftungraded
Experimental context and source evidence
access_level
selected_indexed_full_text_passages
evidence_cache
artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3
experimental_model
HeLa
exposure
DFO/DFP; final 16 hours after 72-hour siRNA experiment
limitations
Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium.
organism
Human cultured cells; mouse xenograft host only for colonization endpoint
plain_language
HRI knockdown suppressed iron-chelator-induced ISR activation.
primary_locator
https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 4G; S3C/D
primary_references
https://doi.org/10.1016/j.molcel.2023.05.031
DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signaling · lines 79–88
Targeted primary-literature curation; selected indexed full-text passages, 2026-09-20. · supports · HeLa · source_derived_draft · unverified_draft
HRI knockdown suppressed iron-chelator-induced ISR activation. primary_references: https://doi.org/10.1016/j.molcel.2023.05.031 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 4G; S3C/D evidence_cache: artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3 access_level: selected_indexed_full_text_passages experimental_model: HeLa organism: Human cultured cells; mouse xenograft host only for colonization endpoint exposure: DFO/DFP; final 16 hours after 72-hour siRNA experiment limitations: Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium. plain_language: HRI knockdown suppressed iron-chelator-induced ISR activation.
Complete structured claim and evidence
OMA1 knockdown did not suppress the tested iron-chelation-induced ISR.
OMA1 knockdown in human cultured cells → Human activating transcription factor 4 / ATF4 source_derived_draftungraded
Experimental context and source evidence
access_level
selected_indexed_full_text_passages
evidence_cache
artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3
experimental_model
HEK293T; HeLa
exposure
DFO/DFP; exact panel dose/time unresolved
limitations
Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium.
organism
Human cultured cells; mouse xenograft host only for colonization endpoint
plain_language
OMA1 knockdown did not suppress the tested iron-chelation-induced ISR.
primary_locator
https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 5C/D
primary_references
https://doi.org/10.1016/j.molcel.2023.05.031
DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signaling · lines 91–100
Targeted primary-literature curation; selected indexed full-text passages, 2026-09-20. · supports · HEK293T; HeLa · source_derived_draft · unverified_draft
OMA1 knockdown did not suppress the tested iron-chelation-induced ISR. primary_references: https://doi.org/10.1016/j.molcel.2023.05.031 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 5C/D evidence_cache: artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3 access_level: selected_indexed_full_text_passages experimental_model: HEK293T; HeLa organism: Human cultured cells; mouse xenograft host only for colonization endpoint exposure: DFO/DFP; exact panel dose/time unresolved limitations: Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium. plain_language: OMA1 knockdown did not suppress the tested iron-chelation-induced ISR.
Complete structured claim and evidence
DELE1 knockout suppressed iron-chelation-induced ATF4 activation.
DELE1 knockout in human cultured cells → Human activating transcription factor 4 / ATF4 source_derived_draftungraded
Experimental context and source evidence
access_level
selected_indexed_full_text_passages
evidence_cache
artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3
experimental_model
HEK293-derived knockout clones 24/51
exposure
16 hours; DFP 1 mM in its arm; DFO concentration unresolved
limitations
Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium.
organism
Human cultured cells; mouse xenograft host only for colonization endpoint
plain_language
DELE1 knockout suppressed iron-chelation-induced ATF4 activation.
primary_locator
https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 4H
primary_references
https://doi.org/10.1016/j.molcel.2023.05.031
DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signaling · lines 103–112
Targeted primary-literature curation; selected indexed full-text passages, 2026-09-20. · supports · HEK293-derived knockout clones 24/51 · source_derived_draft · unverified_draft
DELE1 knockout suppressed iron-chelation-induced ATF4 activation. primary_references: https://doi.org/10.1016/j.molcel.2023.05.031 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 4H evidence_cache: artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3 access_level: selected_indexed_full_text_passages experimental_model: HEK293-derived knockout clones 24/51 organism: Human cultured cells; mouse xenograft host only for colonization endpoint exposure: 16 hours; DFP 1 mM in its arm; DFO concentration unresolved limitations: Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium. plain_language: DELE1 knockout suppressed iron-chelation-induced ATF4 activation.
Complete structured claim and evidence
ABCB7 knockdown attenuated iron-chelator-induced ATF4 expression.
ABCB7 knockdown in human cells → Human activating transcription factor 4 / ATF4 source_derived_draftungraded
Experimental context and source evidence
access_level
selected_indexed_full_text_passages
dose
Unresolved; not inferred from another panel
duration
72-hour siRNA; chelator during final 16 hours
endpoint
ATF4/ISR immunoblot readout
evidence_cache
artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21
experimental_model
HeLa
