L-Cysteine

evidence_access

Primary abstract

experimental_model

Human A549 cytokine-stimulation experiment.

limitations

The experiment supports a chemical-reactivity dependency; it does not establish a human supplement interaction magnitude.

nutrient_topic

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

plain_language

A separately stored thiol changed the signaling result.

primary_references

Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 236–242

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human A549 cytokine-stimulation experiment. · source_derived_draft · unverified_draft

## cucurbitacin-b-cysteine-icam-rescue A separately stored thiol changed the signaling result. Adding L-cysteine attenuated cucurbitacin B inhibition of TNF-alpha-induced ICAM1 expression; L-cysteine had a smaller effect than the other tested thiols. Model: Human A549 cytokine-stimulation experiment. Limitations: The experiment supports a chemical-reactivity dependency; it does not establish a human supplement interaction magnitude. Evidence access: Primary abstract Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130

evidence_access

Primary abstract

experimental_model

Four-group rat feeding study.

limitations

Does not imply all restriction effects are exclusively due to cysteine in every species.

nutrient_topic

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

plain_language

Changing the downstream sulfur supply changed the dietary response.

primary_references

Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase. · 2011 · https://pubmed.ncbi.nlm.nih.gov/20871132/ · DOI 10.1194/jlr.M010215

L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 364–370

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Four-group rat feeding study. · source_derived_draft · unverified_draft

## methionine-rat-cysteine-reversal Changing the downstream sulfur supply changed the dietary response. Adding 0.5% cysteine for twelve weeks largely reversed the low-adiposity and related metabolic phenotype of methionine restriction without restoring serum methionine. Model: Four-group rat feeding study. Limitations: Does not imply all restriction effects are exclusively due to cysteine in every species. Evidence access: Primary abstract Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase. · 2011 · https://pubmed.ncbi.nlm.nih.gov/20871132/ · DOI 10.1194/jlr.M010215

evidence_access

Primary abstract

experimental_model

Mitochondria from mouse Cath.A-derived neuronal cells; radioactive sulfur tracing.

limitations

An isolated-organelle assembly assay is not evidence that more dietary cysteine corrects an iron–sulfur disease.

nutrient_topic

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

plain_language

Cysteine supplies the sulfur half of an iron–sulfur cofactor.

primary_references

Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron and requirements for GTP, NADH, and ATP. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25398879/ · DOI 10.1074/jbc.M114.610402

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 268–274

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mitochondria from mouse Cath.A-derived neuronal cells; radioactive sulfur tracing. · source_derived_draft · unverified_draft

## l-cysteine-fe-s-sulfur-donor Cysteine supplies the sulfur half of an iron–sulfur cofactor. Sulfur-35 cysteine supplied sulfur for newly assembled iron–sulfur clusters incorporated into aconitase and ferredoxins in isolated mouse neuronal-cell mitochondria. Model: Mitochondria from mouse Cath.A-derived neuronal cells; radioactive sulfur tracing. Limitations: An isolated-organelle assembly assay is not evidence that more dietary cysteine corrects an iron–sulfur disease. Evidence access: Primary abstract Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron and requirements for GTP, NADH, and ATP. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25398879/ · DOI 10.1074/jbc.M114.610402

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Protein architecture distinguishes sulfur from selenium at a B6-dependent enzyme.

experimental_model

Recombinant human SCLY; structures and substrate assays

limitations

Engineered gain of function; physiological rates and clinical effects were not tested.

nutrient_topic

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

organism

Homo sapiens

plain_language

A specific enzyme residue helps distinguish selenium from sulfur substrates.

primary_references

[b6-scly-2012] Biochemical Discrimination between Selenium and Sulfur 1: A Single Residue Provides Selenium Specificity to Human Selenocysteine Lyase (2012). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030581 DOI: 10.1371/journal.pone.0030581

tissue_or_cell_type

Purified recombinant protein; no intact tissue

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 937–947

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

### b6-met-scly-specificity Replacing Asp146 with lysine gave human SCLY detectable cysteine-desulfurase activity absent from wild-type activity assays. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A specific enzyme residue helps distinguish selenium from sulfur substrates. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human SCLY; structures and substrate assays limitations: Engineered gain of function; physiological rates and clinical effects were not tested. cross_nutrient: Protein architecture distinguishes sulfur from selenium at a B6-dependent enzyme. [b6-scly-2012] Biochemical Discrimination between Selenium and Sulfur 1: A Single Residue Provides Selenium Specificity to Human Selenocysteine Lyase (2012). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030581 DOI: 10.1371/journal.pone.0030581

evidence_access

Primary abstract

experimental_model

Human and yeast CBS kinetics, with human enzyme kept as this record’s subject.

limitations

Relative pathway dominance in a tissue cannot be read directly from purified-enzyme substrate tests.

nutrient_topic

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

plain_language

An enzyme that helps synthesize cysteine can also use it in sulfur-gas production.

primary_references

Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19531479/ · DOI 10.1074/jbc.M109.010868

L-Cysteine: sulfur allocation, redox supply 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 · Human and yeast CBS kinetics, with human enzyme kept as this record’s subject. · source_derived_draft · unverified_draft

## l-cysteine-cbs-h2s-branch An enzyme that helps synthesize cysteine can also use it in sulfur-gas production. Purified human CBS favored H2S production through replacement of cysteine by homocysteine over the tested alternative cysteine reactions. Model: Human and yeast CBS kinetics, with human enzyme kept as this record’s subject. Limitations: Relative pathway dominance in a tissue cannot be read directly from purified-enzyme substrate tests. Evidence access: Primary abstract Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19531479/ · DOI 10.1074/jbc.M109.010868

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human HEK293 knockout/rescue; fluorescent cystine-reduction assays.

limitations

The paper identifies a major rate-limiting route in tested systems, not the only possible reductase in every tissue.

nutrient_topic

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

plain_language

Importing oxidized cysteine is not enough: the cell must reduce it to use it.

primary_references

TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 60–66

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293 knockout/rescue; fluorescent cystine-reduction assays. · source_derived_draft · unverified_draft

## l-cysteine-trp14-cystine-reduction Importing oxidized cysteine is not enough: the cell must reduce it to use it. TXNDC17 knockout in human HEK293 cells markedly reduced intracellular cystine reduction; wild-type TRP14 re-expression restored activity whereas its active-site mutant did not. Model: Human HEK293 knockout/rescue; fluorescent cystine-reduction assays. Limitations: The paper identifies a major rate-limiting route in tested systems, not the only possible reductase in every tissue. Evidence access: Primary full text TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1

evidence_span

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experimental_model

Purified human CDO1 crystallography, substrate binding, metal analysis and mutants

exposure

L-cysteine oxidation with molecular oxygen

limitations

The overall reaction and iron requirement are recorded; disputed detailed structural intermediates are not assigned as settled.

nutrient_topic

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

organism

Homo sapiens

plain_language

Iron-dependent CDO1 starts an upstream sulfur-breakdown route.

primary_references

[mo-p17135237] An insight into the mechanism of human cysteine dioxygenase. Key roles of the thioether-bonded tyrosine-cysteine cofactor. (2007). https://pubmed.ncbi.nlm.nih.gov/17135237/ DOI: 10.1074/jbc.m609337200

tissue_or_cell_type

Recombinant human cysteine dioxygenase

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 677–688

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human CDO1 crystallography, substrate binding, metal analysis and mutants · source_derived_draft · unverified_draft

### mo-cdo-csa Human CDO1 oxidizes cysteine to cysteine sulfinic acid using molecular oxygen and a non-heme iron center. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron-dependent CDO1 starts an upstream sulfur-breakdown route. organism: Homo sapiens tissue_or_cell_type: Recombinant human cysteine dioxygenase experimental_model: Purified human CDO1 crystallography, substrate binding, metal analysis and mutants limitations: The overall reaction and iron requirement are recorded; disputed detailed structural intermediates are not assigned as settled. exposure: L-cysteine oxidation with molecular oxygen evidence_span: {"source_cache": "artifacts/molybdenum-research/17135237.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ccd6f2de98887d17d935999238a88d8901fe8a66bb9b48c9cbd5d179bf180d6", "start_char": 0, "end_char": 1343, "text_sha256": "3ccd6f2de98887d17d935999238a88d8901fe8a66bb9b48c9cbd5d179bf180d6"} [mo-p17135237] An insight into the mechanism of human cysteine dioxygenase. Key roles of the thioether-bonded tyrosine-cysteine cofactor. (2007). https://pubmed.ncbi.nlm.nih.gov/17135237/ DOI: 10.1074/jbc.m609337200

evidence_span

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experimental_model

Purified human NFS1/ISD11 and MOCS3 rhodanese-domain interaction and sulfur-transfer assays

exposure

L-cysteine sulfur-donor assays

limitations

Truncated and heterologously expressed proteins; cell localization was investigated independently in 2013.

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

Cysteine supplies sulfur that becomes part of the molybdenum cofactor.

primary_references

[mo-p18650437] A novel role for human Nfs1 in the cytoplasm: Nfs1 acts as a sulfur donor for MOCS3, a protein involved in molybdenum cofactor biosynthesis. (2008). https://pubmed.ncbi.nlm.nih.gov/18650437/ DOI: 10.1074/jbc.m804064200

tissue_or_cell_type

Purified proteins

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 352–363

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human NFS1/ISD11 and MOCS3 rhodanese-domain interaction and sulfur-transfer assays · source_derived_draft · unverified_draft

### mo-nfs1-sulfur Human NFS1 transferred sulfur from L-cysteine through an NFS1-bound persulfide intermediate to the rhodanese-like domain of MOCS3. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cysteine supplies sulfur that becomes part of the molybdenum cofactor. organism: Human proteins expressed in Escherichia coli tissue_or_cell_type: Purified proteins experimental_model: Purified human NFS1/ISD11 and MOCS3 rhodanese-domain interaction and sulfur-transfer assays limitations: Truncated and heterologously expressed proteins; cell localization was investigated independently in 2013. exposure: L-cysteine sulfur-donor assays evidence_span: {"source_cache": "artifacts/molybdenum-research/18650437.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8180bd148722e8980ef5acbd4ae4c29a0d9d13da56bbccb91165a5eed4ab6f50", "start_char": 0, "end_char": 1547, "text_sha256": "8180bd148722e8980ef5acbd4ae4c29a0d9d13da56bbccb91165a5eed4ab6f50"} [mo-p18650437] A novel role for human Nfs1 in the cytoplasm: Nfs1 acts as a sulfur donor for MOCS3, a protein involved in molybdenum cofactor biosynthesis. (2008). https://pubmed.ncbi.nlm.nih.gov/18650437/ DOI: 10.1074/jbc.m804064200

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements.

exposure

Four weeks below 0.5 mg/day dietary B6; overnight-fasted tracer protocol.

limitations

Below detection is not zero flux, nor proof that transsulfuration was unchanged.

nutrient_topic

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

organism

Homo sapiens

plain_language

The investigators could measure cysteine turnover but could not reliably quantify one specific input route.

primary_references

[b6-davis2006] Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women (2006). https://pubmed.ncbi.nlm.nih.gov/16424114/ DOI: 10.1093/jn/136.2.373

tissue_or_cell_type

Human blood and whole-body measurements

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1334–1344

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements. · source_derived_draft · unverified_draft

### b6-fasting-cysteine-flux Whole-body cysteine flux and fractional cystathionine synthesis were unchanged; transsulfuration-derived cysteine synthesis was below detection in this fasting protocol. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The investigators could measure cysteine turnover but could not reliably quantify one specific input route. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements. limitations: Below detection is not zero flux, nor proof that transsulfuration was unchanged. exposure: Four weeks below 0.5 mg/day dietary B6; overnight-fasted tracer protocol. [b6-davis2006] Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women (2006). https://pubmed.ncbi.nlm.nih.gov/16424114/ DOI: 10.1093/jn/136.2.373

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B6-dependent sulfur metabolism connects to glutathione, with blood and cellular pools distinguished.

experimental_model

Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements.

exposure

Four weeks below 0.5 mg/day dietary B6; overnight-fasted tracer protocol.

limitations

Plasma total glutathione is not intracellular reduced GSH, tissue antioxidant capacity or synthesis rate.

nutrient_topic

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

organism

Homo sapiens

plain_language

This experiment did not find a universal glutathione collapse.

primary_references

[b6-davis2006] Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women (2006). https://pubmed.ncbi.nlm.nih.gov/16424114/ DOI: 10.1093/jn/136.2.373

tissue_or_cell_type

Human blood and whole-body measurements

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1321–1332

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements. · source_derived_draft · unverified_draft

### b6-fasting-total-glutathione Plasma total glutathione rose 38% during restriction; plasma cysteine, homocysteine and CRP did not significantly change. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This experiment did not find a universal glutathione collapse. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements. limitations: Plasma total glutathione is not intracellular reduced GSH, tissue antioxidant capacity or synthesis rate. exposure: Four weeks below 0.5 mg/day dietary B6; overnight-fasted tracer protocol. cross_nutrient: B6-dependent sulfur metabolism connects to glutathione, with blood and cellular pools distinguished. [b6-davis2006] Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women (2006). https://pubmed.ncbi.nlm.nih.gov/16424114/ DOI: 10.1093/jn/136.2.373

cross_nutrient

B6-dependent sulfur transfer supplies cysteine; glutathione synthesis requires additional enzymes.

experimental_model

Purified human CTH apo/holo crystal structures and assays

limitations

Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.

nutrient_topic

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

organism

Homo sapiens

plain_language

This step releases cysteine for downstream metabolism.

primary_references

[b6-cth-structure-2009] Structural Basis for the Inhibition Mechanism of Human Cystathionine gamma-Lyase, an Enzyme Responsible for the Production of H2S (2009). https://doi.org/10.1074/jbc.M805459200 DOI: 10.1074/jbc.M805459200

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 554–564

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human CTH apo/holo crystal structures and assays · source_derived_draft · unverified_draft

### b6-met-cth-cleavage Human CTH cleaves cystathionine to cysteine, 2-oxobutanoate and ammonia in a PLP-dependent reaction. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This step releases cysteine for downstream metabolism. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human CTH apo/holo crystal structures and assays limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. cross_nutrient: B6-dependent sulfur transfer supplies cysteine; glutathione synthesis requires additional enzymes. [b6-cth-structure-2009] Structural Basis for the Inhibition Mechanism of Human Cystathionine gamma-Lyase, an Enzyme Responsible for the Production of H2S (2009). https://doi.org/10.1074/jbc.M805459200 DOI: 10.1074/jbc.M805459200

cross_nutrient

B6-dependent transsulfuration connects methionine/homocysteine to the cysteine supply for glutathione.

experimental_model

Cultured human hepatoma cell line; metabolic sulfur tracing

limitations

Fraction is culture-specific and traces sulfur, not all glutathione atoms; this experiment did not measure dietary B6 depletion.

