[4Fe-4S] iron-sulfur cluster

evidence_span

{"source_cache": "artifacts/molybdenum-research/15180982.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "722c11f1c29a720fb7105f37962af2652ce95b6734afdb59d675dee0b8302097", "start_char": 0, "end_char": 1828, "text_sha256": "722c11f1c29a720fb7105f37962af2652ce95b6734afdb59d675dee0b8302097"}

experimental_model

Recombinant human MOCS1A, cysteine mutagenesis and multiple spectroscopic methods

exposure

Aerobic versus anaerobic purification; iron-sulfur reconstitution

limitations

Cluster states depend on preparation and oxygen exposure; the paper does not demonstrate a dietary iron or methyl-donor threshold.

nutrient_topic

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

organism

Human protein expressed in Escherichia coli

plain_language

Molybdenum-cofactor assembly itself requires iron-sulfur machinery.

primary_references

[mo-p15180982] Characterization of MOCS1A, an oxygen-sensitive iron-sulfur protein involved in human molybdenum cofactor biosynthesis. (2004). https://pubmed.ncbi.nlm.nih.gov/15180982/ DOI: 10.1074/jbc.m313398200

tissue_or_cell_type

Purified protein and bacterial complementation

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 313–324

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MOCS1A, cysteine mutagenesis and multiple spectroscopic methods · source_derived_draft · unverified_draft

### mo-mocs1a-fes Anaerobic reconstitution yielded human MOCS1A containing two [4Fe-4S] clusters. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Molybdenum-cofactor assembly itself requires iron-sulfur machinery. organism: Human protein expressed in Escherichia coli tissue_or_cell_type: Purified protein and bacterial complementation experimental_model: Recombinant human MOCS1A, cysteine mutagenesis and multiple spectroscopic methods limitations: Cluster states depend on preparation and oxygen exposure; the paper does not demonstrate a dietary iron or methyl-donor threshold. exposure: Aerobic versus anaerobic purification; iron-sulfur reconstitution evidence_span: {"source_cache": "artifacts/molybdenum-research/15180982.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "722c11f1c29a720fb7105f37962af2652ce95b6734afdb59d675dee0b8302097", "start_char": 0, "end_char": 1828, "text_sha256": "722c11f1c29a720fb7105f37962af2652ce95b6734afdb59d675dee0b8302097"} [mo-p15180982] Characterization of MOCS1A, an oxygen-sensitive iron-sulfur protein involved in human molybdenum cofactor biosynthesis. (2004). https://pubmed.ncbi.nlm.nih.gov/15180982/ DOI: 10.1074/jbc.m313398200

cross_nutrient

Direct mechanistic integration of an iron-containing center with B2-derived FAD.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3106343", "locator": "HTML article p", "paragraph_index": 51, "char_start": 0, "char_end": 1197, "evidence_access": "full-text"}]

experimental_model

Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR.

exposure

No nutrient intervention; structural or biochemical characterization.

limitations

Mechanistic inference from mutagenesis/EPR and activity; no dietary iron or B2 intervention.

nutrient_topic

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

organism

Rhodobacter sphaeroides; human ETF/MCAD reagents

plain_language

ETF-QO uses its iron-sulfur center and flavin for different stages of the electron relay.

primary_references

[swanson-2008-etf-qo] The iron-sulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein (2008). https://pubmed.ncbi.nlm.nih.gov/18672901/ DOI: 10.1021/bi800507p

tissue_or_cell_type

Purified proteins

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 794–806

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR. · source_derived_draft · unverified_draft

### b2-met-etf-qo-iron-sulfur-entry Selective effects of ETF-QO FAD-site mutations supported electron entry from ETF through the [4Fe-4S] center, followed by flavin-mediated transfer to ubiquinone. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ETF-QO uses its iron-sulfur center and flavin for different stages of the electron relay. organism: Rhodobacter sphaeroides; human ETF/MCAD reagents tissue_or_cell_type: Purified proteins experimental_model: Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR. limitations: Mechanistic inference from mutagenesis/EPR and activity; no dietary iron or B2 intervention. exposure: No nutrient intervention; structural or biochemical characterization. cross_nutrient: Direct mechanistic integration of an iron-containing center with B2-derived FAD. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3106343", "locator": "HTML article p", "paragraph_index": 51, "char_start": 0, "char_end": 1197, "evidence_access": "full-text"}] [swanson-2008-etf-qo] The iron-sulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein (2008). https://pubmed.ncbi.nlm.nih.gov/18672901/ DOI: 10.1021/bi800507p

cross_nutrient

B2-derived FAD and iron-containing redox centers cooperate within one respiratory complex.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 2, "char_start": 0, "char_end": 1105, "evidence_access": "full-text"}]

experimental_model

Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays.

