Heme

cross_nutrient

B6 and iron-containing heme meet in one enzyme.

experimental_model

Recombinant truncated human CBS crystallography

limitations

Heme binding does not establish iron supplementation as a way to increase CBS flux.

nutrient_topic

Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

organism

Homo sapiens

plain_language

CBS contains both heme and active vitamin B6.

primary_references

[b6-cbs-2001] Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein. (2001). https://pmc.ncbi.nlm.nih.gov/articles/PMC149156/ DOI: 10.1093/emboj/20.15.3910

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 529–539

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant truncated human CBS crystallography · source_derived_draft · unverified_draft

### b6-met-cbs-heme The human CBS structure resolves a heme-binding region distinct from the PLP catalytic site. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CBS contains both heme and active vitamin B6. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant truncated human CBS crystallography limitations: Heme binding does not establish iron supplementation as a way to increase CBS flux. cross_nutrient: B6 and iron-containing heme meet in one enzyme. [b6-cbs-2001] Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein. (2001). https://pmc.ncbi.nlm.nih.gov/articles/PMC149156/ DOI: 10.1093/emboj/20.15.3910

experimental_model

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

exposure_category

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

limitations

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

nutrient_topic

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

plain_language

Iron-containing heme positions peroxide in the enzyme.

primary_references

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

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

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

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

evidence_span

{"source_cache": "artifacts/citrulline-research/10608822.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1600b193cc63f30b204285729710bb81f34bc2918a8ca7f97aa97bc4acd998fd", "start_char": 0, "end_char": 2100, "text_sha256": "1600b193cc63f30b204285729710bb81f34bc2918a8ca7f97aa97bc4acd998fd"}

experimental_model

Purified recombinant enzyme activity and cofactor analysis

exposure

Arginine substrate; BH4, FAD, FMN, heme, iron and zinc measurements

limitations

Biochemical cofactor findings do not show that extra dietary cofactors increase NO in healthy people.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human NOS3 expressed in yeast

plain_language

The nitric-oxide machinery includes an iron-containing heme group.

primary_references

[citrulline-p10608822] Characterization of recombinant human endothelial nitric-oxide synthase purified from the yeast Pichia pastoris. (1999). https://pubmed.ncbi.nlm.nih.gov/10608822/ DOI: 10.1074/jbc.274.53.37658

tissue_or_cell_type

Endothelial NOS enzyme preparation

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 554–565

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

### citrulline-nos-heme Heme and protein-bound iron were detected in purified human eNOS by independent analytical methods. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The nitric-oxide machinery includes an iron-containing heme group. organism: Human NOS3 expressed in yeast tissue_or_cell_type: Endothelial NOS enzyme preparation experimental_model: Purified recombinant enzyme activity and cofactor analysis limitations: Biochemical cofactor findings do not show that extra dietary cofactors increase NO in healthy people. exposure: Arginine substrate; BH4, FAD, FMN, heme, iron and zinc measurements evidence_span: {"source_cache": "artifacts/citrulline-research/10608822.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1600b193cc63f30b204285729710bb81f34bc2918a8ca7f97aa97bc4acd998fd", "start_char": 0, "end_char": 2100, "text_sha256": "1600b193cc63f30b204285729710bb81f34bc2918a8ca7f97aa97bc4acd998fd"} [citrulline-p10608822] Characterization of recombinant human endothelial nitric-oxide synthase purified from the yeast Pichia pastoris. (1999). https://pubmed.ncbi.nlm.nih.gov/10608822/ DOI: 10.1074/jbc.274.53.37658

cross_nutrient

Heme iron participates in a tryptophan-to-niacin upstream enzyme; the structure does not establish a dietary iron threshold.

evidence_span

{"source_cache": "artifacts/niacin-precursors-sources/tdo2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 7–7 (0-based)", "start_char": 5512, "end_char": 7250, "file_sha256": "3f91886745b8ff9fb808232c839dd346b03605dd025d5fa682a3de4f81338ec5", "text_sha256": "057137936657c739cdef730f5d10b930ec40af5e09f0ed4e2abbd813f26db9f0"}

experimental_model

Purified human TDO2 crystallography and spectroscopy; substrate/product complexes

exposure

Biochemical or structural assay; no dietary intervention

limitations

Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.

nutrient_topic

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

organism

Homo sapiens

plain_language

Iron held in heme positions oxygen for this precursor reaction.

primary_references

[b3-pre-tdo2016] Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase. (2016). https://pubmed.ncbi.nlm.nih.gov/27762317/ DOI: 10.1038/srep35169

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 493–505

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human TDO2 crystallography and spectroscopy; substrate/product complexes · source_derived_draft · unverified_draft

### b3-pre-tdo-heme-oxygen In the human TDO2 substrate complex, molecular oxygen was coordinated to the heme iron next to the L-tryptophan substrate. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron held in heme positions oxygen for this precursor reaction. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human TDO2 crystallography and spectroscopy; substrate/product complexes limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention cross_nutrient: Heme iron participates in a tryptophan-to-niacin upstream enzyme; the structure does not establish a dietary iron threshold. evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/tdo2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 7–7 (0-based)", "start_char": 5512, "end_char": 7250, "file_sha256": "3f91886745b8ff9fb808232c839dd346b03605dd025d5fa682a3de4f81338ec5", "text_sha256": "057137936657c739cdef730f5d10b930ec40af5e09f0ed4e2abbd813f26db9f0"} [b3-pre-tdo2016] Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase. (2016). https://pubmed.ncbi.nlm.nih.gov/27762317/ DOI: 10.1038/srep35169

evidence_span

{"source_cache": "artifacts/molybdenum-research/23703616.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9034da6c790ca6e0c60dd765eec631ea2875c6caf65f6d15d59733bc5e0ee0ec", "start_char": 0, "end_char": 1596, "text_sha256": "9034da6c790ca6e0c60dd765eec631ea2875c6caf65f6d15d59733bc5e0ee0ec"}

experimental_model

Human-cell siRNA plus recombinant cytochrome-b5/cofactor reconstitution

exposure

mARC, CYB5B and CYB5A depletion; apo-CYB5

limitations

Expression-dependent cellular contributions; no clinical iron or B2 supplementation test.

nutrient_topic

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

organism

Homo sapiens; separate mouse Cyb5a knockout

plain_language

Removing the iron-containing heme breaks this electron-transfer step.

primary_references

[mo-p23703616] The involvement of mitochondrial amidoxime reducing components 1 and 2 and mitochondrial cytochrome b5 in N-reductive metabolism in human cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23703616/ DOI: 10.1074/jbc.m113.474916

tissue_or_cell_type

HEK293 and second human cell line; purified proteins

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 1002–1013

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human-cell siRNA plus recombinant cytochrome-b5/cofactor reconstitution · source_derived_draft · unverified_draft

