Ferrous iron

cross_nutrient

true

experimental_model

Rat ZIP8-expressing HEK293T radiotracer assay

exposure

2 micromolar labeled zinc and tenfold unlabeled iron excess; uptake medium included ascorbate.

limitations

Transport competition in cells is not a universal dietary zinc/iron ratio or a prediction for mixed meals.

nutrient_topic

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

organism

Rat protein in human cells

plain_language

Iron reduced zinc entry through this transporter system under the tested culture conditions.

primary_references

[zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284

tissue_or_cell_type

HEK293T cells

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 440–451

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat ZIP8-expressing HEK293T radiotracer assay · source_derived_draft · unverified_draft

### zinc-trans-zip8-iron-inhibits-zinc A tenfold molar excess of iron inhibited radiolabeled zinc uptake in HEK293T cells expressing rat ZIP8. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron reduced zinc entry through this transporter system under the tested culture conditions. organism: Rat protein in human cells tissue_or_cell_type: HEK293T cells experimental_model: Rat ZIP8-expressing HEK293T radiotracer assay limitations: Transport competition in cells is not a universal dietary zinc/iron ratio or a prediction for mixed meals. exposure: 2 micromolar labeled zinc and tenfold unlabeled iron excess; uptake medium included ascorbate. cross_nutrient: true [zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284

cross_nutrient

Zinc(II) ion (absorbed_nutrient_ion); Iron (coadministered_nutrient); L-Ascorbate (coadministered_ligand)

evidence_location

Indexed primary abstract.

evidence_span

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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

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

evidence_access

Primary full text

experimental_model

5 micromolar fisetin with FeCl2/CuCl2 titration.

limitations

Cell-culture ratio, not a clinical spacing rule for supplements.

nutrient_topic

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

plain_language

Iron weakened the signaling response under these conditions.

primary_references

Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 160–166

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 5 micromolar fisetin with FeCl2/CuCl2 titration. · source_derived_draft · unverified_draft

## fisetin-iron-signaling-antagonism Iron weakened the signaling response under these conditions. In mouse HT22 cells, added iron reduced fisetin-induced nuclear Nrf2 and ATF4 from an iron:fisetin ratio of 0.5:1; copper did not do so in the tested range. Model: 5 micromolar fisetin with FeCl2/CuCl2 titration. Limitations: Cell-culture ratio, not a clinical spacing rule for supplements. Evidence access: Primary full text Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113

evidence_access

Primary abstract

experimental_model

Purified recombinant human DOHH; EPR, Mossbauer, XAS and Raman spectroscopy.

limitations

Not a clinical iron-deficiency threshold or evidence that extra iron improves spermidine responses.

nutrient_topic

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

plain_language

Iron is part of the enzyme that completes hypusination.

primary_references

Human deoxyhypusine hydroxylase, an enzyme involved in regulating cell growth, activates O2 with a nonheme diiron center. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19706422/ · DOI 10.1073/pnas.0904553106

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 54–60

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified recombinant human DOHH; EPR, Mossbauer, XAS and Raman spectroscopy. · source_derived_draft · unverified_draft

## spermidine-dohh-iron Iron is part of the enzyme that completes hypusination. Spectroscopy established a coupled diiron center in human DOHH, whose reduced state activates oxygen. Model: Purified recombinant human DOHH; EPR, Mossbauer, XAS and Raman spectroscopy. Limitations: Not a clinical iron-deficiency threshold or evidence that extra iron improves spermidine responses. Evidence access: Primary abstract Human deoxyhypusine hydroxylase, an enzyme involved in regulating cell growth, activates O2 with a nonheme diiron center. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19706422/ · DOI 10.1073/pnas.0904553106

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

evidence_span

{"source_cache": "artifacts/lycopene-research/16672231.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "135695c9d3106469d8d64ec0806ba5bf048f0f1df6f3e3cd53e838e50b960445", "start_char": 0, "end_char": 1967, "text_sha256": "135695c9d3106469d8d64ec0806ba5bf048f0f1df6f3e3cd53e838e50b960445"}

experimental_model

Recombinant ferret enzyme and tissue-fraction metabolism

exposure

5-cis, 13-cis and all-trans lycopene; iron; NAD+ or NADH

limitations

Ferret experiments do not quantify human cleavage flux or predict supplement response.

nutrient_topic

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

organism

Ferret

plain_language

The cleavage machinery has a mineral requirement.

primary_references

[lycopene-p16672231] The biochemical characterization of ferret carotene-9',10'-monooxygenase catalyzing cleavage of carotenoids in vitro and in vivo. (2006). https://pubmed.ncbi.nlm.nih.gov/16672231/ DOI: 10.1074/jbc.m512095200

tissue_or_cell_type

BCO2 enzyme; hepatic fractions and lung

Lycopene: absorption, metabolism, nutrient connections and human outcomes (2026-09-17) · lines 325–336

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant ferret enzyme and tissue-fraction metabolism · source_derived_draft · unverified_draft

### lycopene-bco2-iron Iron was an essential cofactor for lycopene cleavage by recombinant ferret BCO2. Condition category: normal nutrient_topic: Lycopene research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cleavage machinery has a mineral requirement. organism: Ferret tissue_or_cell_type: BCO2 enzyme; hepatic fractions and lung experimental_model: Recombinant ferret enzyme and tissue-fraction metabolism limitations: Ferret experiments do not quantify human cleavage flux or predict supplement response. exposure: 5-cis, 13-cis and all-trans lycopene; iron; NAD+ or NADH evidence_span: {"source_cache": "artifacts/lycopene-research/16672231.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "135695c9d3106469d8d64ec0806ba5bf048f0f1df6f3e3cd53e838e50b960445", "start_char": 0, "end_char": 1967, "text_sha256": "135695c9d3106469d8d64ec0806ba5bf048f0f1df6f3e3cd53e838e50b960445"} [lycopene-p16672231] The biochemical characterization of ferret carotene-9',10'-monooxygenase catalyzing cleavage of carotenoids in vitro and in vivo. (2006). https://pubmed.ncbi.nlm.nih.gov/16672231/ DOI: 10.1074/jbc.m512095200

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

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

Context depends on 2-oxoglutarate; this is not a clinical comparison of iron and vitamin C supplements.

nutrient_topic

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

organism

Gallus gallus

plain_language

Adding free iron did not substitute for vitamin C under the tested enzyme conditions.

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 637–648

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-free-iron-not-replacement With 2-oxoglutarate present, added Fe(II) did not partly reactivate the inactivated chick prolyl hydroxylase as ascorbate did; reduction by Fe(II) was possible in the absence of 2-oxoglutarate. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding free iron did not substitute for vitamin C under the tested enzyme conditions. organism: Gallus gallus tissue_or_cell_type: Chick embryo enzyme preparation experimental_model: Purified chick collagen prolyl hydroxylase, EPR and activity measurements limitations: Context depends on 2-oxoglutarate; this is not a clinical comparison of iron and vitamin C supplements. 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

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

evidence_span

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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

evidence_span

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

experimental_model

Purified recombinant human hephaestin

exposure

Fe(II) substrate and apotransferrin assays

limitations

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

nutrient_topic

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

organism

Human protein produced in baby hamster kidney cells

plain_language

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

primary_references

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

tissue_or_cell_type

Purified soluble hephaestin construct

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

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

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

evidence_span

{"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"}

experimental_model

Cell perturbation and xenograft experiments

exposure

DIM; NRF2 overexpression and pharmacological rescue controls

limitations

Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human non-small-cell lung-cancer cells and mouse xenografts

plain_language

Iron-dependent cell-death chemistry connects to the same canonical iron node.

primary_references

[dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z

tissue_or_cell_type

Ferroptosis and AHR/NRF2/GPX4

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1338–1349

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell perturbation and xenograft experiments · source_derived_draft · unverified_draft

### dim-nsclc-iron DIM increased measured cellular ferrous iron in the lung-cancer experiments. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron-dependent cell-death chemistry connects to the same canonical iron node. organism: Human non-small-cell lung-cancer cells and mouse xenografts tissue_or_cell_type: Ferroptosis and AHR/NRF2/GPX4 experimental_model: Cell perturbation and xenograft experiments limitations: Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people. exposure: DIM; NRF2 overexpression and pharmacological rescue controls evidence_span: {"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"} [dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z

evidence_span

{"source_cache": "artifacts/melatonin-research/11747434.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c98a1e028f9c3d7f749d37794a8e976c8c808e0ca9c5f08c394d9d29ae639e06", "start_char": 0, "end_char": 2063, "text_sha256": "c98a1e028f9c3d7f749d37794a8e976c8c808e0ca9c5f08c394d9d29ae639e06"}

experimental_model

NMR substrate/cofactor geometry and enzyme modeling

exposure

L-tryptophan and bound BH2 cofactor analogue

limitations

BH2 was a structural analogue in this experiment, not a demonstration that BH2 replaces physiological BH4. No clinical iron-deficiency threshold measured.

nutrient_topic

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

organism

Recombinant human TPH1 catalytic domain

plain_language

The upstream hydroxylation machinery contains iron; giving more iron is not automatically a way to make more melatonin.

primary_references

[melatonin-p11747434] Conformation of the substrate and pterin cofactor bound to human tryptophan hydroxylase. Important role of Phe313 in substrate specificity. (2001). https://pubmed.ncbi.nlm.nih.gov/11747434/ DOI: 10.1021/bi015722x

tissue_or_cell_type

Non-heme iron active site

Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 162–173

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · NMR substrate/cofactor geometry and enzyme modeling · source_derived_draft · unverified_draft

### melatonin-tph1-iron The human TPH catalytic domain positioned tryptophan and a pterin analogue near its catalytic non-heme iron. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The upstream hydroxylation machinery contains iron; giving more iron is not automatically a way to make more melatonin. organism: Recombinant human TPH1 catalytic domain tissue_or_cell_type: Non-heme iron active site experimental_model: NMR substrate/cofactor geometry and enzyme modeling limitations: BH2 was a structural analogue in this experiment, not a demonstration that BH2 replaces physiological BH4. No clinical iron-deficiency threshold measured. exposure: L-tryptophan and bound BH2 cofactor analogue evidence_span: {"source_cache": "artifacts/melatonin-research/11747434.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c98a1e028f9c3d7f749d37794a8e976c8c808e0ca9c5f08c394d9d29ae639e06", "start_char": 0, "end_char": 2063, "text_sha256": "c98a1e028f9c3d7f749d37794a8e976c8c808e0ca9c5f08c394d9d29ae639e06"} [melatonin-p11747434] Conformation of the substrate and pterin cofactor bound to human tryptophan hydroxylase. Important role of Phe313 in substrate specificity. (2001). https://pubmed.ncbi.nlm.nih.gov/11747434/ DOI: 10.1021/bi015722x

evidence_access

Primary abstract

experimental_model

Cell-free EXAFS study of the specified fulvic fraction.