nutrient_topic

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

organism

Homo sapiens

plain_language

In this cell system, sulfur routed through B6-dependent enzymes helped supply glutathione.

primary_references

[b6-glutathione-2000] The quantitatively important relationship between homocysteine metabolism and glutathione synthesis by the transsulfuration pathway and its regulation by redox changes (2000). https://pubmed.ncbi.nlm.nih.gov/11041866/ DOI: 10.1021/bi001088w

tissue_or_cell_type

Cultured human hepatoma cell line

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 590–600

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured human hepatoma cell line; metabolic sulfur tracing · source_derived_draft · unverified_draft

### b6-met-transsulfuration-glutathione Tracing in a cultured human hepatoma cell line estimated that transsulfuration supplied homocysteine-derived sulfur to approximately half of the intracellular glutathione pool. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this cell system, sulfur routed through B6-dependent enzymes helped supply glutathione. organism: Homo sapiens tissue_or_cell_type: Cultured human hepatoma cell line experimental_model: Cultured human hepatoma cell line; metabolic sulfur tracing limitations: Fraction is culture-specific and traces sulfur, not all glutathione atoms; this experiment did not measure dietary B6 depletion. cross_nutrient: B6-dependent transsulfuration connects methionine/homocysteine to the cysteine supply for glutathione. [b6-glutathione-2000] The quantitatively important relationship between homocysteine metabolism and glutathione synthesis by the transsulfuration pathway and its regulation by redox changes (2000). https://pubmed.ncbi.nlm.nih.gov/11041866/ DOI: 10.1021/bi001088w

evidence_access

Primary abstract

experimental_model

Conditional mouse liver knockout; kidney, adipose and pancreatic measurements.

limitations

This tissue-restricted deletion differs from complete pathway loss and from human deficiency.

nutrient_topic

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

plain_language

Other tissues compensated when liver synthesis was impaired.

primary_references

Extrahepatic tissues compensate for loss of hepatic taurine synthesis in mice with liver-specific knockout of cysteine dioxygenase. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22414809/ · DOI 10.1152/ajpendo.00589.2011

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 97–103

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Conditional mouse liver knockout; kidney, adipose and pancreatic measurements. · source_derived_draft · unverified_draft

## taurine-hepatic-compensation Other tissues compensated when liver synthesis was impaired. Liver-specific Cdo1 deletion increased extrahepatic CDO abundance and hypotaurine; mice maintained taurine, glutathione and sulfate despite a taurine-free diet. Model: Conditional mouse liver knockout; kidney, adipose and pancreatic measurements. Limitations: This tissue-restricted deletion differs from complete pathway loss and from human deficiency. Evidence access: Primary abstract Extrahepatic tissues compensate for loss of hepatic taurine synthesis in mice with liver-specific knockout of cysteine dioxygenase. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22414809/ · DOI 10.1152/ajpendo.00589.2011

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

C3H/HeJ and C57BL/6J mice; in-vivo excretion and renal membrane transport.

limitations

Strain-specific responses; precursor restriction is not isolated taurine withdrawal.

nutrient_topic

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

plain_language

The kidney conserved taurine when dietary supply of its precursors was restricted.

primary_references

Renal transport of taurine adapts to perturbed taurine homeostasis. · 1982 · https://pubmed.ncbi.nlm.nih.gov/6952257/ · DOI 10.1073/pnas.79.6.2101

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 185–191

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · C3H/HeJ and C57BL/6J mice; in-vivo excretion and renal membrane transport. · source_derived_draft · unverified_draft

## taurine-renal-mouse-conservation The kidney conserved taurine when dietary supply of its precursors was restricted. Two weeks of low-protein or low-sulfur-amino-acid feeding lowered plasma taurine and increased renal taurine uptake while reducing fractional urinary excretion in the studied mouse strains. Model: C3H/HeJ and C57BL/6J mice; in-vivo excretion and renal membrane transport. Limitations: Strain-specific responses; precursor restriction is not isolated taurine withdrawal. Evidence access: Primary abstract Renal transport of taurine adapts to perturbed taurine homeostasis. · 1982 · https://pubmed.ncbi.nlm.nih.gov/6952257/ · DOI 10.1073/pnas.79.6.2101

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Rat dietary adaptation and renal transport assays.

limitations

Adaptation over days does not establish equivalent regulation in all human disease states.

nutrient_topic

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

plain_language

Conservation involved more transport capacity rather than greater binding affinity.

primary_references

Renal adaptation to alteration in dietary amino acid intake. · 1983 · https://pubmed.ncbi.nlm.nih.gov/6881333/ · DOI 10.1152/ajprenal.1983.245.2.F159

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 193–199

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Rat dietary adaptation and renal transport assays. · source_derived_draft · unverified_draft

## taurine-renal-rat-capacity Conservation involved more transport capacity rather than greater binding affinity. A diet deficient in cysteine and methionine increased the Vmax of the rat high-affinity renal taurine uptake system without changing apparent Km. Model: Rat dietary adaptation and renal transport assays. Limitations: Adaptation over days does not establish equivalent regulation in all human disease states. Evidence access: Primary abstract Renal adaptation to alteration in dietary amino acid intake. · 1983 · https://pubmed.ncbi.nlm.nih.gov/6881333/ · DOI 10.1152/ajprenal.1983.245.2.F159

evidence_access

Primary abstract

experimental_model

Rat LC-MS metabolism study.

limitations

Not all structures had identical confirmation strength; this record does not infer human rates.

nutrient_topic

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

plain_language

Cysteine also appears in a measured metabolic product.

primary_references

Metabolic fate of the natural anticancer agent cucurbitacin B: an LC-MS/MS-enabled profiling of its major phase I and II conjugates in vivo. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39441433/ · DOI 10.1007/s00216-024-05608-y

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 364–370

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat LC-MS metabolism study. · source_derived_draft · unverified_draft

## cucurbitacin-b-rat-cysteine-metabolism Cysteine also appears in a measured metabolic product. Rat cucurbitacin B metabolism profiling detected a cysteine conjugate among phase-II products; 13 metabolites were identified and seven confirmed in the overall study. Model: Rat LC-MS metabolism study. Limitations: Not all structures had identical confirmation strength; this record does not infer human rates. Evidence access: Primary abstract Metabolic fate of the natural anticancer agent cucurbitacin B: an LC-MS/MS-enabled profiling of its major phase I and II conjugates in vivo. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39441433/ · DOI 10.1007/s00216-024-05608-y

evidence_access

Primary abstract

experimental_model

Human H1299, A549, HCC827 and H661 study panel; exact assay allocation and dose not resolved from the abstract.

limitations

A cellular thiol measurement is not evidence of whole-body cysteine deficiency.

nutrient_topic

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

plain_language

Reactive protein groups decreased after exposure.

primary_references

Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 124–130

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human H1299, A549, HCC827 and H661 study panel; exact assay allocation and dose not resolved from the abstract. · source_derived_draft · unverified_draft

## cucurbitacin-b-thiol-loss Reactive protein groups decreased after exposure. Adding cucurbitacin B rapidly lowered measured protein-thiol levels in human NSCLC cells. Model: Human H1299, A549, HCC827 and H661 study panel; exact assay allocation and dose not resolved from the abstract. Limitations: A cellular thiol measurement is not evidence of whole-body cysteine deficiency. Evidence access: Primary abstract Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008

evidence_access

Primary full text PMC3751690

experimental_model

Purified human cofilin 1 biochemical mapping.

limitations

A protein cysteine residue is not equivalent to free dietary cysteine; these data do not quantify nutritional depletion.

nutrient_topic

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

plain_language

The study identifies individual protein attachment sites.

primary_references

Cucurbitacin covalent bonding to cysteine thiols: the filamentous-actin severing protein Cofilin1 as an exemplary target. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23945128/ · DOI 10.1186/1478-811X-11-58

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 36–42

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human cofilin 1 biochemical mapping. · source_derived_draft · unverified_draft

## cucurbitacin-e-cofilin-sites The study identifies individual protein attachment sites. Mass spectrometry localized cucurbitacin E modification to cofilin Cys39, Cys80 and Cys139, with weaker evidence for Cys147. Model: Purified human cofilin 1 biochemical mapping. Limitations: A protein cysteine residue is not equivalent to free dietary cysteine; these data do not quantify nutritional depletion. Evidence access: Primary full text PMC3751690 Cucurbitacin covalent bonding to cysteine thiols: the filamentous-actin severing protein Cofilin1 as an exemplary target. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23945128/ · DOI 10.1186/1478-811X-11-58

evidence_access

Primary abstract

experimental_model

Purified actin and cellular photoactivation experiments.

limitations

Purified actin species/isoform not established from the accessed abstract; not automatically human ACTB. This study did not find an effect on polymerization.

nutrient_topic

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

plain_language

The filament itself can be stabilized.

primary_references

The natural product cucurbitacin E inhibits depolymerization of actin filaments. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22724897/ · DOI 10.1021/cb300254s

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 52–58

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

## cucurbitacin-e-f-actin The filament itself can be stabilized. Cucurbitacin E covalently modified actin at Cys257 in F-actin and inhibited depolymerization, with effects at substoichiometric compound:actin ratios down to 1:6. Model: Purified actin and cellular photoactivation experiments. Limitations: Purified actin species/isoform not established from the accessed abstract; not automatically human ACTB. This study did not find an effect on polymerization. Evidence access: Primary abstract The natural product cucurbitacin E inhibits depolymerization of actin filaments. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22724897/ · DOI 10.1021/cb300254s

evidence_access

Primary abstract

experimental_model

Human CBS structural study with SAM-bound activated conformation.

limitations

Allosteric regulation does not establish in-vivo flux under every nutritional condition.

nutrient_topic

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

plain_language

A plentiful methyl donor can turn up the sulfur-transfer branch.

primary_references

Structural insight into the molecular mechanism of allosteric activation of human cystathionine β-synthase by S-adenosylmethionine. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25197074/ · DOI 10.1073/pnas.1414545111

L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 204–210

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human CBS structural study with SAM-bound activated conformation. · source_derived_draft · unverified_draft

## methionine-cbs-sam-allostery A plentiful methyl donor can turn up the sulfur-transfer branch. SAM binding rearranged the human CBS regulatory domain and relieved autoinhibition, improving access to its catalytic pocket. Model: Human CBS structural study with SAM-bound activated conformation. Limitations: Allosteric regulation does not establish in-vivo flux under every nutritional condition. Evidence access: Primary abstract Structural insight into the molecular mechanism of allosteric activation of human cystathionine β-synthase by S-adenosylmethionine. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25197074/ · DOI 10.1073/pnas.1414545111

evidence_access

Primary abstract

experimental_model

Controlled feeding; sequential control, moderate and greater restriction periods separated by washouts.

limitations

Small short-term study with fixed diet-period ordering; no lifespan or cancer outcomes.

nutrient_topic

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

plain_language

Restricting one sulfur amino acid is not the same intervention as restricting both.

primary_references

Dietary Methionine and Total Sulfur Amino Acid Restriction in Healthy Adults. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36806866/ · DOI 10.1007/s12603-023-1883-3

L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 396–402

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Controlled feeding; sequential control, moderate and greater restriction periods separated by washouts. · source_derived_draft · unverified_draft

## methionine-human-metr-saar Restricting one sulfur amino acid is not the same intervention as restricting both. In twenty adults, four-week methionine-only restriction changed fewer metabolic markers than combined methionine/cysteine restriction; both increased FGF21 in the reported comparisons. Model: Controlled feeding; sequential control, moderate and greater restriction periods separated by washouts. Limitations: Small short-term study with fixed diet-period ordering; no lifespan or cancer outcomes. Evidence access: Primary abstract Dietary Methionine and Total Sulfur Amino Acid Restriction in Healthy Adults. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36806866/ · DOI 10.1007/s12603-023-1883-3

evidence_access

Primary abstract

experimental_model

Fully supplied plant-based diets, approximately 2 versus 5.6 g/day sulfur amino acids; baseline/sex-adjusted model.

limitations

Combined methionine/cysteine intervention; not proof of isolated methionine causality or long-term safety.

nutrient_topic

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

plain_language

Human evidence includes a short-term weight outcome, not just animal experiments.

primary_references

Dietary sulfur amino acid restriction in humans with overweight and obesity: a translational randomized controlled trial. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38195568/ · DOI 10.1186/s12967-023-04833-w

L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 404–410

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Fully supplied plant-based diets, approximately 2 versus 5.6 g/day sulfur amino acids; baseline/sex-adjusted model. · source_derived_draft · unverified_draft

## methionine-human-saar-weight Human evidence includes a short-term weight outcome, not just animal experiments. An eight-week randomized study of 59 adults found 1.14 kg greater weight loss with lower versus higher sulfur-amino-acid intake; resting metabolic rate did not differ. Model: Fully supplied plant-based diets, approximately 2 versus 5.6 g/day sulfur amino acids; baseline/sex-adjusted model. Limitations: Combined methionine/cysteine intervention; not proof of isolated methionine causality or long-term safety. Evidence access: Primary abstract Dietary sulfur amino acid restriction in humans with overweight and obesity: a translational randomized controlled trial. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38195568/ · DOI 10.1186/s12967-023-04833-w

evidence_access

Primary abstract

experimental_model

Rat liver RNA/protein and serum lipid profiling.

limitations

Desaturation indices are indirect activity readouts; no isolated human enzyme effect is established.

nutrient_topic

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

plain_language

Sulfur-amino-acid composition influenced a lipid-metabolism enzyme.

primary_references

Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase. · 2011 · https://pubmed.ncbi.nlm.nih.gov/20871132/ · DOI 10.1194/jlr.M010215

L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 372–378

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat liver RNA/protein and serum lipid profiling. · source_derived_draft · unverified_draft

## methionine-rat-scd1-response Sulfur-amino-acid composition influenced a lipid-metabolism enzyme. Methionine restriction reduced hepatic Scd1 expression and serum fatty-acid desaturation indices; cysteine supplementation reversed these changes. Model: Rat liver RNA/protein and serum lipid profiling. Limitations: Desaturation indices are indirect activity readouts; no isolated human enzyme effect is established. Evidence access: Primary abstract Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase. · 2011 · https://pubmed.ncbi.nlm.nih.gov/20871132/ · DOI 10.1194/jlr.M010215

evidence_access

Primary abstract

experimental_model

Human carrier expression in Xenopus oocytes.

limitations

Complex identity and chirality matter; this does not demonstrate protection from methionine supplementation.

nutrient_topic

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

plain_language

A toxicant complex can exploit nutrient transport machinery.

primary_references

Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12117417/ · DOI 10.1042/BJ20020841

L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 36–42

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human carrier expression in Xenopus oocytes. · source_derived_draft · unverified_draft