### mo-cyb5b-heme Heme-free apo-CYB5 failed to support N-reduction in the reconstituted system. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing the iron-containing heme breaks this electron-transfer step. organism: Homo sapiens; separate mouse Cyb5a knockout tissue_or_cell_type: HEK293 and second human cell line; purified proteins experimental_model: Human-cell siRNA plus recombinant cytochrome-b5/cofactor reconstitution limitations: Expression-dependent cellular contributions; no clinical iron or B2 supplementation test. exposure: mARC, CYB5B and CYB5A depletion; apo-CYB5 evidence_span: {"source_cache": "artifacts/molybdenum-research/23703616.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9034da6c790ca6e0c60dd765eec631ea2875c6caf65f6d15d59733bc5e0ee0ec", "start_char": 0, "end_char": 1596, "text_sha256": "9034da6c790ca6e0c60dd765eec631ea2875c6caf65f6d15d59733bc5e0ee0ec"} [mo-p23703616] The involvement of mitochondrial amidoxime reducing components 1 and 2 and mitochondrial cytochrome b5 in N-reductive metabolism in human cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23703616/ DOI: 10.1074/jbc.m113.474916

evidence_span

{"source_cache": "artifacts/dim-research/17311915.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4c3f047d0ee4583ca15aae2c7059d2237b02105371fda21bf32639cbaad2d318", "start_char": 0, "end_char": 1400, "text_sha256": "4c3f047d0ee4583ca15aae2c7059d2237b02105371fda21bf32639cbaad2d318"}

experimental_model

X-ray crystallography

exposure

Alpha-naphthoflavone-bound structure at 1.95 angstrom resolution

limitations

Structural enzyme requirement; not proof that DIM depletes iron or that iron supplementation changes DIM response.

nutrient_topic

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

organism

Purified human CYP1A2

plain_language

The induced enzyme still needs its iron-containing catalytic machinery.

primary_references

[dim-p17311915] Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2. (2007). https://pubmed.ncbi.nlm.nih.gov/17311915/ DOI: 10.1074/jbc.m611692200

tissue_or_cell_type

Catalytic pocket

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 259–270

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

### dim-cyp1a2-heme The CYP1A2 structure places its ligand above the heme prosthetic group. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The induced enzyme still needs its iron-containing catalytic machinery. organism: Purified human CYP1A2 tissue_or_cell_type: Catalytic pocket experimental_model: X-ray crystallography limitations: Structural enzyme requirement; not proof that DIM depletes iron or that iron supplementation changes DIM response. exposure: Alpha-naphthoflavone-bound structure at 1.95 angstrom resolution evidence_span: {"source_cache": "artifacts/dim-research/17311915.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4c3f047d0ee4583ca15aae2c7059d2237b02105371fda21bf32639cbaad2d318", "start_char": 0, "end_char": 1400, "text_sha256": "4c3f047d0ee4583ca15aae2c7059d2237b02105371fda21bf32639cbaad2d318"} [dim-p17311915] Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2. (2007). https://pubmed.ncbi.nlm.nih.gov/17311915/ DOI: 10.1074/jbc.m611692200

cross_nutrient

true

evidence_location

Primary abstract and structure PDB 3C6G.

experimental_model

Purified human enzyme crystallography

exposure

CYP2R1-D3 crystal complex; PDB 3C6G.

limitations

A structural iron requirement is not evidence that iron supplements increase vitamin D activation in iron-replete people.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens protein

plain_language

D3 activation uses an iron-containing heme enzyme.

primary_references

[strushkevich2008] Structural analysis of CYP2R1 in complex with vitamin D3. (2008). https://pubmed.ncbi.nlm.nih.gov/18511070/ DOI: 10.1016/j.jmb.2008.03.065

tissue_or_cell_type

CYP2R1 active site

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 377–390

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

### vd-act-cyp2r1-heme The human CYP2R1-D3 structure contained heme, with the vitamin D3 side chain directed toward this catalytic prosthetic group. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: D3 activation uses an iron-containing heme enzyme. organism: Homo sapiens protein tissue_or_cell_type: CYP2R1 active site experimental_model: Purified human enzyme crystallography limitations: A structural iron requirement is not evidence that iron supplements increase vitamin D activation in iron-replete people. exposure: CYP2R1-D3 crystal complex; PDB 3C6G. cross_nutrient: true evidence_location: Primary abstract and structure PDB 3C6G. nutrient: Vitamin D2 and D3 [strushkevich2008] Structural analysis of CYP2R1 in complex with vitamin D3. (2008). https://pubmed.ncbi.nlm.nih.gov/18511070/ DOI: 10.1016/j.jmb.2008.03.065

cross_nutrient

true

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/36537574.txt", "start_char": 17835, "end_char": 18855, "text_sha256": "6771d21482631bf712dfa882f1d08e4f40e02507211c65a60c7ef47f0d02e5d4", "text_characters": 1020, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

Cryo-EM of recombinant human TPO extracellular domain with antibody fragments

exposure

Human TPO residues 1–839 expressed in High Five insect cells and bound to 2G4 or 4F5 antibody fragments.

limitations

A structural observation; no selenium catalytic requirement or dietary iron dose is demonstrated.

nutrient_topic

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

organism

Homo sapiens protein; Trichoplusia ni expression cells

plain_language

TPO contains an iron-bearing heme group at its catalytic center.

primary_references

[iodine-syn-tpo2023] Cryo-electron microscopy structures of human thyroid peroxidase (TPO) in complex with TPO antibodies. (2023). https://pubmed.ncbi.nlm.nih.gov/36537574/ DOI: 10.1530/jme-22-0149

tissue_or_cell_type

Purified extracellular-domain antibody complexes

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 604–616

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM of recombinant human TPO extracellular domain with antibody fragments · source_derived_draft · unverified_draft

### iodine-syn-tpo-heme-structure Cryo-EM structures of the human TPO extracellular domain resolve heme at the peroxidase active site. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: TPO contains an iron-bearing heme group at its catalytic center. organism: Homo sapiens protein; Trichoplusia ni expression cells tissue_or_cell_type: Purified extracellular-domain antibody complexes experimental_model: Cryo-EM of recombinant human TPO extracellular domain with antibody fragments limitations: A structural observation; no selenium catalytic requirement or dietary iron dose is demonstrated. exposure: Human TPO residues 1–839 expressed in High Five insect cells and bound to 2G4 or 4F5 antibody fragments. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/36537574.txt", "start_char": 17835, "end_char": 18855, "text_sha256": "6771d21482631bf712dfa882f1d08e4f40e02507211c65a60c7ef47f0d02e5d4", "text_characters": 1020, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tpo2023] Cryo-electron microscopy structures of human thyroid peroxidase (TPO) in complex with TPO antibodies. (2023). https://pubmed.ncbi.nlm.nih.gov/36537574/ DOI: 10.1530/jme-22-0149

evidence_span

{"source_cache": "artifacts/iron-research/15049686.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76bcb8ae12316350b1161f32c1633e2b5c752fcbf7e158940385b354ee3452d2", "start_char": 0, "end_char": 1167, "text_sha256": "76bcb8ae12316350b1161f32c1633e2b5c752fcbf7e158940385b354ee3452d2"}

experimental_model

Product-bound human HO-1 structure

exposure

Biliverdin-bound structure compared with heme-bound enzyme

limitations

Product release interpretation from structure; no in-vivo flux measurement.

