Chloride ion

evidence_access

Primary abstract

experimental_model

Human T2 crystallography.

limitations

Binding-site evidence does not establish dietary chloride limitation or clinical repletion effects.

nutrient_topic

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

plain_language

A second ion occupies a structural site in the same enzyme.

primary_references

Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17371050/ · DOI 10.1021/bi6026192

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 242–248

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human T2 crystallography. · source_derived_draft · unverified_draft

## isoleucine-acat1-chloride A second ion occupies a structural site in the same enzyme. Human T2 structures identified a copurified chloride ion at a high-affinity site near catalytic loops at the dimer interface. Model: Human T2 crystallography. Limitations: Binding-site evidence does not establish dietary chloride limitation or clinical repletion effects. Evidence access: Primary abstract Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17371050/ · DOI 10.1021/bi6026192

evidence_access

Primary abstract

experimental_model

Human placental membrane proteoliposomes.

limitations

Alternative anions supported at most 30% of control uptake; this does not define a dietary chloride threshold.

nutrient_topic

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

plain_language

Chloride is part of the transport cycle.

primary_references

Solubilization and functional reconstitution of the human placental taurine transporter. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8431457/ · DOI 10.1016/0005-2736(93)90296-c

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 121–127

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

## taurine-placental-chloride Chloride is part of the transport cycle. Taurine uptake by reconstituted human placental membranes required chloride; chloride kinetics supported one chloride per taurine. Model: Human placental membrane proteoliposomes. Limitations: Alternative anions supported at most 30% of control uptake; this does not define a dietary chloride threshold. Evidence access: Primary abstract Solubilization and functional reconstitution of the human placental taurine transporter. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8431457/ · DOI 10.1016/0005-2736(93)90296-c

evidence_span

{"source_cache": "artifacts/choline-research/11068039.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5", "start_char": 0, "end_char": 1088, "text_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5"}

experimental_model

Human CHT1 expression in Xenopus oocytes

exposure

Choline, sodium and chloride titrations; hemicholinium-3 inhibition

limitations

Assay EC50 values and Hill coefficients are not dietary requirements or exact ion-coupling stoichiometry.

nutrient_topic

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

organism

Human transporter; Xenopus oocyte host

plain_language

Cl− was part of the transport requirement, not just a background nutrient.

primary_references

[choline-p11068039] Functional characterization of the human high-affinity choline transporter. (2000). https://pubmed.ncbi.nlm.nih.gov/11068039/ DOI: 10.1016/s0014-5793(00)02134-7

tissue_or_cell_type

Plasma-membrane transport assay

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 308–319

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CHT1 expression in Xenopus oocytes · source_derived_draft · unverified_draft

### choline-cht1-chloride Human CHT1-mediated choline uptake depended on Cl− in the oocyte assay. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cl− was part of the transport requirement, not just a background nutrient. organism: Human transporter; Xenopus oocyte host tissue_or_cell_type: Plasma-membrane transport assay experimental_model: Human CHT1 expression in Xenopus oocytes limitations: Assay EC50 values and Hill coefficients are not dietary requirements or exact ion-coupling stoichiometry. exposure: Choline, sodium and chloride titrations; hemicholinium-3 inhibition evidence_span: {"source_cache": "artifacts/choline-research/11068039.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5", "start_char": 0, "end_char": 1088, "text_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5"} [choline-p11068039] Functional characterization of the human high-affinity choline transporter. (2000). https://pubmed.ncbi.nlm.nih.gov/11068039/ DOI: 10.1016/s0014-5793(00)02134-7

evidence_span

{"source_cache": "artifacts/chloride-research/15722449.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c71785a489a9e9a0f3865c12c2b66cbf1db4c9e036f08398da846fbb766fbf82", "start_char": 0, "end_char": 1748, "text_sha256": "c71785a489a9e9a0f3865c12c2b66cbf1db4c9e036f08398da846fbb766fbf82"}

experimental_model

Structure and kinetics

exposure

N298S variant with and without chloride

limitations

Variant-focused structural mechanism; not a clinical maldigestion threshold.