## methionine-toxicant-mimicry A toxicant complex can exploit nutrient transport machinery. Methylmercury-L-cysteine used human LAT1/LAT2 in oocyte assays, with substrate exchange characteristics resembling methionine. Model: Human carrier expression in Xenopus oocytes. Limitations: Complex identity and chirality matter; this does not demonstrate protection from methionine supplementation. Evidence access: Primary abstract Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12117417/ · DOI 10.1042/BJ20020841

evidence_span

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experimental_model

Human enzyme mutagenesis, kinetics and molecular dynamics

exposure

S-loop variants; established biosynthetic reactions described in the introduction

limitations

Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human GSS

plain_language

The induced machinery still needs its amino-acid building blocks.

primary_references

[sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008

tissue_or_cell_type

Glutathione synthesis and substrate binding

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 840–851

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme mutagenesis, kinetics and molecular dynamics · source_derived_draft · unverified_draft

### sulforaphane-gcl-first-step Glutamate-cysteine ligase joins glutamate and cysteine to form gamma-glutamylcysteine in the first glutathione-synthesis step. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The induced machinery still needs its amino-acid building blocks. organism: Human GSS tissue_or_cell_type: Glutathione synthesis and substrate binding experimental_model: Human enzyme mutagenesis, kinetics and molecular dynamics limitations: Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency. exposure: S-loop variants; established biosynthetic reactions described in the introduction evidence_span: {"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 762, "end_char": 1092, "text_sha256": "927fa13b085700c20b578ecabc7c8c17a66ea4600b90809e3061d12bcaea3849"} [sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

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experimental_model

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

exposure

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

limitations

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

nutrient_topic

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

organism

Rat enzyme in a bacterial expression host

plain_language

Swapping selenium for sulphur leaves an enzyme that barely works and only in the wrong conditions.

primary_references

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

tissue_or_cell_type

Purified enzyme

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 465–476

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

### hbot-trxr-secys-mutant-activity The SeCys498 to Cys enzyme retained catalytic activity in thioredoxin reduction with a 100-fold lower kcat and a 10-fold lower Km, and its pH optimum shifted from 7 to 9, strongly suggesting involvement of the low-pKa selenol in the mechanism. Condition category: nutrient_deficiency nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Swapping selenium for sulphur leaves an enzyme that barely works and only in the wrong conditions. organism: Rat enzyme in a bacterial expression host tissue_or_cell_type: Purified enzyme experimental_model: Recombinant rat thioredoxin reductase with selenocysteine mutations expressed in E. coli limitations: The truncated construct is described by the authors as the form expected in selenium deficiency, which is what links this enzyme chemistry to nutrient supply. It remains a recombinant model, not a measurement in a selenium-deficient animal. exposure: SeCys498 replaced by cysteine or serine, and a truncated protein lacking the C-terminal SeCys-Gly dipeptide evidence_span: {"source_cache": "artifacts/hbot-research/10849437.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90", "start_char": 0, "end_char": 1374, "text_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90"} [hbot-p10849437] Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations. (2000). https://pubmed.ncbi.nlm.nih.gov/10849437/ DOI: 10.1074/jbc.m000690200

evidence_span

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experimental_model

Chemical modification, peptide sequencing, mass spectrometry and redox titration of mammalian thioredoxin reductase

exposure

Oxidised and NADPH-reduced enzyme states

limitations

Enzyme chemistry on purified protein. It establishes the selenium-containing active site; it is not a statement about selenium intake.

nutrient_topic

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

organism

Rat and human enzyme

plain_language

The enzyme’s working end is built from a selenium amino acid paired with a cysteine.

primary_references

[hbot-p10801974] Structure and mechanism of mammalian thioredoxin reductase: the active site is a redox-active selenolthiol/selenenylsulfide formed from the conserved cysteine-selenocysteine sequence. (2000). https://pubmed.ncbi.nlm.nih.gov/10801974/ DOI: 10.1073/pnas.100114897

tissue_or_cell_type

Purified enzyme

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 452–463

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemical modification, peptide sequencing, mass spectrometry and redox titration of mammalian thioredoxin reductase · source_derived_draft · unverified_draft

### hbot-trxr-selenocysteine-site Mammalian thioredoxin reductase carries an essential selenocysteine in the conserved C-terminal sequence Gly-Cys-SeCys-Gly, forming a selenenylsulfide between Cys497 and SeCys498 that becomes a selenolthiol on reduction, alongside a separate Cys59-Cys64 disulfide identical to the glutathione reductase active site. 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 enzyme’s working end is built from a selenium amino acid paired with a cysteine. organism: Rat and human enzyme tissue_or_cell_type: Purified enzyme experimental_model: Chemical modification, peptide sequencing, mass spectrometry and redox titration of mammalian thioredoxin reductase limitations: Enzyme chemistry on purified protein. It establishes the selenium-containing active site; it is not a statement about selenium intake. exposure: Oxidised and NADPH-reduced enzyme states evidence_span: {"source_cache": "artifacts/hbot-research/10801974.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1627b8b48962b6d2b9bead351b64b71fb60b9681378b44f77a3fc288d35119e3", "start_char": 0, "end_char": 1719, "text_sha256": "1627b8b48962b6d2b9bead351b64b71fb60b9681378b44f77a3fc288d35119e3"} [hbot-p10801974] Structure and mechanism of mammalian thioredoxin reductase: the active site is a redox-active selenolthiol/selenenylsulfide formed from the conserved cysteine-selenocysteine sequence. (2000). https://pubmed.ncbi.nlm.nih.gov/10801974/ DOI: 10.1073/pnas.100114897

evidence_access

Primary full text, pathway background citing original reconstitution

experimental_model

Pathway description in the primary EgtE paper, citing the original reconstitution.

limitations

This step is cited background, not a new EgtA experiment in this paper; microbial and human pathways remain separate.

nutrient_topic

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

plain_language

A separately encoded enzyme prepares the sulfur donor.

primary_references

Mechanistic studies of a novel C-S lyase in ergothioneine biosynthesis: the involvement of a sulfenic acid intermediate. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26149121/ · DOI 10.1038/srep11870

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 560–566

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pathway description in the primary EgtE paper, citing the original reconstitution. · source_derived_draft · unverified_draft

## ergothioneine-egta-precursor A separately encoded enzyme prepares the sulfur donor. The described Mycobacterium smegmatis pathway uses EgtA to condense glutamate and cysteine into gamma-glutamylcysteine. Model: Pathway description in the primary EgtE paper, citing the original reconstitution. Limitations: This step is cited background, not a new EgtA experiment in this paper; microbial and human pathways remain separate. Evidence access: Primary full text, pathway background citing original reconstitution Mechanistic studies of a novel C-S lyase in ergothioneine biosynthesis: the involvement of a sulfenic acid intermediate. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26149121/ · DOI 10.1038/srep11870

evidence_span

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experimental_model

Cell-culture thiol transport and glutathione experiments

exposure

Lipoic acid/DHLA treatment and extracellular thiol measurements

limitations

Cell-type and extracellular-substrate dependence; no demonstration of general methylation-vitamin depletion.

nutrient_topic

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

organism

Human, rat and mouse cells as specified

plain_language

The cells could import ready-to-use cysteine instead of relying on cystine uptake.

primary_references

[ala-p9288403] Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. (1997). https://pubmed.ncbi.nlm.nih.gov/9288403/ DOI: 10.1002/biof.5520060303

tissue_or_cell_type

Human lymphocytes, Jurkat cells and erythrocytes; rat C6 and mouse NB41A3 cells

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 806–817

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

### ala-cysteine-gsh-route Increased extracellular cysteine supported cellular uptake and glutathione synthesis, bypassing dependence on cystine transport in the studied cells. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cells could import ready-to-use cysteine instead of relying on cystine uptake. organism: Human, rat and mouse cells as specified tissue_or_cell_type: Human lymphocytes, Jurkat cells and erythrocytes; rat C6 and mouse NB41A3 cells experimental_model: Cell-culture thiol transport and glutathione experiments limitations: Cell-type and extracellular-substrate dependence; no demonstration of general methylation-vitamin depletion. exposure: Lipoic acid/DHLA treatment and extracellular thiol measurements evidence_span: {"source_cache": "artifacts/ala-research/9288403.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2", "start_char": 0, "end_char": 1497, "text_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2"} [ala-p9288403] Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. (1997). https://pubmed.ncbi.nlm.nih.gov/9288403/ DOI: 10.1002/biof.5520060303

evidence_span

{"source_cache": "artifacts/ala-research/9288403.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2", "start_char": 0, "end_char": 1497, "text_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2"}

experimental_model

Cell-culture thiol transport and glutathione experiments

exposure

Lipoic acid/DHLA treatment and extracellular thiol measurements

limitations

Cell-type and extracellular-substrate dependence; no demonstration of general methylation-vitamin depletion.

nutrient_topic

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

organism

Human, rat and mouse cells as specified

plain_language

Reduced lipoic acid made a glutathione building block more available.

primary_references

[ala-p9288403] Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. (1997). https://pubmed.ncbi.nlm.nih.gov/9288403/ DOI: 10.1002/biof.5520060303

tissue_or_cell_type

Human lymphocytes, Jurkat cells and erythrocytes; rat C6 and mouse NB41A3 cells

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 793–804

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

### ala-dhla-cystine-cysteine Cell-derived DHLA reduced extracellular cystine to cysteine in the tested cultures. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reduced lipoic acid made a glutathione building block more available. organism: Human, rat and mouse cells as specified tissue_or_cell_type: Human lymphocytes, Jurkat cells and erythrocytes; rat C6 and mouse NB41A3 cells experimental_model: Cell-culture thiol transport and glutathione experiments limitations: Cell-type and extracellular-substrate dependence; no demonstration of general methylation-vitamin depletion. exposure: Lipoic acid/DHLA treatment and extracellular thiol measurements evidence_span: {"source_cache": "artifacts/ala-research/9288403.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2", "start_char": 0, "end_char": 1497, "text_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2"} [ala-p9288403] Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. (1997). https://pubmed.ncbi.nlm.nih.gov/9288403/ DOI: 10.1002/biof.5520060303

evidence_access

Primary full text; Fig. 4 and transport methods

experimental_model

Human HEK293T isolated lysosomes; radiolabeled cysteine transport.

limitations

This is lysosomal import; the separate pigment-cell findings connect the same protein to melanosomes. Purified-protein sufficiency was not established.

nutrient_topic

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

plain_language

Pigment-related machinery also handles another amino acid in non-pigmented cells.

primary_references

MFSD12 mediates the import of cysteine into melanosomes and lysosomes. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33208952/ · DOI 10.1038/s41586-020-2937-x

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 172–178

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293T isolated lysosomes; radiolabeled cysteine transport. · source_derived_draft · unverified_draft

## l-tyrosine-mfsd12-cysteine Pigment-related machinery also handles another amino acid in non-pigmented cells. Lysosomes isolated from human HEK293T cells with MFSD12 accumulated more labeled cysteine than lysosomes from MFSD12-knockout cells. Model: Human HEK293T isolated lysosomes; radiolabeled cysteine transport. Limitations: This is lysosomal import; the separate pigment-cell findings connect the same protein to melanosomes. Purified-protein sufficiency was not established. Evidence access: Primary full text; Fig. 4 and transport methods MFSD12 mediates the import of cysteine into melanosomes and lysosomes. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33208952/ · DOI 10.1038/s41586-020-2937-x

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text; Fig. 2d–f

experimental_model

Human SKMEL30 loss-of-function; analogous mouse experiments were separately reported.

limitations

Lysosomal storage and melanosomal pigment endpoints differ.

nutrient_topic

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

plain_language

A missing transporter can redirect pigment chemistry even when precursors exist elsewhere.

primary_references

MFSD12 mediates the import of cysteine into melanosomes and lysosomes. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33208952/ · DOI 10.1038/s41586-020-2937-x

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 180–186

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human SKMEL30 loss-of-function; analogous mouse experiments were separately reported. · source_derived_draft · unverified_draft

## l-tyrosine-mfsd12-loss A missing transporter can redirect pigment chemistry even when precursors exist elsewhere. MFSD12 loss in human SKMEL30 cells reduced melanosomal cystine and cellular cysteinyldopas. Model: Human SKMEL30 loss-of-function; analogous mouse experiments were separately reported. Limitations: Lysosomal storage and melanosomal pigment endpoints differ. Evidence access: Primary full text; Fig. 2d–f MFSD12 mediates the import of cysteine into melanosomes and lysosomes. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33208952/ · DOI 10.1038/s41586-020-2937-x

evidence_access

Primary full text; Fig. 4d

experimental_model

Matched lysosome preparations; 500 nM radiolabeled tyrosine uptake.

limitations

This control does not identify the tyrosine transporter.

nutrient_topic

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

plain_language

Sharing an organelle does not mean sharing its transport route.

primary_references

MFSD12 mediates the import of cysteine into melanosomes and lysosomes. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33208952/ · DOI 10.1038/s41586-020-2937-x

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 188–194

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Matched lysosome preparations; 500 nM radiolabeled tyrosine uptake. · source_derived_draft · unverified_draft

## l-tyrosine-mfsd12-tyrosine-control Sharing an organelle does not mean sharing its transport route. Human HEK293T lysosomes with and without MFSD12 accumulated labeled tyrosine similarly despite the cysteine transport deficit. Model: Matched lysosome preparations; 500 nM radiolabeled tyrosine uptake. Limitations: This control does not identify the tyrosine transporter. Evidence access: Primary full text; Fig. 4d MFSD12 mediates the import of cysteine into melanosomes and lysosomes. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33208952/ · DOI 10.1038/s41586-020-2937-x

cross_nutrient

true

evidence_location

Primary abstract; indexed article Introduction/Figure 1

experimental_model

Purified human MMACHC thiol substitution assays

exposure

GSH versus cysteine or homocysteine

limitations

No implication that cysteine availability is irrelevant to cellular GSH synthesis; that upstream pathway was not tested here.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

Having a thiol group was not enough; the enzyme required glutathione in these assays.

primary_references

[kim-2009-gsh-dealkylation] A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins (2009). https://pubmed.ncbi.nlm.nih.gov/19801555/ DOI: 10.1074/jbc.M109.057877

tissue_or_cell_type

Cell-free assay

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 739–751

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

### b12-mmachc-thiol-specificity In the human MMACHC dealkylation study, cysteine and homocysteine did not substitute for glutathione as the thiol co-substrate. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Having a thiol group was not enough; the enzyme required glutathione in these assays. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Purified human MMACHC thiol substitution assays limitations: No implication that cysteine availability is irrelevant to cellular GSH synthesis; that upstream pathway was not tested here. exposure: GSH versus cysteine or homocysteine cross_nutrient: true evidence_location: Primary abstract; indexed article Introduction/Figure 1 [kim-2009-gsh-dealkylation] A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins (2009). https://pubmed.ncbi.nlm.nih.gov/19801555/ DOI: 10.1074/jbc.M109.057877

evidence_access

Primary abstract

experimental_model

Human SiHa extracts and purified recombinant human LAT1 in proteoliposomes.

limitations

In-vitro exchange does not establish whole-body competition or supplement ratios.

nutrient_topic

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

plain_language

The transporter exchanges substrates, so both sides of the membrane matter.

primary_references

LAT1 is the transport competent unit of the LAT1/CD98 heterodimeric amino acid transporter. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26256001/ · DOI 10.1016/j.biocel.2015.08.004

transport_effect

depends Recorded as antiport, including exchange with internal cysteine, tyrosine or glutamine.

transport_pool

the cytosol across the plasma membrane Recorded as antiport, including exchange with internal cysteine, tyrosine or glutamine.