nutrient_topic

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

organism

Human enzyme

plain_language

Breaking open heme makes its iron available for reuse.

primary_references

[iron-p15049686] Crystal structure of human heme oxygenase-1 in a complex with biliverdin. (2004). https://pubmed.ncbi.nlm.nih.gov/15049686/ DOI: 10.1021/bi035451l

tissue_or_cell_type

Purified heme oxygenase-1

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 576–587

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Product-bound human HO-1 structure · source_derived_draft · unverified_draft

### iron-heme-oxygenase Heme oxygenase oxidatively cleaves heme to biliverdin with release of iron and carbon monoxide. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Breaking open heme makes its iron available for reuse. organism: Human enzyme tissue_or_cell_type: Purified heme oxygenase-1 experimental_model: Product-bound human HO-1 structure limitations: Product release interpretation from structure; no in-vivo flux measurement. exposure: Biliverdin-bound structure compared with heme-bound enzyme evidence_span: {"source_cache": "artifacts/iron-research/15049686.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76bcb8ae12316350b1161f32c1633e2b5c752fcbf7e158940385b354ee3452d2", "start_char": 0, "end_char": 1167, "text_sha256": "76bcb8ae12316350b1161f32c1633e2b5c752fcbf7e158940385b354ee3452d2"} [iron-p15049686] Crystal structure of human heme oxygenase-1 in a complex with biliverdin. (2004). https://pubmed.ncbi.nlm.nih.gov/15049686/ DOI: 10.1021/bi035451l

experimental_model

Human isotope meal experiments with heme substrate.

limitations

A shared mucosal mechanism was proposed, not directly localized to a named protein.

nutrient_topic

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

organism

Homo sapiens

plain_language

The acute interaction was not limited to nonheme iron.

primary_references

[cal-clin-hallberg1991] Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans (1991). https://pubmed.ncbi.nlm.nih.gov/1984335/ DOI: 10.1093/ajcn/53.1.112

tissue_or_cell_type

Human clinical or absorption endpoint

Calcium: mechanism-first literature curation (2026-09-17) · lines 1423–1432

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human isotope meal experiments with heme substrate. · source_derived_draft · unverified_draft

### cal-meal-heme-iron Calcium also reduced heme-iron absorption in the meal experiments. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The acute interaction was not limited to nonheme iron. organism: Homo sapiens tissue_or_cell_type: Human clinical or absorption endpoint experimental_model: Human isotope meal experiments with heme substrate. limitations: A shared mucosal mechanism was proposed, not directly localized to a named protein. [cal-clin-hallberg1991] Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans (1991). https://pubmed.ncbi.nlm.nih.gov/1984335/ DOI: 10.1093/ajcn/53.1.112

evidence_span

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

experimental_model

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

exposure

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

limitations

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

nutrient_topic

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

organism

Human

plain_language

The proposed protection is locking away the iron that would otherwise turn peroxide into a more dangerous radical.

primary_references

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

tissue_or_cell_type

Circulating lymphocytes

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 322–333

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

### hbot-iron-sequestration-hypothesis The authors suggest that increased sequestration of iron as a consequence of induced heme oxygenase-1 might be involved in the adaptive protection, and that induction of DNA damage is not the trigger for it. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The proposed protection is locking away the iron that would otherwise turn peroxide into a more dangerous radical. organism: Human tissue_or_cell_type: Circulating lymphocytes experimental_model: Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement limitations: A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron. exposure: 100% oxygen at 2.5 ATA for three 20-minute periods evidence_span: {"source_cache": "artifacts/hbot-research/11023535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d", "start_char": 0, "end_char": 1576, "text_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d"} [hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

evidence_access

Primary abstract

experimental_model

Human IDO1 structure and mutagenesis.

limitations

Catalytic heme dependence does not establish benefit from extra dietary iron.

nutrient_topic

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

plain_language

An immune-regulated enzyme opens a different route for tryptophan.

primary_references

Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16477023/ · DOI 10.1073/pnas.0508996103

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 170–176

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human IDO1 structure and mutagenesis. · source_derived_draft · unverified_draft

## tryptophan-ido-ring-cleavage An immune-regulated enzyme opens a different route for tryptophan. Human IDO1 uses heme-bound oxygen to cleave the tryptophan indole ring, incorporating both oxygen atoms during N-formylkynurenine formation. Model: Human IDO1 structure and mutagenesis. Limitations: Catalytic heme dependence does not establish benefit from extra dietary iron. Evidence access: Primary abstract Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16477023/ · DOI 10.1073/pnas.0508996103

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Purified human erythrocyte enzyme plus mouse/bovine preparations; four affected patients.

limitations

The metabolite is associated with FAH deficiency, not demonstrated as a consequence of ordinary tyrosine supplements.

nutrient_topic

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

plain_language

A blocked tyrosine pathway can interfere with heme production.

primary_references

Hereditary tyrosinemia and the heme biosynthetic pathway. Profound inhibition of delta-aminolevulinic acid dehydratase activity by succinylacetone. · 1983 · https://pubmed.ncbi.nlm.nih.gov/6826727/ · DOI 10.1172/jci110809

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 284–290

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human erythrocyte enzyme plus mouse/bovine preparations; four affected patients. · source_derived_draft · unverified_draft

## l-tyrosine-sa-alad A blocked tyrosine pathway can interfere with heme production. Succinylacetone competitively inhibited purified human erythrocyte ALAD; the study reported submicromolar inhibition constants across human and animal preparations. Model: Purified human erythrocyte enzyme plus mouse/bovine preparations; four affected patients. Limitations: The metabolite is associated with FAH deficiency, not demonstrated as a consequence of ordinary tyrosine supplements. Evidence access: Primary abstract Hereditary tyrosinemia and the heme biosynthetic pathway. Profound inhibition of delta-aminolevulinic acid dehydratase activity by succinylacetone. · 1983 · https://pubmed.ncbi.nlm.nih.gov/6826727/ · DOI 10.1172/jci110809

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Cultured avian hepatocytes with direct metabolite exposure.

limitations

The cellular effect is avian; the human ALAD inhibition is recorded separately.

nutrient_topic

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

plain_language

One pathway blockage can reduce machinery used by other pathways.

