Cystine

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

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

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

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

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

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_span

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experimental_model

Human xCT expression and oxidative-stress response

exposure

hxCTb with 4F2hc; diethyl maleate challenge

limitations

Sodium independence belongs to this transporter; other cysteine-entry routes differ.

nutrient_topic

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

organism

Human transporter; Xenopus expression host

plain_language

The precursor-entry route depends on two transporter subunits.

primary_references

[glutathione-p11406111] Human cystine/glutamate transporter: cDNA cloning and upregulation by oxidative stress in glioma cells. (2001). https://pubmed.ncbi.nlm.nih.gov/11406111/ DOI: 10.1016/s0005-2736(01)00338-8

tissue_or_cell_type

Oocyte membranes and human U87 glioma cells

transport_effect

depends The record names the cystine/glutamate exchange pair and the 4F2hc requirement, not which way cystine crossed.

transport_pool

the cytosol across the plasma membrane The record names the cystine/glutamate exchange pair and the 4F2hc requirement, not which way cystine crossed.

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 736–747

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human xCT expression and oxidative-stress response · source_derived_draft · unverified_draft

### glutathione-xct-cystine Human hxCTb required 4F2hc for sodium-independent cystine/glutamate transport in oocytes. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The precursor-entry route depends on two transporter subunits. organism: Human transporter; Xenopus expression host tissue_or_cell_type: Oocyte membranes and human U87 glioma cells experimental_model: Human xCT expression and oxidative-stress response limitations: Sodium independence belongs to this transporter; other cysteine-entry routes differ. exposure: hxCTb with 4F2hc; diethyl maleate challenge evidence_span: {"source_cache": "artifacts/glutathione-research/11406111.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7118afd8c6055ed926ee24dbb7a07538f676163d605115ae0d32d49fbef7fdc", "start_char": 0, "end_char": 1364, "text_sha256": "e7118afd8c6055ed926ee24dbb7a07538f676163d605115ae0d32d49fbef7fdc"} [glutathione-p11406111] Human cystine/glutamate transporter: cDNA cloning and upregulation by oxidative stress in glioma cells. (2001). https://pubmed.ncbi.nlm.nih.gov/11406111/ DOI: 10.1016/s0005-2736(01)00338-8

evidence_span

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experimental_model

Chemotherapy-associated intestinal injury experiment

exposure

Cystine plus theanine during 5-fluorouracil exposure

limitations

Combination product, not isolated theanine. Preservation of antitumor activity in the tested model does not establish compatibility with every human chemotherapy regimen.

nutrient_topic

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

organism

Mice

plain_language

This result belongs to the tested two-ingredient mixture and its chemotherapy context.

primary_references

[theanine-p34922485] Oral administration of cystine and theanine attenuates 5-fluorouracil-induced intestinal mucositis and diarrhea by suppressing both glutathione level decrease and ROS production in the small intestine of mucositis mouse model. (2021). https://pubmed.ncbi.nlm.nih.gov/34922485/ DOI: 10.1186/s12885-021-09057-z

tissue_or_cell_type

Intestinal redox balance and crypt injury

L-Theanine: metabolism, neural signaling, nutrient connections and human outcomes (2026-09-17) · lines 783–794

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemotherapy-associated intestinal injury experiment · source_derived_draft · unverified_draft

### theanine-ct-diarrhea The cystine-theanine mixture reduced diarrhea in the mouse chemotherapy model. Condition category: normal nutrient_topic: L-Theanine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This result belongs to the tested two-ingredient mixture and its chemotherapy context. organism: Mice tissue_or_cell_type: Intestinal redox balance and crypt injury experimental_model: Chemotherapy-associated intestinal injury experiment limitations: Combination product, not isolated theanine. Preservation of antitumor activity in the tested model does not establish compatibility with every human chemotherapy regimen. exposure: Cystine plus theanine during 5-fluorouracil exposure evidence_span: {"source_cache": "artifacts/theanine-research/34922485.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5828410d2c083fec47a3c7e1907b801a2dc616dbbb7e5ed36e59d503bceeb282", "start_char": 0, "end_char": 1703, "text_sha256": "5828410d2c083fec47a3c7e1907b801a2dc616dbbb7e5ed36e59d503bceeb282"} [theanine-p34922485] Oral administration of cystine and theanine attenuates 5-fluorouracil-induced intestinal mucositis and diarrhea by suppressing both glutathione level decrease and ROS production in the small intestine of mucositis mouse model. (2021). https://pubmed.ncbi.nlm.nih.gov/34922485/ DOI: 10.1186/s12885-021-09057-z