exposure

No nutrient intervention; structural or biochemical characterization.

limitations

Structural co-dependence does not show that B2 corrects iron deficiency or that iron supplementation improves this reaction.

nutrient_topic

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

organism

Homo sapiens

plain_language

Complex II couples a B2-derived flavin with separate iron-sulfur centers.

primary_references

[du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120

tissue_or_cell_type

HEK293F-derived purified complex II

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 649–661

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. · source_derived_draft · unverified_draft

### b2-met-human-sdhb-iron-sulfur Human complex II structure and EPR resolved SDHB-associated [2Fe-2S], [4Fe-4S] and [3Fe-4S] redox centers adjacent to its SDHA FAD system. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Complex II couples a B2-derived flavin with separate iron-sulfur centers. organism: Homo sapiens tissue_or_cell_type: HEK293F-derived purified complex II experimental_model: Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. limitations: Structural co-dependence does not show that B2 corrects iron deficiency or that iron supplementation improves this reaction. exposure: No nutrient intervention; structural or biochemical characterization. cross_nutrient: B2-derived FAD and iron-containing redox centers cooperate within one respiratory complex. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 2, "char_start": 0, "char_end": 1105, "evidence_access": "full-text"}] [du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120

evidence_span

{"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"}

experimental_model

Purified human LIAS turnover and cluster-transfer assays

exposure

LIAS with candidate iron-sulfur cluster donors

limitations

Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells.

nutrient_topic

Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid

organism

Human recombinant proteins

plain_language

Two iron-sulfur clusters perform different jobs in the same enzyme.

primary_references

[ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020

tissue_or_cell_type

Mitochondrial lipoyl synthesis machinery

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 299–310

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human LIAS turnover and cluster-transfer assays · source_derived_draft · unverified_draft

### ala-lias-two-clusters LIAS has distinct radical-SAM and auxiliary [4Fe-4S] clusters; the latter supplies sulfur during lipoyl synthesis. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two iron-sulfur clusters perform different jobs in the same enzyme. organism: Human recombinant proteins tissue_or_cell_type: Mitochondrial lipoyl synthesis machinery experimental_model: Purified human LIAS turnover and cluster-transfer assays limitations: Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells. exposure: LIAS with candidate iron-sulfur cluster donors evidence_span: {"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"} [ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3106343", "locator": "HTML article p", "paragraph_index": 2, "char_start": 0, "char_end": 1789, "evidence_access": "full-text"}]

experimental_model

Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR.

exposure

Site-directed mutants compared with wild type.

limitations

Bacterial variant experiment; mechanism cannot be assigned quantitatively to human disease variants.

nutrient_topic

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

organism

Rhodobacter sphaeroides; human ETF/MCAD reagents

plain_language

Changing the flavin environment selectively impaired the quinone-reducing step.

primary_references

[swanson-2008-etf-qo] The iron-sulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein (2008). https://pubmed.ncbi.nlm.nih.gov/18672901/ DOI: 10.1021/bi800507p

tissue_or_cell_type

Purified recombinant proteins

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 781–792

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR. · source_derived_draft · unverified_draft

### b2-met-etf-qo-fad-quinone-function Rhodobacter ETF-QO N338T and N338A lowered FAD redox potentials and quinone-reductase activity while minimally affecting ETF semiquinone disproportionation. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing the flavin environment selectively impaired the quinone-reducing step. organism: Rhodobacter sphaeroides; human ETF/MCAD reagents tissue_or_cell_type: Purified recombinant proteins experimental_model: Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR. limitations: Bacterial variant experiment; mechanism cannot be assigned quantitatively to human disease variants. exposure: Site-directed mutants compared with wild type. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3106343", "locator": "HTML article p", "paragraph_index": 2, "char_start": 0, "char_end": 1789, "evidence_access": "full-text"}] [swanson-2008-etf-qo] The iron-sulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein (2008). https://pubmed.ncbi.nlm.nih.gov/18672901/ DOI: 10.1021/bi800507p

cross_nutrient

B2-derived FAD and iron-containing cluster are distinct required molecular components; this does not establish supplement interactions.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC1637562", "locator": "HTML article p", "paragraph_index": 10, "char_start": 0, "char_end": 3701, "evidence_access": "full-text"}]

experimental_model

Purified porcine ETF-QO crystal structures with and without bound ubiquinone.