primary_references

Hereditary tyrosinemia and the heme biosynthetic pathway. Profound inhibition of delta-aminolevulinic acid dehydratase activity by succinylacetone. · 1983 · https://pubmed.ncbi.nlm.nih.gov/6826727/ · DOI 10.1172/jci110809

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 292–298

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured avian hepatocytes with direct metabolite exposure. · source_derived_draft · unverified_draft

## l-tyrosine-sa-heme One pathway blockage can reduce machinery used by other pathways. Adding succinylacetone to avian hepatocytes reduced cellular heme and cytochrome P450 content. Model: Cultured avian hepatocytes with direct metabolite exposure. Limitations: The cellular effect is avian; the human ALAD inhibition is recorded separately. Evidence access: Primary abstract Hereditary tyrosinemia and the heme biosynthetic pathway. Profound inhibition of delta-aminolevulinic acid dehydratase activity by succinylacetone. · 1983 · https://pubmed.ncbi.nlm.nih.gov/6826727/ · DOI 10.1172/jci110809

evidence_span

{"source_cache": "artifacts/citrulline-research/31514202.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3001c79d449d8a5545278fdaa6dd7a2dd9e1a67b6e4553d78bbc5848a35362d", "start_char": 0, "end_char": 991, "text_sha256": "e3001c79d449d8a5545278fdaa6dd7a2dd9e1a67b6e4553d78bbc5848a35362d"}

experimental_model

Cryo-EM structures in multiple functional states

exposure

NO-bound and other functional enzyme states

limitations

Structural signal transduction, not a clinical citrulline efficacy experiment.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human soluble guanylate cyclase alpha1-beta1

plain_language

NO is a signal received by another enzyme, rather than the final vascular response.

primary_references

[citrulline-p31514202] Structural insights into the mechanism of human soluble guanylate cyclase. (2019). https://pubmed.ncbi.nlm.nih.gov/31514202/ DOI: 10.1038/s41586-019-1584-6

tissue_or_cell_type

NO sensor, transducer and catalytic modules

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 684–695

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM structures in multiple functional states · source_derived_draft · unverified_draft

### citrulline-no-sgc NO binding to the beta1 H-NOX region drove structural changes that increased human soluble guanylate cyclase activity. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: NO is a signal received by another enzyme, rather than the final vascular response. organism: Human soluble guanylate cyclase alpha1-beta1 tissue_or_cell_type: NO sensor, transducer and catalytic modules experimental_model: Cryo-EM structures in multiple functional states limitations: Structural signal transduction, not a clinical citrulline efficacy experiment. exposure: NO-bound and other functional enzyme states evidence_span: {"source_cache": "artifacts/citrulline-research/31514202.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3001c79d449d8a5545278fdaa6dd7a2dd9e1a67b6e4553d78bbc5848a35362d", "start_char": 0, "end_char": 991, "text_sha256": "e3001c79d449d8a5545278fdaa6dd7a2dd9e1a67b6e4553d78bbc5848a35362d"} [citrulline-p31514202] Structural insights into the mechanism of human soluble guanylate cyclase. (2019). https://pubmed.ncbi.nlm.nih.gov/31514202/ DOI: 10.1038/s41586-019-1584-6

cross_nutrient

true

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/9492031.json", "json_field": "abstractText", "text_sha256": "4a73f43b4e982a85a7e632cc57a8db51a590eb23fa1d578a448cab52b2d8405f", "text_characters": 2006, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

Recombinant human TPO ectodomain residues 1–848 expressed in Chinese hamster ovary cells

exposure

1 mg/L hemin, hematin or protoporphyrin IX in expression cultures; human ectodomain 1–848.

limitations

Guaiacol assay and recombinant construct; not a human dietary iron-repletion experiment.

nutrient_topic

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

organism

Homo sapiens protein; Cricetulus griseus host cells

plain_language

Iron-containing heme helps TPO become an active enzyme.

primary_references

[iodine-syn-tpo1998] The greater glycan content of recombinant human thyroid peroxidase of mammalian than of insect cell origin facilitates purification to homogeneity of enzymatically protein remaining soluble at high concentration. (1998). https://pubmed.ncbi.nlm.nih.gov/9492031/ DOI: 10.1210/endo.139.3.5782

tissue_or_cell_type

CHO expression system; purified protein

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 562–574

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human TPO ectodomain residues 1–848 expressed in Chinese hamster ovary cells · source_derived_draft · unverified_draft

### iodine-syn-heme-activity Adding hemin or hematin to CHO expression cultures increased heme incorporation and guaiacol activity of purified human TPO ectodomain relative to the iron-free porphyrin comparison. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron-containing heme helps TPO become an active enzyme. organism: Homo sapiens protein; Cricetulus griseus host cells tissue_or_cell_type: CHO expression system; purified protein experimental_model: Recombinant human TPO ectodomain residues 1–848 expressed in Chinese hamster ovary cells limitations: Guaiacol assay and recombinant construct; not a human dietary iron-repletion experiment. exposure: 1 mg/L hemin, hematin or protoporphyrin IX in expression cultures; human ectodomain 1–848. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/9492031.json", "json_field": "abstractText", "text_sha256": "4a73f43b4e982a85a7e632cc57a8db51a590eb23fa1d578a448cab52b2d8405f", "text_characters": 2006, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tpo1998] The greater glycan content of recombinant human thyroid peroxidase of mammalian than of insect cell origin facilitates purification to homogeneity of enzymatically protein remaining soluble at high concentration. (1998). https://pubmed.ncbi.nlm.nih.gov/9492031/ DOI: 10.1210/endo.139.3.5782

cross_nutrient

true

evidence_span

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

experimental_model

CHO cells expressing human TPO; additional primary thyroid cultures

exposure

Succinylacetone; concentration not stated in abstract.

limitations

Pharmacological heme synthesis perturbation; not evidence of a dietary iron threshold.

nutrient_topic

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

organism

Homo sapiens protein; Cricetulus griseus host cells

plain_language

Blocking heme production kept much of TPO from reaching the surface.

primary_references

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

tissue_or_cell_type

CHO endoplasmic reticulum and cell surface

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 576–588

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

### iodine-syn-heme-trafficking In CHO cells expressing human TPO, inhibition of heme biosynthesis by succinylacetone decreased surface TPO expression by approximately 80%. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blocking heme production kept much of TPO from reaching the surface. organism: Homo sapiens protein; Cricetulus griseus host cells tissue_or_cell_type: CHO endoplasmic reticulum and cell surface experimental_model: CHO cells expressing human TPO; additional primary thyroid cultures limitations: Pharmacological heme synthesis perturbation; not evidence of a dietary iron threshold. exposure: Succinylacetone; concentration not stated in abstract. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/10187846.json", "json_field": "abstractText", "text_sha256": "97f8a86c7effd5754e2b61c65d769de9e86678a7398c5eb20a0e88ac49a8fdbb", "text_characters": 1855, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tpo1999] Role of heme in intracellular trafficking of thyroperoxidase and involvement of H2O2 generated at the apical surface of thyroid cells in autocatalytic covalent heme binding. (1999). https://pubmed.ncbi.nlm.nih.gov/10187846/ DOI: 10.1074/jbc.274.15.10533

cross_nutrient

true

evidence_span

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

experimental_model

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

exposure

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

limitations

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

nutrient_topic

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

organism

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

plain_language

Human TPO can drive hormone formation on human thyroglobulin.