evidence_span

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experimental_model

Chemotherapy-associated intestinal injury experiment

exposure

Cystine plus theanine during 5-fluorouracil exposure

limitations

Combination product, not isolated theanine. Preservation of antitumor activity in the tested model does not establish compatibility with every human chemotherapy regimen.

nutrient_topic

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

organism

Mice

plain_language

This result belongs to the tested two-ingredient mixture and its chemotherapy context.

primary_references

[theanine-p34922485] Oral administration of cystine and theanine attenuates 5-fluorouracil-induced intestinal mucositis and diarrhea by suppressing both glutathione level decrease and ROS production in the small intestine of mucositis mouse model. (2021). https://pubmed.ncbi.nlm.nih.gov/34922485/ DOI: 10.1186/s12885-021-09057-z

tissue_or_cell_type

Intestinal redox balance and crypt injury

L-Theanine: metabolism, neural signaling, nutrient connections and human outcomes (2026-09-17) · lines 757–768

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemotherapy-associated intestinal injury experiment · source_derived_draft · unverified_draft

### theanine-ct-redox The cystine-theanine mixture restored the intestinal GSH/GSSG ratio during 5-fluorouracil exposure. Condition category: normal nutrient_topic: L-Theanine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This result belongs to the tested two-ingredient mixture and its chemotherapy context. organism: Mice tissue_or_cell_type: Intestinal redox balance and crypt injury experimental_model: Chemotherapy-associated intestinal injury experiment limitations: Combination product, not isolated theanine. Preservation of antitumor activity in the tested model does not establish compatibility with every human chemotherapy regimen. exposure: Cystine plus theanine during 5-fluorouracil exposure evidence_span: {"source_cache": "artifacts/theanine-research/34922485.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5828410d2c083fec47a3c7e1907b801a2dc616dbbb7e5ed36e59d503bceeb282", "start_char": 0, "end_char": 1703, "text_sha256": "5828410d2c083fec47a3c7e1907b801a2dc616dbbb7e5ed36e59d503bceeb282"} [theanine-p34922485] Oral administration of cystine and theanine attenuates 5-fluorouracil-induced intestinal mucositis and diarrhea by suppressing both glutathione level decrease and ROS production in the small intestine of mucositis mouse model. (2021). https://pubmed.ncbi.nlm.nih.gov/34922485/ DOI: 10.1186/s12885-021-09057-z

evidence_span

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experimental_model

Chemotherapy-associated intestinal injury experiment

exposure

Cystine plus theanine during 5-fluorouracil exposure

limitations

Combination product, not isolated theanine. Preservation of antitumor activity in the tested model does not establish compatibility with every human chemotherapy regimen.

nutrient_topic

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

organism

Mice

plain_language

This result belongs to the tested two-ingredient mixture and its chemotherapy context.

primary_references

[theanine-p34922485] Oral administration of cystine and theanine attenuates 5-fluorouracil-induced intestinal mucositis and diarrhea by suppressing both glutathione level decrease and ROS production in the small intestine of mucositis mouse model. (2021). https://pubmed.ncbi.nlm.nih.gov/34922485/ DOI: 10.1186/s12885-021-09057-z

tissue_or_cell_type

Intestinal redox balance and crypt injury

L-Theanine: metabolism, neural signaling, nutrient connections and human outcomes (2026-09-17) · lines 770–781

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemotherapy-associated intestinal injury experiment · source_derived_draft · unverified_draft