limitations

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

nutrient_topic

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

plain_language

Acidity changed the iron-redox outcome.

primary_references

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

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

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

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

acting_entity

s-allylcysteine

dose

Not specified in accessed abstract

duration

Not specified in accessed abstract

evidence_access

Primary abstract

experimental_comparison

SAC in metal-binding and oxidative challenge assays

experimental_model

Ferrozine, electrochemistry and rat brain homogenate

interpretation_status

Source-derived research curation; not independent primary verification

limitations

No binding constant or dietary iron-absorption effect was available from the accessed abstract.

nutrient_topic

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

organism

Cell-free assays and rat brain preparation

plain_language

Iron binding is distinct from radical scavenging.

primary_references

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

route

In vitro

tissue_or_cell_type

Ferrozine, electrochemistry and rat brain homogenate

S-allylcysteine: sulfur signaling, redox responses and cross-nutrient mechanisms (2026-09-20) · lines 113–120

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

## s-allylcysteine-iron-ii-binding Iron binding is distinct from radical scavenging. Ferrozine competition supported SAC binding of Fe2+ in a chemical assay. Model: Ferrozine, electrochemistry and rat brain homogenate Limitations: No binding constant or dietary iron-absorption effect was available from the accessed abstract. Evidence access: Primary abstract [18422331] Antioxidant and iron-binding properties of curcumin, capsaicin, and S-allylcysteine reduce oxidative stress in rat brain homogenate. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18422331/ · DOI 10.1021/jf0734931 Structured context: {"organism": "Cell-free assays and rat brain preparation", "tissue_or_cell_type": "Ferrozine, electrochemistry and rat brain homogenate", "dose": "Not specified in accessed abstract", "duration": "Not specified in accessed abstract", "route": "In vitro", "experimental_comparison": "SAC in metal-binding and oxidative challenge assays", "acting_entity": "s-allylcysteine", "interpretation_status": "Source-derived research curation; not independent primary verification"}

evidence_span

{"source_cache": "artifacts/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

evidence_span

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

experimental_model

Ferroxidase kinetics and site-directed mutants

exposure

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

limitations

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

nutrient_topic

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

organism

Human recombinant ferritin and human liver apoferritin

plain_language

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

primary_references

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

tissue_or_cell_type

Purified ferritin subunits/assemblies

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

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

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

evidence_span

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

experimental_model

Purified recombinant human hephaestin

exposure

Fe(II) substrate and apotransferrin assays

limitations

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

nutrient_topic

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

organism

Human protein produced in baby hamster kidney cells

plain_language

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

primary_references

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

tissue_or_cell_type

Purified soluble hephaestin construct

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

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

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

evidence_access

Primary full text, recombinant methods and enzyme kinetics

experimental_model

Human PHD2 residues 181–402; NMR and enzymatic assays.

limitations

Millimolar assay exposure is relevant to local gut questions, not evidence of inhibition throughout the body at normal blood levels.

nutrient_topic

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

plain_language

It also directly affected an enzyme that normally marks HIF for degradation.

primary_references

Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34190032/ · DOI 10.1080/19490976.2021.1938380

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 246–252

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human PHD2 residues 181–402; NMR and enzymatic assays. · source_derived_draft · unverified_draft

## butyrate-phd2-inhibition It also directly affected an enzyme that normally marks HIF for degradation. Butyrate bound and inhibited a recombinant human PHD2 catalytic fragment; kinetic analysis gave a noncompetitive Ki of 5.3 ± 0.5 mM relative to 2-oxoglutarate. Model: Human PHD2 residues 181–402; NMR and enzymatic assays. Limitations: Millimolar assay exposure is relevant to local gut questions, not evidence of inhibition throughout the body at normal blood levels. Evidence access: Primary full text, recombinant methods and enzyme kinetics Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34190032/ · DOI 10.1080/19490976.2021.1938380

evidence_access

Primary abstract

experimental_model

Cell-free chemical system.

limitations

Not a human nutrient requirement or treatment for iron overload.

nutrient_topic

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

plain_language

Metal binding and radical chemistry can act together.

primary_references

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

Luteolin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 308–314

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cell-free chemical system. · source_derived_draft · unverified_draft

## luteolin-iron-fenton Metal binding and radical chemistry can act together. Luteolin suppressed Fenton radical generation through combined Fe(II) chelation and radical scavenging. Model: Cell-free chemical system. Limitations: Not a human nutrient requirement or treatment for iron overload. Evidence access: Primary abstract Spectroscopic and electrochemical studies on the evaluation of the radical scavenging activities of luteolin by chelating iron · 2014 · https://pubs.rsc.org/en/content/articlelanding/2014/ra/c4ra01396d · DOI 10.1039/C4RA01396D

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human HepG2 loss/gain-of-function experiments.

limitations

Not a selective rescue test proving all luteolin effects require SLC7A11.

nutrient_topic

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

plain_language

Precursor handling and peroxide defense are linked.

primary_references

Luteolin attenuates CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38755566/ · DOI 10.1186/s12906-024-04486-2

trigger_kind

machinery_impairment Imported condition classification; unverified.

Luteolin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 524–530

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human HepG2 loss/gain-of-function experiments. · source_derived_draft · unverified_draft

## luteolin-slc7a11-knockdown Precursor handling and peroxide defense are linked. SLC7A11 silencing lowered GPX4/FTMT expression and total glutathione while worsening ferroptosis-associated measurements in HepG2 cells. Model: Human HepG2 loss/gain-of-function experiments. Limitations: Not a selective rescue test proving all luteolin effects require SLC7A11. Evidence access: Primary full text Luteolin attenuates CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38755566/ · DOI 10.1186/s12906-024-04486-2

evidence_access

Primary abstract

experimental_model

Human NSCLC cell experiments.

limitations

Rescue does not establish exclusive cell-death causation or clinical cancer efficacy.

nutrient_topic

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

plain_language

Iron chelation and lipid-radical inhibitors changed the outcome.

primary_references

Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 252–258

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

## cucurbitacin-b-ferroptosis-rescue Iron chelation and lipid-radical inhibitors changed the outcome. In human H358 and A549 cells, deferoxamine, ferrostatin-1 and liproxstatin-1 reversed cucurbitacin B growth inhibition, supporting a ferroptotic component. Model: Human NSCLC cell experiments. Limitations: Rescue does not establish exclusive cell-death causation or clinical cancer efficacy. Evidence access: Primary abstract Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805

evidence_access

Primary abstract

experimental_model

Human NSCLC experiments; concentration and duration unavailable in accessed abstract.

limitations

Associated readouts do not by themselves order iron release, glutathione loss and lipid oxidation.

nutrient_topic

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

plain_language

Iron and antioxidant balance changed together with membrane damage.

primary_references

Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 260–266

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NSCLC experiments; concentration and duration unavailable in accessed abstract. · source_derived_draft · unverified_draft

## cucurbitacin-b-lipid-iron Iron and antioxidant balance changed together with membrane damage. Cucurbitacin B increased lipid ROS, malondialdehyde and measured ferrous iron while lowering glutathione in H358 and A549 experiments. Model: Human NSCLC experiments; concentration and duration unavailable in accessed abstract. Limitations: Associated readouts do not by themselves order iron release, glutathione loss and lipid oxidation. Evidence access: Primary abstract Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human H358/A549 genetic perturbation experiments.

limitations

This establishes model-specific pathway involvement, not universal STAT3 control of ferroptosis.

nutrient_topic

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

plain_language

Changing a signaling protein altered the iron-dependent response.

primary_references

Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805

trigger_kind

machinery_impairment Imported condition classification; unverified.

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 276–282

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human H358/A549 genetic perturbation experiments. · source_derived_draft · unverified_draft

## cucurbitacin-b-stat3-rescue Changing a signaling protein altered the iron-dependent response. STAT3 overexpression reversed tested cucurbitacin B-associated lipid ROS and iron changes, whereas STAT3 silencing enhanced them. Model: Human H358/A549 genetic perturbation experiments. Limitations: This establishes model-specific pathway involvement, not universal STAT3 control of ferroptosis. Evidence access: Primary abstract Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805

evidence_access

Primary full text

experimental_model

Ammonium metavanadate diets reported as 30 or 45 mg V/kg feed; 42-day duck study.

limitations

Observational pathway measurements after exposure, not direct enzyme inhibition or a human ferroptosis mechanism. Methods inconsistently say three and four groups while listing control plus two exposure groups.

nutrient_topic

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

plain_language

An animal toxicity study links the exposure to a lipid-defense pathway.

primary_references

Dual-pathway mechanism of vanadium-induced hepatotoxicity in ducks: Synergistic crosstalk between glucose homeostasis disruption and NADH/FSP1/COQ10 axis-driven ferroptosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41362732/ · DOI 10.7150/ijbs.123482

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 358–364

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Ammonium metavanadate diets reported as 30 or 45 mg V/kg feed; 42-day duck study. · source_derived_draft · unverified_draft

## vanadium-duck-redox-axis An animal toxicity study links the exposure to a lipid-defense pathway. Dietary vanadium overexposure in ducks was associated with lower NADH/FSP1/CoQ10-axis measures and increased hepatic lipid peroxidation and Fe2+ accumulation. Model: Ammonium metavanadate diets reported as 30 or 45 mg V/kg feed; 42-day duck study. Limitations: Observational pathway measurements after exposure, not direct enzyme inhibition or a human ferroptosis mechanism. Methods inconsistently say three and four groups while listing control plus two exposure groups. Evidence access: Primary full text Dual-pathway mechanism of vanadium-induced hepatotoxicity in ducks: Synergistic crosstalk between glucose homeostasis disruption and NADH/FSP1/COQ10 axis-driven ferroptosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41362732/ · DOI 10.7150/ijbs.123482

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human osteoblast-like cell inhibitor study.

limitations

Does not prove direct silicon binding or silicon as an obligatory enzyme cofactor.

nutrient_topic

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

plain_language

Intact collagen-processing machinery was needed for the response.

primary_references

Orthosilicic acid stimulates collagen type 1 synthesis and osteoblastic differentiation in human osteoblast-like cells in vitro. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12633784/ · DOI 10.1016/s8756-3282(02)00950-x

trigger_kind

machinery_impairment Imported condition classification; unverified.