nutrient_topic

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

organism

Human pancreatic alpha-amylase variant

plain_language

Chloride directly helps a starch-digesting enzyme function.

primary_references

[chloride-p15722449] Structural and mechanistic studies of chloride induced activation of human pancreatic alpha-amylase. (2005). https://pubmed.ncbi.nlm.nih.gov/15722449/ DOI: 10.1110/ps.041079305

tissue_or_cell_type

Purified digestive enzyme

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 588–599

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

### chloride-amylase-activation Chloride binding increased catalytic rates and altered pH dependence of the human pancreatic amylase variant. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride directly helps a starch-digesting enzyme function. organism: Human pancreatic alpha-amylase variant tissue_or_cell_type: Purified digestive enzyme experimental_model: Structure and kinetics limitations: Variant-focused structural mechanism; not a clinical maldigestion threshold. exposure: N298S variant with and without chloride evidence_span: {"source_cache": "artifacts/chloride-research/15722449.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c71785a489a9e9a0f3865c12c2b66cbf1db4c9e036f08398da846fbb766fbf82", "start_char": 0, "end_char": 1748, "text_sha256": "c71785a489a9e9a0f3865c12c2b66cbf1db4c9e036f08398da846fbb766fbf82"} [chloride-p15722449] Structural and mechanistic studies of chloride induced activation of human pancreatic alpha-amylase. (2005). https://pubmed.ncbi.nlm.nih.gov/15722449/ DOI: 10.1110/ps.041079305

evidence_span

{"source_cache": "artifacts/chloride-research/15722449.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c71785a489a9e9a0f3865c12c2b66cbf1db4c9e036f08398da846fbb766fbf82", "start_char": 0, "end_char": 1748, "text_sha256": "c71785a489a9e9a0f3865c12c2b66cbf1db4c9e036f08398da846fbb766fbf82"}

experimental_model

Structure and kinetics

exposure

N298S variant with and without chloride

limitations

N298S variant evidence; this is not a claim that all alpha-amylases require chloride.

nutrient_topic

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

organism

Human pancreatic alpha-amylase variant

plain_language

The ion helps position catalytic parts of the enzyme.

primary_references

[chloride-p15722449] Structural and mechanistic studies of chloride induced activation of human pancreatic alpha-amylase. (2005). https://pubmed.ncbi.nlm.nih.gov/15722449/ DOI: 10.1110/ps.041079305

tissue_or_cell_type

Purified digestive enzyme

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 601–612

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

### chloride-amylase-geometry Chloride binding influenced E233 positioning and the structural region that orients D300 in pancreatic amylase. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The ion helps position catalytic parts of the enzyme. organism: Human pancreatic alpha-amylase variant tissue_or_cell_type: Purified digestive enzyme experimental_model: Structure and kinetics limitations: N298S variant evidence; this is not a claim that all alpha-amylases require chloride. exposure: N298S variant with and without chloride evidence_span: {"source_cache": "artifacts/chloride-research/15722449.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c71785a489a9e9a0f3865c12c2b66cbf1db4c9e036f08398da846fbb766fbf82", "start_char": 0, "end_char": 1748, "text_sha256": "c71785a489a9e9a0f3865c12c2b66cbf1db4c9e036f08398da846fbb766fbf82"} [chloride-p15722449] Structural and mechanistic studies of chloride induced activation of human pancreatic alpha-amylase. (2005). https://pubmed.ncbi.nlm.nih.gov/15722449/ DOI: 10.1110/ps.041079305

evidence_span

{"source_cache": "artifacts/chloride-research/2012204.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac", "start_char": 0, "end_char": 1695, "text_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac"}

experimental_model

Perfused isolated juxtaglomerular apparatus

exposure

Luminal ion substitutions and 1 µM bumetanide

limitations

Tubular luminal signal; plasma chloride alone does not reproduce it.