### theanine-ct-ros The cystine-theanine mixture reduced reactive oxygen species in intestinal crypts. Condition category: normal nutrient_topic: L-Theanine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This result belongs to the tested two-ingredient mixture and its chemotherapy context. organism: Mice tissue_or_cell_type: Intestinal redox balance and crypt injury experimental_model: Chemotherapy-associated intestinal injury experiment limitations: Combination product, not isolated theanine. Preservation of antitumor activity in the tested model does not establish compatibility with every human chemotherapy regimen. exposure: Cystine plus theanine during 5-fluorouracil exposure evidence_span: {"source_cache": "artifacts/theanine-research/34922485.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5828410d2c083fec47a3c7e1907b801a2dc616dbbb7e5ed36e59d503bceeb282", "start_char": 0, "end_char": 1703, "text_sha256": "5828410d2c083fec47a3c7e1907b801a2dc616dbbb7e5ed36e59d503bceeb282"} [theanine-p34922485] Oral administration of cystine and theanine attenuates 5-fluorouracil-induced intestinal mucositis and diarrhea by suppressing both glutathione level decrease and ROS production in the small intestine of mucositis mouse model. (2021). https://pubmed.ncbi.nlm.nih.gov/34922485/ DOI: 10.1186/s12885-021-09057-z

evidence_span

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experimental_model

Aged-animal influenza challenge and immunization

exposure

Oral cystine plus theanine before influenza challenge

limitations

Animal combination study; enzyme-subunit identity is not inferred from the generic gamma-glutamylcysteine synthetase wording. No proof theanine alone prevents human influenza.

nutrient_topic

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

organism

Aged mice

plain_language

Precursor supplementation was linked to expression of glutathione-synthesis machinery, not proof of every downstream antioxidant benefit.

primary_references

[theanine-p19940390] Combined administration of (L)-cystine and (L)-theanine enhances immune functions and protects against influenza virus infection in aged mice. (2010). https://pubmed.ncbi.nlm.nih.gov/19940390/ DOI: 10.1292/jvms.09-0067

tissue_or_cell_type

Spleen and lung

L-Theanine: metabolism, neural signaling, nutrient connections and human outcomes (2026-09-17) · lines 796–807

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Aged-animal influenza challenge and immunization · source_derived_draft · unverified_draft

### theanine-ct-splenic-expression Cystine plus theanine increased splenic gamma-glutamylcysteine synthetase mRNA in aged mice. Condition category: normal nutrient_topic: L-Theanine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Precursor supplementation was linked to expression of glutathione-synthesis machinery, not proof of every downstream antioxidant benefit. organism: Aged mice tissue_or_cell_type: Spleen and lung experimental_model: Aged-animal influenza challenge and immunization limitations: Animal combination study; enzyme-subunit identity is not inferred from the generic gamma-glutamylcysteine synthetase wording. No proof theanine alone prevents human influenza. exposure: Oral cystine plus theanine before influenza challenge evidence_span: {"source_cache": "artifacts/theanine-research/19940390.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1fddde12da03a7fd75a7415e00207f4ac2c34c9215ab504ea1b3735e36db3a26", "start_char": 0, "end_char": 1786, "text_sha256": "1fddde12da03a7fd75a7415e00207f4ac2c34c9215ab504ea1b3735e36db3a26"} [theanine-p19940390] Combined administration of (L)-cystine and (L)-theanine enhances immune functions and protects against influenza virus infection in aged mice. (2010). https://pubmed.ncbi.nlm.nih.gov/19940390/ DOI: 10.1292/jvms.09-0067

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 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

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 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 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

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

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

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_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

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

Neuronal hybrid-cell transport, glutathione and peroxide assays.

limitations

A specific experimental toxicity mechanism is retained without inferring normal food-related brain injury.

nutrient_topic

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

plain_language

Oxidative injury arose through precursor supply, a different route from opening an excitatory receptor.

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 338–344

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

## glutamate-extracellular-gsh-loss Oxidative injury arose through precursor supply, a different route from opening an excitatory receptor. Extracellular glutamate exposure lowered glutathione and increased intracellular peroxides in N18-RE-105 cells alongside inhibited cystine uptake. Model: Neuronal hybrid-cell transport, glutathione and peroxide assays. Limitations: A specific experimental toxicity mechanism is retained without inferring normal food-related brain injury. 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

availability_state

machinery_impairment Imported condition classification; unverified.