L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 58–64

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human SiHa extracts and purified recombinant human LAT1 in proteoliposomes. · source_derived_draft · unverified_draft

## histidine-lat1-exchange The transporter exchanges substrates, so both sides of the membrane matter. Reconstituted human LAT1 supported histidine antiport, including exchange with internal cysteine, tyrosine or glutamine; external histidine affinity exceeded internal affinity. Model: Human SiHa extracts and purified recombinant human LAT1 in proteoliposomes. Limitations: In-vitro exchange does not establish whole-body competition or supplement ratios. Evidence access: Primary abstract LAT1 is the transport competent unit of the LAT1/CD98 heterodimeric amino acid transporter. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26256001/ · DOI 10.1016/j.biocel.2015.08.004

evidence_access

Primary abstract

experimental_model

Human cDNA cloning and transporter characterization.

limitations

Substrate overlap alone does not quantify competition during ordinary dietary intake.

nutrient_topic

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

plain_language

Several amino acids share a cellular entry and exchange route.

primary_references

Human neutral amino acid transporter ASCT1: structure of the gene (SLC1A4) and localization to chromosome 2p13-p15. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7896285/ · DOI 10.1006/geno.1994.1577

transport_effect

depends A substrate-selectivity record. ASCT1 is an obligatory exchanger and no direction is stated.

transport_pool

the cytosol across the plasma membrane A substrate-selectivity record. ASCT1 is an obligatory exchanger and no direction is stated.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 18–24

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cDNA cloning and transporter characterization. · source_derived_draft · unverified_draft

## l-threonine-asct1-substrate Several amino acids share a cellular entry and exchange route. Cloned human ASCT1 transported alanine, serine, cysteine and threonine rather than glutamate or aspartate. Model: Human cDNA cloning and transporter characterization. Limitations: Substrate overlap alone does not quantify competition during ordinary dietary intake. Evidence access: Primary abstract Human neutral amino acid transporter ASCT1: structure of the gene (SLC1A4) and localization to chromosome 2p13-p15. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7896285/ · DOI 10.1006/geno.1994.1577

evidence_access

Primary full text

experimental_model

Human-cell functional signaling assays.

limitations

Not evidence of dietary calcium or cysteine requirements for this response.

nutrient_topic

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

plain_language

Protein turnover connected an oxygen-sensing step to signaling outputs.

primary_references

Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31273118/ · DOI 10.1126/science.aaw0112

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 436–442

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

## l-cysteine-ado-calcium-signals Protein turnover connected an oxygen-sensing step to signaling outputs. Manipulating ADO altered G-protein-coupled calcium signals and MAP-kinase activity in the studied human cells. Model: Human-cell functional signaling assays. Limitations: Not evidence of dietary calcium or cysteine requirements for this response. Evidence access: Primary full text Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31273118/ · DOI 10.1126/science.aaw0112

evidence_access

Primary full text

experimental_model

Human ADO biochemistry, peptide substrates and human-cell experiments.

limitations

This is a protein-residue reaction, not evidence that ADO is the ordinary free-cysteine catabolic enzyme.

nutrient_topic

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

plain_language

A cysteine already built into a protein can serve as part of an oxygen-sensitive degradation signal.

primary_references

Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31273118/ · DOI 10.1126/science.aaw0112

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 420–426

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

## l-cysteine-ado-nterminal-oxidation A cysteine already built into a protein can serve as part of an oxygen-sensitive degradation signal. Human ADO oxidized exposed N-terminal cysteine residues in RGS4/5 peptides to the corresponding sulfinic-acid state using molecular oxygen. Model: Human ADO biochemistry, peptide substrates and human-cell experiments. Limitations: This is a protein-residue reaction, not evidence that ADO is the ordinary free-cysteine catabolic enzyme. Evidence access: Primary full text Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31273118/ · DOI 10.1126/science.aaw0112

evidence_access

Primary full text

experimental_model

Human-cell ADO and oxygen perturbations with N-degron readouts.

limitations

The downstream pathway requires additional machinery; dietary cysteine effects were not tested.

nutrient_topic

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

plain_language

Oxidation can mark a signaling regulator for degradation rather than merely damage it.

primary_references

Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31273118/ · DOI 10.1126/science.aaw0112

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 428–434

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human-cell ADO and oxygen perturbations with N-degron readouts. · source_derived_draft · unverified_draft

## l-cysteine-ado-protein-stability Oxidation can mark a signaling regulator for degradation rather than merely damage it. ADO-dependent N-terminal cysteine oxidation regulated RGS4/5 stability through the N-degron pathway in human cells. Model: Human-cell ADO and oxygen perturbations with N-degron readouts. Limitations: The downstream pathway requires additional machinery; dietary cysteine effects were not tested. Evidence access: Primary full text Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31273118/ · DOI 10.1126/science.aaw0112

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse systemic depletion with sympathetic and adrenergic perturbations.

limitations

Does not establish that cysteine directly binds the adrenergic receptor or that dietary changes reproduce the genetic model.

nutrient_topic

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

plain_language

The whole-body response involved nerve-to-fat signaling.

primary_references

Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 372–378

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse systemic depletion with sympathetic and adrenergic perturbations. · source_derived_draft · unverified_draft

## l-cysteine-adrenergic-depletion-response The whole-body response involved nerve-to-fat signaling. The study linked cysteine-depletion-induced adipose browning and weight loss to sympathetic noradrenaline signaling through beta-3 adrenergic receptors. Model: Mouse systemic depletion with sympathetic and adrenergic perturbations. Limitations: Does not establish that cysteine directly binds the adrenergic receptor or that dietary changes reproduce the genetic model. Evidence access: Primary full text Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human-cell nutrient-withdrawal experiments with AMPK-pathway perturbation.

limitations

This is an adaptive response under culture deprivation, not evidence that chronic dietary deprivation is beneficial.

nutrient_topic

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

plain_language

The response to scarcity helped cells survive it.

primary_references

CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 148–154

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

## l-cysteine-ampk-adaptation The response to scarcity helped cells survive it. Blocking AMPK activation increased cell death under cysteine-deficient conditions in the tested cultures. Model: Human-cell nutrient-withdrawal experiments with AMPK-pathway perturbation. Limitations: This is an adaptive response under culture deprivation, not evidence that chronic dietary deprivation is beneficial. Evidence access: Primary abstract CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse cysteine repletion with or without dietary B5; subsequent tissue GSH/CoA and weight measurements.

limitations

A direct cross-nutrient repletion experiment in mice; not an established human treatment protocol. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8

nutrient_topic

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

plain_language

Restoring one nutrient repaired one branch but left another branch short of its other substrate.

primary_references

Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 324–330

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse cysteine repletion with or without dietary B5; subsequent tissue GSH/CoA and weight measurements. · source_derived_draft · unverified_draft

## l-cysteine-b5-blocks-coa-recovery Restoring one nutrient repaired one branch but left another branch short of its other substrate. After seven days of cysteine depletion, Cse-null mice repleted with cysteine but kept B5-deficient had persistently lower CoA and less weight recovery than mice receiving both nutrients, despite restored liver glutathione. Model: Mouse cysteine repletion with or without dietary B5; subsequent tissue GSH/CoA and weight measurements. Limitations: A direct cross-nutrient repletion experiment in mice; not an established human treatment protocol. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse sequential nutrient-depletion/repletion experiment.

limitations

The endpoint was recovery from induced wasting, not weight gain or energy improvement in healthy people. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8

nutrient_topic

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

plain_language

A second missing nutrient limited recovery after the first was restored.

primary_references

Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 332–338

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse sequential nutrient-depletion/repletion experiment. · source_derived_draft · unverified_draft

## l-cysteine-b5-restores-weight-recovery A second missing nutrient limited recovery after the first was restored. Adding B5 to drinking water after seven days on the cysteine-sufficient, B5-deficient recovery diet promptly rescued the weight-recovery difference. Model: Mouse sequential nutrient-depletion/repletion experiment. Limitations: The endpoint was recovery from induced wasting, not weight gain or energy improvement in healthy people. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract and indexed primary figure descriptions

experimental_model

Human 293T and cancer-cell experimental program.

limitations

CaMKK2 identity does not by itself show dietary calcium depletion or calcium-supplement rescue.

nutrient_topic

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

plain_language

The sensing protein helped bring a kinase and its target together.

primary_references

CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 140–146

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human 293T and cancer-cell experimental program. · source_derived_draft · unverified_draft

## l-cysteine-cars-camkk2-bridge The sensing protein helped bring a kinase and its target together. Under cysteine-deficient conditions, CARS promoted AMPK association with CaMKK2 and CaMKK2-dependent AMPK phosphorylation. Model: Human 293T and cancer-cell experimental program. Limitations: CaMKK2 identity does not by itself show dietary calcium depletion or calcium-supplement rescue. Evidence access: Primary abstract and indexed primary figure descriptions CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract and indexed primary figure descriptions

experimental_model

Human 293T-centered cell and binding experiments; extracellular cystine withdrawal or 0–200 micromolar titration for eight hours.

limitations

Medium cystine manipulation changes intracellular cysteine; do not relabel it as a controlled human dietary intake.

nutrient_topic

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

plain_language

A protein-synthesis enzyme also helped sense the availability of its amino acid.

primary_references

CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 132–138

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human 293T-centered cell and binding experiments; extracellular cystine withdrawal or 0–200 micromolar titration for eight hours. · source_derived_draft · unverified_draft

## l-cysteine-cars-sensing A protein-synthesis enzyme also helped sense the availability of its amino acid. Cysteine scarcity promoted CARS association with AMPK gamma-2, whereas cysteine inhibited this association in the reported experiments. Model: Human 293T-centered cell and binding experiments; extracellular cystine withdrawal or 0–200 micromolar titration for eight hours. Limitations: Medium cystine manipulation changes intracellular cysteine; do not relabel it as a controlled human dietary intake. Evidence access: Primary abstract and indexed primary figure descriptions CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028

evidence_access

Primary abstract

experimental_model

Mouse-centered brown-adipocyte and in vivo experimental program.

limitations

Abstract does not fully resolve each chemical intermediate; do not equate free H2S, CysSSH and protein-bound persulfides.

nutrient_topic

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

plain_language

Sulfur chemistry fed back to the transcription machinery.

primary_references

Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 396–402

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse-centered brown-adipocyte and in vivo experimental program. · source_derived_draft · unverified_draft

## l-cysteine-cars2-ebf2-persulfidation Sulfur chemistry fed back to the transcription machinery. Cars2-derived cysteine persulfide/H2S signaling promoted EBF2 persulfidation and interaction with PPARgamma or BRG1, supporting thermogenic gene recruitment. Model: Mouse-centered brown-adipocyte and in vivo experimental program. Limitations: Abstract does not fully resolve each chemical intermediate; do not equate free H2S, CysSSH and protein-bound persulfides. Evidence access: Primary abstract Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse thermogenic-fat Cars2 loss.

limitations

This is not the same intervention as Cth loss plus a cysteine-free diet.

nutrient_topic

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

plain_language

A tissue-specific enzyme defect produced a different response from whole-body nutrient withdrawal.

primary_references

Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 404–410

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse thermogenic-fat Cars2 loss. · source_derived_draft · unverified_draft

## l-cysteine-cars2-fat-loss A tissue-specific enzyme defect produced a different response from whole-body nutrient withdrawal. Loss of Cars2 in thermogenic fat impaired brown-fat formation and reduced thermogenesis and energy expenditure in mice. Model: Mouse thermogenic-fat Cars2 loss. Limitations: This is not the same intervention as Cth loss plus a cysteine-free diet. Evidence access: Primary abstract Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human HEK293T imaging and mutant rescue.

limitations

This does not show that free-cysteine supplementation repairs mitochondrial disease.

nutrient_topic

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

plain_language

Sulfur chemistry contributed to mitochondrial behavior beyond protein production.

primary_references

Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29079736/ · DOI 10.1038/s41467-017-01311-y

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 172–178

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293T imaging and mutant rescue. · source_derived_draft · unverified_draft

## l-cysteine-cars2-mitochondrial-shape Sulfur chemistry contributed to mitochondrial behavior beyond protein production. CARS2-deficient human cells had fragmented or shrunken mitochondria; re-expression of wild-type or persulfide-competent C78/257D CARS2 improved morphology, unlike the tested persulfide-impaired lysine mutants. Model: Human HEK293T imaging and mutant rescue. Limitations: This does not show that free-cysteine supplementation repairs mitochondrial disease. Evidence access: Primary full text Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29079736/ · DOI 10.1038/s41467-017-01311-y

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human HEK293T knockout/rescue and LC–MS/MS persulfide assays.

limitations

Assay and mutation-dependent evidence; the proposed importance of this route is not proof of identical dominance in all human tissues.

nutrient_topic

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

plain_language

One enzyme had separable roles in protein synthesis and sulfur chemistry.

primary_references

Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29079736/ · DOI 10.1038/s41467-017-01311-y

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 164–170

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293T knockout/rescue and LC–MS/MS persulfide assays. · source_derived_draft · unverified_draft

## l-cysteine-cars2-persulfide One enzyme had separable roles in protein synthesis and sulfur chemistry. CARS2 disruption lowered cysteine-persulfide production in human cells, and wild-type or the C78/257D mutant restored it despite differing effects on translation. Model: Human HEK293T knockout/rescue and LC–MS/MS persulfide assays. Limitations: Assay and mutation-dependent evidence; the proposed importance of this route is not proof of identical dominance in all human tissues. Evidence access: Primary full text Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29079736/ · DOI 10.1038/s41467-017-01311-y

evidence_access

Primary abstract

experimental_model

Mouse high-fat-diet and brown-adipocyte experiments.

limitations

Abstract-only intervention details; no human dose, route equivalence or cysteine-plus-B6 synergy is established.

nutrient_topic

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

plain_language

A B6-derived coenzyme and a sulfur donor were separately tested inputs to this pathway.

primary_references

Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 412–418

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse high-fat-diet and brown-adipocyte experiments. · source_derived_draft · unverified_draft