nutrient_topic

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

organism

Rabbit

plain_language

The kidney’s salt sensor responded specifically to chloride delivery in this experiment.

primary_references

[chloride-p2012204] Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport. (1991). https://pubmed.ncbi.nlm.nih.gov/2012204/ DOI: 10.1152/ajprenal.1991.260.4.f486

tissue_or_cell_type

Macula densa and renin-secreting apparatus

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 562–573

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Perfused isolated juxtaglomerular apparatus · source_derived_draft · unverified_draft

### chloride-macula-chloride-renin Adding luminal choline chloride or RbCl reduced renin release, whereas the tested sodium salts without chloride did not. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidney’s salt sensor responded specifically to chloride delivery in this experiment. organism: Rabbit tissue_or_cell_type: Macula densa and renin-secreting apparatus experimental_model: Perfused isolated juxtaglomerular apparatus limitations: Tubular luminal signal; plasma chloride alone does not reproduce it. exposure: Luminal ion substitutions and 1 µM bumetanide evidence_span: {"source_cache": "artifacts/chloride-research/2012204.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac", "start_char": 0, "end_char": 1695, "text_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac"} [chloride-p2012204] Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport. (1991). https://pubmed.ncbi.nlm.nih.gov/2012204/ DOI: 10.1152/ajprenal.1991.260.4.f486

evidence_span

{"source_cache": "artifacts/chloride-research/21730057.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ef83bc710cfeb47a0815a2e11c431a5bb16a8927aa81eccc38b774c0dda454af", "start_char": 0, "end_char": 691, "text_sha256": "ef83bc710cfeb47a0815a2e11c431a5bb16a8927aa81eccc38b774c0dda454af"}

experimental_model

Mutagenesis, flux measurements and modeling

exposure

Asn101 substitutions and chloride-coupling assays

limitations

Transporter mechanism; no evidence that dietary chloride changes treat a mood disorder.

nutrient_topic

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

organism

Human SERT

plain_language

Chloride participates in neurotransmitter retrieval as well as in electrical signaling.

primary_references

[chloride-p21730057] A conserved asparagine residue in transmembrane segment 1 (TM1) of serotonin transporter dictates chloride-coupled neurotransmitter transport. (2011). https://pubmed.ncbi.nlm.nih.gov/21730057/ DOI: 10.1074/jbc.m111.250308

tissue_or_cell_type

Expressed membrane transporter

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 445–456

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mutagenesis, flux measurements and modeling · source_derived_draft · unverified_draft

### chloride-sert-chloride-coupling SERT Asn101 experiments linked chloride binding to concentrative serotonin uptake. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride participates in neurotransmitter retrieval as well as in electrical signaling. organism: Human SERT tissue_or_cell_type: Expressed membrane transporter experimental_model: Mutagenesis, flux measurements and modeling limitations: Transporter mechanism; no evidence that dietary chloride changes treat a mood disorder. exposure: Asn101 substitutions and chloride-coupling assays evidence_span: {"source_cache": "artifacts/chloride-research/21730057.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ef83bc710cfeb47a0815a2e11c431a5bb16a8927aa81eccc38b774c0dda454af", "start_char": 0, "end_char": 691, "text_sha256": "ef83bc710cfeb47a0815a2e11c431a5bb16a8927aa81eccc38b774c0dda454af"} [chloride-p21730057] A conserved asparagine residue in transmembrane segment 1 (TM1) of serotonin transporter dictates chloride-coupled neurotransmitter transport. (2011). https://pubmed.ncbi.nlm.nih.gov/21730057/ DOI: 10.1074/jbc.m111.250308