exposure

No nutrient intervention; structural or biochemical characterization.

limitations

Static structure; the exact electron-entry sequence required additional functional experiments.

nutrient_topic

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

organism

Sus scrofa

plain_language

ETF-QO combines flavin and iron-sulfur chemistry in one protein downstream of ETF.

primary_references

[zhang-2006-etf-qo] Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool (2006). https://pubmed.ncbi.nlm.nih.gov/17050691/ DOI: 10.1073/pnas.0604567103

tissue_or_cell_type

Purified porcine mitochondrial ETF-QO

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 767–779

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified porcine ETF-QO crystal structures with and without bound ubiquinone. · source_derived_draft · unverified_draft

### b2-met-porcine-etfdh-cofactors Porcine ETF-QO crystal structures resolved one FAD and one [4Fe-4S] cluster per protein, together with a separate ubiquinone-binding region. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ETF-QO combines flavin and iron-sulfur chemistry in one protein downstream of ETF. organism: Sus scrofa tissue_or_cell_type: Purified porcine mitochondrial ETF-QO experimental_model: Purified porcine ETF-QO crystal structures with and without bound ubiquinone. limitations: Static structure; the exact electron-entry sequence required additional functional experiments. exposure: No nutrient intervention; structural or biochemical characterization. cross_nutrient: B2-derived FAD and iron-containing cluster are distinct required molecular components; this does not establish supplement interactions. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC1637562", "locator": "HTML article p", "paragraph_index": 10, "char_start": 0, "char_end": 3701, "evidence_access": "full-text"}] [zhang-2006-etf-qo] Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool (2006). https://pubmed.ncbi.nlm.nih.gov/17050691/ DOI: 10.1073/pnas.0604567103

evidence_span

{"source_cache": "artifacts/ala-research/35343688.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689", "start_char": 0, "end_char": 670, "text_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689"}

experimental_model

Recombinant protein interaction and cluster-insertion analysis

exposure

NFU1-ISCA1 donor complex

limitations

Loading the radical-SAM site is distinct from recycling the auxiliary sulfur-donor site.

nutrient_topic

Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid

organism

Human proteins

plain_language

A separate assembly route equips the radical-generating site.

primary_references

[ala-p35343688] Protein-Interaction Affinity Gradient Drives [4Fe-4S] Cluster Insertion in Human Lipoyl Synthase. (2022). https://pubmed.ncbi.nlm.nih.gov/35343688/ DOI: 10.1021/jacs.1c13626

tissue_or_cell_type

LIAS radical-SAM site

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 364–375

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant protein interaction and cluster-insertion analysis · source_derived_draft · unverified_draft

### ala-nfu1-isca1-radical-site An NFU1-ISCA1 heterodimer delivers a [4Fe-4S] cluster to the radical-SAM site of LIAS. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate assembly route equips the radical-generating site. organism: Human proteins tissue_or_cell_type: LIAS radical-SAM site experimental_model: Recombinant protein interaction and cluster-insertion analysis limitations: Loading the radical-SAM site is distinct from recycling the auxiliary sulfur-donor site. exposure: NFU1-ISCA1 donor complex evidence_span: {"source_cache": "artifacts/ala-research/35343688.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689", "start_char": 0, "end_char": 670, "text_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689"} [ala-p35343688] Protein-Interaction Affinity Gradient Drives [4Fe-4S] Cluster Insertion in Human Lipoyl Synthase. (2022). https://pubmed.ncbi.nlm.nih.gov/35343688/ DOI: 10.1021/jacs.1c13626

cross_nutrient

true

evidence_location

Figure 6C

experimental_model

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

exposure

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

limitations

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

nutrient_topic

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

organism

Homo sapiens

plain_language

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

primary_references

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

tissue_or_cell_type

NSCLC cell cultures

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

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

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

cross_nutrient

true

evidence_location

Figure 6D

experimental_model

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

exposure

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

limitations

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

nutrient_topic

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

organism

Homo sapiens

plain_language

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

primary_references

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

tissue_or_cell_type

NSCLC cell cultures

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

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

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

cross_nutrient

true

evidence_location

Figure 6D

experimental_model

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

exposure

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

limitations

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

nutrient_topic

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

organism

Homo sapiens

plain_language

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

primary_references

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

tissue_or_cell_type

NSCLC cell cultures

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

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

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

evidence_span

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experimental_model

Recombinant human MOCS1A, cysteine mutagenesis and multiple spectroscopic methods

exposure

Aerobic versus anaerobic purification; iron-sulfur reconstitution

limitations

Purified protein exposure; not evidence that normal breathing causes cofactor deficiency.