## l-cysteine-cars2-plp-intervention A B6-derived coenzyme and a sulfur donor were separately tested inputs to this pathway. PLP treatment or an H2S donor improved brown-adipocyte function and reduced obesity progression in the reported high-fat-fed mouse experiments. Model: Mouse high-fat-diet and brown-adipocyte experiments. Limitations: Abstract-only intervention details; no human dose, route equivalence or cysteine-plus-B6 synergy is established. Evidence access: Primary abstract Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human HEK293T CARS2-deficient cells and C78/257D versus lysine-motif mutant complementation.

limitations

MTCO1 expression is a translation-related readout, not a direct measurement of dietary cysteine incorporation.

nutrient_topic

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

plain_language

Mitochondria need their own enzyme to place cysteine into proteins.

primary_references

Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29079736/ · DOI 10.1038/s41467-017-01311-y

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 156–162

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293T CARS2-deficient cells and C78/257D versus lysine-motif mutant complementation. · source_derived_draft · unverified_draft

## l-cysteine-cars2-translation Mitochondria need their own enzyme to place cysteine into proteins. CARS2 disruption reduced mitochondrial cysteinyl-tRNA synthetase function, assessed in part through mitochondrial MTCO1 expression; mutant rescue distinguished this from persulfide synthesis. Model: Human HEK293T CARS2-deficient cells and C78/257D versus lysine-motif mutant complementation. Limitations: MTCO1 expression is a translation-related readout, not a direct measurement of dietary cysteine incorporation. Evidence access: Primary full text Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29079736/ · DOI 10.1038/s41467-017-01311-y

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse Cth deletion with controlled low cyst(e)ine feeding.

limitations

Genetic plus dietary intervention; this does not establish a dose threshold for healthy people.

nutrient_topic

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

plain_language

Diet became essential when the animal could not make enough internally.

primary_references

Cystathionine gamma-Lyase-deficient mice require dietary cysteine to protect against acute lethal myopathy and oxidative injury. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20566639/ · DOI 10.1074/jbc.M110.147439

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 300–306

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse Cth deletion with controlled low cyst(e)ine feeding. · source_derived_draft · unverified_draft

## l-cysteine-cth-diet-myopathy Diet became essential when the animal could not make enough internally. Cth-null mice on a low cyst(e)ine diet developed reduced liver/muscle glutathione, acute skeletal myopathy and fatal paralysis in the reported model. Model: Mouse Cth deletion with controlled low cyst(e)ine feeding. Limitations: Genetic plus dietary intervention; this does not establish a dose threshold for healthy people. Evidence access: Primary abstract Cystathionine gamma-Lyase-deficient mice require dietary cysteine to protect against acute lethal myopathy and oxidative injury. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20566639/ · DOI 10.1074/jbc.M110.147439

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human CTNS site-directed mutagenesis and transport measurements.

limitations

Experimental mutations and disease-associated variants are not a dietary deficiency.

nutrient_topic

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

plain_language

A correctly located transporter may still fail to recognize or move its substrate.

primary_references

Structure and mechanism of human cystine exporter cystinosin. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36113465/ · DOI 10.1016/j.cell.2022.08.020

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 36–42

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human CTNS site-directed mutagenesis and transport measurements. · source_derived_draft · unverified_draft

## l-cysteine-ctns-binding-residues A correctly located transporter may still fail to recognize or move its substrate. Mutating human cystinosin K273, K280, D305, W138, N166 or F142 abolished cystine transport in the reported assays. Model: Human CTNS site-directed mutagenesis and transport measurements. Limitations: Experimental mutations and disease-associated variants are not a dietary deficiency. Evidence access: Primary full text Structure and mechanism of human cystine exporter cystinosin. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36113465/ · DOI 10.1016/j.cell.2022.08.020

evidence_access

Primary full text

experimental_model

Human CTNS mutagenesis and double electron–electron resonance spectroscopy at pH 5.2 and 7.4.

limitations

A structure-supported protonation model is not a demonstrated effect of changing dietary acid or mineral intake.

nutrient_topic

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

plain_language

The transporter couples substrate movement to an acidic compartment.

primary_references

Structure and mechanism of human cystine exporter cystinosin. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36113465/ · DOI 10.1016/j.cell.2022.08.020

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 44–50

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human CTNS mutagenesis and double electron–electron resonance spectroscopy at pH 5.2 and 7.4. · source_derived_draft · unverified_draft

## l-cysteine-ctns-proton-switch The transporter couples substrate movement to an acidic compartment. D346N substitution abolished the pH-dependent conformational switch; the authors proposed D346 as a key protonation site controlling human cystinosin transitions. Model: Human CTNS mutagenesis and double electron–electron resonance spectroscopy at pH 5.2 and 7.4. Limitations: A structure-supported protonation model is not a demonstrated effect of changing dietary acid or mineral intake. Evidence access: Primary full text Structure and mechanism of human cystine exporter cystinosin. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36113465/ · DOI 10.1016/j.cell.2022.08.020

evidence_access

Primary full text

experimental_model

Human cystinosin cryo-EM and interaction experiments.

limitations

This does not demonstrate that oral cysteine directly activates mTORC1.

nutrient_topic

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

plain_language

Transport machinery can also affect how the cell senses nutrient availability.

primary_references

Structure and mechanism of human cystine exporter cystinosin. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36113465/ · DOI 10.1016/j.cell.2022.08.020

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 52–58

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

## l-cysteine-ctns-ragulator Transport machinery can also affect how the cell senses nutrient availability. The human CTNS N288K variant altered conformation and suppressed engagement with Ragulator–Rag, linking transporter state with a nutrient-signaling complex. Model: Human cystinosin cryo-EM and interaction experiments. Limitations: This does not demonstrate that oral cysteine directly activates mTORC1. Evidence access: Primary full text Structure and mechanism of human cystine exporter cystinosin. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36113465/ · DOI 10.1016/j.cell.2022.08.020

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human cancer-cell transporter manipulation, glucose withdrawal and metabolic assays.

limitations

Complete glucose withdrawal in culture is not ordinary fasting or dietary carbohydrate restriction.

nutrient_topic

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

plain_language

Importing more oxidized nutrient also creates more work for the reducing system.

primary_references

Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32231310/ · DOI 10.1038/s41556-020-0496-x

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 236–242

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell transporter manipulation, glucose withdrawal and metabolic assays. · source_derived_draft · unverified_draft

## l-cysteine-cystine-nadph-demand Importing more oxidized nutrient also creates more work for the reducing system. High SLC7A11-mediated cystine uptake increased reliance on glucose and the pentose phosphate pathway; glucose deprivation depleted NADPH and promoted intracellular disulfide accumulation. Model: Human cancer-cell transporter manipulation, glucose withdrawal and metabolic assays. Limitations: Complete glucose withdrawal in culture is not ordinary fasting or dietary carbohydrate restriction. Evidence access: Primary full text Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32231310/ · DOI 10.1038/s41556-020-0496-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human cancer-cell glucose/cystine manipulation.

limitations

This is distinct from cystine-withdrawal ferroptosis under other conditions; no universal benefit of removing cystine is implied.

nutrient_topic

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

plain_language

Reducing the incoming load helped when the cell could not process it.

primary_references

Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32231310/ · DOI 10.1038/s41556-020-0496-x

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 244–250

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell glucose/cystine manipulation. · source_derived_draft · unverified_draft

## l-cysteine-cystine-reduction-rescue Reducing the incoming load helped when the cell could not process it. Preventing cystine uptake or removing cystine relieved the disulfide stress associated with glucose deprivation in SLC7A11-high cells. Model: Human cancer-cell glucose/cystine manipulation. Limitations: This is distinct from cystine-withdrawal ferroptosis under other conditions; no universal benefit of removing cystine is implied. Evidence access: Primary full text Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32231310/ · DOI 10.1038/s41556-020-0496-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse tissue/urine metabolomics during combined genetic and dietary depletion.

limitations

Metabolite abundance alone is not complete pathway flux or a human diagnostic signature. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8

nutrient_topic

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

plain_language

The shortage affected how efficiently the animal retained and used fuel.

primary_references

Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 316–322

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse tissue/urine metabolomics during combined genetic and dietary depletion. · source_derived_draft · unverified_draft

## l-cysteine-depletion-carbon-loss The shortage affected how efficiently the animal retained and used fuel. Cysteine-depleted Cse-null mice excreted more intermediary metabolites, including pyruvate, citrate, 2-oxoglutarate and orotate, with altered hepatic glycolytic and TCA-cycle metabolism. Model: Mouse tissue/urine metabolomics during combined genetic and dietary depletion. Limitations: Metabolite abundance alone is not complete pathway flux or a human diagnostic signature. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse genetic/dietary depletion; tissue CoA measurements at days 2 and 7.

limitations

CoA depletion accompanies several changes; do not assign all weight loss to one metabolite. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8

nutrient_topic

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

plain_language

A cysteine shortage reduced an energy-metabolism cofactor as well as an antioxidant.

primary_references

Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 308–314

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse genetic/dietary depletion; tissue CoA measurements at days 2 and 7. · source_derived_draft · unverified_draft

## l-cysteine-depletion-coa A cysteine shortage reduced an energy-metabolism cofactor as well as an antioxidant. Combined Cse loss and cysteine-free feeding reduced liver and muscle CoA, alongside glutathione depletion and major metabolic changes. Model: Mouse genetic/dietary depletion; tissue CoA measurements at days 2 and 7. Limitations: CoA depletion accompanies several changes; do not assign all weight loss to one metabolite. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract and primary publisher figure descriptions

experimental_model

Human cancer cultures, chemical proteomics and cell-biological assays.

limitations

Experimental deprivation; do not infer this occurs whenever blood glucose falls modestly.

nutrient_topic

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

plain_language

The damage involved cross-linked structural proteins rather than the same lipid-peroxide pathway.

primary_references

Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36747082/ · DOI 10.1038/s41556-023-01091-2

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 252–258

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer cultures, chemical proteomics and cell-biological assays. · source_derived_draft · unverified_draft

## l-cysteine-disulfidptosis-actin The damage involved cross-linked structural proteins rather than the same lipid-peroxide pathway. Glucose starvation of SLC7A11-high human cancer cells induced abnormal disulfide bonding in actin-cytoskeleton proteins, F-actin collapse and disulfidptosis, distinct from apoptosis and ferroptosis. Model: Human cancer cultures, chemical proteomics and cell-biological assays. Limitations: Experimental deprivation; do not infer this occurs whenever blood glucose falls modestly. Evidence access: Primary abstract and primary publisher figure descriptions Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36747082/ · DOI 10.1038/s41556-023-01091-2

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human cancer-cell CRISPR screens and functional perturbations.

limitations

A complex-level finding is not assigned to every WAVE subunit or Rac isoform without resolution.

nutrient_topic

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

plain_language

The state of the actin-assembly machinery changed vulnerability to sulfur stress.

primary_references

Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36747082/ · DOI 10.1038/s41556-023-01091-2

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 260–266

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell CRISPR screens and functional perturbations. · source_derived_draft · unverified_draft

## l-cysteine-disulfidptosis-wave The state of the actin-assembly machinery changed vulnerability to sulfur stress. Inactivation of the WAVE regulatory complex suppressed disulfidptosis, whereas constitutive Rac activation promoted it in the studied cells. Model: Human cancer-cell CRISPR screens and functional perturbations. Limitations: A complex-level finding is not assigned to every WAVE subunit or Rac isoform without resolution. Evidence access: Primary abstract Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36747082/ · DOI 10.1038/s41556-023-01091-2

evidence_access

Primary abstract

experimental_model

Mouse brown-fat study and cellular differentiation experiments.

limitations

Abstract-level extraction; detailed promoter occupancy and construct conditions require full-method review.

nutrient_topic

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

plain_language

A transcription factor increased the machinery for a sulfur-signaling pathway.

primary_references

Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 388–394

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse brown-fat study and cellular differentiation experiments. · source_derived_draft · unverified_draft

## l-cysteine-ebf2-cars2-expression A transcription factor increased the machinery for a sulfur-signaling pathway. The study reported direct EBF2 induction of Cars2 during brown-adipocyte differentiation. Model: Mouse brown-fat study and cellular differentiation experiments. Limitations: Abstract-level extraction; detailed promoter occupancy and construct conditions require full-method review. Evidence access: Primary abstract Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690

evidence_access

Primary abstract

experimental_model

Human ERO1A structural and biochemical study.

limitations

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

nutrient_topic

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

plain_language

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

primary_references

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

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

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

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

evidence_access

Primary abstract

experimental_model

Human ERO1A hyperactive and inactive crystal structures.

limitations

This is enzyme regulation, not proof that additional cysteine increases protein folding or antioxidant capacity.

nutrient_topic

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

plain_language

Cysteine bonds can regulate an enzyme as well as stabilize folded proteins.

primary_references

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

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 492–498

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human ERO1A hyperactive and inactive crystal structures. · source_derived_draft · unverified_draft

## l-cysteine-ero1-regulatory-disulfides Cysteine bonds can regulate an enzyme as well as stabilize folded proteins. Regulatory cysteines in a flexible ERO1A loop change disulfide arrangements and electron transfer, restraining its oxidative activity. Model: Human ERO1A hyperactive and inactive crystal structures. Limitations: This is enzyme regulation, not proof that additional cysteine increases protein folding or antioxidant capacity. Evidence access: Primary abstract Crystal structures of human Ero1α reveal the mechanisms of regulated and targeted oxidation of PDI. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20834232/ · DOI 10.1038/emboj.2010.222

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Fgf21-null versus control mice on no-methionine/no-cysteine diets; separate from the Cse-null cysteine-only experiment.

limitations

Do not silently replace the combined restriction with cysteine-only restriction. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8

nutrient_topic

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

plain_language

A stress hormone contributed under combined sulfur-amino-acid withdrawal.

primary_references

Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 340–346

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Fgf21-null versus control mice on no-methionine/no-cysteine diets; separate from the Cse-null cysteine-only experiment. · source_derived_draft · unverified_draft

## l-cysteine-fgf21-combined-restriction A stress hormone contributed under combined sulfur-amino-acid withdrawal. Fgf21 knockout attenuated weight loss in mice fed a diet lacking both methionine and cysteine. Model: Fgf21-null versus control mice on no-methionine/no-cysteine diets; separate from the Cse-null cysteine-only experiment. Limitations: Do not silently replace the combined restriction with cysteine-only restriction. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Cth-null versus Cth/Fgf21 double-null mice on cysteine-free diet for five days.

limitations

Different genotype and diet from the combined methionine/cysteine restriction study; no universal FGF21 dependence is assigned.

nutrient_topic

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

plain_language

An increased hormone level did not make that hormone necessary for this outcome.

primary_references

Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 364–370

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cth-null versus Cth/Fgf21 double-null mice on cysteine-free diet for five days. · source_derived_draft · unverified_draft

## l-cysteine-fgf21-cysteine-only-limit An increased hormone level did not make that hormone necessary for this outcome. Additional Fgf21 deletion in Cth-null mice did not prevent the rapid weight-loss phenotype during cysteine-free feeding. Model: Cth-null versus Cth/Fgf21 double-null mice on cysteine-free diet for five days. Limitations: Different genotype and diet from the combined methionine/cysteine restriction study; no universal FGF21 dependence is assigned. Evidence access: Primary full text Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human CALERIE-II biopsy metabolomics during caloric restriction.