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chloride-research/6823316.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ce2ab2d15d30590a4e4d13e12060fc8656238cea8856a2aad03ed9e2e4dcee4", "start_char": 0, "end_char": 642, "text_sha256": "8ce2ab2d15d30590a4e4d13e12060fc8656238cea8856a2aad03ed9e2e4dcee4"}

experimental_model

Microperfusion of isolated sweat ducts

exposure

Cystic fibrosis versus control

limitations

Predates molecular CFTR identification; does not equate sweat chloride with blood chloride.

nutrient_topic

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

organism

Human controls and cystic fibrosis patients

plain_language

A salty sweat measurement can reflect failure to reclaim salt, not excessive intake.

primary_references

[chloride-p6823316] Chloride impermeability in cystic fibrosis. (1983). https://pubmed.ncbi.nlm.nih.gov/6823316/ DOI: 10.1038/301421a0

tissue_or_cell_type

Sweat duct

trigger_kind

machinery_impairment Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 874–885

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microperfusion of isolated sweat ducts · source_derived_draft · unverified_draft

### chloride-sweat-reabsorption CF sweat ducts showed low chloride permeability and impaired NaCl reabsorption. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A salty sweat measurement can reflect failure to reclaim salt, not excessive intake. organism: Human controls and cystic fibrosis patients tissue_or_cell_type: Sweat duct experimental_model: Microperfusion of isolated sweat ducts limitations: Predates molecular CFTR identification; does not equate sweat chloride with blood chloride. exposure: Cystic fibrosis versus control evidence_span: {"source_cache": "artifacts/chloride-research/6823316.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ce2ab2d15d30590a4e4d13e12060fc8656238cea8856a2aad03ed9e2e4dcee4", "start_char": 0, "end_char": 642, "text_sha256": "8ce2ab2d15d30590a4e4d13e12060fc8656238cea8856a2aad03ed9e2e4dcee4"} [chloride-p6823316] Chloride impermeability in cystic fibrosis. (1983). https://pubmed.ncbi.nlm.nih.gov/6823316/ DOI: 10.1038/301421a0

evidence_span

{"source_cache": "artifacts/chloride-research/24803536.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb", "start_char": 0, "end_char": 1200, "text_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb"}

experimental_model

Crystallography and kinase mutagenesis

exposure

Chloride binding and chloride-pocket mutants

limitations

Cell-free sensing; plasma chloride is not identical to kinase-site chloride.

nutrient_topic

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

organism

Human WNK1 kinase constructs

plain_language

Chloride can act as a direct signal to a kinase, not just as an accompanying ion.

primary_references

[chloride-p24803536] Chloride sensing by WNK1 involves inhibition of autophosphorylation. (2014). https://pubmed.ncbi.nlm.nih.gov/24803536/ DOI: 10.1126/scisignal.2005050

tissue_or_cell_type

Purified kinase domain

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 315–326

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

### chloride-wnk1-binding Chloride bound the WNK1 catalytic region and stabilized its inactive conformation. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride can act as a direct signal to a kinase, not just as an accompanying ion. organism: Human WNK1 kinase constructs tissue_or_cell_type: Purified kinase domain experimental_model: Crystallography and kinase mutagenesis limitations: Cell-free sensing; plasma chloride is not identical to kinase-site chloride. exposure: Chloride binding and chloride-pocket mutants evidence_span: {"source_cache": "artifacts/chloride-research/24803536.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb", "start_char": 0, "end_char": 1200, "text_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb"} [chloride-p24803536] Chloride sensing by WNK1 involves inhibition of autophosphorylation. (2014). https://pubmed.ncbi.nlm.nih.gov/24803536/ DOI: 10.1126/scisignal.2005050

evidence_span

{"source_cache": "artifacts/chloride-research/24803536.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb", "start_char": 0, "end_char": 1200, "text_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb"}

experimental_model

Crystallography and kinase mutagenesis

exposure

Chloride binding and chloride-pocket mutants

limitations

Cell-free sensing; plasma chloride is not identical to kinase-site chloride.