primary_references

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

tissue_or_cell_type

Purified-protein reconstitution

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

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

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

cross_nutrient

true

evidence_span

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

experimental_model

CHO cells expressing human TPO; additional primary thyroid cultures

exposure

10 micromolar H2O2, 10 minutes.

limitations

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

nutrient_topic

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

organism

Homo sapiens protein; Cricetulus griseus host cells

plain_language

Peroxide exposure helped activate surface TPO in this cell model.

primary_references

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

tissue_or_cell_type

CHO cell surface

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

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

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

evidence_span

{"source_cache": "artifacts/molybdenum-research/20861021.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f430936dcc4701e5d57040edcab4b0418e3c49c59620e0f7d5f54aff41e7877", "start_char": 0, "end_char": 1557, "text_sha256": "0f430936dcc4701e5d57040edcab4b0418e3c49c59620e0f7d5f54aff41e7877"}

experimental_model

Recombinant human mARC1/mARC2 biochemical and spectroscopic reconstitution

exposure

N-hydroxylated substrates; cofactor reconstitution

limitations

The 2010 paper could not identify the Mo-ligating cysteine; later structural/mutagenesis work resolves that point. Its earlier inference is not imported as current fact.

nutrient_topic

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

organism

Human proteins expressed in Escherichia coli

plain_language

Niacin, riboflavin, iron and molybdenum meet in one electron-transfer chain.

primary_references

[mo-p20861021] Biochemical and spectroscopic characterization of the human mitochondrial amidoxime reducing components hmARC-1 and hmARC-2 suggests the existence of a new molybdenum enzyme family in eukaryotes. (2010). https://pubmed.ncbi.nlm.nih.gov/20861021/ DOI: 10.1074/jbc.m110.169532

tissue_or_cell_type

Purified enzyme system

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 963–974

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human mARC1/mARC2 biochemical and spectroscopic reconstitution · source_derived_draft · unverified_draft

### mo-marc-fad-nadh The reconstituted mARC system used NADH/FAD-dependent cytochrome b5 reductase and heme-containing cytochrome b5. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Niacin, riboflavin, iron and molybdenum meet in one electron-transfer chain. organism: Human proteins expressed in Escherichia coli tissue_or_cell_type: Purified enzyme system experimental_model: Recombinant human mARC1/mARC2 biochemical and spectroscopic reconstitution limitations: The 2010 paper could not identify the Mo-ligating cysteine; later structural/mutagenesis work resolves that point. Its earlier inference is not imported as current fact. exposure: N-hydroxylated substrates; cofactor reconstitution evidence_span: {"source_cache": "artifacts/molybdenum-research/20861021.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f430936dcc4701e5d57040edcab4b0418e3c49c59620e0f7d5f54aff41e7877", "start_char": 0, "end_char": 1557, "text_sha256": "0f430936dcc4701e5d57040edcab4b0418e3c49c59620e0f7d5f54aff41e7877"} [mo-p20861021] Biochemical and spectroscopic characterization of the human mitochondrial amidoxime reducing components hmARC-1 and hmARC-2 suggests the existence of a new molybdenum enzyme family in eukaryotes. (2010). https://pubmed.ncbi.nlm.nih.gov/20861021/ DOI: 10.1074/jbc.m110.169532

evidence_span

{"source_cache": "artifacts/molybdenum-research/31127934.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de", "start_char": 0, "end_char": 1649, "text_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de"}

experimental_model

Human SUOX Gly362Ser patient fibroblasts and recombinant enzyme maturation assays

exposure

G362S versus WT protein; Moco reconstitution and molybdate supplementation in culture

limitations

One genotype; in-vitro molybdate rescue is not demonstrated clinical treatment for all SUOX defects.

nutrient_topic

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

organism

Homo sapiens

plain_language

Molybdenum and iron-containing heme perform different jobs within this enzyme.

primary_references

[mo-p31127934] Impaired mitochondrial maturation of sulfite oxidase in a patient with severe sulfite oxidase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/31127934/ DOI: 10.1093/hmg/ddz109

tissue_or_cell_type

Mitochondrial intermembrane space; patient fibroblasts

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 599–610

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SUOX Gly362Ser patient fibroblasts and recombinant enzyme maturation assays · source_derived_draft · unverified_draft

### mo-suox-cofactors SUOX sulfite oxidation depends on Moco at the catalytic site and a separate heme cofactor. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Molybdenum and iron-containing heme perform different jobs within this enzyme. organism: Homo sapiens tissue_or_cell_type: Mitochondrial intermembrane space; patient fibroblasts experimental_model: Human SUOX Gly362Ser patient fibroblasts and recombinant enzyme maturation assays limitations: One genotype; in-vitro molybdate rescue is not demonstrated clinical treatment for all SUOX defects. exposure: G362S versus WT protein; Moco reconstitution and molybdate supplementation in culture evidence_span: {"source_cache": "artifacts/molybdenum-research/31127934.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de", "start_char": 0, "end_char": 1649, "text_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de"} [mo-p31127934] Impaired mitochondrial maturation of sulfite oxidase in a patient with severe sulfite oxidase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/31127934/ DOI: 10.1093/hmg/ddz109

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/molybdenum-research/22854042.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01970920183b87fde6830ca30d612aff75fc4b1a30672a3b9cc2f0c408294884", "start_char": 0, "end_char": 1268, "text_sha256": "01970920183b87fde6830ca30d612aff75fc4b1a30672a3b9cc2f0c408294884"}

experimental_model

Mammalian sulfite-oxidase targeting, cofactor depletion and maturation experiments

exposure

Targeting-sequence constructs and absence of Moco

limitations

Sequential maturation in the studied models; not a universal ranking of nutrient needs.

nutrient_topic

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

organism

Mammalian/human cell models

plain_language

Iron-containing heme is loaded after the molybdenum cofactor.

primary_references

[mo-p22854042] Cofactor-dependent maturation of mammalian sulfite oxidase links two mitochondrial import pathways. (2012). https://pubmed.ncbi.nlm.nih.gov/22854042/ DOI: 10.1242/jcs.110114

tissue_or_cell_type

Mitochondrial intermembrane space and cytosol

trigger_kind

machinery_impairment Imported condition classification; unverified.