limitations

This did not isolate cysteine restriction or demonstrate that lowering cysteine caused human weight loss.

nutrient_topic

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

plain_language

A human tissue measurement motivated further animal experiments.

primary_references

Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8

trigger_kind

biomarker_context Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 348–354

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human CALERIE-II biopsy metabolomics during caloric restriction. · source_derived_draft · unverified_draft

## l-cysteine-human-adipose-marker A human tissue measurement motivated further animal experiments. Adipose metabolomics after caloric restriction showed reduced cysteine in the sampled human white adipose tissue. Model: Human CALERIE-II biopsy metabolomics during caloric restriction. Limitations: This did not isolate cysteine restriction or demonstrate that lowering cysteine caused human weight loss. Evidence access: Primary full text Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8

evidence_access

Primary full text

experimental_model

Human CTNS crystallography, cryo-EM, transport and spectroscopic assays.

limitations

Transport was assayed with engineered constructs; normal dietary intake does not bypass a defective lysosomal exporter.

nutrient_topic

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

plain_language

Protein recycling supplies sulfur only if its breakdown products can leave the lysosome.

primary_references

Structure and mechanism of human cystine exporter cystinosin. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36113465/ · DOI 10.1016/j.cell.2022.08.020

transport_effect

raises Recorded as proton-coupled export from the lysosomal lumen toward the cytosol. The lysosomal pool falls in the same step.

transport_pool

cytosolic cystine Recorded as proton-coupled export from the lysosomal lumen toward the cytosol. The lysosomal pool falls in the same step.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 28–34

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human CTNS crystallography, cryo-EM, transport and spectroscopic assays. · source_derived_draft · unverified_draft

## l-cysteine-lysosomal-export Protein recycling supplies sulfur only if its breakdown products can leave the lysosome. Human cystinosin structures and functional assays support proton-coupled cystine export from the lysosomal lumen toward the cytosol. Model: Human CTNS crystallography, cryo-EM, transport and spectroscopic assays. Limitations: Transport was assayed with engineered constructs; normal dietary intake does not bypass a defective lysosomal exporter. Evidence access: Primary full text Structure and mechanism of human cystine exporter cystinosin. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36113465/ · DOI 10.1016/j.cell.2022.08.020

evidence_access

Primary abstract

experimental_model

Six-day dietary periods followed by oral tracers and fasting/fed measurements on day seven.

limitations

This endpoint and regimen do not disprove every methionine-sparing effect or define current intake recommendations.

nutrient_topic

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

plain_language

A plausible nutrient-saving relationship was not detectable with this particular short-term measurement.

primary_references

Effect of cystine intake on methionine kinetics and oxidation determined with oral tracers of methionine and cysteine in healthy adults. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9250106/ · DOI 10.1093/ajcn/66.2.283

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 444–450

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Six-day dietary periods followed by oral tracers and fasting/fed measurements on day seven. · source_derived_draft · unverified_draft

## l-cysteine-methionine-sparing-limit A plausible nutrient-saving relationship was not detectable with this particular short-term measurement. In eight healthy adults, adding 6.5 mg/kg/day cystine to a diet containing 5 mg/kg/day methionine did not significantly change methionine oxidation compared with the same low-methionine diet without cystine. Model: Six-day dietary periods followed by oral tracers and fasting/fed measurements on day seven. Limitations: This endpoint and regimen do not disprove every methionine-sparing effect or define current intake recommendations. Evidence access: Primary abstract Effect of cystine intake on methionine kinetics and oxidation determined with oral tracers of methionine and cysteine in healthy adults. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9250106/ · DOI 10.1093/ajcn/66.2.283

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Genetically engineered mice with established pancreatic tumors.

limitations

Not all tumors or normal tissues have the same dependency; dietary deprivation was not this intervention.

nutrient_topic

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

plain_language

A transporter dependency could be targeted in this animal cancer model.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 228–234

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Genetically engineered mice with established pancreatic tumors. · source_derived_draft · unverified_draft

## l-cysteine-mouse-pdac-import-loss A transporter dependency could be targeted in this animal cancer model. Deleting Slc7a11 in established genetically engineered mouse PDAC induced tumor-selective ferroptosis and inhibited growth. Model: Genetically engineered mice with established pancreatic tumors. Limitations: Not all tumors or normal tissues have the same dependency; dietary deprivation was not this intervention. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

evidence_access

Primary abstract and primary figure descriptions

experimental_model

Purified human MPST kinetics; concentrations and acceptors varied.

limitations

Some small-thiol assays used millimolar concentrations; these are not demonstrated effects of oral cysteine or lipoic acid.

nutrient_topic

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

plain_language

Sharing a sulfur-transfer route does not make these acceptors equally effective inside cells.

primary_references

Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23698001/ · DOI 10.1074/jbc.M113.466177

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 460–466

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human MPST kinetics; concentrations and acceptors varied. · source_derived_draft · unverified_draft

## l-cysteine-mpst-acceptor-choice Sharing a sulfur-transfer route does not make these acceptors equally effective inside cells. Human MPST supported H2S production with thioredoxin and several low-molecular-weight acceptors, including cysteine, glutathione and dihydrolipoic acid. Model: Purified human MPST kinetics; concentrations and acceptors varied. Limitations: Some small-thiol assays used millimolar concentrations; these are not demonstrated effects of oral cysteine or lipoic acid. Evidence access: Primary abstract and primary figure descriptions Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23698001/ · DOI 10.1074/jbc.M113.466177

evidence_access

Primary abstract

experimental_model

Recombinant human MPST assays.

limitations

This does not negate NAC metabolism to cysteine or its other mechanisms.

nutrient_topic

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

plain_language

A cysteine precursor does not necessarily substitute for cysteine in each chemical reaction.

primary_references

Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32179647/ · DOI 10.1074/jbc.RA120.012616

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 476–482

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human MPST assays. · source_derived_draft · unverified_draft

## l-cysteine-mpst-nac-distinction A cysteine precursor does not necessarily substitute for cysteine in each chemical reaction. N-acetylcysteine was a poor MPST sulfur acceptor in the reported kinetic experiments. Model: Recombinant human MPST assays. Limitations: This does not negate NAC metabolism to cysteine or its other mechanisms. Evidence access: Primary abstract Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32179647/ · DOI 10.1074/jbc.RA120.012616

evidence_access

Primary abstract and primary figure descriptions

experimental_model

Purified human MPST structure and kinetics at pH 7.4.

limitations

The upstream cysteine transamination is pathway context; this experiment does not identify its dominant human tissue isoenzyme.

nutrient_topic

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

plain_language

A cysteine-derived intermediate hands sulfur to an enzyme before it reaches another acceptor.

primary_references

Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23698001/ · DOI 10.1074/jbc.M113.466177

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 452–458

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human MPST structure and kinetics at pH 7.4. · source_derived_draft · unverified_draft

## l-cysteine-mpst-sulfur-transfer A cysteine-derived intermediate hands sulfur to an enzyme before it reaches another acceptor. Human MPST transfers sulfur from 3-mercaptopyruvate to its active-site Cys248, releasing pyruvate and forming an enzyme-bound persulfide. Model: Purified human MPST structure and kinetics at pH 7.4. Limitations: The upstream cysteine transamination is pathway context; this experiment does not identify its dominant human tissue isoenzyme. Evidence access: Primary abstract and primary figure descriptions Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23698001/ · DOI 10.1074/jbc.M113.466177

evidence_access

Primary abstract

experimental_model

Recombinant human MPST isoform kinetics.

limitations

Predicted tissue sulfur allocation was based on simulations; no human dietary response was measured.

nutrient_topic

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

plain_language

More of a redox partner did not simply produce a faster reaction.

primary_references

Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32179647/ · DOI 10.1074/jbc.RA120.012616

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 468–474

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human MPST isoform kinetics. · source_derived_draft · unverified_draft

## l-cysteine-mpst-thioredoxin-inhibition More of a redox partner did not simply produce a faster reaction. Thioredoxin showed substrate inhibition in human MPST assays and increased the apparent Km for 3-mercaptopyruvate relative to other acceptors. Model: Recombinant human MPST isoform kinetics. Limitations: Predicted tissue sulfur allocation was based on simulations; no human dietary response was measured. Evidence access: Primary abstract Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32179647/ · DOI 10.1074/jbc.RA120.012616

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse Slc1a1 deletion with NAC treatment.

limitations

NAC is the tested intervention, not free L-cysteine; no human cognitive benefit is established.

nutrient_topic

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

plain_language

A different precursor bypassed part of the uptake limitation in this animal model.

primary_references

Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16311588/ · DOI 10.1038/nn1609

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 108–114

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse Slc1a1 deletion with NAC treatment. · source_derived_draft · unverified_draft

## l-cysteine-nac-neuronal-rescue A different precursor bypassed part of the uptake limitation in this animal model. N-acetylcysteine treatment reversed reduced neuronal glutathione and oxidant-related abnormalities in EAAC1-deficient mice. Model: Mouse Slc1a1 deletion with NAC treatment. Limitations: NAC is the tested intervention, not free L-cysteine; no human cognitive benefit is established. Evidence access: Primary abstract Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16311588/ · DOI 10.1038/nn1609

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse EAAC1 gene deletion, hippocampal slices and aging observations.

limitations

Does not establish a human oral cysteine treatment or make neuronal and astrocytic transport interchangeable.

nutrient_topic

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

plain_language

A neuron can lack usable cysteine even when the amino acid exists elsewhere.

primary_references

Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16311588/ · DOI 10.1038/nn1609

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 100–106

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse EAAC1 gene deletion, hippocampal slices and aging observations. · source_derived_draft · unverified_draft

## l-cysteine-neuronal-uptake-gate A neuron can lack usable cysteine even when the amino acid exists elsewhere. Slc1a1-null mice had lower neuronal glutathione, increased oxidant susceptibility and age-dependent brain atrophy and behavioral changes. Model: Mouse EAAC1 gene deletion, hippocampal slices and aging observations. Limitations: Does not establish a human oral cysteine treatment or make neuronal and astrocytic transport interchangeable. Evidence access: Primary abstract Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16311588/ · DOI 10.1038/nn1609

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse knockout, zinc measurements and transient ischemia.

limitations

The experiment did not test dietary zinc deficiency or toxicity thresholds.

nutrient_topic

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

plain_language

Impaired cysteine supply affected metal handling as well as antioxidant capacity.

primary_references

EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21084597/ · DOI 10.1523/JNEUROSCI.2084-10.2010

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 116–122

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse knockout, zinc measurements and transient ischemia. · source_derived_draft · unverified_draft

## l-cysteine-neuronal-zinc-link Impaired cysteine supply affected metal handling as well as antioxidant capacity. EAAC1-null mice had increased vesicular/cytosolic hippocampal zinc and greater zinc redistribution and neuronal injury after transient cerebral ischemia. Model: Mouse knockout, zinc measurements and transient ischemia. Limitations: The experiment did not test dietary zinc deficiency or toxicity thresholds. Evidence access: Primary abstract EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21084597/ · DOI 10.1523/JNEUROSCI.2084-10.2010

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse EAAC1-null ischemia model.

limitations

NAC and chelators are separate interventions; the study does not show that extra dietary cysteine and zinc are synergistic.

nutrient_topic

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

plain_language

Restoring precursor supply and binding excess labile zinc were distinct rescue routes.

primary_references

EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21084597/ · DOI 10.1523/JNEUROSCI.2084-10.2010

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 124–130

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse EAAC1-null ischemia model. · source_derived_draft · unverified_draft

## l-cysteine-neuronal-zinc-rescue Restoring precursor supply and binding excess labile zinc were distinct rescue routes. NAC restored neuronal glutathione and normalized basal zinc levels in EAAC1-null mice; NAC or zinc chelation reduced ischemia-associated zinc movement, superoxide and neuronal death. Model: Mouse EAAC1-null ischemia model. Limitations: NAC and chelators are separate interventions; the study does not show that extra dietary cysteine and zinc are synergistic. Evidence access: Primary abstract EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21084597/ · DOI 10.1523/JNEUROSCI.2084-10.2010

evidence_access

Primary abstract

experimental_model

Mouse-cell isolated mitochondrial experiments.

limitations

The proposed GTPase/reductase mediators were not individually established by this study; do not assign a universal ATP requirement to each substep.

nutrient_topic

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

plain_language

The pathway has several gates, with different requirements at different steps.

primary_references

Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron and requirements for GTP, NADH, and ATP. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25398879/ · DOI 10.1074/jbc.M114.610402

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 276–282

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

## l-cysteine-nfs1-persulfide-gate The pathway has several gates, with different requirements at different steps. Labeled NFS1-bound persulfide was an intermediate; its sulfur release required iron, GTP and NADH, whereas ATP was required for the overall assembly pathway but not this release step. Model: Mouse-cell isolated mitochondrial experiments. Limitations: The proposed GTPase/reductase mediators were not individually established by this study; do not assign a universal ATP requirement to each substep. Evidence access: Primary abstract Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron and requirements for GTP, NADH, and ATP. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25398879/ · DOI 10.1074/jbc.M114.610402

evidence_access

Primary full text

experimental_model

Human PDAC stable-isotope tracing.

limitations

No labeling of taurine, lactate, citrate or glutamate was detected in these assays; that does not abolish those routes in other tissues.

nutrient_topic

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

plain_language

Cysteine-derived material entered more than one protective metabolic pool.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 188–194

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC stable-isotope tracing. · source_derived_draft · unverified_draft

## l-cysteine-pdac-carbon-tracing Cysteine-derived material entered more than one protective metabolic pool. Carbon-13 cystine tracing showed labeling of glutathione and CoA over the experiment, including CoA labeling over 24 hours. Model: Human PDAC stable-isotope tracing. Limitations: No labeling of taurine, lactate, citrate or glutamate was detected in these assays; that does not abolish those routes in other tissues. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human PDAC cultures with cystine-import inhibition and metabolomics.

limitations

Pantothenate accumulation is not proof of B5 toxicity or a clinical biomarker threshold.

nutrient_topic

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

plain_language

Vitamin B5 could accumulate while its downstream product fell because another substrate was missing.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 196–202

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC cultures with cystine-import inhibition and metabolomics. · source_derived_draft · unverified_draft

## l-cysteine-pdac-coa-branch Vitamin B5 could accumulate while its downstream product fell because another substrate was missing. System xc− inhibition lowered CoA and increased upstream pantothenate in the tested pancreatic cancer cells. Model: Human PDAC cultures with cystine-import inhibition and metabolomics. Limitations: Pantothenate accumulation is not proof of B5 toxicity or a clinical biomarker threshold. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human PDAC culture and exogenous CoA treatment.