nutrient_topic

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

organism

Human WNK1 kinase constructs

plain_language

When the chloride brake is released, this kinase can activate itself.

primary_references

[chloride-p24803536] Chloride sensing by WNK1 involves inhibition of autophosphorylation. (2014). https://pubmed.ncbi.nlm.nih.gov/24803536/ DOI: 10.1126/scisignal.2005050

tissue_or_cell_type

Purified kinase domain

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 328–339

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

### chloride-wnk1-inhibition Chloride inhibited WNK1 autophosphorylation; binding-site mutations reduced this inhibition. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: When the chloride brake is released, this kinase can activate itself. organism: Human WNK1 kinase constructs tissue_or_cell_type: Purified kinase domain experimental_model: Crystallography and kinase mutagenesis limitations: Cell-free sensing; plasma chloride is not identical to kinase-site chloride. exposure: Chloride binding and chloride-pocket mutants evidence_span: {"source_cache": "artifacts/chloride-research/24803536.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb", "start_char": 0, "end_char": 1200, "text_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb"} [chloride-p24803536] Chloride sensing by WNK1 involves inhibition of autophosphorylation. (2014). https://pubmed.ncbi.nlm.nih.gov/24803536/ DOI: 10.1126/scisignal.2005050

evidence_span

{"source_cache": "artifacts/chloride-research/33689398.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9", "start_char": 0, "end_char": 1308, "text_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9"}

experimental_model

Biochemistry and structural measurements

exposure

PEG400 or ethylene glycol osmotic challenge

limitations

Artificial osmolytes; supports additional regulation, not a universal chloride-only switch.

nutrient_topic

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

organism

Human WNK1 and WNK3 constructs

plain_language

Water balance and chloride jointly influence the kinase.

primary_references

[chloride-p33689398] Osmosensing by WNK Kinases. (2021). https://pubmed.ncbi.nlm.nih.gov/33689398/ DOI: 10.1091/mbc.e20-01-0089

tissue_or_cell_type

Purified kinase domains

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 341–352

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

### chloride-wnk1-osmotic Chloride opposed osmolyte-stimulated WNK1 autophosphorylation. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Water balance and chloride jointly influence the kinase. organism: Human WNK1 and WNK3 constructs tissue_or_cell_type: Purified kinase domains experimental_model: Biochemistry and structural measurements limitations: Artificial osmolytes; supports additional regulation, not a universal chloride-only switch. exposure: PEG400 or ethylene glycol osmotic challenge evidence_span: {"source_cache": "artifacts/chloride-research/33689398.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9", "start_char": 0, "end_char": 1308, "text_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9"} [chloride-p33689398] Osmosensing by WNK Kinases. (2021). https://pubmed.ncbi.nlm.nih.gov/33689398/ DOI: 10.1091/mbc.e20-01-0089

evidence_span

{"source_cache": "artifacts/chloride-research/33689398.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9", "start_char": 0, "end_char": 1308, "text_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9"}

experimental_model

Biochemistry and structural measurements

exposure

PEG400 or ethylene glycol osmotic challenge

limitations

Artificial osmolytes; supports additional regulation, not a universal chloride-only switch.

nutrient_topic

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

organism

Human WNK1 and WNK3 constructs

plain_language

Related kinases can share this regulation while remaining separate proteins.