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 651–662

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mammalian sulfite-oxidase targeting, cofactor depletion and maturation experiments · source_derived_draft · unverified_draft

### mo-suox-heme-order Heme binding occurred only after Moco integration in the studied SUOX maturation pathway. Condition category: machinery_impairment nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron-containing heme is loaded after the molybdenum cofactor. organism: Mammalian/human cell models tissue_or_cell_type: Mitochondrial intermembrane space and cytosol experimental_model: Mammalian sulfite-oxidase targeting, cofactor depletion and maturation experiments limitations: Sequential maturation in the studied models; not a universal ranking of nutrient needs. exposure: Targeting-sequence constructs and absence of Moco evidence_span: {"source_cache": "artifacts/molybdenum-research/22854042.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01970920183b87fde6830ca30d612aff75fc4b1a30672a3b9cc2f0c408294884", "start_char": 0, "end_char": 1268, "text_sha256": "01970920183b87fde6830ca30d612aff75fc4b1a30672a3b9cc2f0c408294884"} [mo-p22854042] Cofactor-dependent maturation of mammalian sulfite oxidase links two mitochondrial import pathways. (2012). https://pubmed.ncbi.nlm.nih.gov/22854042/ DOI: 10.1242/jcs.110114

evidence_span

{"source_cache": "artifacts/molybdenum-research/31127934.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de", "start_char": 0, "end_char": 1649, "text_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de"}

experimental_model

Human SUOX Gly362Ser patient fibroblasts and recombinant enzyme maturation assays

exposure

G362S versus WT protein; Moco reconstitution and molybdate supplementation in culture

limitations

One genotype; in-vitro molybdate rescue is not demonstrated clinical treatment for all SUOX defects.

nutrient_topic

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

organism

Homo sapiens

plain_language

SUOX clears sulfite by changing it into sulfate.

primary_references

[mo-p31127934] Impaired mitochondrial maturation of sulfite oxidase in a patient with severe sulfite oxidase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/31127934/ DOI: 10.1093/hmg/ddz109

tissue_or_cell_type

Mitochondrial intermembrane space; patient fibroblasts

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 586–597

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SUOX Gly362Ser patient fibroblasts and recombinant enzyme maturation assays · source_derived_draft · unverified_draft

### mo-suox-reaction Human sulfite oxidase converts sulfite to sulfate in the terminal oxidative step of cysteine catabolism. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: SUOX clears sulfite by changing it into sulfate. organism: Homo sapiens tissue_or_cell_type: Mitochondrial intermembrane space; patient fibroblasts experimental_model: Human SUOX Gly362Ser patient fibroblasts and recombinant enzyme maturation assays limitations: One genotype; in-vitro molybdate rescue is not demonstrated clinical treatment for all SUOX defects. exposure: G362S versus WT protein; Moco reconstitution and molybdate supplementation in culture evidence_span: {"source_cache": "artifacts/molybdenum-research/31127934.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de", "start_char": 0, "end_char": 1649, "text_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de"} [mo-p31127934] Impaired mitochondrial maturation of sulfite oxidase in a patient with severe sulfite oxidase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/31127934/ DOI: 10.1093/hmg/ddz109

cross_nutrient

NADPH and heme-containing P450 machinery support retinoid oxidation; nutritional deficiency was not tested.

evidence_location

Abstract

experimental_model

Human CYP26A1/CYP26B1 expressed in insect cells; purified/reconstituted metabolism and tissue assays.

exposure

All-trans-retinoic-acid concentration series with P450 reductase and NADPH.

limitations

Assay kinetics are not whole-body clearance; hydroxylated products are not assumed biologically inert.

nutrient_topic

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

organism

Homo sapiens recombinant protein in insect cells

outcome

Recombinant human CYP26A1 hydroxylated all-trans-retinoic acid to 4-hydroxy-retinoic acid.

plain_language

This P450 begins oxidative removal of the signaling retinoid.

primary_references

[va-topletz-2012] Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases (2012). https://pubmed.ncbi.nlm.nih.gov/22020119/ DOI: 10.1016/j.bcp.2011.10.007

tissue_or_cell_type

Reconstituted enzyme/microsomes

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 601–614

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CYP26A1/CYP26B1 expressed in insect cells; purified/reconstituted metabolism and tissue assays. · source_derived_draft · unverified_draft

### va-cyp26a1-primary-hydroxylation Recombinant human CYP26A1 hydroxylated all-trans-retinoic acid to 4-hydroxy-retinoic acid. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: This P450 begins oxidative removal of the signaling retinoid. organism: Homo sapiens recombinant protein in insect cells tissue_or_cell_type: Reconstituted enzyme/microsomes experimental_model: Human CYP26A1/CYP26B1 expressed in insect cells; purified/reconstituted metabolism and tissue assays. limitations: Assay kinetics are not whole-body clearance; hydroxylated products are not assumed biologically inert. exposure: All-trans-retinoic-acid concentration series with P450 reductase and NADPH. outcome: Recombinant human CYP26A1 hydroxylated all-trans-retinoic acid to 4-hydroxy-retinoic acid. evidence_location: Abstract cross_nutrient: NADPH and heme-containing P450 machinery support retinoid oxidation; nutritional deficiency was not tested. [va-topletz-2012] Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases (2012). https://pubmed.ncbi.nlm.nih.gov/22020119/ DOI: 10.1016/j.bcp.2011.10.007

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/16765986.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "177ab81c08f82c99c81c69d1cb582e52216234e290066ae5aa380a887fb0e38c", "start_char": 0, "end_char": 1284, "text_sha256": "177ab81c08f82c99c81c69d1cb582e52216234e290066ae5aa380a887fb0e38c"}

experimental_model

High-resolution crystallographic comparison

exposure

1.25 angstrom structural refinement

limitations

Structural oxygen-ligand geometry, not a supplementation or oxygen-delivery clinical trial.

nutrient_topic

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

organism

Human hemoglobin A

plain_language

Hemoglobin holds oxygen at carefully organized heme sites so oxygen binding can be controlled.

primary_references

[iron-p16765986] 1.25 A resolution crystal structures of human haemoglobin in the oxy, deoxy and carbonmonoxy forms. (2006). https://pubmed.ncbi.nlm.nih.gov/16765986/ DOI: 10.1016/j.jmb.2006.05.036

tissue_or_cell_type

Purified oxy-, deoxy- and carbonmonoxyhemoglobin

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 537–548

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

### iron-hemoglobin-oxygen-site Oxyhemoglobin structures resolved hydrogen bonding between the oxygen ligand and distal histidine in both alpha and beta subunits. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Hemoglobin holds oxygen at carefully organized heme sites so oxygen binding can be controlled. organism: Human hemoglobin A tissue_or_cell_type: Purified oxy-, deoxy- and carbonmonoxyhemoglobin experimental_model: High-resolution crystallographic comparison limitations: Structural oxygen-ligand geometry, not a supplementation or oxygen-delivery clinical trial. exposure: 1.25 angstrom structural refinement evidence_span: {"source_cache": "artifacts/iron-research/16765986.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "177ab81c08f82c99c81c69d1cb582e52216234e290066ae5aa380a887fb0e38c", "start_char": 0, "end_char": 1284, "text_sha256": "177ab81c08f82c99c81c69d1cb582e52216234e290066ae5aa380a887fb0e38c"} [iron-p16765986] 1.25 A resolution crystal structures of human haemoglobin in the oxy, deoxy and carbonmonoxy forms. (2006). https://pubmed.ncbi.nlm.nih.gov/16765986/ DOI: 10.1016/j.jmb.2006.05.036