nutrient_topic

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

organism

Human protein expressed in Escherichia coli

plain_language

The assembly protein contains oxygen-sensitive clusters.

primary_references

[mo-p15180982] Characterization of MOCS1A, an oxygen-sensitive iron-sulfur protein involved in human molybdenum cofactor biosynthesis. (2004). https://pubmed.ncbi.nlm.nih.gov/15180982/ DOI: 10.1074/jbc.m313398200

tissue_or_cell_type

Purified protein and bacterial complementation

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 339–350

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MOCS1A, cysteine mutagenesis and multiple spectroscopic methods · source_derived_draft · unverified_draft

### mo-mocs1a-oxygen Oxygen rapidly degraded both reconstituted MOCS1A [4Fe-4S] clusters, producing different semistable cluster intermediates. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: The assembly protein contains oxygen-sensitive clusters. organism: Human protein expressed in Escherichia coli tissue_or_cell_type: Purified protein and bacterial complementation experimental_model: Recombinant human MOCS1A, cysteine mutagenesis and multiple spectroscopic methods limitations: Purified protein exposure; not evidence that normal breathing causes cofactor deficiency. exposure: Aerobic versus anaerobic purification; iron-sulfur reconstitution evidence_span: {"source_cache": "artifacts/molybdenum-research/15180982.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "722c11f1c29a720fb7105f37962af2652ce95b6734afdb59d675dee0b8302097", "start_char": 0, "end_char": 1828, "text_sha256": "722c11f1c29a720fb7105f37962af2652ce95b6734afdb59d675dee0b8302097"} [mo-p15180982] Characterization of MOCS1A, an oxygen-sensitive iron-sulfur protein involved in human molybdenum cofactor biosynthesis. (2004). https://pubmed.ncbi.nlm.nih.gov/15180982/ DOI: 10.1074/jbc.m313398200

evidence_span

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experimental_model

Recombinant human MOCS1A, cysteine mutagenesis and multiple spectroscopic methods

exposure

Aerobic versus anaerobic purification; iron-sulfur reconstitution

limitations

The human protein study characterized clusters and essential cysteines; no human methylation-cycle depletion or clinical SAM requirement was measured.

nutrient_topic

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

organism

Human protein expressed in Escherichia coli

plain_language

SAM participates in radical chemistry here; this is a different use from donating a methyl group to DNA.

primary_references

[mo-p15180982] Characterization of MOCS1A, an oxygen-sensitive iron-sulfur protein involved in human molybdenum cofactor biosynthesis. (2004). https://pubmed.ncbi.nlm.nih.gov/15180982/ DOI: 10.1074/jbc.m313398200

tissue_or_cell_type

Purified protein and bacterial complementation

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 326–337

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MOCS1A, cysteine mutagenesis and multiple spectroscopic methods · source_derived_draft · unverified_draft

### mo-mocs1a-radical-sam MOCS1A contains a redox-active N-terminal [4Fe-4S] cluster coordinated by the conserved radical-SAM cysteine motif. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: SAM participates in radical chemistry here; this is a different use from donating a methyl group to DNA. organism: Human protein expressed in Escherichia coli tissue_or_cell_type: Purified protein and bacterial complementation experimental_model: Recombinant human MOCS1A, cysteine mutagenesis and multiple spectroscopic methods limitations: The human protein study characterized clusters and essential cysteines; no human methylation-cycle depletion or clinical SAM requirement was measured. exposure: Aerobic versus anaerobic purification; iron-sulfur reconstitution evidence_span: {"source_cache": "artifacts/molybdenum-research/15180982.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "722c11f1c29a720fb7105f37962af2652ce95b6734afdb59d675dee0b8302097", "start_char": 0, "end_char": 1828, "text_sha256": "722c11f1c29a720fb7105f37962af2652ce95b6734afdb59d675dee0b8302097"} [mo-p15180982] Characterization of MOCS1A, an oxygen-sensitive iron-sulfur protein involved in human molybdenum cofactor biosynthesis. (2004). https://pubmed.ncbi.nlm.nih.gov/15180982/ DOI: 10.1074/jbc.m313398200

evidence_span

{"source_cache": "artifacts/iron-research/1502165.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1fc2a7abe3fbac12a5196a163c8d6f21f5847bd89c049958dfb4055302a14a56", "start_char": 0, "end_char": 1583, "text_sha256": "1fc2a7abe3fbac12a5196a163c8d6f21f5847bd89c049958dfb4055302a14a56"}

experimental_model

Iron-sulfur manipulation and enzyme/RNA-binding assays

exposure

Iron and Fe-S cluster manipulation

limitations

IRP1/aconitase switch; no assertion that IRP2 has the same catalytic switch.