primary_references

[chloride-p33689398] Osmosensing by WNK Kinases. (2021). https://pubmed.ncbi.nlm.nih.gov/33689398/ DOI: 10.1091/mbc.e20-01-0089

tissue_or_cell_type

Purified kinase domains

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 354–365

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

### chloride-wnk3-osmotic Chloride also opposed osmolyte-stimulated WNK3 autophosphorylation. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Related kinases can share this regulation while remaining separate proteins. organism: Human WNK1 and WNK3 constructs tissue_or_cell_type: Purified kinase domains experimental_model: Biochemistry and structural measurements limitations: Artificial osmolytes; supports additional regulation, not a universal chloride-only switch. exposure: PEG400 or ethylene glycol osmotic challenge evidence_span: {"source_cache": "artifacts/chloride-research/33689398.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9", "start_char": 0, "end_char": 1308, "text_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9"} [chloride-p33689398] Osmosensing by WNK Kinases. (2021). https://pubmed.ncbi.nlm.nih.gov/33689398/ DOI: 10.1091/mbc.e20-01-0089

evidence_access

Primary abstract

experimental_model

Rat immune-cell ion substitution and antagonist experiments.

limitations

Pharmacology does not uniquely identify a receptor-subunit combination; high-dose strychnine behaved differently.

nutrient_topic

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

plain_language

The ionic environment was required for the observed response.

primary_references

Kupffer cells contain a glycine-gated chloride channel. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9227496/ · DOI 10.1152/ajpgi.1997.272.6.G1581

Glycine: supply, one-carbon allocation, receptors 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 · Rat immune-cell ion substitution and antagonist experiments. · source_derived_draft · unverified_draft

## glycine-kupffer-chloride-dependence The ionic environment was required for the observed response. Chloride-free buffer abolished the reported glycine effect, and 1 micromolar strychnine reversed it; glycine hyperpolarized the tested Kupffer cells. Model: Rat immune-cell ion substitution and antagonist experiments. Limitations: Pharmacology does not uniquely identify a receptor-subunit combination; high-dose strychnine behaved differently. Evidence access: Primary abstract Kupffer cells contain a glycine-gated chloride channel. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9227496/ · DOI 10.1152/ajpgi.1997.272.6.G1581

cross_nutrient

Chloride concentration gates a kinase linking K sensing to Na transport.

evidence_location

Figure 3; equimolar chloride/gluconate kinase assay.

experimental_model

Purified kinase domains; SPAK substrate

limitations

Does not directly measure native DCT chloride or WNK4 autophosphorylation.

nutrient_topic

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

organism

Recombinant proteins

plain_language

Chloride restrains WNK4, a kinase upstream of sodium-chloride transport.

primary_references

[terker-2016-wnk4-chloride] Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4814375/ DOI: 10.1038/ki.2015.289

tissue_or_cell_type

Cell-free assay

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 138–149

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified kinase domains; SPAK substrate · source_derived_draft · unverified_draft

### renal-chloride-inhibits-wnk4 Increasing chloride inhibited recombinant WNK4 phosphorylation of SPAK more strongly than WNK1/3 in matched assays. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride restrains WNK4, a kinase upstream of sodium-chloride transport. organism: Recombinant proteins tissue_or_cell_type: Cell-free assay experimental_model: Purified kinase domains; SPAK substrate limitations: Does not directly measure native DCT chloride or WNK4 autophosphorylation. cross_nutrient: Chloride concentration gates a kinase linking K sensing to Na transport. evidence_location: Figure 3; equimolar chloride/gluconate kinase assay. [terker-2016-wnk4-chloride] Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4814375/ DOI: 10.1038/ki.2015.289

experimental_model

Purified LPO transient kinetics; pH 7, 15 °C; preparation species unresolved in abstract.

exposure_category

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

limitations

Purified enzyme kinetics; concentrations, substrate competition and reaction order determine relevance in tissues.

nutrient_topic

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

plain_language

Abundant chloride cannot simply replace iodide in this enzyme reaction.

primary_references

Reaction of lactoperoxidase compound I with halides and thiocyanate. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12269834/ · DOI 10.1021/bi026326x

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 208–214

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Purified LPO transient kinetics; pH 7, 15 °C; preparation species unresolved in abstract. · source_derived_draft · unverified_draft