exposure
DFO or DFP; concentrations unresolved
limitations
Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.
organism
Human
primary_locator
https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 6I/J
primary_references
https://doi.org/10.1016/j.molcel.2023.05.031
Requirements for iron-triggered DELE1 signaling · lines 6–17
Primary study 10.1016/j.molcel.2023.05.031; targeted counterevidence curation, 2026-09-20. · supports · HeLa · source_derived_draft · unverified_draft
ABCB7 knockdown attenuated iron-chelator-induced ATF4 expression. primary_references: https://doi.org/10.1016/j.molcel.2023.05.031 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 6I/J evidence_cache: artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21 access_level: selected_indexed_full_text_passages organism: Human experimental_model: HeLa duration: 72-hour siRNA; chelator during final 16 hours exposure: DFO or DFP; concentrations unresolved dose: Unresolved; not inferred from another panel endpoint: ATF4/ISR immunoblot readout limitations: Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.
Complete structured claim and evidence
ABCB7 knockdown reduced DELE1 stabilization during iron chelation.
ABCB7 knockdown in human cells → Human DELE1 protein stabilization readout source_derived_draftungraded
Experimental context and source evidence
access_level
selected_indexed_full_text_passages
dose
Unresolved; not inferred from another panel
duration
72-hour siRNA; DFO for 16 hours; CHX chase final 30 minutes
endpoint
DELE1 protein stability immunoblot readout
evidence_cache
artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21
experimental_model
Endogenous DELE1-HA HEK293T
exposure
DFO and CHX concentrations unresolved
limitations
Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.
organism
Human
primary_locator
https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 6K/L
primary_references
https://doi.org/10.1016/j.molcel.2023.05.031
Requirements for iron-triggered DELE1 signaling · lines 20–31
Primary study 10.1016/j.molcel.2023.05.031; targeted counterevidence curation, 2026-09-20. · supports · Endogenous DELE1-HA HEK293T · source_derived_draft · unverified_draft
ABCB7 knockdown reduced DELE1 stabilization during iron chelation. primary_references: https://doi.org/10.1016/j.molcel.2023.05.031 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 6K/L evidence_cache: artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21 access_level: selected_indexed_full_text_passages organism: Human experimental_model: Endogenous DELE1-HA HEK293T duration: 72-hour siRNA; DFO for 16 hours; CHX chase final 30 minutes exposure: DFO and CHX concentrations unresolved dose: Unresolved; not inferred from another panel endpoint: DELE1 protein stability immunoblot readout limitations: Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.
Complete structured claim and evidence
ABCB7 knockdown did not similarly impair the tested CCCP-induced ISR.
ABCB7 knockdown in human cells → Human activating transcription factor 4 / ATF4 source_derived_draftungraded
Experimental context and source evidence
access_level
selected_indexed_full_text_passages
dose
Unresolved; not inferred from another panel
duration
72-hour siRNA; CCCP during final 16 hours
endpoint
ATF4/ISR immunoblot readout
evidence_cache
artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21
experimental_model
HeLa
exposure
CCCP concentration unresolved
limitations
Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.
organism
Human
primary_locator
https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 6I/J
primary_references
https://doi.org/10.1016/j.molcel.2023.05.031
Requirements for iron-triggered DELE1 signaling · lines 34–45
Primary study 10.1016/j.molcel.2023.05.031; targeted counterevidence curation, 2026-09-20. · supports · HeLa · source_derived_draft · unverified_draft
ABCB7 knockdown did not similarly impair the tested CCCP-induced ISR. primary_references: https://doi.org/10.1016/j.molcel.2023.05.031 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 6I/J evidence_cache: artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21 access_level: selected_indexed_full_text_passages organism: Human experimental_model: HeLa duration: 72-hour siRNA; CCCP during final 16 hours exposure: CCCP concentration unresolved dose: Unresolved; not inferred from another panel endpoint: ATF4/ISR immunoblot readout limitations: Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.
Complete structured claim and evidence
ISCU depletion attenuated iron-chelation-induced ISR activation.
ISCU knockdown in human cells → Human activating transcription factor 4 / ATF4 source_derived_draftungraded
Experimental context and source evidence
access_level
selected_indexed_full_text_passages
dose
Unresolved; not inferred from another panel
duration
72-hour siRNA reported; exact supplementary exposure schedule unresolved
endpoint
ATF4/ISR immunoblot readout
evidence_cache
artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21
experimental_model
Human cultured cells; precise supplementary-panel cell assignment unresolved
exposure
Iron chelation; panel-specific agent and concentration unresolved
limitations
Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.
organism
Human
primary_locator
https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Results discussing Figure S6B/C
primary_references
https://doi.org/10.1016/j.molcel.2023.05.031
Requirements for iron-triggered DELE1 signaling · lines 48–59