limitations

Cell-culture rescue does not establish oral CoA absorption, intact cellular uptake in vivo or clinical efficacy.

nutrient_topic

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

plain_language

Restoring a downstream metabolite bypassed part of an upstream block in culture.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 220–226

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC culture and exogenous CoA treatment. · source_derived_draft · unverified_draft

## l-cysteine-pdac-coa-rescue Restoring a downstream metabolite bypassed part of an upstream block in culture. Adding CoA prevented ferroptosis induced by imidazole ketone erastin in the reported PDAC cell experiments. Model: Human PDAC culture and exogenous CoA treatment. Limitations: Cell-culture rescue does not establish oral CoA absorption, intact cellular uptake in vivo or clinical efficacy. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human pancreatic cancer cultures; nutrient withdrawal, oxidation and viability assays.

limitations

Culture starvation is not dietary treatment; one of the tested lines differed.

nutrient_topic

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

plain_language

Dependence on external sulfur varied between cancer-cell models.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 180–186

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human pancreatic cancer cultures; nutrient withdrawal, oxidation and viability assays. · source_derived_draft · unverified_draft

## l-cysteine-pdac-cystine-withdrawal Dependence on external sulfur varied between cancer-cell models. Cystine starvation induced lipid oxidation and ferroptosis in four of five tested human PDAC cell lines. Model: Human pancreatic cancer cultures; nutrient withdrawal, oxidation and viability assays. Limitations: Culture starvation is not dietary treatment; one of the tested lines differed. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human PDAC culture; pharmacological PANKi/BSO combination.

limitations

This is a demonstrated drug-combination interaction in this assay, not evidence for oral B5/cysteine supplement synergy.

nutrient_topic

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

plain_language

Two protective branches were experimentally blocked together.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 212–218

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC culture; pharmacological PANKi/BSO combination. · source_derived_draft · unverified_draft

## l-cysteine-pdac-dual-block Two protective branches were experimentally blocked together. Pantothenate-kinase inhibition combined with BSO synergistically induced ferroptosis in the reported PDAC assays. Model: Human PDAC culture; pharmacological PANKi/BSO combination. Limitations: This is a demonstrated drug-combination interaction in this assay, not evidence for oral B5/cysteine supplement synergy. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human PDAC cultures, BSO and viability/lipid-ROS assays.

limitations

This null result is model-specific; it does not make glutathione dispensable in general.

nutrient_topic

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

plain_language

Loss of glutathione alone did not explain the whole cysteine-depletion effect.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 204–210

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC cultures, BSO and viability/lipid-ROS assays. · source_derived_draft · unverified_draft

## l-cysteine-pdac-gsh-only-limit Loss of glutathione alone did not explain the whole cysteine-depletion effect. Buthionine sulfoximine lowered glutathione without inducing lipid oxidation or loss of viability under the tested PDAC conditions. Model: Human PDAC cultures, BSO and viability/lipid-ROS assays. Limitations: This null result is model-specific; it does not make glutathione dispensable in general. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

evidence_access

Primary full text

experimental_model

Recombinant human Prx2; cysteinylation and hydrogen-peroxide reduction assays.

limitations

TRP14 repairs this modification; it is not being assigned the ordinary catalytic peroxide-reduction cycle of thioredoxin.

nutrient_topic

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

plain_language

A cysteine modification can temporarily obstruct another antioxidant enzyme.

primary_references

TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 84–90

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human Prx2; cysteinylation and hydrogen-peroxide reduction assays. · source_derived_draft · unverified_draft

## l-cysteine-protein-decysteinylation A cysteine modification can temporarily obstruct another antioxidant enzyme. TRP14 removed cysteinyl mixed-disulfide modifications from human peroxiredoxin 2 and restored its peroxide-reducing activity in vitro. Model: Recombinant human Prx2; cysteinylation and hydrogen-peroxide reduction assays. Limitations: TRP14 repairs this modification; it is not being assigned the ordinary catalytic peroxide-reduction cycle of thioredoxin. Evidence access: Primary full text TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1

evidence_access

Primary full text

experimental_model

Human transporter cryo-EM and functional study; structural ligand was arginine.

limitations

Do not describe the arginine-bound structure as a captured cystine-bound state or infer dietary competition from binding alone.

nutrient_topic

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

plain_language

The kidney and intestine use a two-protein exchange system to handle cystine.

primary_references

Cryo-EM structure of the human heteromeric amino acid transporter b0,+AT-rBAT. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32494597/ · DOI 10.1126/sciadv.aay6379

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 20–26

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human transporter cryo-EM and functional study; structural ligand was arginine. · source_derived_draft · unverified_draft

## l-cysteine-renal-cystine-exchange The kidney and intestine use a two-protein exchange system to handle cystine. Human SLC7A9 and SLC3A1 form the b0,+AT–rBAT obligatory exchanger for cystine/cationic amino-acid influx coupled to neutral amino-acid efflux. Model: Human transporter cryo-EM and functional study; structural ligand was arginine. Limitations: Do not describe the arginine-bound structure as a captured cystine-bound state or infer dietary competition from binding alone. Evidence access: Primary full text Cryo-EM structure of the human heteromeric amino acid transporter b0,+AT-rBAT. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32494597/ · DOI 10.1126/sciadv.aay6379

evidence_access

Primary abstract

experimental_model

Simulation based on purified CBS/CSE kinetics with assumed equimolar enzyme concentrations.

limitations

A modeled 25–70% contribution is not a directly measured universal human tissue fraction.

nutrient_topic

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

plain_language

Methylation-cycle chemistry can influence a sulfur-signaling branch.

primary_references

Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19531479/ · DOI 10.1074/jbc.M109.010868

L-Cysteine: sulfur allocation, redox supply 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 · Simulation based on purified CBS/CSE kinetics with assumed equimolar enzyme concentrations. · source_derived_draft · unverified_draft

## l-cysteine-sam-sulfur-partition Methylation-cycle chemistry can influence a sulfur-signaling branch. Kinetic simulations predicted that SAM-dependent activation changes the relative CBS contribution to H2S generation at specified substrate concentrations. Model: Simulation based on purified CBS/CSE kinetics with assumed equimolar enzyme concentrations. Limitations: A modeled 25–70% contribution is not a directly measured universal human tissue fraction. Evidence access: Primary abstract Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19531479/ · DOI 10.1074/jbc.M109.010868

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse genetic/dietary depletion and repletion; lean and obese models.

limitations

Severe induced deficiency is not evidence for a safe human weight-loss strategy.

nutrient_topic

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

plain_language

Loss of the nutrient caused systemic stress, not simply a desirable fat-burning switch.

primary_references

Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 356–362

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse genetic/dietary depletion and repletion; lean and obese models. · source_derived_draft · unverified_draft

## l-cysteine-systemic-depletion-reversal Loss of the nutrient caused systemic stress, not simply a desirable fat-burning switch. Whole-body Cth-null mice fed a cysteine-free diet developed rapid fat loss and adipose browning; restoring cysteine reversed the phenotype, whereas prolonged depletion could be lethal. Model: Mouse genetic/dietary depletion and repletion; lean and obese models. Limitations: Severe induced deficiency is not evidence for a safe human weight-loss strategy. Evidence access: Primary full text Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human HEK293 metabolic tracing and enzyme perturbation.

limitations

Compensation requires intact transsulfuration and does not prove that B6 supplementation rescues every transport defect.

nutrient_topic

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

plain_language

An internal synthesis route compensated when imported cystine was harder to use.

primary_references

TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 76–82

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293 metabolic tracing and enzyme perturbation. · source_derived_draft · unverified_draft

## l-cysteine-trp14-compensation An internal synthesis route compensated when imported cystine was harder to use. TXNDC17 knockout shifted human-cell cysteine supply toward transsulfuration, as assessed using labeled methionine and downstream sulfur metabolites. Model: Human HEK293 metabolic tracing and enzyme perturbation. Limitations: Compensation requires intact transsulfuration and does not prove that B6 supplementation rescues every transport defect. Evidence access: Primary full text TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1

evidence_access

Primary full text

experimental_model

Purified enzyme systems, including human peroxiredoxin-2 decysteinylation.

limitations

This establishes a biochemical dependency; selenium or niacin depletion/repletion was not tested in this study.

nutrient_topic

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

plain_language

The sulfur-supply step depends on an electron supply and another enzyme.

primary_references

TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 68–74

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified enzyme systems, including human peroxiredoxin-2 decysteinylation. · source_derived_draft · unverified_draft

## l-cysteine-trp14-electron-supply The sulfur-supply step depends on an electron supply and another enzyme. The reconstituted TRP14 system used thioredoxin reductase 1 and NADPH to drive disulfide-reduction reactions. Model: Purified enzyme systems, including human peroxiredoxin-2 decysteinylation. Limitations: This establishes a biochemical dependency; selenium or niacin depletion/repletion was not tested in this study. Evidence access: Primary full text TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse genetic deletion and experimental acute pancreatitis.

limitations

Not a recommendation to inhibit TRP14; the finding does not contradict its cystine-reduction role.

nutrient_topic

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

plain_language

An enzyme defect can trigger protective compensation in a specific stress model.

primary_references

TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 92–98

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse genetic deletion and experimental acute pancreatitis. · source_derived_draft · unverified_draft

## l-cysteine-trp14-mouse-adaptation An enzyme defect can trigger protective compensation in a specific stress model. Txndc17 knockout mice showed protection in the acute pancreatitis model, accompanied by Nrf2-pathway activation and increased transsulfuration. Model: Mouse genetic deletion and experimental acute pancreatitis. Limitations: Not a recommendation to inhibit TRP14; the finding does not contradict its cystine-reduction role. Evidence access: Primary full text TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse double-knockout comparisons, six-day diet and metabolic-cage analysis.

limitations

UCP1-independent weight loss must not be generalized to UCP1-independent heat production or identical energy expenditure.

nutrient_topic

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

plain_language

Persistence of weight loss does not mean every thermogenic measurement was unchanged.

primary_references

Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 380–386

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse double-knockout comparisons, six-day diet and metabolic-cage analysis. · source_derived_draft · unverified_draft

## l-cysteine-ucp1-endpoint-limit Persistence of weight loss does not mean every thermogenic measurement was unchanged. Cth/Ucp1 double-null mice still lost weight during cysteine deprivation; body-mass-adjusted energy expenditure was lower than in Cth-null mice in the reported comparison. Model: Mouse double-knockout comparisons, six-day diet and metabolic-cage analysis. Limitations: UCP1-independent weight loss must not be generalized to UCP1-independent heat production or identical energy expenditure. Evidence access: Primary full text Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8

evidence_access

Primary abstract

experimental_model

Biochemical catecholaldehyde comparisons.

limitations

No universal antioxidant ranking follows.

nutrient_topic

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

plain_language

Different scavengers favor different aldehydes.

primary_references

Biochemical characterization of the catecholaldehyde reactivity of L-carnosine and its therapeutic potential in human myocardium. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30191330/ · DOI 10.1007/s00726-018-2647-y

Carnosine: synthesis, transport, carbonyl chemistry and nutrient interactions (2026-09-19) · lines 276–282

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Biochemical catecholaldehyde comparisons. · source_derived_draft · unverified_draft

## carnosine-dopal Different scavengers favor different aldehydes. Carnosine reacted with DOPAL and DOPEGAL; glutathione showed little DOPAL reactivity under the tested conditions. Model: Biochemical catecholaldehyde comparisons. Limitations: No universal antioxidant ranking follows. Evidence access: Primary abstract Biochemical characterization of the catecholaldehyde reactivity of L-carnosine and its therapeutic potential in human myocardium. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30191330/ · DOI 10.1007/s00726-018-2647-y

evidence_access

Primary abstract

experimental_model

Atrial tissue from cardiac-surgery patients, ex vivo.

limitations

No oral intervention or clinical cardiac benefit established.

nutrient_topic

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

plain_language

A chemical difference translated into protection in sampled heart tissue.

primary_references

Biochemical characterization of the catecholaldehyde reactivity of L-carnosine and its therapeutic potential in human myocardium. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30191330/ · DOI 10.1007/s00726-018-2647-y

Carnosine: synthesis, transport, carbonyl chemistry and nutrient interactions (2026-09-19) · lines 292–298

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Atrial tissue from cardiac-surgery patients, ex vivo. · source_derived_draft · unverified_draft

## carnosine-human-heart-respiration A chemical difference translated into protection in sampled heart tissue. Carnosine pretreatment attenuated DOPAL suppression of ADP-stimulated respiration in permeabilized human atrial fibers; GSH and cysteine did not. Model: Atrial tissue from cardiac-surgery patients, ex vivo. Limitations: No oral intervention or clinical cardiac benefit established. Evidence access: Primary abstract Biochemical characterization of the catecholaldehyde reactivity of L-carnosine and its therapeutic potential in human myocardium. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30191330/ · DOI 10.1007/s00726-018-2647-y

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Neuronal hybrid-cell nutrient-withdrawal experiment.

limitations

The deficient precursor is cystine/cysteine supply, not glutamate; no human dietary threshold is established.

nutrient_topic

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

plain_language

Removing the missing precursor reproduced the supply failure.

primary_references

Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2576375/ · DOI 10.1016/0896-6273(89)90043-3

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 346–352

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Neuronal hybrid-cell nutrient-withdrawal experiment. · source_derived_draft · unverified_draft

## glutamate-cystine-shortage Removing the missing precursor reproduced the supply failure. Lowering culture-medium cystine mimicked glutamate-associated glutathione loss and oxidative cytotoxicity in N18-RE-105 cells. Model: Neuronal hybrid-cell nutrient-withdrawal experiment. Limitations: The deficient precursor is cystine/cysteine supply, not glutamate; no human dietary threshold is established. Evidence access: Primary abstract Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2576375/ · DOI 10.1016/0896-6273(89)90043-3

evidence_access

Primary abstract

experimental_model

Neuroblastoma/primary-retina hybrid-cell culture; transport and toxicity assays.

limitations

The early paper does not genetically resolve SLC7A11; it is not an oral glutamate exposure study.

nutrient_topic

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

plain_language

The same molecule used to build an antioxidant can obstruct another required ingredient when outside these cells.

primary_references

Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2576375/ · DOI 10.1016/0896-6273(89)90043-3

L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 330–336

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Neuroblastoma/primary-retina hybrid-cell culture; transport and toxicity assays. · source_derived_draft · unverified_draft