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/iron-research/23395172.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9ffc7159cfb418fed987d6f3f9e34829861a8f4ede0fe564a2714ef0bc96968b", "start_char": 0, "end_char": 1074, "text_sha256": "9ffc7159cfb418fed987d6f3f9e34829861a8f4ede0fe564a2714ef0bc96968b"}

experimental_model

Macrophage depletion, localization and human variant assays

exposure

Hrg1 depletion and missense variants

limitations

Recycling pathway experiment; no estimate of dietary iron requirements is derived.

nutrient_topic

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

organism

Mouse macrophages and human HRG1 variants

plain_language

A blocked recycling step can trap useful material inside a cellular compartment.

primary_references

[iron-p23395172] HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis. (2013). https://pubmed.ncbi.nlm.nih.gov/23395172/ DOI: 10.1016/j.cmet.2013.01.005

tissue_or_cell_type

Phagolysosomes during erythrophagocytosis

trigger_kind

machinery_impairment Imported condition classification; unverified.

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 563–574

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Macrophage depletion, localization and human variant assays · source_derived_draft · unverified_draft

### iron-hrg1-loss Hrg1 depletion attenuated heme transport from macrophage phagolysosomes. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: A blocked recycling step can trap useful material inside a cellular compartment. organism: Mouse macrophages and human HRG1 variants tissue_or_cell_type: Phagolysosomes during erythrophagocytosis experimental_model: Macrophage depletion, localization and human variant assays limitations: Recycling pathway experiment; no estimate of dietary iron requirements is derived. exposure: Hrg1 depletion and missense variants evidence_span: {"source_cache": "artifacts/iron-research/23395172.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9ffc7159cfb418fed987d6f3f9e34829861a8f4ede0fe564a2714ef0bc96968b", "start_char": 0, "end_char": 1074, "text_sha256": "9ffc7159cfb418fed987d6f3f9e34829861a8f4ede0fe564a2714ef0bc96968b"} [iron-p23395172] HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis. (2013). https://pubmed.ncbi.nlm.nih.gov/23395172/ DOI: 10.1016/j.cmet.2013.01.005

evidence_span

{"source_cache": "artifacts/iron-research/23395172.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9ffc7159cfb418fed987d6f3f9e34829861a8f4ede0fe564a2714ef0bc96968b", "start_char": 0, "end_char": 1074, "text_sha256": "9ffc7159cfb418fed987d6f3f9e34829861a8f4ede0fe564a2714ef0bc96968b"}

experimental_model

Macrophage depletion, localization and human variant assays

exposure

Hrg1 depletion and missense variants

limitations

Recycling pathway experiment; no estimate of dietary iron requirements is derived.

nutrient_topic

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

organism

Mouse macrophages and human HRG1 variants

plain_language

Macrophages must move heme out of the compartment where old red cells are broken down.

primary_references

[iron-p23395172] HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis. (2013). https://pubmed.ncbi.nlm.nih.gov/23395172/ DOI: 10.1016/j.cmet.2013.01.005

tissue_or_cell_type

Phagolysosomes during erythrophagocytosis

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 550–561

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Macrophage depletion, localization and human variant assays · source_derived_draft · unverified_draft

### iron-hrg1-recycling Hrg1 localized to phagolysosomal membranes during erythrophagocytosis and transported heme toward the macrophage cytoplasm. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Macrophages must move heme out of the compartment where old red cells are broken down. organism: Mouse macrophages and human HRG1 variants tissue_or_cell_type: Phagolysosomes during erythrophagocytosis experimental_model: Macrophage depletion, localization and human variant assays limitations: Recycling pathway experiment; no estimate of dietary iron requirements is derived. exposure: Hrg1 depletion and missense variants evidence_span: {"source_cache": "artifacts/iron-research/23395172.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9ffc7159cfb418fed987d6f3f9e34829861a8f4ede0fe564a2714ef0bc96968b", "start_char": 0, "end_char": 1074, "text_sha256": "9ffc7159cfb418fed987d6f3f9e34829861a8f4ede0fe564a2714ef0bc96968b"} [iron-p23395172] HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis. (2013). https://pubmed.ncbi.nlm.nih.gov/23395172/ DOI: 10.1016/j.cmet.2013.01.005

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/iron-research/11726526.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6182d43925454a0208a74bed0b7da46736b9ff456509b215aa87e3051fe92eb3", "start_char": 0, "end_char": 1056, "text_sha256": "6182d43925454a0208a74bed0b7da46736b9ff456509b215aa87e3051fe92eb3"}

experimental_model

Targeted gene disruption with iron-deficient feeding

exposure

Hri deletion crossed with iron deficiency

limitations

Combined gene-loss and nutritional stress; the unusual knockout anemia pattern is not the standard description of ordinary iron deficiency.

nutrient_topic

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

organism

Mice

plain_language

Without the protective brake, cells kept making protein they could not safely assemble.

primary_references

[iron-p11726526] Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency. (2001). https://pubmed.ncbi.nlm.nih.gov/11726526/ DOI: 10.1093/emboj/20.23.6909

tissue_or_cell_type

Erythroid precursors and red cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1122–1133

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted gene disruption with iron-deficient feeding · source_derived_draft · unverified_draft

### iron-hri-globin-aggregation Iron-deficient Hri-null mice accumulated globin aggregates lacking heme within red cells and their precursors. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Without the protective brake, cells kept making protein they could not safely assemble. organism: Mice tissue_or_cell_type: Erythroid precursors and red cells experimental_model: Targeted gene disruption with iron-deficient feeding limitations: Combined gene-loss and nutritional stress; the unusual knockout anemia pattern is not the standard description of ordinary iron deficiency. exposure: Hri deletion crossed with iron deficiency evidence_span: {"source_cache": "artifacts/iron-research/11726526.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6182d43925454a0208a74bed0b7da46736b9ff456509b215aa87e3051fe92eb3", "start_char": 0, "end_char": 1056, "text_sha256": "6182d43925454a0208a74bed0b7da46736b9ff456509b215aa87e3051fe92eb3"} [iron-p11726526] Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency. (2001). https://pubmed.ncbi.nlm.nih.gov/11726526/ DOI: 10.1093/emboj/20.23.6909