Primary study 10.1016/j.molcel.2023.05.031; targeted counterevidence curation, 2026-09-20. · supports · Human cultured cells; precise supplementary-panel cell assignment unresolved · source_derived_draft · unverified_draft
ISCU depletion attenuated iron-chelation-induced ISR activation. primary_references: https://doi.org/10.1016/j.molcel.2023.05.031 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Results discussing Figure S6B/C evidence_cache: artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21 access_level: selected_indexed_full_text_passages organism: Human experimental_model: Human cultured cells; precise supplementary-panel cell assignment unresolved duration: 72-hour siRNA reported; exact supplementary exposure schedule unresolved exposure: Iron chelation; panel-specific agent and concentration unresolved dose: Unresolved; not inferred from another panel endpoint: ATF4/ISR immunoblot readout limitations: Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.
Complete structured claim and evidence
ISCU depletion attenuated DELE1 stabilization during iron chelation.
ISCU knockdown in human cells → Human DELE1 protein stabilization readout source_derived_draftungraded
Experimental context and source evidence
access_level
selected_indexed_full_text_passages
dose
Unresolved; not inferred from another panel
duration
72-hour siRNA reported; exact supplementary exposure schedule unresolved
endpoint
DELE1 protein stability immunoblot readout
evidence_cache
artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21
experimental_model
Human cultured cells; precise supplementary-panel cell assignment unresolved
exposure
Iron chelation; panel-specific agent and concentration unresolved
limitations
Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.
organism
Human
primary_locator
https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Results discussing Figure S6B/C
primary_references
https://doi.org/10.1016/j.molcel.2023.05.031
Requirements for iron-triggered DELE1 signaling · lines 62–73
Primary study 10.1016/j.molcel.2023.05.031; targeted counterevidence curation, 2026-09-20. · supports · Human cultured cells; precise supplementary-panel cell assignment unresolved · source_derived_draft · unverified_draft
ISCU depletion attenuated DELE1 stabilization during iron chelation. primary_references: https://doi.org/10.1016/j.molcel.2023.05.031 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Results discussing Figure S6B/C evidence_cache: artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21 access_level: selected_indexed_full_text_passages organism: Human experimental_model: Human cultured cells; precise supplementary-panel cell assignment unresolved duration: 72-hour siRNA reported; exact supplementary exposure schedule unresolved exposure: Iron chelation; panel-specific agent and concentration unresolved dose: Unresolved; not inferred from another panel endpoint: DELE1 protein stability immunoblot readout limitations: Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.
Complete structured claim and evidence
VAPB knockdown reduced MITOL-mediated HMOX2 ubiquitination in HeLa cells.
VAPB knockdown in human cells → MITOL-associated HMOX2 K68 ubiquitination readout source_derived_draftungraded
Experimental context and source evidence
access_level
selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review
evidence_cache
artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a
experimental_model
HeLa; MERBiT reporter derivative where stated
exposure
48-hour siRNA exposure; indicated vectors transfected 20 hours before IP-immunoblot; siRNA concentration unresolved
limitations
Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
organism
Human
primary_locator
Figure 2e; Results on MERCs integrity
primary_references
https://doi.org/10.1038/s41556-026-01974-0
Glutathione, ER-mitochondria contacts, and iron: observed components · lines 50–58
Targeted primary-literature curation, 2026-09-20. DOIs 10.1038/s41467-025-56666-4 and 10.1038/s41556-026-01974-0. · supports · Human HeLa cells · source_derived_draft · unverified_draft
VAPB knockdown reduced MITOL-mediated HMOX2 ubiquitination in HeLa cells. primary_references: https://doi.org/10.1038/s41556-026-01974-0 primary_locator: Figure 2e; Results on MERCs integrity evidence_cache: artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a access_level: selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review organism: Human experimental_model: HeLa; MERBiT reporter derivative where stated exposure: 48-hour siRNA exposure; indicated vectors transfected 20 hours before IP-immunoblot; siRNA concentration unresolved limitations: Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
Complete structured claim and evidence
HMOX2 knockout reduced total iron measured in isolated HeLa mitochondria.
HMOX2 knockout in HeLa cells → Total iron in isolated human-cell mitochondria source_derived_draftungraded
Experimental context and source evidence
access_level
selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review
evidence_cache
artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a
experimental_model
HeLa; MERBiT reporter derivative where stated
exposure
Stable CRISPR knockout; ICP-MS after digestion; pg iron per microgram mitochondrial protein; three independent experiments
limitations
Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
organism
Human
primary_locator
Figure 4c
primary_references
https://doi.org/10.1038/s41556-026-01974-0
Glutathione, ER-mitochondria contacts, and iron: observed components · lines 61–69
Targeted primary-literature curation, 2026-09-20. DOIs 10.1038/s41467-025-56666-4 and 10.1038/s41556-026-01974-0. · supports · Human HeLa cells · source_derived_draft · unverified_draft