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"}

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

cross_nutrient

false

evidence_location

Primary indexed abstract, including metabolite-tracing conclusion.

experimental_model

Radiolabeled cystine metabolite-tracing experiment in cultured patient fibroblasts

exposure

Pantethine or cystamine treatment; specific concentration not retrieved from the primary abstract.

limitations

Disease-derived cultured cells; no molecular exporter is assigned without evidence. Formation and efflux of a mixed disulfide do not prove that pantothenate alone treats cystinosis.

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

Export of the new disulfide helped remove the stored cystine.

primary_references

[b5-clin-butler1984] Pantethine and cystamine deplete cystine from cystinotic fibroblasts via efflux of cysteamine-cysteine mixed disulfide. (1984). https://pubmed.ncbi.nlm.nih.gov/6746900/ DOI: 10.1172/jci111436

tissue_or_cell_type

Cystinotic fibroblast lysosomes and extracellular medium

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1509–1521

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabeled cystine metabolite-tracing experiment in cultured patient fibroblasts · source_derived_draft · unverified_draft

### b5-clin-mixed-disulfide-efflux The cysteamine-cysteine mixed disulfide left treated cystinotic fibroblasts, contributing to depletion of accumulated cellular cystine. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Export of the new disulfide helped remove the stored cystine. organism: Homo sapiens tissue_or_cell_type: Cystinotic fibroblast lysosomes and extracellular medium experimental_model: Radiolabeled cystine metabolite-tracing experiment in cultured patient fibroblasts limitations: Disease-derived cultured cells; no molecular exporter is assigned without evidence. Formation and efflux of a mixed disulfide do not prove that pantothenate alone treats cystinosis. exposure: Pantethine or cystamine treatment; specific concentration not retrieved from the primary abstract. cross_nutrient: false evidence_location: Primary indexed abstract, including metabolite-tracing conclusion. [b5-clin-butler1984] Pantethine and cystamine deplete cystine from cystinotic fibroblasts via efflux of cysteamine-cysteine mixed disulfide. (1984). https://pubmed.ncbi.nlm.nih.gov/6746900/ DOI: 10.1172/jci111436

cross_nutrient

false

evidence_location

Primary indexed abstract, including metabolite-tracing conclusion.

experimental_model

Radiolabeled cystine metabolite-tracing experiment in cultured patient fibroblasts

exposure

Pantethine or cystamine treatment; specific concentration not retrieved from the primary abstract.

limitations

Disease-derived cultured cells; no molecular exporter is assigned without evidence. Formation and efflux of a mixed disulfide do not prove that pantothenate alone treats cystinosis.

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

The derivative changed accumulated cystine into a different disulfide product in these patient cells.

primary_references

[b5-clin-butler1984] Pantethine and cystamine deplete cystine from cystinotic fibroblasts via efflux of cysteamine-cysteine mixed disulfide. (1984). https://pubmed.ncbi.nlm.nih.gov/6746900/ DOI: 10.1172/jci111436

tissue_or_cell_type

Cystinotic fibroblast lysosomes and extracellular medium

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1495–1507

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabeled cystine metabolite-tracing experiment in cultured patient fibroblasts · source_derived_draft · unverified_draft

### b5-clin-pantethine-mixed-disulfide Radiolabeled cystine tracing in cystinotic fibroblasts supported formation of cysteamine-cysteine mixed disulfide during pantethine treatment. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The derivative changed accumulated cystine into a different disulfide product in these patient cells. organism: Homo sapiens tissue_or_cell_type: Cystinotic fibroblast lysosomes and extracellular medium experimental_model: Radiolabeled cystine metabolite-tracing experiment in cultured patient fibroblasts limitations: Disease-derived cultured cells; no molecular exporter is assigned without evidence. Formation and efflux of a mixed disulfide do not prove that pantothenate alone treats cystinosis. exposure: Pantethine or cystamine treatment; specific concentration not retrieved from the primary abstract. cross_nutrient: false evidence_location: Primary indexed abstract, including metabolite-tracing conclusion. [b5-clin-butler1984] Pantethine and cystamine deplete cystine from cystinotic fibroblasts via efflux of cysteamine-cysteine mixed disulfide. (1984). https://pubmed.ncbi.nlm.nih.gov/6746900/ DOI: 10.1172/jci111436