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 136–142

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human osteoblast-like cell inhibitor study. · source_derived_draft · unverified_draft

## silica-hydroxylase-block Intact collagen-processing machinery was needed for the response. Prolyl hydroxylase inhibitors abolished the orthosilicic-acid-associated collagen increase. Model: Human osteoblast-like cell inhibitor study. Limitations: Does not prove direct silicon binding or silicon as an obligatory enzyme cofactor. Evidence access: Primary abstract Orthosilicic acid stimulates collagen type 1 synthesis and osteoblastic differentiation in human osteoblast-like cells in vitro. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12633784/ · DOI 10.1016/s8756-3282(02)00950-x

evidence_access

Primary abstract

experimental_model

Human endothelial cells; released silicon in the ppm range.

limitations

Accessed abstract does not establish direct inhibitor binding; HIF PHD2 differs from collagen prolyl hydroxylase.

nutrient_topic

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

plain_language

A biomaterial study implicated oxygen-sensing machinery.

primary_references

Promoting angiogenesis with mesoporous microcarriers through a synergistic action of delivered silicon ion and VEGF. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27918936/ · DOI 10.1016/j.biomaterials.2016.11.053

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 272–278

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human endothelial cells; released silicon in the ppm range. · source_derived_draft · unverified_draft

## silica-microcarrier-hif A biomaterial study implicated oxygen-sensing machinery. Silicon-releasing microcarriers increased HIF1A expression and stabilization, attributed to reduced PHD2 activity in HUVECs. Model: Human endothelial cells; released silicon in the ppm range. Limitations: Accessed abstract does not establish direct inhibitor binding; HIF PHD2 differs from collagen prolyl hydroxylase. Evidence access: Primary abstract Promoting angiogenesis with mesoporous microcarriers through a synergistic action of delivered silicon ion and VEGF. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27918936/ · DOI 10.1016/j.biomaterials.2016.11.053

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

evidence_span

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experimental_model

Isolated mitochondrial and iron-redox assays

exposure

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

limitations

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

nutrient_topic

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

organism

Rattus norvegicus and cell-free chemistry

plain_language

Binding iron altered its ability to drive membrane oxidation.

primary_references

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

tissue_or_cell_type

Liver mitochondria

Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 666–677

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

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

evidence_span

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

experimental_model

Isolated mitochondrial and iron-redox assays

exposure

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

limitations

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

nutrient_topic

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

organism

Rattus norvegicus and cell-free chemistry

plain_language

The iron oxidation state shifted.

primary_references

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

tissue_or_cell_type

Liver mitochondria

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

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

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

evidence_access

Primary abstract

experimental_model

Rat proximal-tubule suspensions; 1 mM deferoxamine pretreatment.

limitations

Does not exclude every oxidative mechanism or establish ferroptosis; distinguishes marker suppression from survival rescue.

nutrient_topic

Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice

plain_language

Blocking one injury marker did not rescue the cells.

primary_references

[1853344] The role of altered mitochondrial function in citrinin-induced toxicity to rat renal proximal tubule suspensions. · 1991 · https://pubmed.ncbi.nlm.nih.gov/1853344/ · DOI 10.1016/0041-008x(91)90008-3

Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 324–330

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat proximal-tubule suspensions; 1 mM deferoxamine pretreatment. · source_derived_draft · unverified_draft

## red-yeast-rice-citrinin-iron-rescue-failure Blocking one injury marker did not rescue the cells. Deferoxamine pretreatment prevented iron-mediated lipid peroxidation but did not protect rat tubules from citrinin-induced death. Model: Rat proximal-tubule suspensions; 1 mM deferoxamine pretreatment. Limitations: Does not exclude every oxidative mechanism or establish ferroptosis; distinguishes marker suppression from survival rescue. Evidence access: Primary abstract [1853344] The role of altered mitochondrial function in citrinin-induced toxicity to rat renal proximal tubule suspensions. · 1991 · https://pubmed.ncbi.nlm.nih.gov/1853344/ · DOI 10.1016/0041-008x(91)90008-3

evidence_access

Primary full text; reaction background distinguished from new structural experiments

experimental_model

Human PAH structural study; established reaction described in the full-text introduction.

limitations

This record describes the established reaction, not a new dietary intervention or a human iron-deficiency threshold.

nutrient_topic

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

plain_language

Making tyrosine requires a working enzyme and its chemical helpers.

primary_references

Structural basis for ligand-dependent dimerization of phenylalanine hydroxylase regulatory domain. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27049649/ · DOI 10.1038/srep23748

L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 14–20

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PAH structural study; established reaction described in the full-text introduction. · source_derived_draft · unverified_draft

## l-phenylalanine-pah-conversion Making tyrosine requires a working enzyme and its chemical helpers. PAH catalyzes phenylalanine hydroxylation to tyrosine using BH4, molecular oxygen and non-heme ferrous iron. Model: Human PAH structural study; established reaction described in the full-text introduction. Limitations: This record describes the established reaction, not a new dietary intervention or a human iron-deficiency threshold. Evidence access: Primary full text; reaction background distinguished from new structural experiments Structural basis for ligand-dependent dimerization of phenylalanine hydroxylase regulatory domain. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27049649/ · DOI 10.1038/srep23748

evidence_access

Primary abstract

experimental_model

Purified bacterial pathway.

limitations

Does not mean iron supplements increase human synthesis.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Iron supports a microbial synthesis enzyme.

primary_references

In vitro reconstitution of Mycobacterial ergothioneine biosynthesis. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20420449/ · DOI 10.1021/ja101721e

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 176–182

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified bacterial pathway. · source_derived_draft · unverified_draft

## ergothioneine-bacterial-iron-step Iron supports a microbial synthesis enzyme. Reconstituted Mycobacterium smegmatis biosynthesis required an iron(II)-dependent oxidative sulfurization step. Model: Purified bacterial pathway. Limitations: Does not mean iron supplements increase human synthesis. Evidence access: Primary abstract In vitro reconstitution of Mycobacterial ergothioneine biosynthesis. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20420449/ · DOI 10.1021/ja101721e

evidence_access

Primary abstract

experimental_model

Crystal structure and enzyme mechanism study.

limitations

Non-heme iron coordination supports a proposed radical mechanism, not direct observation of every intermediate.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A cysteine-containing precursor supplies sulfur.

primary_references

Structure of the sulfoxide synthase EgtB from the ergothioneine biosynthetic pathway. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25597398/ · DOI 10.1002/anie.201410045

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 184–190

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Crystal structure and enzyme mechanism study. · source_derived_draft · unverified_draft

## ergothioneine-egtb-sulfur-donor A cysteine-containing precursor supplies sulfur. Mycobacterium thermoresistibile EgtB coupled gamma-glutamylcysteine to hercynine through an oxygen-dependent C-S bond-forming reaction. Model: Crystal structure and enzyme mechanism study. Limitations: Non-heme iron coordination supports a proposed radical mechanism, not direct observation of every intermediate. Evidence access: Primary abstract Structure of the sulfoxide synthase EgtB from the ergothioneine biosynthetic pathway. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25597398/ · DOI 10.1002/anie.201410045

evidence_access

Primary abstract

experimental_model

Acinetobacter enzyme redox spectroscopy and site-directed mutants.

limitations

Bacterial cofactor dependence does not show that human B2 or iron supplementation increases TMAO.

nutrient_topic

L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine

plain_language

Riboflavin-derived FMN, iron centers and NADH connect to microbial carnitine chemistry.

primary_references

Carnitine metabolism in the human gut: characterization of the two-component carnitine monooxygenase CntAB from Acinetobacter baumannii. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32694223/ · DOI 10.1074/jbc.RA120.014266

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 394–400

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Acinetobacter enzyme redox spectroscopy and site-directed mutants. · source_derived_draft · unverified_draft

## l-carnitine-cntb-redox Riboflavin-derived FMN, iron centers and NADH connect to microbial carnitine chemistry. CntB passed NADH-derived electrons through FMN and iron-sulfur centers to support CntA oxygen activation. Model: Acinetobacter enzyme redox spectroscopy and site-directed mutants. Limitations: Bacterial cofactor dependence does not show that human B2 or iron supplementation increases TMAO. Evidence access: Primary abstract Carnitine metabolism in the human gut: characterization of the two-component carnitine monooxygenase CntAB from Acinetobacter baumannii. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32694223/ · DOI 10.1074/jbc.RA120.014266

cross_nutrient

true

experimental_model

Mouse ZIP14 in Xenopus oocytes

exposure

Radiolabeled ferrous iron uptake with competing zinc.

limitations

Ferrous and ferric iron are distinct. This competition does not establish in vivo dietary interactions; transport properties vary by substrate.

nutrient_topic

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

organism

Mouse protein in Xenopus laevis oocytes

plain_language

Zinc interfered with ferrous iron entry through ZIP14 in the transport assay.

primary_references

[zinc-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

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 505–516

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse ZIP14 in Xenopus oocytes · source_derived_draft · unverified_draft

### zinc-trans-zip14-zinc-inhibits-iron Zinc inhibited mouse ZIP14-mediated Fe(II) uptake in Xenopus oocytes. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc interfered with ferrous iron entry through ZIP14 in the transport assay. organism: Mouse protein in Xenopus laevis oocytes tissue_or_cell_type: Oocyte plasma membrane experimental_model: Mouse ZIP14 in Xenopus oocytes limitations: Ferrous and ferric iron are distinct. This competition does not establish in vivo dietary interactions; transport properties vary by substrate. exposure: Radiolabeled ferrous iron uptake with competing zinc. cross_nutrient: true [zinc-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

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

experimental_model

ZIP8 suppression in BeWo trophoblast-derived cells

exposure

Endogenous ZIP8 knockdown compared with controls.

limitations

This is iron uptake in a placental cell line, not direct transplacental zinc flux or an in vivo fetal iron requirement for dietary zinc.

nutrient_topic

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

organism

Homo sapiens

plain_language

ZIP8 contributed to iron entry in a human placental cell model.

primary_references

[zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284

tissue_or_cell_type

BeWo placental cell line

trigger_kind

machinery_impairment Imported condition classification; unverified.