HMOX2 knockout reduced total iron measured in isolated HeLa mitochondria. primary_references: https://doi.org/10.1038/s41556-026-01974-0 primary_locator: Figure 4c evidence_cache: artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a access_level: selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review organism: Human experimental_model: HeLa; MERBiT reporter derivative where stated exposure: Stable CRISPR knockout; ICP-MS after digestion; pg iron per microgram mitochondrial protein; three independent experiments limitations: Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
Complete structured claim and evidence
K68R HMOX2 re-expression failed to restore mitochondrial iron as wild-type HMOX2 did in HMOX2-knockout HeLa cells.
K68R HMOX2 re-expression in HMOX2-null HeLa cells → Total iron in isolated human-cell mitochondria source_derived_draftungraded
Experimental context and source evidence
access_level
selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review
evidence_cache
artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a
experimental_model
HeLa; MERBiT reporter derivative where stated
exposure
Stable re-expression in HMOX2 KO clone 1; ICP-MS total iron; comparison with wild-type re-expression
limitations
Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
organism
Human
primary_locator
Figure 4f
primary_references
https://doi.org/10.1038/s41556-026-01974-0
Glutathione, ER-mitochondria contacts, and iron: observed components · lines 72–80
Targeted primary-literature curation, 2026-09-20. DOIs 10.1038/s41467-025-56666-4 and 10.1038/s41556-026-01974-0. · supports · Human HeLa cells · source_derived_draft · unverified_draft
K68R HMOX2 re-expression failed to restore mitochondrial iron as wild-type HMOX2 did in HMOX2-knockout HeLa cells. primary_references: https://doi.org/10.1038/s41556-026-01974-0 primary_locator: Figure 4f evidence_cache: artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a access_level: selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review organism: Human experimental_model: HeLa; MERBiT reporter derivative where stated exposure: Stable re-expression in HMOX2 KO clone 1; ICP-MS total iron; comparison with wild-type re-expression limitations: Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
Complete structured claim and evidence
VAPB knockout reduced total iron measured in isolated HeLa mitochondria.
VAPB knockout in HeLa cells → Total iron in isolated human-cell mitochondria source_derived_draftungraded
Experimental context and source evidence
access_level
selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review
evidence_cache
artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a
experimental_model
HeLa; MERBiT reporter derivative where stated
exposure
Stable CRISPR knockout; ICP-MS after digestion; pg metal per microgram mitochondrial protein; three independent experiments
limitations
Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
organism
Human
primary_locator
Figure 4g
primary_references
https://doi.org/10.1038/s41556-026-01974-0
Glutathione, ER-mitochondria contacts, and iron: observed components · lines 83–91
Targeted primary-literature curation, 2026-09-20. DOIs 10.1038/s41467-025-56666-4 and 10.1038/s41556-026-01974-0. · supports · Human HeLa cells · source_derived_draft · unverified_draft
VAPB knockout reduced total iron measured in isolated HeLa mitochondria. primary_references: https://doi.org/10.1038/s41556-026-01974-0 primary_locator: Figure 4g evidence_cache: artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a access_level: selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review organism: Human experimental_model: HeLa; MERBiT reporter derivative where stated exposure: Stable CRISPR knockout; ICP-MS after digestion; pg metal per microgram mitochondrial protein; three independent experiments limitations: Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
Complete structured claim and evidence
HMOX2 knockout reduced basal respiration in HeLa cells.
HMOX2 knockout in HeLa cells → Basal mitochondrial oxygen consumption source_derived_draftungraded
Experimental context and source evidence
access_level
selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review
evidence_cache
artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a
experimental_model
HeLa; MERBiT reporter derivative where stated
exposure
Stable CRISPR knockout; Seahorse OCR normalized to protein content; three independent experiments
limitations
Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
organism
Human
primary_locator
Figure 5a,b
primary_references
https://doi.org/10.1038/s41556-026-01974-0
Glutathione, ER-mitochondria contacts, and iron: observed components · lines 94–102
Targeted primary-literature curation, 2026-09-20. DOIs 10.1038/s41467-025-56666-4 and 10.1038/s41556-026-01974-0. · supports · Human HeLa cells · source_derived_draft · unverified_draft
HMOX2 knockout reduced basal respiration in HeLa cells. primary_references: https://doi.org/10.1038/s41556-026-01974-0 primary_locator: Figure 5a,b evidence_cache: artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a access_level: selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review organism: Human experimental_model: HeLa; MERBiT reporter derivative where stated exposure: Stable CRISPR knockout; Seahorse OCR normalized to protein content; three independent experiments limitations: Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
Complete structured claim and evidence