nutrient_topic

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

organism

Mammalian IRE-binding protein systems

plain_language

One protein can act as an enzyme or an iron-responsive RNA-binding regulator, depending on its cluster state.

primary_references

[iron-p1502165] Reciprocal control of RNA-binding and aconitase activity in the regulation of the iron-responsive element binding protein: role of the iron-sulfur cluster. (1992). https://pubmed.ncbi.nlm.nih.gov/1502165/ DOI: 10.1073/pnas.89.16.7536

tissue_or_cell_type

Purified/recombinant IRE-BP and cultured cells

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 667–678

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Iron-sulfur manipulation and enzyme/RNA-binding assays · source_derived_draft · unverified_draft

### iron-irp1-switch Manipulations of the IRE-binding protein Fe-S cluster reciprocally altered RNA-binding and aconitase activities. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: One protein can act as an enzyme or an iron-responsive RNA-binding regulator, depending on its cluster state. organism: Mammalian IRE-binding protein systems tissue_or_cell_type: Purified/recombinant IRE-BP and cultured cells experimental_model: Iron-sulfur manipulation and enzyme/RNA-binding assays limitations: IRP1/aconitase switch; no assertion that IRP2 has the same catalytic switch. exposure: Iron and Fe-S cluster manipulation evidence_span: {"source_cache": "artifacts/iron-research/1502165.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1fc2a7abe3fbac12a5196a163c8d6f21f5847bd89c049958dfb4055302a14a56", "start_char": 0, "end_char": 1583, "text_sha256": "1fc2a7abe3fbac12a5196a163c8d6f21f5847bd89c049958dfb4055302a14a56"} [iron-p1502165] Reciprocal control of RNA-binding and aconitase activity in the regulation of the iron-responsive element binding protein: role of the iron-sulfur cluster. (1992). https://pubmed.ncbi.nlm.nih.gov/1502165/ DOI: 10.1073/pnas.89.16.7536

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Full text line 181; Fig. 4C–E

experimental_model

Yeast PPT2-deletion and LIP5-deletion comparison

exposure

Genetic deletion of PPT2, compared with wild type and LIP5 deletion.

limitations

Aconitase activity is the measured endpoint. The separate sulfite-reductase result is retained in the source, without duplicating it as another claim. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

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

organism

Saccharomyces cerevisiae

plain_language

Failure to install the carrier arm affected an iron–sulfur enzyme beyond the lipoate pathway.

primary_references

[b5-met-acp2016] The mitochondrial acyl carrier protein (ACP) coordinates mitochondrial fatty acid synthesis with iron sulfur cluster biogenesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27540631/ DOI: 10.7554/elife.17828

tissue_or_cell_type

Whole-cell enzyme assay; mitochondrial aconitase

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 907–919

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Yeast PPT2-deletion and LIP5-deletion comparison · source_derived_draft · unverified_draft

### b5-met-yeast-ppt2-fe-s Yeast PPT2 deletion, preventing mitochondrial ACP phosphopantetheinylation, reduced aconitase activity; a lipoate-synthesis LIP5 deletion control retained normal activity. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Failure to install the carrier arm affected an iron–sulfur enzyme beyond the lipoate pathway. organism: Saccharomyces cerevisiae tissue_or_cell_type: Whole-cell enzyme assay; mitochondrial aconitase experimental_model: Yeast PPT2-deletion and LIP5-deletion comparison limitations: Aconitase activity is the measured endpoint. The separate sulfite-reductase result is retained in the source, without duplicating it as another claim. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Genetic deletion of PPT2, compared with wild type and LIP5 deletion. cross_nutrient: true evidence_location: Full text line 181; Fig. 4C–E [b5-met-acp2016] The mitochondrial acyl carrier protein (ACP) coordinates mitochondrial fatty acid synthesis with iron sulfur cluster biogenesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27540631/ DOI: 10.7554/elife.17828