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 466–477

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ZIP8 suppression in BeWo trophoblast-derived cells · source_derived_draft · unverified_draft

### zinc-trans-zip8-placental-iron Suppressing endogenous human ZIP8 in BeWo placental cells reduced iron uptake by approximately 40%. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: ZIP8 contributed to iron entry in a human placental cell model. organism: Homo sapiens tissue_or_cell_type: BeWo placental cell line experimental_model: ZIP8 suppression in BeWo trophoblast-derived cells limitations: This is iron uptake in a placental cell line, not direct transplacental zinc flux or an in vivo fetal iron requirement for dietary zinc. exposure: Endogenous ZIP8 knockdown compared with controls. cross_nutrient: true [zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284

cross_nutrient

true

experimental_model

Rat ZIP8-expressing HEK293T radiotracer assay

exposure

2 micromolar labeled iron with ascorbate and tenfold unlabeled zinc excess.

limitations

The assay contains reduction chemistry and soluble ions; this is not direct evidence for the magnitude of human meal-iron inhibition.

nutrient_topic

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

organism

Rat protein in human cells

plain_language

Zinc strongly reduced iron entry in this cultured transport system.

primary_references

[zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284

tissue_or_cell_type

HEK293T cells

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 453–464

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat ZIP8-expressing HEK293T radiotracer assay · source_derived_draft · unverified_draft

### zinc-trans-zip8-zinc-inhibits-iron A tenfold molar excess of zinc inhibited iron uptake by more than 90% in rat ZIP8-expressing HEK293T cells under the study conditions. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc strongly reduced iron entry in this cultured transport system. organism: Rat protein in human cells tissue_or_cell_type: HEK293T cells experimental_model: Rat ZIP8-expressing HEK293T radiotracer assay limitations: The assay contains reduction chemistry and soluble ions; this is not direct evidence for the magnitude of human meal-iron inhibition. exposure: 2 micromolar labeled iron with ascorbate and tenfold unlabeled zinc excess. cross_nutrient: true [zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284

cross_nutrient

Ferrous iron (competing_ion); Zinc(II) ion (absorbed_ion)

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

A ligand changed the interaction between iron and zinc in this experiment.

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 1256–1269

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-histidine-iron Adding histidine to the high-iron water solution attenuated inhibition, with zinc absorption of 47% compared with 34% at the high iron ratio without that ligand. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: A ligand changed the interaction between iron and zinc in this experiment. 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: Ferrous iron (competing_ion); Zinc(II) ion (absorbed_ion) 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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse cells; pharmacological GPX4 inhibition plus iron.

limitations

Not proof that fisetin worsens ordinary selenium deficiency; RSL3 and dietary selenium shortage differ.

nutrient_topic

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

plain_language

Protection can fail when a different defense step is blocked.

primary_references

Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113

trigger_kind

machinery_impairment Imported condition classification; unverified.

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 168–174

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse cells; pharmacological GPX4 inhibition plus iron. · source_derived_draft · unverified_draft

## fisetin-gpx4-block-metal-injury Protection can fail when a different defense step is blocked. With RSL3-mediated GPX4 inhibition, 5 micromolar fisetin enhanced iron-potentiated HT22 toxicity at iron concentrations of 2.5 micromolar or higher. Model: Mouse cells; pharmacological GPX4 inhibition plus iron. Limitations: Not proof that fisetin worsens ordinary selenium deficiency; RSL3 and dietary selenium shortage differ. Evidence access: Primary full text Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113

evidence_access

Primary abstract

experimental_model

Spectroscopy, competition assays and structural calculations.

limitations

Fisetin bound iron less strongly than EDTA and citrate under tested conditions; no human iron-depletion outcome measured.

nutrient_topic

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

plain_language

The same molecule binds metal differently as conditions change.

primary_references

Comparative spectroscopic and mechanistic study of chelation properties of fisetin with iron in aqueous buffered solutions. Implications on in vitro antioxidant activity. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21431152/ · DOI 10.1039/c0dt01834a

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 136–142

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Spectroscopy, competition assays and structural calculations. · source_derived_draft · unverified_draft

## fisetin-iron-chelation The same molecule binds metal differently as conditions change. Buffered chemical assays identified 1:1 and 1:2 iron-fisetin complexes with pH-dependent coordination sites. Model: Spectroscopy, competition assays and structural calculations. Limitations: Fisetin bound iron less strongly than EDTA and citrate under tested conditions; no human iron-depletion outcome measured. Evidence access: Primary abstract Comparative spectroscopic and mechanistic study of chelation properties of fisetin with iron in aqueous buffered solutions. Implications on in vitro antioxidant activity. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21431152/ · DOI 10.1039/c0dt01834a

evidence_access

Primary full text

experimental_model

Mouse HT22 cells; separately added FeCl2/CuCl2, 0.5-10 micromolar.

limitations

Not a dietary deficiency experiment or evidence of systemic metal removal.

nutrient_topic

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

plain_language

Protection depended on the way oxidative stress was induced.

primary_references

Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 152–158

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse HT22 cells; separately added FeCl2/CuCl2, 0.5-10 micromolar. · source_derived_draft · unverified_draft

## fisetin-metal-gsh-protection Protection depended on the way oxidative stress was induced. At 5 micromolar, fisetin limited iron- or copper-potentiated glutathione loss and cell death in glutamate-challenged mouse HT22 cells. Model: Mouse HT22 cells; separately added FeCl2/CuCl2, 0.5-10 micromolar. Limitations: Not a dietary deficiency experiment or evidence of systemic metal removal. Evidence access: Primary full text Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse microglial cells; Nrf2 knockdown and metal comparisons.

limitations

Endpoint-specific response; not total suppression of immunity.

nutrient_topic

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

plain_language

Even inflammatory outputs had different dependencies.

primary_references

Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113

trigger_kind

machinery_impairment Imported condition classification; unverified.

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 176–182

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse microglial cells; Nrf2 knockdown and metal comparisons. · source_derived_draft · unverified_draft

## fisetin-microglial-nrf2-dependence Even inflammatory outputs had different dependencies. Nrf2 siRNA weakened fisetin suppression of nitric oxide and IL-6, but not TNF-alpha to the same extent, in LPS-treated mouse BV2 cells. Model: Mouse microglial cells; Nrf2 knockdown and metal comparisons. Limitations: Endpoint-specific response; not total suppression of immunity. Evidence access: Primary full text Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113

evidence_access

Primary abstract

experimental_model

Human enzyme; 1.7-angstrom structures and spectroscopy.

limitations

DOHH is not a collagen-type 2-oxoglutarate hydroxylase; do not infer the same vitamin C requirement.

nutrient_topic

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

plain_language

Oxygen chemistry completes the protein modification.

primary_references

Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25865244/ · DOI 10.1016/j.str.2015.03.002

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 62–68

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme; 1.7-angstrom structures and spectroscopy. · source_derived_draft · unverified_draft

## spermidine-dohh-oxygen Oxygen chemistry completes the protein modification. Human DOHH structures resolved a peroxo-diiron intermediate involved in hydroxylating deoxyhypusine-eIF5A. Model: Human enzyme; 1.7-angstrom structures and spectroscopy. Limitations: DOHH is not a collagen-type 2-oxoglutarate hydroxylase; do not infer the same vitamin C requirement. Evidence access: Primary abstract Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25865244/ · DOI 10.1016/j.str.2015.03.002

evidence_access

Primary full text

experimental_model

Human prostate cancer cells; 1.25–5 micromolar erastin, 24-hour viability assays.

limitations

Not evidence of cancer prevention or a safe self-treatment combination.

nutrient_topic

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

plain_language

A cancer-cell context can turn the response toward iron-dependent injury.

primary_references

Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40486852/ · DOI 10.1016/j.apsb.2025.02.023

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 502–508

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human prostate cancer cells; 1.25–5 micromolar erastin, 24-hour viability assays. · source_derived_draft · unverified_draft

## spermidine-erastin-sensitization A cancer-cell context can turn the response toward iron-dependent injury. One micromolar spermidine enhanced erastin-associated lipid peroxidation and cell death in PC3 and DU145 cells. Model: Human prostate cancer cells; 1.25–5 micromolar erastin, 24-hour viability assays. Limitations: Not evidence of cancer prevention or a safe self-treatment combination. Evidence access: Primary full text Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40486852/ · DOI 10.1016/j.apsb.2025.02.023

evidence_access

Primary full text

experimental_model

Human prostate cancer combination-treatment model.

limitations

NRF2/HMOX1 direction depends on cell state and iron handling; no universal ferroptosis prediction.

nutrient_topic

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

plain_language

Heme breakdown links this response to iron availability.

primary_references

Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40486852/ · DOI 10.1016/j.apsb.2025.02.023

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 526–532

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human prostate cancer combination-treatment model. · source_derived_draft · unverified_draft

## spermidine-hmox1-iron Heme breakdown links this response to iron availability. The study linked elevated NRF2 to HMOX1 upregulation and increased labile ferrous iron during combination treatment. Model: Human prostate cancer combination-treatment model. Limitations: NRF2/HMOX1 direction depends on cell state and iron handling; no universal ferroptosis prediction. Evidence access: Primary full text Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40486852/ · DOI 10.1016/j.apsb.2025.02.023

evidence_access

Primary abstract

experimental_model

Cell-free iron-loaded liposomes.

limitations

Ascorbate participated in the oxidation-initiating system; this is not evidence that vitamin C regenerates astaxanthin or that astaxanthin removes body iron.

nutrient_topic

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

plain_language

Its effect depended on the surrounding iron and oxidant chemistry.

primary_references

Astaxanthin and peridinin inhibit oxidative damage in Fe(2+)-loaded liposomes: scavenging oxyradicals or changing membrane permeability? · 2001 · https://pubmed.ncbi.nlm.nih.gov/11594777/ · DOI 10.1006/bbrc.2001.5765

Astaxanthin: transport, membrane chemistry, signaling and nutrient interactions (2026-09-19) · lines 174–180