## glutamate-extracellular-cystine-block The same molecule used to build an antioxidant can obstruct another required ingredient when outside these cells. Added extracellular glutamate inhibited cystine uptake in N18-RE-105 neuronal hybrid cells, and toxicity tracked that inhibition. Model: Neuroblastoma/primary-retina hybrid-cell culture; transport and toxicity assays. Limitations: The early paper does not genetically resolve SLC7A11; it is not an oral glutamate exposure study. Evidence access: Primary abstract Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2576375/ · DOI 10.1016/0896-6273(89)90043-3

evidence_access

Primary abstract

experimental_model

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

limitations

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

nutrient_topic

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

plain_language

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

primary_references

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

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

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

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

evidence_span

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experimental_model

Xanthinuria families with recombinant human MOCOS-domain assays and a plant XDH homolog assay

exposure

PLP quantification, cysteine desulfurase assays and Moco/MPT binding

limitations

Human XDH C150F was functionally modeled using Arabidopsis XDH1 C161S, not purified human C150F; MOCOS assays used isolated domains.

nutrient_topic

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

organism

Human genetics and human MOCOS proteins; plant XDH variant experiment separately

plain_language

Vitamin B6 chemistry helps supply the sulfur used to activate these molybdenum enzymes.

primary_references

[mo-p34356852] Classical Xanthinuria in Nine Israeli Families and Two Isolated Cases from Germany: Molecular, Biochemical and Population Genetics Aspects. (2021). https://pubmed.ncbi.nlm.nih.gov/34356852/ DOI: 10.3390/biomedicines9070788

tissue_or_cell_type

Patient samples and purified domains

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 534–545

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Xanthinuria families with recombinant human MOCOS-domain assays and a plant XDH homolog assay · source_derived_draft · unverified_draft

### mo-mocos-plp The purified human MOCOS NifS-like domain bound PLP and exhibited cysteine desulfurase activity. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin B6 chemistry helps supply the sulfur used to activate these molybdenum enzymes. organism: Human genetics and human MOCOS proteins; plant XDH variant experiment separately tissue_or_cell_type: Patient samples and purified domains experimental_model: Xanthinuria families with recombinant human MOCOS-domain assays and a plant XDH homolog assay limitations: Human XDH C150F was functionally modeled using Arabidopsis XDH1 C161S, not purified human C150F; MOCOS assays used isolated domains. exposure: PLP quantification, cysteine desulfurase assays and Moco/MPT binding evidence_span: {"source_cache": "artifacts/molybdenum-research/34356852.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8bf3a09c4f88994cf8adc50faf391e62ac27e7572e59e6606147f2c689212d07", "start_char": 41304, "end_char": 42029, "text_sha256": "b9b02aae5eb537bdffc178ceaa33177cef6448738c19cb1a8477ad543f4e970c"} [mo-p34356852] Classical Xanthinuria in Nine Israeli Families and Two Isolated Cases from Germany: Molecular, Biochemical and Population Genetics Aspects. (2021). https://pubmed.ncbi.nlm.nih.gov/34356852/ DOI: 10.3390/biomedicines9070788

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Primary murine neurons, chemical reaction assays and tungstate-induced MoCD mice

exposure

SSC/sulfite exposure; receptor/calcium/calpain inhibition

limitations

Mechanistic model evidence. Mouse drug rescue does not establish human treatment efficacy; sulfite also has SSC-independent toxicity.

nutrient_topic

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

organism

Mus musculus neurons and mice; chemical reaction assays

plain_language

The oxidized and reduced forms of cysteine behave differently.

primary_references

[mo-p29106383] S-sulfocysteine/NMDA receptor-dependent signaling underlies neurodegeneration in molybdenum cofactor deficiency. (2017). https://pubmed.ncbi.nlm.nih.gov/29106383/ DOI: 10.1172/jci89885

tissue_or_cell_type

Neuronal receptors, intracellular calcium and inhibitory synapses

trigger_kind

machinery_impairment Imported condition classification; unverified.

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 1236–1247

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary murine neurons, chemical reaction assays and tungstate-induced MoCD mice · source_derived_draft · unverified_draft

### mo-ssc-formation Sulfite reacted stoichiometrically with cystine to form SSC; reduced cysteine did not form SSC in the same assay. Condition category: machinery_impairment nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: The oxidized and reduced forms of cysteine behave differently. organism: Mus musculus neurons and mice; chemical reaction assays tissue_or_cell_type: Neuronal receptors, intracellular calcium and inhibitory synapses experimental_model: Primary murine neurons, chemical reaction assays and tungstate-induced MoCD mice limitations: Mechanistic model evidence. Mouse drug rescue does not establish human treatment efficacy; sulfite also has SSC-independent toxicity. exposure: SSC/sulfite exposure; receptor/calcium/calpain inhibition evidence_span: {"source_cache": "artifacts/molybdenum-research/29106383.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d7cfb311498ba2a88e3fc04be988dcffda740bbd1d93ada686cabf801861cf2a", "start_char": 14310, "end_char": 15490, "text_sha256": "9a181fcee8488d6f7513a0fa1759320721a8663e58658ef9344c1354716e3284"} [mo-p29106383] S-sulfocysteine/NMDA receptor-dependent signaling underlies neurodegeneration in molybdenum cofactor deficiency. (2017). https://pubmed.ncbi.nlm.nih.gov/29106383/ DOI: 10.1172/jci89885

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/molybdenum-research/33271457.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "619710a31160db0927e01193e458277773ebe5e5423629e7dab58888ab6bc617", "start_char": 0, "end_char": 1479, "text_sha256": "619710a31160db0927e01193e458277773ebe5e5423629e7dab58888ab6bc617"}

experimental_model

CRISPR SUOX/GOT1/GOT2 perturbations and sulfur-metabolite assays

exposure

Cysteine-sulfinate and H2S pathway experiments

limitations

Cell-specific contributions; a higher concentration is not a direct measurement of pathway flux.

nutrient_topic

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

organism

Homo sapiens

plain_language

Glutathione and cysteine sulfur chemistry also changed.

primary_references

[mo-p33271457] The role of glutamate oxaloacetate transaminases in sulfite biosynthesis and H₂S metabolism. (2021). https://pubmed.ncbi.nlm.nih.gov/33271457/ DOI: 10.1016/j.redox.2020.101800

tissue_or_cell_type

HEK293T cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 716–727

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CRISPR SUOX/GOT1/GOT2 perturbations and sulfur-metabolite assays · source_derived_draft · unverified_draft

### mo-suox-persulfides SUOX-deficient cells accumulated persulfidated glutathione and cysteine. Condition category: machinery_impairment nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione and cysteine sulfur chemistry also changed. organism: Homo sapiens tissue_or_cell_type: HEK293T cells experimental_model: CRISPR SUOX/GOT1/GOT2 perturbations and sulfur-metabolite assays limitations: Cell-specific contributions; a higher concentration is not a direct measurement of pathway flux. exposure: Cysteine-sulfinate and H2S pathway experiments evidence_span: {"source_cache": "artifacts/molybdenum-research/33271457.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "619710a31160db0927e01193e458277773ebe5e5423629e7dab58888ab6bc617", "start_char": 0, "end_char": 1479, "text_sha256": "619710a31160db0927e01193e458277773ebe5e5423629e7dab58888ab6bc617"} [mo-p33271457] The role of glutamate oxaloacetate transaminases in sulfite biosynthesis and H₂S metabolism. (2021). https://pubmed.ncbi.nlm.nih.gov/33271457/ DOI: 10.1016/j.redox.2020.101800

evidence_span

{"source_cache": "artifacts/iron-research/28634302.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "82faf07d78311d063c1d990ebb922062650054be372fb324fa67020790c9fa04", "start_char": 0, "end_char": 1850, "text_sha256": "82faf07d78311d063c1d990ebb922062650054be372fb324fa67020790c9fa04"}

experimental_model

Crystallography, electron microscopy, kinetics and cell studies

exposure

SDA-complex structural analysis

limitations

Hybrid structural system: bacterial ACP must not be silently labeled human NDUFAB1. Direct dietary B6/B5 effects were not tested.

nutrient_topic

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

organism

Human NFS1/ISD11 with bacterial ACP in the recombinant structural complex

plain_language

Iron needs an assembly system and a sulfur supply before it becomes a working iron-sulfur cofactor.

primary_references

[iron-p28634302] Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions. (2017). https://pubmed.ncbi.nlm.nih.gov/28634302/ DOI: 10.1073/pnas.1702849114

tissue_or_cell_type

Mitochondrial Fe-S assembly machinery

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1161–1172

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystallography, electron microscopy, kinetics and cell studies · source_derived_draft · unverified_draft

### iron-sda-assembly The NFS1–ISD11–ACP core associates with ISCU, frataxin and ferredoxin to support Fe-S cluster biosynthesis. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron needs an assembly system and a sulfur supply before it becomes a working iron-sulfur cofactor. organism: Human NFS1/ISD11 with bacterial ACP in the recombinant structural complex tissue_or_cell_type: Mitochondrial Fe-S assembly machinery experimental_model: Crystallography, electron microscopy, kinetics and cell studies limitations: Hybrid structural system: bacterial ACP must not be silently labeled human NDUFAB1. Direct dietary B6/B5 effects were not tested. exposure: SDA-complex structural analysis evidence_span: {"source_cache": "artifacts/iron-research/28634302.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "82faf07d78311d063c1d990ebb922062650054be372fb324fa67020790c9fa04", "start_char": 0, "end_char": 1850, "text_sha256": "82faf07d78311d063c1d990ebb922062650054be372fb324fa67020790c9fa04"} [iron-p28634302] Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions. (2017). https://pubmed.ncbi.nlm.nih.gov/28634302/ DOI: 10.1073/pnas.1702849114

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human constructs in heterologous functional assays and canine MDCK cells.

limitations

The accessed abstract reports glutamate/cysteine assays; do not mislabel them as direct aspartate uptake measurements.

nutrient_topic

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

plain_language

Having a transporter gene is insufficient if the protein fails to reach the membrane.

primary_references

Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21123949/ · DOI 10.1172/JCI44474

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 42–48

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human constructs in heterologous functional assays and canine MDCK cells. · source_derived_draft · unverified_draft

## l-aspartate-renal-trafficking Having a transporter gene is insufficient if the protein fails to reach the membrane. The disease-associated human SLC1A1 variants showed near-absent cell-surface expression in a canine kidney cell model, with impaired glutamate and cysteine transport in functional assays. Model: Human constructs in heterologous functional assays and canine MDCK cells. Limitations: The accessed abstract reports glutamate/cysteine assays; do not mislabel them as direct aspartate uptake measurements. Evidence access: Primary abstract Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21123949/ · DOI 10.1172/JCI44474

cross_nutrient

false

experimental_model

Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution

exposure

1 mM ATP versus 1 mM CTP, with 1.5 mM phosphopantothenate and 5 mM cysteine; 37°C.

limitations

Reported relative assay efficiency, not a universal kinetic constant; the paper contrasts the stronger CTP preference of E. coli PPCS.

nutrient_topic

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

organism

Homo sapiens

plain_language

Human PPCS favors ATP; bacterial nucleotide preferences should not be substituted for the human result.

primary_references

[b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 535–546

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution · source_derived_draft · unverified_draft

### b5-bio-ppcs-atp-preference Under the reported coupled-assay conditions, human PPCS activated substrate with ATP about four times more efficiently than with CTP. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human PPCS favors ATP; bacterial nucleotide preferences should not be substituted for the human result. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution limitations: Reported relative assay efficiency, not a universal kinetic constant; the paper contrasts the stronger CTP preference of E. coli PPCS. exposure: 1 mM ATP versus 1 mM CTP, with 1.5 mM phosphopantothenate and 5 mM cysteine; 37°C. cross_nutrient: false [b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200

cross_nutrient

true

experimental_model

Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution

exposure

Coupled PPCS assay: 1.5 mM phosphopantothenate, 5 mM cysteine and 1 mM ATP or CTP; 2 mM MgCl2, pH 8.0, 37°C.

limitations

Human enzyme expressed in E. coli; assay substrate supply is not evidence that oral cysteine raises human CoA or that low blood cysteine gates B5 repletion.

nutrient_topic

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

organism

Homo sapiens

plain_language

Cysteine supplies the sulfur-containing portion of the developing CoA molecule.

primary_references

[b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 522–533

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution · source_derived_draft · unverified_draft

### b5-bio-ppcs-ligation Recombinant human PPCS ligated L-cysteine to 4′-phosphopantothenate in a nucleotide-dependent reaction forming 4′-phosphopantothenoylcysteine. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cysteine supplies the sulfur-containing portion of the developing CoA molecule. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution limitations: Human enzyme expressed in E. coli; assay substrate supply is not evidence that oral cysteine raises human CoA or that low blood cysteine gates B5 repletion. exposure: Coupled PPCS assay: 1.5 mM phosphopantothenate, 5 mM cysteine and 1 mM ATP or CTP; 2 mM MgCl2, pH 8.0, 37°C. cross_nutrient: true [b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200

evidence_span

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experimental_model

X-ray crystallography of yeast ADH1 at 2.4 angstrom with site-directed mutagenesis

exposure

Coenzyme-bound closed and open subunit conformations

limitations

A yeast enzyme, used because its asymmetric tetramer captures two catalytic states. The zinc coordination chemistry is conserved, but kinetic numbers are yeast numbers.

nutrient_topic

Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. · Ethanol

organism

Yeast enzyme

plain_language

Three amino acids hold the zinc, and a fourth swings in to hand over the alcohol.

primary_references

[alcohol-p25157460] Yeast alcohol dehydrogenase structure and catalysis. (2014). https://pubmed.ncbi.nlm.nih.gov/25157460/ DOI: 10.1021/bi5006442

tissue_or_cell_type

Purified homotetramer

Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 72–83

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray crystallography of yeast ADH1 at 2.4 angstrom with site-directed mutagenesis · source_derived_draft · unverified_draft

### alcohol-zinc-coordination-chemistry In the closed subunits the catalytic zinc holds the substrate oxygen in classical tetrahedral coordination with Cys-43, Cys-153 and His-66, while in the open subunits the zinc takes an inverted coordination that adds the carboxylate of Glu-67, which may be an intermediate in displacing the zinc-bound water with the alcohol substrate. Condition category: normal nutrient_topic: Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. plain_language: Three amino acids hold the zinc, and a fourth swings in to hand over the alcohol. organism: Yeast enzyme tissue_or_cell_type: Purified homotetramer experimental_model: X-ray crystallography of yeast ADH1 at 2.4 angstrom with site-directed mutagenesis limitations: A yeast enzyme, used because its asymmetric tetramer captures two catalytic states. The zinc coordination chemistry is conserved, but kinetic numbers are yeast numbers. exposure: Coenzyme-bound closed and open subunit conformations evidence_span: {"source_cache": "artifacts/alcohol-research/25157460.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c91a7069c53b4af61096bdc09ce952b0277d63d547a94e5d3870d2980aa31e20", "start_char": 0, "end_char": 1560, "text_sha256": "c91a7069c53b4af61096bdc09ce952b0277d63d547a94e5d3870d2980aa31e20"} [alcohol-p25157460] Yeast alcohol dehydrogenase structure and catalysis. (2014). https://pubmed.ncbi.nlm.nih.gov/25157460/ DOI: 10.1021/bi5006442