## ki-lpo-halides Abundant chloride cannot simply replace iodide in this enzyme reaction. Chloride did not act as electron donor; bromide reacted much more slowly, at (4.1 ± 0.1) × 10^4 M−1 s−1. Model: Purified LPO transient kinetics; pH 7, 15 °C; preparation species unresolved in abstract. Limitations: Purified enzyme kinetics; concentrations, substrate competition and reaction order determine relevance in tissues. Evidence location: Primary abstract Reaction of lactoperoxidase compound I with halides and thiocyanate. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12269834/ · DOI 10.1021/bi026326x

evidence_access

Primary full text

experimental_model

Rat VGLUT2 expressed in insect cells, purified and reconstituted; membrane-potential-driven uptake.

limitations

Chloride regulation in vesicles is not equivalent to an effect of dietary salt.

nutrient_topic

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

plain_language

An ion regulates whether the vesicle-loading transporter works.

primary_references

Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002

L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 274–280

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat VGLUT2 expressed in insect cells, purified and reconstituted; membrane-potential-driven uptake. · source_derived_draft · unverified_draft

## glutamate-vglut2-chloride An ion regulates whether the vesicle-loading transporter works. Chloride activated glutamate uptake by purified rat VGLUT2 in reconstituted proteoliposomes. Model: Rat VGLUT2 expressed in insect cells, purified and reconstituted; membrane-potential-driven uptake. Limitations: Chloride regulation in vesicles is not equivalent to an effect of dietary salt. Evidence access: Primary full text Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002

evidence_access

Primary full text

experimental_model

Human VGLUT3 expressed in insect cells and reconstituted separately from rat VGLUT2.

limitations

Isoforms and species are kept distinct; no nutritional chloride threshold was tested.

nutrient_topic

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

plain_language

A human transporter isoform shares a tested regulatory input.

primary_references

Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002

L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 290–296

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human VGLUT3 expressed in insect cells and reconstituted separately from rat VGLUT2. · source_derived_draft · unverified_draft

## glutamate-vglut3-chloride A human transporter isoform shares a tested regulatory input. Purified human VGLUT3 also showed chloride-dependent glutamate transport in reconstituted vesicles. Model: Human VGLUT3 expressed in insect cells and reconstituted separately from rat VGLUT2. Limitations: Isoforms and species are kept distinct; no nutritional chloride threshold was tested. Evidence access: Primary full text Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002

evidence_span

{"source_cache": "artifacts/chloride-research/1712984.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d35ab648c3b60da00912ec5a2921115c14aa33b138ed2aa408e66d5153aa9d3b", "start_char": 0, "end_char": 849, "text_sha256": "d35ab648c3b60da00912ec5a2921115c14aa33b138ed2aa408e66d5153aa9d3b"}

experimental_model

CFTR expression and pore-residue mutagenesis

exposure

K95 or K335 substitutions

limitations

Selectivity experiment; not a supplementation study.

nutrient_topic

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

organism

Human CFTR in expression systems

plain_language

CFTR provides a route through which chloride can cross a membrane.

primary_references

[chloride-p1712984] Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. (1991). https://pubmed.ncbi.nlm.nih.gov/1712984/ DOI: 10.1126/science.1712984

tissue_or_cell_type

Cell plasma membrane

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 224–235

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CFTR expression and pore-residue mutagenesis · source_derived_draft · unverified_draft

### chloride-cftr-channel CFTR pore-region mutations changed anion selectivity, demonstrating that CFTR forms an anion channel. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: CFTR provides a route through which chloride can cross a membrane. organism: Human CFTR in expression systems tissue_or_cell_type: Cell plasma membrane experimental_model: CFTR expression and pore-residue mutagenesis limitations: Selectivity experiment; not a supplementation study. exposure: K95 or K335 substitutions evidence_span: {"source_cache": "artifacts/chloride-research/1712984.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d35ab648c3b60da00912ec5a2921115c14aa33b138ed2aa408e66d5153aa9d3b", "start_char": 0, "end_char": 849, "text_sha256": "d35ab648c3b60da00912ec5a2921115c14aa33b138ed2aa408e66d5153aa9d3b"} [chloride-p1712984] Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. (1991). https://pubmed.ncbi.nlm.nih.gov/1712984/ DOI: 10.1126/science.1712984