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cell-free iron-loaded liposomes. · source_derived_draft · unverified_draft

## astaxanthin-iron-ascorbate Its effect depended on the surrounding iron and oxidant chemistry. Astaxanthin reduced lipid damage in iron-loaded liposomes challenged using peroxide or ascorbate-dependent initiating systems. Model: Cell-free iron-loaded liposomes. Limitations: Ascorbate participated in the oxidation-initiating system; this is not evidence that vitamin C regenerates astaxanthin or that astaxanthin removes body iron. Evidence access: Primary abstract Astaxanthin and peridinin inhibit oxidative damage in Fe(2+)-loaded liposomes: scavenging oxyradicals or changing membrane permeability? · 2001 · https://pubmed.ncbi.nlm.nih.gov/11594777/ · DOI 10.1006/bbrc.2001.5765

evidence_access

Primary abstract

experimental_model

Cell-free phospholipid liposomes.

limitations

Regional chemistry was inferred from oxidation products, not direct proof of a permanently membrane-spanning orientation.

nutrient_topic

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

plain_language

Different regions of the molecule may participate in radical trapping.

primary_references

Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11406102/ · DOI 10.1016/s0005-2736(01)00326-1

Astaxanthin: transport, membrane chemistry, signaling and nutrient interactions (2026-09-19) · lines 158–164

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cell-free phospholipid liposomes. · source_derived_draft · unverified_draft

## astaxanthin-iron-liposome Different regions of the molecule may participate in radical trapping. Astaxanthin inhibited ADP/Fe2+-initiated liposome peroxidation more strongly than beta-carotene in this assay; chemical degradation patterns suggested contributions from both its polyene and terminal rings. Model: Cell-free phospholipid liposomes. Limitations: Regional chemistry was inferred from oxidation products, not direct proof of a permanently membrane-spanning orientation. Evidence access: Primary abstract Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11406102/ · DOI 10.1016/s0005-2736(01)00326-1

cross_nutrient

This step follows the canonical PLP-dependent KYNU reaction and uses a nonheme iron enzyme.

evidence_span

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experimental_model

Human HAAO cDNA from HepG2 library, expressed in HEK-293 cells and assayed biochemically

exposure

Biochemical or structural assay; no dietary intervention

limitations

The immediate HAAO product is ACMS, which cyclizes to quinolinate; the indexed abstract uses pathway-level quinolinate wording. This claim does not assert direct NAD+ synthesis.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

Expressed human HAAO processed the product made by B6-dependent KYNU.

primary_references

[b3-pre-haao1994] Molecular cloning and functional expression of human 3-hydroxyanthranilic-acid dioxygenase. (1994). https://pubmed.ncbi.nlm.nih.gov/7514594/ DOI: 10.1016/s0021-9258(17)36717-0 [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

supporting_evidence_spans

[{"source_cache": "artifacts/niacin-precursors-sources/haao2017.paragraphs.txt", "locator": "Normalized full-text paragraphs 14–14 (0-based)", "start_char": 4395, "end_char": 7197, "file_sha256": "d02386a59595104ccae2e62943e69030930da86ec005769b469f2001e31a6eb5", "text_sha256": "3b52b56d1b671c24721b47204cd30d19cd004f8a461fecd4875e94d3f491dbf6"}]

tissue_or_cell_type

HEK-293 cells expressing human HAAO; biochemical activity assay

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 521–535

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HAAO cDNA from HepG2 library, expressed in HEK-293 cells and assayed biochemically · source_derived_draft · unverified_draft

### b3-pre-haao-human-activity Human HAAO expressed in HEK-293 cells was enzymatically active toward 3-hydroxyanthranilate, with an apparent substrate Km near 2 micromolar in the study of the quinolinate-producing pathway step. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Expressed human HAAO processed the product made by B6-dependent KYNU. organism: Homo sapiens tissue_or_cell_type: HEK-293 cells expressing human HAAO; biochemical activity assay experimental_model: Human HAAO cDNA from HepG2 library, expressed in HEK-293 cells and assayed biochemically limitations: The immediate HAAO product is ACMS, which cyclizes to quinolinate; the indexed abstract uses pathway-level quinolinate wording. This claim does not assert direct NAD+ synthesis. exposure: Biochemical or structural assay; no dietary intervention cross_nutrient: This step follows the canonical PLP-dependent KYNU reaction and uses a nonheme iron enzyme. evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/haao1994.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 1874, "file_sha256": "a79697b138bcb2957b0eff9580266c7879a1c5853aba34898f891559b4e435f8", "text_sha256": "a79697b138bcb2957b0eff9580266c7879a1c5853aba34898f891559b4e435f8"} supporting_evidence_spans: [{"source_cache": "artifacts/niacin-precursors-sources/haao2017.paragraphs.txt", "locator": "Normalized full-text paragraphs 14–14 (0-based)", "start_char": 4395, "end_char": 7197, "file_sha256": "d02386a59595104ccae2e62943e69030930da86ec005769b469f2001e31a6eb5", "text_sha256": "3b52b56d1b671c24721b47204cd30d19cd004f8a461fecd4875e94d3f491dbf6"}] [b3-pre-haao1994] Molecular cloning and functional expression of human 3-hydroxyanthranilic-acid dioxygenase. (1994). https://pubmed.ncbi.nlm.nih.gov/7514594/ DOI: 10.1016/s0021-9258(17)36717-0 [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

evidence_access

Primary abstract

experimental_model

Cell-free 10 mM amino-acid comparison.

limitations

Not evidence that dietary histidine damages human DNA.

nutrient_topic

Carnosine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnosine / beta-alanyl-L-histidine

plain_language

The breakdown product did not behave like the intact peptide.

primary_references

Antioxidant properties of carnosine re-evaluated with oxidizing systems involving iron and copper ions. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15853927/ · DOI 10.1111/j.1742-7843.2005.pto_03.x

Carnosine: synthesis, transport, carbonyl chemistry and nutrient interactions (2026-09-19) · lines 316–322

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cell-free 10 mM amino-acid comparison. · source_derived_draft · unverified_draft

## carnosine-histidine-metal The breakdown product did not behave like the intact peptide. Histidine increased DNA damage in the tested iron/peroxide/ascorbate system and weakened carnosine protection when combined with it. Model: Cell-free 10 mM amino-acid comparison. Limitations: Not evidence that dietary histidine damages human DNA. Evidence access: Primary abstract Antioxidant properties of carnosine re-evaluated with oxidizing systems involving iron and copper ions. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15853927/ · DOI 10.1111/j.1742-7843.2005.pto_03.x

evidence_access

Primary abstract

experimental_model

Cell-free metal-catalyzed oxidation.

limitations

Millimolar assay; does not show safe systemic metal chelation.

nutrient_topic

Carnosine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnosine / beta-alanyl-L-histidine

plain_language

Its chemical protection depended on the oxidation system.

primary_references

Antioxidant properties of carnosine re-evaluated with oxidizing systems involving iron and copper ions. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15853927/ · DOI 10.1111/j.1742-7843.2005.pto_03.x

Carnosine: synthesis, transport, carbonyl chemistry and nutrient interactions (2026-09-19) · lines 308–314

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cell-free metal-catalyzed oxidation. · source_derived_draft · unverified_draft

## carnosine-metal-dna Its chemical protection depended on the oxidation system. At 10 mM, carnosine reduced DNA damage caused by copper- or iron/peroxide/ascorbate systems. Model: Cell-free metal-catalyzed oxidation. Limitations: Millimolar assay; does not show safe systemic metal chelation. Evidence access: Primary abstract Antioxidant properties of carnosine re-evaluated with oxidizing systems involving iron and copper ions. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15853927/ · DOI 10.1111/j.1742-7843.2005.pto_03.x

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

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

evidence_span

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

experimental_model

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

exposure

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

limitations

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

nutrient_topic

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

organism

Homo sapiens

plain_language

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

primary_references

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

tissue_or_cell_type

Golgi glycosylation in HEK cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

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

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

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

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

experimental_model

Purified chick-embryo enzyme kinetics.

limitations

Family-level enzyme preparation, not a human PLOD isoform comparison or lysine-supplement trial.

organism

Chicken

plain_language

Vitamin C supports the reaction, but is not consumed in every coupled turnover.

primary_references

[plod-cofactor-1980] Studies on the lysyl hydroxylase reaction. I. Initial velocity kinetics and related aspects. (1980). https://pubmed.ncbi.nlm.nih.gov/6766066/ DOI: 10.1016/0005-2744(80)90040-6

tissue_or_cell_type

Not specified as a whole tissue; see experimental model.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 427–435

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

### ascorbate-lysyl-hydroxylase Ascorbate supports sustained lysyl-hydroxylase activity; the enzyme can initially turn over without ascorbate. Plain language: Vitamin C supports the reaction, but is not consumed in every coupled turnover. Condition category: normal organism: Chicken tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Purified chick-embryo enzyme kinetics. limitations: Family-level enzyme preparation, not a human PLOD isoform comparison or lysine-supplement trial. [plod-cofactor-1980] Studies on the lysyl hydroxylase reaction. I. Initial velocity kinetics and related aspects. (1980). https://pubmed.ncbi.nlm.nih.gov/6766066/ DOI: 10.1016/0005-2744(80)90040-6

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

experimental_model

Human DOHH structures and spectroscopy.

limitations

DOHH is a diiron enzyme, not a 2-oxoglutarate-dependent hydroxylase. This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome.

organism

Human

plain_language

A second enzyme completes the special modification.

primary_references

[dohh-2015] Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination (2015). https://pubmed.ncbi.nlm.nih.gov/25865244/ DOI: 10.1016/j.str.2015.03.002

tissue_or_cell_type

Not specified as a whole tissue; see experimental model.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 588–596

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DOHH structures and spectroscopy. · source_derived_draft · unverified_draft

### dohh-eif5a-hypusine DOHH hydroxylates deoxyhypusine-eIF5A to hypusine-eIF5A using its oxygen-activating diiron center. Plain language: A second enzyme completes the special modification. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human DOHH structures and spectroscopy. limitations: DOHH is a diiron enzyme, not a 2-oxoglutarate-dependent hydroxylase. This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [dohh-2015] Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination (2015). https://pubmed.ncbi.nlm.nih.gov/25865244/ DOI: 10.1016/j.str.2015.03.002

experimental_model

Human JMJD2A catalytic-domain structures and methylated peptide assays.