Availability and dependencies

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

Iron must reach mitochondria before red cells can make heme

Condition: machinery_impairment · Mitoferrin deletion

Normal role: Mitoferrin supplies mitochondrial iron.

Recorded consequence: Impaired iron incorporation into heme and erythroid maturation.

Scope: Mouse stem-cell-derived erythroblasts; zebrafish corroboration

Recycling old red-cell iron needs a heme transport step

Condition: machinery_impairment · Hrg1 depletion

Normal role: HRG1 exports engulfed red-cell heme from phagolysosomes.

Recorded consequence: Reduced heme transport out of the phagolysosomal compartment.

Scope: Mouse macrophages

Iron restriction changes chromium accumulation

Condition: nutrient_deficiency · Experimental iron-restricted rat diets combined with chromium propionate.

Normal role: Iron supports its own essential functions and shares carrier chemistry with other metals.

Recorded consequence: The increase in tissue chromium after supplementation was smaller with iron restriction.

Scope: Female rats, six weeks; the deficient nutrient here is iron.

Losing an iron chaperone reduces storage while increasing free availability

Condition: machinery_impairment · PCBP1 depletion

Normal role: PCBP1 delivers cytosolic iron to ferritin.

Recorded consequence: Less ferritin loading and a larger cytosolic iron pool.

Scope: Human cultured cells

Stored iron is not useful unless cells can release it

Condition: machinery_impairment · NCOA4 depletion

Normal role: NCOA4-dependent ferritin turnover releases stored intracellular iron.

Recorded consequence: Impaired ferritin degradation and reduced bioavailable intracellular iron.

Scope: Human cell experiments

Curcumin exposure when dietary iron is already low

Condition: nutrient_deficiency · Curcumin feeding on the lowest-iron background.

Normal role: Iron supports hemoglobin and tissue iron stores.

Recorded consequence: Hemoglobin and circulating iron indices declined further.

Scope: 26-week mouse feeding experiment

Low iron changes the lifetime of an iron-control protein

Condition: nutrient_deficiency · Experimental iron or oxygen depletion

Normal role: FBXL5 supports degradation of IRP2 under iron-replete conditions.

Recorded consequence: FBXL5 degradation alters IRP2 control.

Scope: Cultured-cell iron-sensing experiments

Loss of an iron-control signal can produce overload

Condition: machinery_impairment · Bmp6 deletion

Normal role: BMP6 supports hepcidin expression.

Recorded consequence: Low hepcidin with tissue iron overload.

Scope: Bmp6-null mice

Recovery from blood loss needs an iron-mobilizing signal

Condition: machinery_impairment · Erfe deletion followed by hemorrhage

Normal role: ERFE helps suppress hepcidin when red-cell production rises.

Recorded consequence: Delayed hepcidin suppression and blood-loss recovery.

Scope: Mouse hemorrhage experiment

The intestine can lose its ability to maintain iron uptake

Condition: machinery_impairment · Intestinal Hif2a deletion

Normal role: HIF-2alpha promotes DMT1 expression.

Recorded consequence: Reduced serum and liver iron despite compensatory lower hepcidin.

Scope: Conditional mouse knockout

Inflammation can restrict circulating iron without proving depleted stores

Condition: biomarker_context · IL-6-driven inflammatory response

Normal role: Hepcidin controls ferroportin-dependent iron release.

Recorded consequence: Higher hepcidin and lower circulating iron.

Scope: Human cell/volunteer and mouse experiments

Iron deficiency can weaken an iodine-using enzyme

Condition: nutrient_deficiency · Iron-deficient feeding

Normal role: TPO uses heme in thyroid-hormone synthesis.

Recorded consequence: Lower TPO activity, with food intake as an additional influence.

Scope: Rat dietary and pair-feeding experiment

ZIP8 suppression in placental cells

Condition: machinery_impairment · ZIP8 siRNA in BeWo cells

Normal role: ZIP8 provides multimetal entry capacity in the tested cellular system.

Recorded consequence: Reduced cellular iron uptake

Scope: Homo sapiens; Endogenous ZIP8 knockdown compared with controls.

An inherited regulatory defect can prevent the expected response to oral iron

Condition: machinery_impairment · Germline TMPRSS6 impairment

Normal role: TMPRSS6 regulates hepcidin expression.

Recorded consequence: Iron-deficiency anemia refractory to oral iron.

Scope: Human genetic families

Microcytic anemia and liver iron overload can occur together

Condition: machinery_impairment · Inherited DMT1 dysfunction

Normal role: DMT1 supports intestinal uptake and endosomal iron release.

Recorded consequence: Poorly iron-responsive anemia with progressive liver loading.

Scope: Human SLC11A2 case series context

Correcting iron deficiency improved the thyroid-size response while iodine was supplied.

Condition: nutrient_deficiency · Goiter and documented iron deficiency despite iodized-salt consumption. Same iron-deficient trial population.

Normal role: Iron supports thyroid biochemistry, including heme enzymes, but the clinical trial does not isolate a particular molecular step.

Recorded consequence: At 20 weeks, thyroid volume fell 22.8 ± 10.7% with iron treatment versus 12.7 ± 10.1% with placebo in children already using iodized salt (P<0.01). The iron and placebo groups showed no significant difference in serum thyroxine or whole-blood thyrotropin at baseline or during the intervention.