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/iron-research/12097675.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "26b7a5ddb0985abdb2325c7ecd505c46f02604bd4d35f68ed0c9ad67113a148e", "start_char": 0, "end_char": 1527, "text_sha256": "26b7a5ddb0985abdb2325c7ecd505c46f02604bd4d35f68ed0c9ad67113a148e"}

experimental_model

Controlled iron-deficient diets with pair-fed controls

exposure

Four weeks of graded iron restriction; separate food-restriction controls

limitations

Food restriction also reduced TPO; the iron effect was separately estimated. No human serum threshold or automatic iodine-treatment failure rule.

nutrient_topic

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

organism

84 male weanling rats

plain_language

Iodine supply is only part of thyroid-hormone synthesis; its working enzyme also depends on iron-containing heme.

primary_references

[iron-p12097675] Iron deficiency anemia reduces thyroid peroxidase activity in rats. (2002). https://pubmed.ncbi.nlm.nih.gov/12097675/ DOI: 10.1093/jn/132.7.1951

tissue_or_cell_type

Thyroid and blood

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 901–912

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled iron-deficient diets with pair-fed controls · source_derived_draft · unverified_draft

### iron-iron-tpo-deficiency Iron-deficiency anemia independently reduced thyroid peroxidase activity after accounting for food restriction in the rat experiment. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iodine supply is only part of thyroid-hormone synthesis; its working enzyme also depends on iron-containing heme. organism: 84 male weanling rats tissue_or_cell_type: Thyroid and blood experimental_model: Controlled iron-deficient diets with pair-fed controls limitations: Food restriction also reduced TPO; the iron effect was separately estimated. No human serum threshold or automatic iodine-treatment failure rule. exposure: Four weeks of graded iron restriction; separate food-restriction controls evidence_span: {"source_cache": "artifacts/iron-research/12097675.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "26b7a5ddb0985abdb2325c7ecd505c46f02604bd4d35f68ed0c9ad67113a148e", "start_char": 0, "end_char": 1527, "text_sha256": "26b7a5ddb0985abdb2325c7ecd505c46f02604bd4d35f68ed0c9ad67113a148e"} [iron-p12097675] Iron deficiency anemia reduces thyroid peroxidase activity in rats. (2002). https://pubmed.ncbi.nlm.nih.gov/12097675/ DOI: 10.1093/jn/132.7.1951

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_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

evidence_span

{"source_cache": "artifacts/coumarin-research/15665333.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "79f42118f337ffe818b92138941685126173355131f8e12ca7cae9a437800a5b", "start_char": 0, "end_char": 1689, "text_sha256": "79f42118f337ffe818b92138941685126173355131f8e12ca7cae9a437800a5b"}

experimental_model

Purified human CYP2A6 kinetic experiments

exposure

Coumarin oxidation; stopped-flow and steady-state kinetics, selected measures at 23 C

limitations

Biochemical rates do not measure whole-body clearance; accessory b5 species is not specified in the abstract.

nutrient_topic

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

organism

Human CYP2A6 with reconstituted accessory proteins

plain_language

CYP2A6 adds an oxygen-containing group to coumarin.

primary_references

[coumarin-p15665333] Kinetic analysis of oxidation of coumarins by human cytochrome P450 2A6. (2005). https://pubmed.ncbi.nlm.nih.gov/15665333/ DOI: 10.1074/jbc.m411019200

tissue_or_cell_type

Reconstituted enzyme system

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 137–148

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human CYP2A6 kinetic experiments · source_derived_draft · unverified_draft

### coumarin-2a6-7oh Human CYP2A6 catalyzed conversion of coumarin to 7-hydroxycoumarin. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP2A6 adds an oxygen-containing group to coumarin. organism: Human CYP2A6 with reconstituted accessory proteins tissue_or_cell_type: Reconstituted enzyme system experimental_model: Purified human CYP2A6 kinetic experiments limitations: Biochemical rates do not measure whole-body clearance; accessory b5 species is not specified in the abstract. exposure: Coumarin oxidation; stopped-flow and steady-state kinetics, selected measures at 23 C evidence_span: {"source_cache": "artifacts/coumarin-research/15665333.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "79f42118f337ffe818b92138941685126173355131f8e12ca7cae9a437800a5b", "start_char": 0, "end_char": 1689, "text_sha256": "79f42118f337ffe818b92138941685126173355131f8e12ca7cae9a437800a5b"} [coumarin-p15665333] Kinetic analysis of oxidation of coumarins by human cytochrome P450 2A6. (2005). https://pubmed.ncbi.nlm.nih.gov/15665333/ DOI: 10.1074/jbc.m411019200

evidence_span

{"source_cache": "artifacts/coumarin-research/15665333.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "79f42118f337ffe818b92138941685126173355131f8e12ca7cae9a437800a5b", "start_char": 0, "end_char": 1689, "text_sha256": "79f42118f337ffe818b92138941685126173355131f8e12ca7cae9a437800a5b"}

experimental_model

Purified human CYP2A6 kinetic experiments

exposure

Coumarin oxidation; stopped-flow and steady-state kinetics, selected measures at 23 C

limitations

Biochemical rates do not measure whole-body clearance; accessory b5 species is not specified in the abstract.

nutrient_topic

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

organism

Human CYP2A6 with reconstituted accessory proteins

plain_language

An accessory electron carrier improved the enzyme reaction.

primary_references

[coumarin-p15665333] Kinetic analysis of oxidation of coumarins by human cytochrome P450 2A6. (2005). https://pubmed.ncbi.nlm.nih.gov/15665333/ DOI: 10.1074/jbc.m411019200

tissue_or_cell_type

Reconstituted enzyme system

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 150–161

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human CYP2A6 kinetic experiments · source_derived_draft · unverified_draft

### coumarin-b5-enhancement Cytochrome b5 increased CYP2A6-mediated coumarin hydroxylation; kinetic experiments supported electron transfer to the oxygenated enzyme. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An accessory electron carrier improved the enzyme reaction. organism: Human CYP2A6 with reconstituted accessory proteins tissue_or_cell_type: Reconstituted enzyme system experimental_model: Purified human CYP2A6 kinetic experiments limitations: Biochemical rates do not measure whole-body clearance; accessory b5 species is not specified in the abstract. exposure: Coumarin oxidation; stopped-flow and steady-state kinetics, selected measures at 23 C evidence_span: {"source_cache": "artifacts/coumarin-research/15665333.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "79f42118f337ffe818b92138941685126173355131f8e12ca7cae9a437800a5b", "start_char": 0, "end_char": 1689, "text_sha256": "79f42118f337ffe818b92138941685126173355131f8e12ca7cae9a437800a5b"} [coumarin-p15665333] Kinetic analysis of oxidation of coumarins by human cytochrome P450 2A6. (2005). https://pubmed.ncbi.nlm.nih.gov/15665333/ DOI: 10.1074/jbc.m411019200