limitations

This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome.

organism

Human

plain_language

An iron-dependent enzyme erases a different class of methyl mark.

primary_references

[kdm4a-2006] Structural insights into histone demethylation by JMJD2 family members (2006). https://pubmed.ncbi.nlm.nih.gov/16677698/ DOI: 10.1016/j.cell.2006.04.024 [kdm4a-specificity-2007] Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase (2007). https://pubmed.ncbi.nlm.nih.gov/17589523/ DOI: 10.1038/nsmb1273

tissue_or_cell_type

Not specified as a whole tissue; see experimental model.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 567–576

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human JMJD2A catalytic-domain structures and methylated peptide assays. · source_derived_draft · unverified_draft

### kdm4a-h3k9-demethylation KDM4A/JMJD2A can convert H3K9me3 to H3K9me2 using Fe(II), oxygen and 2-oxoglutarate. Plain language: An iron-dependent enzyme erases a different class of methyl mark. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human JMJD2A catalytic-domain structures and methylated peptide assays. limitations: This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [kdm4a-2006] Structural insights into histone demethylation by JMJD2 family members (2006). https://pubmed.ncbi.nlm.nih.gov/16677698/ DOI: 10.1016/j.cell.2006.04.024 [kdm4a-specificity-2007] Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase (2007). https://pubmed.ncbi.nlm.nih.gov/17589523/ DOI: 10.1038/nsmb1273

experimental_model

Recombinant human PLOD3 structural and biochemical assays.

limitations

This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome.

organism

Human

plain_language

The collagen enzyme needs an iron-containing catalytic site and reaction partners.

primary_references

[plod3-2018] Molecular architecture of the multifunctional collagen lysyl hydroxylase and glycosyltransferase LH3 (2018). https://www.nature.com/articles/s41467-018-05631-5 DOI: 10.1038/s41467-018-05631-5

tissue_or_cell_type

Not specified as a whole tissue; see experimental model.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 417–425

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PLOD3 structural and biochemical assays. · source_derived_draft · unverified_draft

### plod3-collagen-hydroxylation PLOD3 hydroxylates peptidyl lysine using Fe(II), 2-oxoglutarate and oxygen. Plain language: The collagen enzyme needs an iron-containing catalytic site and reaction partners. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Recombinant human PLOD3 structural and biochemical assays. limitations: This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [plod3-2018] Molecular architecture of the multifunctional collagen lysyl hydroxylase and glycosyltransferase LH3 (2018). https://www.nature.com/articles/s41467-018-05631-5 DOI: 10.1038/s41467-018-05631-5

experimental_model

Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays

limitations

The substrate is free trimethyllysine after proteolysis, not ordinary free lysine.

organism

Homo sapiens

plain_language

TMLHE begins conversion of released trimethyllysine toward carnitine.

primary_references

[lesniak2017] Human carnitine biosynthesis proceeds via (2S,3S)-3-hydroxy-Nε-trimethyllysine (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5644716/ DOI: 10.1039/C6CC08381A [tmlh2016scope] Substrate scope for trimethyllysine hydroxylase catalysis (2016). https://pubs.rsc.org/en/content/articlehtml/2016/cc/c6cc07845a DOI: 10.1039/C6CC07845A

tissue_or_cell_type

Mitochondrial carnitine-biosynthesis step

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 166–175

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays · source_derived_draft · unverified_draft

### tmlhe-hydroxylation Human TMLHE hydroxylates free trimethyllysine to (2S,3S)-hydroxytrimethyllysine, coupled to 2-oxoglutarate oxidation. Plain language: TMLHE begins conversion of released trimethyllysine toward carnitine. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial carnitine-biosynthesis step experimental_model: Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays limitations: The substrate is free trimethyllysine after proteolysis, not ordinary free lysine. [lesniak2017] Human carnitine biosynthesis proceeds via (2S,3S)-3-hydroxy-Nε-trimethyllysine (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5644716/ DOI: 10.1039/C6CC08381A [tmlh2016scope] Substrate scope for trimethyllysine hydroxylase catalysis (2016). https://pubs.rsc.org/en/content/articlehtml/2016/cc/c6cc07845a DOI: 10.1039/C6CC07845A

dose

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

duration

Kinetic assays; urine collected 2-4 h after ingestion

evidence_access

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

evidence_scope

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

experimental_model

Cell-free biochemical systems and four human volunteers

limitations

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

nutrient_topic

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

organism

Cell-free biochemical systems and four human volunteers

plain_language

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

primary_references

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

route

In vitro addition; separate oral juice arm

tissue

Lipid emulsions, membranes, LDL; urine arm separate

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

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

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

cross_nutrient

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

experimental_model

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

exposure

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

limitations

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

nutrient_topic

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

organism

Homo sapiens

plain_language

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

primary_references

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

tissue_or_cell_type

Human Caco-2 apical cell surface and culture medium

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

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

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

cross_nutrient

true

evidence_location

Primary abstract rate/extent and substrate comparisons

experimental_model

Purified enzyme with human HIF-1 alpha-derived peptide substrate

exposure

Ascorbate versus omission/alternative reducing agents; exact concentrations and enzyme constructs not recovered from primary abstract.

limitations

Peptide hydroxylation does not directly establish HIF degradation or transcription changes in intact cells; ankyrin probe is not physiological HIF.

nutrient_topic

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

organism

Human HIF-1 alpha substrate; purified recombinant hydroxylase

plain_language

Vitamin C also supported a different HIF enzyme that modifies an asparagine site.

primary_references

[c-reg-flashman] Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. (2010). https://pubmed.ncbi.nlm.nih.gov/20055761/ DOI: 10.1042/bj20091609

tissue_or_cell_type

Cell-free

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1131–1143

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzyme with human HIF-1 alpha-derived peptide substrate · source_derived_draft · unverified_draft

### c-reg-fih-ascorbate Ascorbate increased the initial rate and extent of FIH-catalyzed asparaginyl hydroxylation of human HIF-1 alpha peptide; the study separately tested a consensus ankyrin-repeat peptide. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C also supported a different HIF enzyme that modifies an asparagine site. organism: Human HIF-1 alpha substrate; purified recombinant hydroxylase tissue_or_cell_type: Cell-free experimental_model: Purified enzyme with human HIF-1 alpha-derived peptide substrate limitations: Peptide hydroxylation does not directly establish HIF degradation or transcription changes in intact cells; ankyrin probe is not physiological HIF. exposure: Ascorbate versus omission/alternative reducing agents; exact concentrations and enzyme constructs not recovered from primary abstract. cross_nutrient: true evidence_location: Primary abstract rate/extent and substrate comparisons [c-reg-flashman] Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. (2010). https://pubmed.ncbi.nlm.nih.gov/20055761/ DOI: 10.1042/bj20091609

cross_nutrient

true

evidence_location

Figure 2A–B; hydroxylation Methods

experimental_model

Recombinant human PHD enzymes; HIF-1 alpha 556–574 peptide hydroxylation detected by VHL/elongin B/C binding

exposure

10 µM FeSO4, 0.5 mM 2-oxoglutarate, pH 7.5, room temperature, 1 h; ascorbate omission/titration and GSH titration; standard ascorbate 2 mM.

limitations

Alternative reductant effects vary with substrate and assay; this is not a nutritional substitution recommendation or proof of in-vivo compensation mechanism.

nutrient_topic

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

organism

Homo sapiens proteins

plain_language

These oxygen-sensing enzymes could use support from glutathione when vitamin C was absent in the test tube.

primary_references

[c-reg-nytko] Vitamin C is dispensable for oxygen sensing in vivo. (2011). https://pubmed.ncbi.nlm.nih.gov/21346252/ DOI: 10.1182/blood-2010-09-307637

tissue_or_cell_type

Cell-free

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1145–1157

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PHD enzymes; HIF-1 alpha 556–574 peptide hydroxylation detected by VHL/elongin B/C binding · source_derived_draft · unverified_draft

### c-reg-gsh-substitutes-phd Reduced glutathione stimulated all three tested PHD isoforms in the absence of ascorbate; millimolar GSH could substitute in the peptide assay, indicating reductant redundancy in this setting. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: These oxygen-sensing enzymes could use support from glutathione when vitamin C was absent in the test tube. organism: Homo sapiens proteins tissue_or_cell_type: Cell-free experimental_model: Recombinant human PHD enzymes; HIF-1 alpha 556–574 peptide hydroxylation detected by VHL/elongin B/C binding limitations: Alternative reductant effects vary with substrate and assay; this is not a nutritional substitution recommendation or proof of in-vivo compensation mechanism. exposure: 10 µM FeSO4, 0.5 mM 2-oxoglutarate, pH 7.5, room temperature, 1 h; ascorbate omission/titration and GSH titration; standard ascorbate 2 mM. cross_nutrient: true evidence_location: Figure 2A–B; hydroxylation Methods [c-reg-nytko] Vitamin C is dispensable for oxygen sensing in vivo. (2011). https://pubmed.ncbi.nlm.nih.gov/21346252/ DOI: 10.1182/blood-2010-09-307637

cross_nutrient

true

evidence_location

Figure 2C

experimental_model

Recombinant human PHD enzymes; HIF-1 alpha 556–574 peptide hydroxylation detected by VHL/elongin B/C binding; HPLC of reaction ascorbate

exposure

10 µM FeSO4, 0.5 mM 2-oxoglutarate, pH 7.5, room temperature, 1 h; ascorbate omission/titration and GSH titration; standard ascorbate 2 mM. Ascorbate measured before and after 1 h.

limitations

Minor air oxidation remained possible; result does not exclude ascorbate consumption during uncoupled or oxidative-damage reactions.

nutrient_topic

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

organism

Homo sapiens protein

plain_language

Vitamin C was not used up once for every hydroxylation event in this enzyme assay.

primary_references

[c-reg-nytko] Vitamin C is dispensable for oxygen sensing in vivo. (2011). https://pubmed.ncbi.nlm.nih.gov/21346252/ DOI: 10.1182/blood-2010-09-307637

tissue_or_cell_type

Cell-free

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1159–1171

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PHD enzymes; HIF-1 alpha 556–574 peptide hydroxylation detected by VHL/elongin B/C binding; HPLC of reaction ascorbate · source_derived_draft · unverified_draft