Scope: Randomized double-blind placebo-controlled trial in 166 goitrous iron-deficient children aged 5–14 in Côte d’Ivoire; All consumed iodized salt providing 10–30 mg iodine/kg salt at household level; iron group received 60 mg elemental Fe/day, four days/week for 16 weeks; outcomes followed to 20 weeks.

Microcytic anemia and liver iron overload can occur together

Condition: biomarker_context · Inherited DMT1 dysfunction

Normal role: DMT1 supports intestinal uptake and endosomal iron release.

Recorded consequence: Poorly iron-responsive anemia with progressive liver loading.

Scope: Human SLC11A2 case series context

Adding iron improved the response to the same amount of iodine in this trial.

Condition: nutrient_deficiency · High iron-deficiency/anemia prevalence among goitrous children. Same goitrous population with high anemia prevalence.

Normal role: Iron supports thyroid biochemistry, including heme enzymes, but the clinical trial does not isolate a particular molecular step.

Recorded consequence: Mean thyroid-volume reduction at 40 weeks was 38% with dual iron–iodine salt versus 18% with iodine-only salt (P<0.01). Serum thyroxine was higher with dual-fortified salt than with iodized salt alone (P<0.05), with lower reported hypothyroidism and goiter prevalence (P<0.01).

Scope: Nine-month randomized double-blind controlled trial in 377 goitrous children aged 6–15 with high anemia prevalence; Iodized salt 25 micrograms iodine/g versus dual-fortified salt with the same iodine plus 1 mg iron/g as microencapsulated ferrous sulfate; 40-week measurements.

Iron-sulfur assembly can affect both ends of heme synthesis

Condition: machinery_impairment · GLRX5 variants in congenital sideroblastic anemia

Normal role: GLRX5 supports Fe-S-dependent mitochondrial function.

Recorded consequence: Low ferrochelatase activity, altered ALAS2 and mitochondrial dysfunction.

Scope: Human patient-derived cells

An adaptation protects red cells when iron is scarce

Condition: machinery_impairment · Hri deletion combined with iron deficiency

Normal role: HRI matches globin synthesis to heme availability.

Recorded consequence: Unpaired globin aggregation and loss of erythroid cells.

Scope: Iron-deficient Hri-null mice

An inherited iron-control defect can lead to excessive storage

Condition: machinery_impairment · HFE-associated hereditary hemochromatosis

Normal role: HFE participates in systemic iron regulation.

Recorded consequence: Multiorgan iron loading.

Scope: Historical human gene-discovery cohort

Iron-related symptoms can be studied before anemia appears

Condition: biomarker_context · Fatigue with low ferritin under this trial definition

Normal role: Iron supports functions beyond hemoglobin concentration.

Recorded consequence: Iron reduced reported fatigue more than placebo in the selected population.

Scope: Nonanemic menstruating women in a randomized trial

Inflammation changes how a storage marker should be read

Condition: biomarker_context · Infection or inflammation

Normal role: Ferritin is used to estimate iron stores.

Recorded consequence: Unadjusted ferritin can underestimate population prevalence of depleted stores.

Scope: Multicountry cross-sectional population surveys

Iron treatment can work without routine added vitamin C

Condition: nutrient_deficiency · Newly diagnosed iron-deficiency anemia.

Normal role: Iron supports hemoglobin synthesis; the trial assessed recovery using blood hemoglobin and ferritin rather than measuring all cellular iron reactions.

Recorded consequence: Iron alone met the trial equivalence criterion for early hemoglobin recovery.

Scope: Open-label single-center trial, overwhelmingly women.

The sources

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

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Calcium: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signalingTargeted primary-literature curation; selected indexed full-text passages, 2026-09-20. · unverified_draftRead preserved source
Glutathione, ER-mitochondria contacts, and iron: observed componentsTargeted primary-literature curation, 2026-09-20. DOIs 10.1038/s41467-025-56666-4 and 10.1038/s41556-026-01974-0. · unverified_draftRead preserved source
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
L-Lysine: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Requirements for iron-triggered DELE1 signalingPrimary study 10.1016/j.molcel.2023.05.031; targeted counterevidence curation, 2026-09-20. · unverified_draftRead preserved source
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

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

Acute iron absorption and long-term iron status are different outcomesMeal-level absorption inhibition cannot be extrapolated into inevitable iron deficiency. Adaptation is a candidate explanation; these experiments do not establish its molecular basis.Read the recorded disagreement
Does vitamin A enhance nonheme iron absorption from cereal meals?The 1998 human studies reported enhancement; five follow-up experiments explicitly failed to reproduce it. The disagreement concerns direct meal iron absorption, separate from longer-term anemia responses.Read the recorded disagreement

Open questions in this collection

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

Which route dominates ordinary human dietary heme uptake?Macrophage HRG1 heme recycling is directly recorded here; it is not relabeled as the intestinal heme importer, and historical HCP1 terminology is not accepted as settled identity.
Which dietary-supplement regimens produce the best long-term clinical outcomes in each iron-deficiency setting?Short absorption experiments, genetic refractory anemia and intravenous formulation trials answer different questions.
Which shared-cofactor dependencies become limiting at ordinary human nutrient intakes?An enzyme needing iron, copper, PLP, flavin or phosphopantetheine does not establish that supplementation of all these nutrients is beneficial.
Which combinations of local and systemic measurements best identify usable iron in each tissue?Plasma iron, ferritin, total stores and iron available to an intracellular enzyme are different quantities.