### c-reg-phd-ascorbate-not-stoichiometric HPLC showed only a small decline in ascorbate during the PHD2 peptide reaction, independent of hydroxyl-acceptor substrate, providing no evidence that coupled prolyl hydroxylation consumed ascorbate stoichiometrically. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C was not used up once for every hydroxylation event in this enzyme assay. organism: Homo sapiens protein tissue_or_cell_type: Cell-free experimental_model: Recombinant human PHD enzymes; HIF-1 alpha 556–574 peptide hydroxylation detected by VHL/elongin B/C binding; HPLC of reaction ascorbate limitations: Minor air oxidation remained possible; result does not exclude ascorbate consumption during uncoupled or oxidative-damage reactions. exposure: 10 µM FeSO4, 0.5 mM 2-oxoglutarate, pH 7.5, room temperature, 1 h; ascorbate omission/titration and GSH titration; standard ascorbate 2 mM. Ascorbate measured before and after 1 h. cross_nutrient: true evidence_location: Figure 2C [c-reg-nytko] Vitamin C is dispensable for oxygen sensing in vivo. (2011). https://pubmed.ncbi.nlm.nih.gov/21346252/ DOI: 10.1182/blood-2010-09-307637

cross_nutrient

true

evidence_location

Primary abstract rate/extent and substrate comparisons

experimental_model

Purified enzyme with human HIF-1 alpha-derived peptide substrate

exposure

Ascorbate versus omission/alternative reducing agents; exact concentrations and enzyme constructs not recovered from primary abstract.

limitations

Peptide hydroxylation does not directly establish HIF degradation or transcription changes in intact cells; ankyrin probe is not physiological HIF.

nutrient_topic

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

organism

Human HIF-1 alpha substrate; purified recombinant hydroxylase

plain_language

Vitamin C increased the activity of an isolated oxygen-sensing proline hydroxylase.

primary_references

[c-reg-flashman] Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. (2010). https://pubmed.ncbi.nlm.nih.gov/20055761/ DOI: 10.1042/bj20091609

tissue_or_cell_type

Cell-free

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1117–1129

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzyme with human HIF-1 alpha-derived peptide substrate · source_derived_draft · unverified_draft

### c-reg-phd2-ascorbate Ascorbate increased the initial rate and extent of PHD2-catalyzed hydroxylation at both tested human HIF-1 alpha prolyl sites in purified-enzyme peptide experiments. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C increased the activity of an isolated oxygen-sensing proline hydroxylase. organism: Human HIF-1 alpha substrate; purified recombinant hydroxylase tissue_or_cell_type: Cell-free experimental_model: Purified enzyme with human HIF-1 alpha-derived peptide substrate limitations: Peptide hydroxylation does not directly establish HIF degradation or transcription changes in intact cells; ankyrin probe is not physiological HIF. exposure: Ascorbate versus omission/alternative reducing agents; exact concentrations and enzyme constructs not recovered from primary abstract. cross_nutrient: true evidence_location: Primary abstract rate/extent and substrate comparisons [c-reg-flashman] Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. (2010). https://pubmed.ncbi.nlm.nih.gov/20055761/ DOI: 10.1042/bj20091609

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

cross_nutrient

true

evidence_location

Figure 1D; Figure S1B–D

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. Substrate-free preincubation up to 30 min.

limitations

A conditional biochemical null result; it does not negate ascorbate enhancement in cells or more oxidizing buffers.

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

With usable iron maintained in this assay, the enzyme did not require extra vitamin C to keep working.

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 1033–1045

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-sufficient-ferrous-iron At pH 6.8 with sufficient Fe(II), murine TET1-CD remained active without ascorbate and adding ascorbate did not increase the measured activity; substrate-free preincubation also did not rapidly destroy activity. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: With usable iron maintained in this assay, the enzyme did not require extra vitamin C to keep working. 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: A conditional biochemical null result; it does not negate ascorbate enhancement in cells or more oxidizing buffers. 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. Substrate-free preincubation up to 30 min. cross_nutrient: true evidence_location: Figure 1D; Figure S1B–D [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

cross_nutrient

true

evidence_location

Figure 3a; Methods Tet activity assay

experimental_model

Purified recombinant human TET1 catalytic-domain assay; antibody detection of hydroxymethylated biotinylated DNA

exposure

10 min at 37°C; 1.2 µg enzyme, 178.2 ng DNA, 3.7 µM ammonium iron(II) sulfate, 1 mM 2-oxoglutarate, titrated vitamin C (Sigma A5960).

limitations

Purified-domain result; oxidation-prone buffer differs from cellular iron conditions. Exact plotted titration values not transcribed.

nutrient_topic

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

organism

Homo sapiens protein

plain_language

Vitamin C helped the isolated human enzyme modify DNA under these test conditions.

primary_references

[c-reg-blaschke] Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23812591/ DOI: 10.1038/nature12362

tissue_or_cell_type

Cell-free

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 963–975

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human TET1 catalytic-domain assay; antibody detection of hydroxymethylated biotinylated DNA · source_derived_draft · unverified_draft

### c-reg-tet1-human-activity Vitamin C increased hydroxymethylcytosine production by recombinant human TET1 catalytic domain in the reported pH 8.0 assay containing Fe(II) and 2-oxoglutarate. This demonstrates assay enhancement, without establishing obligatory ascorbate binding. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C helped the isolated human enzyme modify DNA under these test conditions. organism: Homo sapiens protein tissue_or_cell_type: Cell-free experimental_model: Purified recombinant human TET1 catalytic-domain assay; antibody detection of hydroxymethylated biotinylated DNA limitations: Purified-domain result; oxidation-prone buffer differs from cellular iron conditions. Exact plotted titration values not transcribed. exposure: 10 min at 37°C; 1.2 µg enzyme, 178.2 ng DNA, 3.7 µM ammonium iron(II) sulfate, 1 mM 2-oxoglutarate, titrated vitamin C (Sigma A5960). cross_nutrient: true evidence_location: Figure 3a; Methods Tet activity assay [c-reg-blaschke] Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23812591/ DOI: 10.1038/nature12362

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

cross_nutrient

Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.

experimental_model

Purified chick prolyl and partially purified lysyl collagen hydroxylases

exposure

Peptide substrate present or absent; uncoupled 2-oxoglutarate decarboxylation assays.

limitations

This statement concerns coupled turnover; it must not be transferred to copper monooxygenases.

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 is not a one-for-one consumed ingredient in every successful collagen hydroxylation.

primary_references

[myllyla1984] Ascorbate is consumed stoichiometrically in the uncoupled reactions catalyzed by prolyl 4-hydroxylase and lysyl hydroxylase. (1984). https://pubmed.ncbi.nlm.nih.gov/6325436/ DOI: 10.1016/s0021-9258(18)91023-9

tissue_or_cell_type

Chick embryo enzyme preparations

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 585–596

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified chick prolyl and partially purified lysyl collagen hydroxylases · source_derived_draft · unverified_draft

### vc-enzyme-coupled-ascorbate-use In chick collagen hydroxylase assays, complete proline hydroxylation was coupled to 2-oxoglutarate decarboxylation while ascorbate was not consumed in most catalytic cycles. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C is not a one-for-one consumed ingredient in every successful collagen hydroxylation. organism: Gallus gallus tissue_or_cell_type: Chick embryo enzyme preparations experimental_model: Purified chick prolyl and partially purified lysyl collagen hydroxylases limitations: This statement concerns coupled turnover; it must not be transferred to copper monooxygenases. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Peptide substrate present or absent; uncoupled 2-oxoglutarate decarboxylation assays. [myllyla1984] Ascorbate is consumed stoichiometrically in the uncoupled reactions catalyzed by prolyl 4-hydroxylase and lysyl hydroxylase. (1984). https://pubmed.ncbi.nlm.nih.gov/6325436/ DOI: 10.1016/s0021-9258(18)91023-9

cross_nutrient

Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.

experimental_model

Purified chick-embryo collagen prolyl hydroxylase kinetics

exposure

Ascorbate omitted or added in purified-enzyme assays; initial 5–10 seconds versus approximately 1 minute.

limitations

Purified assay with cofactor omission; does not quantify a dietary requirement or establish an identical turnover number in human cells.

nutrient_topic

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

organism

Gallus gallus

plain_language

The collagen enzyme can start working without vitamin C, but sustained work needs vitamin C support.

primary_references

[myllyla1978] The role of ascorbate in the prolyl hydroxylase reaction. (1978). https://pubmed.ncbi.nlm.nih.gov/212056/ DOI: 10.1016/0006-291x(78)91010-0

tissue_or_cell_type

Chick embryo enzyme preparation

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 572–583

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified chick-embryo collagen prolyl hydroxylase kinetics · source_derived_draft · unverified_draft

### vc-enzyme-initial-p4h-turnover Purified chick collagen prolyl hydroxylase completed approximately 15–30 rapid catalytic cycles in 5–10 seconds without added ascorbate before activity declined. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The collagen enzyme can start working without vitamin C, but sustained work needs vitamin C support. organism: Gallus gallus tissue_or_cell_type: Chick embryo enzyme preparation experimental_model: Purified chick-embryo collagen prolyl hydroxylase kinetics limitations: Purified assay with cofactor omission; does not quantify a dietary requirement or establish an identical turnover number in human cells. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Ascorbate omitted or added in purified-enzyme assays; initial 5–10 seconds versus approximately 1 minute. [myllyla1978] The role of ascorbate in the prolyl hydroxylase reaction. (1978). https://pubmed.ncbi.nlm.nih.gov/212056/ DOI: 10.1016/0006-291x(78)91010-0

cross_nutrient

Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.

experimental_model

Purified chick prolyl and partially purified lysyl collagen hydroxylases

exposure

Peptide substrate present or absent; uncoupled 2-oxoglutarate decarboxylation assays.

limitations

Substrate-free enzyme reaction; frequency and quantitative vitamin C cost of uncoupled cycles in human tissues were not measured.

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 is consumed when this collagen enzyme runs a reaction cycle without hydroxylating its peptide target.

primary_references

[myllyla1984] Ascorbate is consumed stoichiometrically in the uncoupled reactions catalyzed by prolyl 4-hydroxylase and lysyl hydroxylase. (1984). https://pubmed.ncbi.nlm.nih.gov/6325436/ DOI: 10.1016/s0021-9258(18)91023-9

tissue_or_cell_type

Chick embryo enzyme preparations

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 611–622

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified chick prolyl and partially purified lysyl collagen hydroxylases · source_derived_draft · unverified_draft

### vc-enzyme-lysyl-uncoupled-consumption Chick collagen lysyl hydroxylase consumed ascorbate stoichiometrically during uncoupled 2-oxoglutarate decarboxylation in the absence of peptide substrate. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C is consumed when this collagen enzyme runs a reaction cycle without hydroxylating its peptide target. organism: Gallus gallus tissue_or_cell_type: Chick embryo enzyme preparations experimental_model: Purified chick prolyl and partially purified lysyl collagen hydroxylases limitations: Substrate-free enzyme reaction; frequency and quantitative vitamin C cost of uncoupled cycles in human tissues were not measured. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Peptide substrate present or absent; uncoupled 2-oxoglutarate decarboxylation assays. [myllyla1984] Ascorbate is consumed stoichiometrically in the uncoupled reactions catalyzed by prolyl 4-hydroxylase and lysyl hydroxylase. (1984). https://pubmed.ncbi.nlm.nih.gov/6325436/ DOI: 10.1016/s0021-9258(18)91023-9

cross_nutrient

Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.

experimental_model

Purified chick prolyl and partially purified lysyl collagen hydroxylases

exposure

Peptide substrate present or absent; uncoupled 2-oxoglutarate decarboxylation assays.

limitations

Substrate-free enzyme reaction; frequency and quantitative vitamin C cost of uncoupled cycles in human tissues were not measured.

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 is consumed when this collagen enzyme runs a reaction cycle without hydroxylating its peptide target.

primary_references

[myllyla1984] Ascorbate is consumed stoichiometrically in the uncoupled reactions catalyzed by prolyl 4-hydroxylase and lysyl hydroxylase. (1984). https://pubmed.ncbi.nlm.nih.gov/6325436/ DOI: 10.1016/s0021-9258(18)91023-9

tissue_or_cell_type

Chick embryo enzyme preparations

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 598–609

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified chick prolyl and partially purified lysyl collagen hydroxylases · source_derived_draft · unverified_draft

### vc-enzyme-prolyl-uncoupled-consumption Chick collagen prolyl hydroxylase consumed ascorbate stoichiometrically during uncoupled 2-oxoglutarate decarboxylation in the absence of peptide substrate. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C is consumed when this collagen enzyme runs a reaction cycle without hydroxylating its peptide target. organism: Gallus gallus tissue_or_cell_type: Chick embryo enzyme preparations experimental_model: Purified chick prolyl and partially purified lysyl collagen hydroxylases limitations: Substrate-free enzyme reaction; frequency and quantitative vitamin C cost of uncoupled cycles in human tissues were not measured. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Peptide substrate present or absent; uncoupled 2-oxoglutarate decarboxylation assays. [myllyla1984] Ascorbate is consumed stoichiometrically in the uncoupled reactions catalyzed by prolyl 4-hydroxylase and lysyl hydroxylase. (1984). https://pubmed.ncbi.nlm.nih.gov/6325436/ DOI: 10.1016/s0021-9258(18)91023-9

cross_nutrient

Vitamin C + iron support hydroxylation of a modified lysine precursor; downstream existing SHMT steps use B6-derived PLP and ALDH9A1 uses NAD+.

experimental_model

Recombinant human MBP-TMLH-a; mass spectrometry and NMR

exposure

500 micromolar trimethyllysine and 3 micromolar enzyme, FeSO4/2OG/ascorbate, 37 C for 30 minutes; cofactor omission controls.

limitations

New record isolates the ascorbate cofactor dependence; the existing substrate-to-product UUID is reused. Fusion-protein assay does not quantify whole-body flux.

nutrient_topic

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

organism

Homo sapiens

plain_language

The first carnitine-synthesis hydroxylation needs vitamin C support alongside iron and 2-oxoglutarate.

primary_references

[tmlh2016] Substrate scope for trimethyllysine hydroxylase catalysis. (2016). https://pubmed.ncbi.nlm.nih.gov/27730239/ DOI: 10.1039/c6cc07845a

tissue_or_cell_type

Cell-free recombinant enzyme

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 689–700

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MBP-TMLH-a; mass spectrometry and NMR · source_derived_draft · unverified_draft

### vc-enzyme-tmlh-ascorbate-dependency Omission controls with recombinant human MBP-TMLH-a showed that ascorbate, Fe(II) and 2-oxoglutarate were each needed for efficient conversion of free trimethyllysine to 3-hydroxytrimethyllysine. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The first carnitine-synthesis hydroxylation needs vitamin C support alongside iron and 2-oxoglutarate. organism: Homo sapiens tissue_or_cell_type: Cell-free recombinant enzyme experimental_model: Recombinant human MBP-TMLH-a; mass spectrometry and NMR limitations: New record isolates the ascorbate cofactor dependence; the existing substrate-to-product UUID is reused. Fusion-protein assay does not quantify whole-body flux. cross_nutrient: Vitamin C + iron support hydroxylation of a modified lysine precursor; downstream existing SHMT steps use B6-derived PLP and ALDH9A1 uses NAD+. exposure: 500 micromolar trimethyllysine and 3 micromolar enzyme, FeSO4/2OG/ascorbate, 37 C for 30 minutes; cofactor omission controls. [tmlh2016] Substrate scope for trimethyllysine hydroxylase catalysis. (2016). https://pubmed.ncbi.nlm.nih.gov/27730239/ DOI: 10.1039/c6cc07845a

cross_nutrient

Iron and zinc are not interchangeable RPE65 cofactors in the tested preparation.

experimental_model

Metal-rescue comparison

limitations

Does not test systemic zinc status or other zinc-dependent visual functions.

nutrient_topic

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

organism

Bos taurus

plain_language

Zinc could not replace iron in this enzyme assay.

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

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 689–699

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metal-rescue comparison · source_derived_draft · unverified_draft

### a-vision-rpe65-zinc-not-substitute ZnCl2 did not restore isomerohydrolase activity after metal chelation in the bovine RPE assay, whereas FeSO4 did. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc could not replace iron in this enzyme assay. organism: Bos taurus tissue_or_cell_type: RPE microsomes experimental_model: Metal-rescue comparison limitations: Does not test systemic zinc status or other zinc-dependent visual functions. cross_nutrient: Iron and zinc are not interchangeable RPE65 cofactors in the tested preparation. [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

cross_nutrient

Retinoid/iron chemistry; hypothesis boundary retained.

experimental_model

Cell-free pH-shift experiment.

limitations

Solubility alone neither proves a defined retinoid-iron complex nor absorption in vivo.

nutrient_topic

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

organism

Homo sapiens

plain_language

A laboratory solubility result supported a proposed explanation for the meal findings.

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

Cell-free chemistry

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1554–1564

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free pH-shift experiment. · source_derived_draft · unverified_draft

### va-retinoid-iron-solubility-assay Adding beta-carotene or vitamin A retained more iron in solution when the assay pH rose from acidic toward near-neutral. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: A laboratory solubility result supported a proposed explanation for the meal findings. organism: Homo sapiens tissue_or_cell_type: Cell-free chemistry experimental_model: Cell-free pH-shift experiment. limitations: Solubility alone neither proves a defined retinoid-iron complex nor absorption in vivo. cross_nutrient: Retinoid/iron chemistry; hypothesis boundary retained. [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

cross_nutrient

true

experimental_model

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

exposure

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

limitations

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

nutrient_topic

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

organism

Homo sapiens

plain_language

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

primary_references

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

tissue_or_cell_type

Cell-free enzyme

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

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

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

evidence_span

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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

evidence_span

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experimental_model

Transporter/reductase discovery and expression assays

exposure

Cybrd1 expression and physiological modulation of iron absorption

limitations

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

nutrient_topic

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

organism

Mouse Cybrd1 expressed in Xenopus oocytes and cultured cells

plain_language

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

primary_references

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

tissue_or_cell_type

Duodenal brush border and expression systems

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

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

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

evidence_span

{"source_cache": "artifacts/iron-research/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

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

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

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

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

evidence_span

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

experimental_model

Positional cloning, overexpression and deficient-mouse experiments

exposure

Steap3 deficiency and overexpression

limitations

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

nutrient_topic

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

organism

Mice and mouse Steap3 expression systems

plain_language

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

primary_references

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

tissue_or_cell_type

Erythroid endosomes

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

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

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

evidence_span

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

experimental_model

DMPO-competition ESR assay and peroxide challenge

exposure

Variable DMPO concentrations; nasunin below 50 micromolar in homogenate experiments

limitations

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

nutrient_topic

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

organism

Cell-free reaction and rat brain homogenate

plain_language

Preventing a radical from forming differs from catching it afterward.

primary_references

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

tissue_or_cell_type

Fenton chemistry and lipid-peroxidation markers

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

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

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

evidence_access

Primary abstract

experimental_model

Human proteins translated in wheat-germ extract and assembled in liposomes.

limitations

The tested substrate was stearoyl-CoA, not vaccenic acid; nutrient status was not tested.

nutrient_topic

CLA collection; isomer, preparation, species, exposure and manipulation remain explicit. · Conjugated linoleic acid / CLA isomer family

plain_language

The desaturation machinery needs metal-containing partners.

primary_references

Wheat germ cell-free translation, purification, and assembly of a functional human stearoyl-CoA desaturase complex. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18765284/ · DOI 10.1016/j.pep.2008.08.002

Conjugated linoleic acid: isomers, signaling, nutrient interactions and discovery (2026-09-19) · lines 46–52

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human proteins translated in wheat-germ extract and assembled in liposomes. · source_derived_draft · unverified_draft

## cla-scd-cofactors The desaturation machinery needs metal-containing partners. Reconstituting the non-heme iron and heme sites of a human SCD/cytochrome-b5 proteoliposome complex restored conversion of stearoyl-CoA to oleoyl-CoA. Model: Human proteins translated in wheat-germ extract and assembled in liposomes. Limitations: The tested substrate was stearoyl-CoA, not vaccenic acid; nutrient status was not tested. Evidence access: Primary abstract Wheat germ cell-free translation, purification, and assembly of a functional human stearoyl-CoA desaturase complex. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18765284/ · DOI 10.1016/j.pep.2008.08.002