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

Evidence, AI assistance and curation standards

Iron

The mechanisms

Duodenal Cybrd1 expression induced ferric reductase activity in oocytes and cultured cells and localized to the enterocyte brush border.

Rat DCT1/DMT1 mediated proton-coupled Fe(II) transport that depended on membrane potential.

Recombinant copper-containing human hephaestin oxidized Fe(II), with an apparent substrate Km of 2.1 micromolar.

Hepcidin bound ferroportin in tissue-culture cells.

Hepcidin-induced ferroportin removal reduced cellular iron export.

IL-6 induced hepcidin in the tested human liver-cell, mouse and volunteer systems.

The transferrin-cycle model supported by the binding experiments releases iron in acidified endosomes while apotransferrin remains receptor-bound.

Mitoferrin function was required for mitochondrial iron assimilation and heme synthesis in the tested vertebrate erythroblasts.

Human ALAS2 uses PLP to condense glycine and succinyl-CoA into 5-aminolevulinate, releasing CoA and carbon dioxide.

Human ferrochelatase inserts ferrous iron into protoporphyrin to form heme.

The NFS1-containing desulfurase complex structure resolved a solvent-exposed PLP cofactor and an unusual substrate-channel architecture.

Ferric carboxymaltose increased biologically active FGF23 in the substudy; the mean within-person increase at the week-two peak was approximately 303%, versus 10% with ferumoxytol.

The original rat DCT1 expression assay also transported Mn(II), among other divalent metals.

Apotransferrin bound receptors at pH 5.4 but dissociated rapidly when pH was raised to 7.0.

Steap3 colocalized with transferrin-cycle endosomes and promoted iron reduction and transferrin-dependent iron uptake.

Mfrn-null mouse embryonic-stem-cell-derived erythroblasts arrested maturation and had severely impaired incorporation of iron-55 into heme.

Abcb10 interacted with Mfrn1, enhanced its stability and promoted Mfrn1-dependent mitochondrial iron import.

Fech interacted with both Mfrn1 and Abcb10 in the studied erythroid systems.

The human ferrochelatase homodimer contained two uniquely coordinated, nitric-oxide-sensitive [2Fe-2S] clusters.

Oxyhemoglobin structures resolved hydrogen bonding between the oxygen ligand and distal histidine in both alpha and beta subunits.

Hrg1 localized to phagolysosomal membranes during erythrophagocytosis and transported heme toward the macrophage cytoplasm.

Hrg1 depletion attenuated heme transport from macrophage phagolysosomes.

Heme oxygenase oxidatively cleaves heme to biliverdin with release of iron and carbon monoxide.

PCBP1 bound iron and ferritin and facilitated iron loading into ferritin in vitro and in cellular systems.

PCBP1 depletion inhibited ferritin iron loading and increased cytosolic iron pools in human cells.

Human H-chain ferritin catalyzed Fe(II) oxidation; mutation of its proposed ferroxidase ligands Glu62 and His65 abolished most activity.

Recombinant human L-chain ferritin lacked ferroxidase activity, although H/L assembly composition altered whole-ferritin oxidation kinetics.

NCOA4 associated with ferritin heavy/light chains and was required for their delivery to lysosomes.

NCOA4-deficient cells could not degrade ferritin normally and had decreased bioavailable intracellular iron.

Manipulations of the IRE-binding protein Fe-S cluster reciprocally altered RNA-binding and aconitase activities.

A SKP1-CUL1-FBXL5 ligase complex associated with IRP2 and promoted its iron-dependent ubiquitination and degradation.

Iron or oxygen depletion triggered FBXL5 degradation through a process requiring its N-terminal hemerythrin-like iron-binding domain.

Hepcidin binding induced ferroportin internalization and degradation.

Hepcidin occupied outward-open ferroportin and blocked its iron-efflux pathway.

Iron increased hepcidin affinity for ferroportin approximately 80-fold in the measured binding system.

The study demonstrated a physical interaction between BMP6 and soluble hemojuvelin fusion protein.

BMP6 increased hepcidin expression and reduced serum iron in mice.

Bmp6-null mice had reduced hepcidin expression and tissue iron overload.

Erythroblasts produced erythroferrone in response to erythropoietin.

Erythroferrone mediated hepcidin suppression during stress erythropoiesis.

ERFE-deficient mice failed to suppress hepcidin rapidly after hemorrhage and recovered more slowly from blood loss.

Intestinal HIF-2alpha directly regulated DMT1 transcription and was required for iron balance; HIF-1alpha was not required for iron absorption in this study.

Intestinal Hif2a deletion lowered serum and liver iron and markedly reduced liver hepcidin expression.

The IL-6–hepcidin axis mediated inflammation-associated hypoferremia in the studied systems.

Iron-deficiency anemia independently reduced thyroid peroxidase activity after accounting for food restriction in the rat experiment.

Very-high-iron feeding caused low serum/tissue copper, reduced circulating ceruloplasmin activity, anemia and cardiac hypertrophy in the studied rats.

Additional copper prevented the reported growth, cardiac and anemia disturbances under high-iron feeding, but increased hepatic nonheme iron loading.

Phosphate below 2.0 mg/dL occurred in 50.8% with ferric carboxymaltose versus 0.9% with ferumoxytol; low phosphate persisted at five weeks in 29.1% versus none.

The rise in active FGF23 was associated with increased renal phosphate wasting and hypophosphatemia.

The FGF23 rise was associated with lower calcitriol and serum calcium and higher PTH concentrations.

Hypophosphatemia occurred in 7.9% versus 75.0% in trial A and 8.1% versus 73.7% in trial B with derisomaltose versus carboxymaltose.

Iron absorption was significantly higher when tea was consumed one hour after the meal than when consumed simultaneously (P=0.046).

Germline TMPRSS6 mutations caused iron-deficiency anemia refractory to oral iron therapy in the studied families.

The patient had microcytic anemia from birth and progressive liver iron overload with compound-heterozygous DMT1 mutations.

The reported DMT1-deficiency syndrome included liver iron overload despite normal to moderately elevated serum ferritin.

Cybrd1 deletion had little or no effect on mouse body iron stores even during iron deficiency, implying alternative reduction routes.

Ferrochelatase protein abundance increased in patient-derived cells, while its catalytic activity was drastically reduced.

ALAS2 activity was altered in the GLRX5-deficient cells; a problem in succinyl-CoA supply was proposed as a contributor.

Patient-derived cells showed reduced glutathione and aconitase activity, damaged/depleted mitochondrial DNA, lower complex I/IV activities and lower ATP content.

When intracellular heme declined, HRI inhibited translation initiation and restrained both alpha- and beta-globin synthesis in erythroid precursors.

Iron-deficient Hri-null mice accumulated globin aggregates lacking heme within red cells and their precursors.

Hri-null mice under iron deficiency had accelerated erythroid apoptosis and reduced red-cell counts.

The NFS1–ISD11–ACP core associates with ISCU, frataxin and ferredoxin to support Fe-S cluster biosynthesis.

Human RRM2 radical-center tyrosine mutations abolished the detectable stable radical and ribonucleotide-reductase activity in the tested assays.

The corresponding conserved-tyrosine perturbation also disabled the radical and catalytic activity of the human p53R2/RRM2B system.

Intracellular iron chelation removed the ribonucleotide-reductase tyrosyl radical, with depletion and regeneration kinetics depending on the chelator.

A major HFE missense alteration was homozygous in 83% of 178 hereditary-hemochromatosis patients in the discovery cohort.

Erastin-induced ferroptosis depended on intracellular iron and was distinct from apoptosis, necrosis and autophagy in the study.

Erastin inhibited cystine uptake through system xc-minus, weakening antioxidant defenses before iron-dependent oxidative death.

Glutathione depletion in response to one class of ferroptosis inducers inactivated glutathione peroxidases, while another class directly inhibited GPX4.

GPX4 overexpression or knockdown altered lethality of all 12 tested ferroptosis inducers, but not 11 compounds with other lethal mechanisms.

Doses of at least 60 mg raised hepcidin at 24 hours and reduced fractional absorption of subsequent iron by 35–45%.

Increasing the dose from 40 to 240 mg reduced fractional absorption but increased the absolute amount absorbed from 6.7 to 18.1 mg.

Fractional iron absorption on the initial and alternate-day doses was 40–50% higher than on the consecutive-day dose.

Fatigue scores decreased 47.7% with iron versus 28.8% with placebo; the between-group difference was significant (P=0.02).

Adjusting ferritin for inflammation increased estimated depleted-store prevalence by 7–25 median percentage points in children and 2–8 points in women, depending on the method.

Ascorbate enhanced ferric-NTA iron uptake; ascorbate oxidase and Fe(II) chelators inhibited the enhancement, supporting a required Fe(III)-to-Fe(II) reduction step in this cell model.

Apical ascorbic acid at 100 and 1000 micromolar increased apical-to-basolateral iron transport 5.6-fold and 30-fold, respectively, in the ferric-NTA system.