evidence_span

{"source_cache": "artifacts/chloride-research/19131966.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04e75eb135b2ed1c3a14a69b20f602132fc4a55cc0e1d3f6a11ee2834692a79e", "start_char": 0, "end_char": 1161, "text_sha256": "04e75eb135b2ed1c3a14a69b20f602132fc4a55cc0e1d3f6a11ee2834692a79e"}

experimental_model

Absolute proton-flux imaging

exposure

Proton gradients and S168 substitutions

limitations

Assay stoichiometry, not dietary requirements.

nutrient_topic

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

organism

Mammalian ClC-5 in Xenopus oocytes

plain_language

This protein couples chloride transport to proton movement at a measured ratio.

primary_references

[chloride-p19131966] Conversion of the 2 Cl(-)/1 H+ antiporter ClC-5 in a NO3(-)/H+ antiporter by a single point mutation. (2009). https://pubmed.ncbi.nlm.nih.gov/19131966/ DOI: 10.1038/emboj.2008.284

tissue_or_cell_type

Expressed plasma membrane

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 666–677

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Absolute proton-flux imaging · source_derived_draft · unverified_draft

### chloride-clc5-stoichiometry Measured ClC-5 transport stoichiometry was two chloride ions per proton. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: This protein couples chloride transport to proton movement at a measured ratio. organism: Mammalian ClC-5 in Xenopus oocytes tissue_or_cell_type: Expressed plasma membrane experimental_model: Absolute proton-flux imaging limitations: Assay stoichiometry, not dietary requirements. exposure: Proton gradients and S168 substitutions evidence_span: {"source_cache": "artifacts/chloride-research/19131966.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04e75eb135b2ed1c3a14a69b20f602132fc4a55cc0e1d3f6a11ee2834692a79e", "start_char": 0, "end_char": 1161, "text_sha256": "04e75eb135b2ed1c3a14a69b20f602132fc4a55cc0e1d3f6a11ee2834692a79e"} [chloride-p19131966] Conversion of the 2 Cl(-)/1 H+ antiporter ClC-5 in a NO3(-)/H+ antiporter by a single point mutation. (2009). https://pubmed.ncbi.nlm.nih.gov/19131966/ DOI: 10.1038/emboj.2008.284

evidence_span

{"source_cache": "artifacts/chloride-research/21527911.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1a83cfa67615e467858b2a56c2e6b6e1ae8414a28c553b8a645d7789987f53c5", "start_char": 0, "end_char": 1081, "text_sha256": "1a83cfa67615e467858b2a56c2e6b6e1ae8414a28c553b8a645d7789987f53c5"}

experimental_model

Electrophysiology of plasma-membrane-targeted constructs

exposure

ClC-7 sorting-motif mutations and Ostm1 constructs

limitations

Engineering enabled measurement outside lysosomes. Species checked in author manuscript https://edoc.mdc-berlin.de/id/eprint/11621/1/11621oa.pdf, Results; native direction depends on gradients.

nutrient_topic

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

organism

Human and rat ClC-7; Xenopus oocytes and mammalian cells

plain_language

The bone-related chloride transporter is a coupled exchanger, not a simple chloride pore.

primary_references

[chloride-p21527911] ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1 for transport activity. (2011). https://pubmed.ncbi.nlm.nih.gov/21527911/ DOI: 10.1038/emboj.2011.137

tissue_or_cell_type

Engineered plasma membrane

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 744–755

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Electrophysiology of plasma-membrane-targeted constructs · source_derived_draft · unverified_draft

### chloride-clc7-stoichiometry Tail-current reversal potentials supported two chloride ions exchanged per proton by ClC-7/Ostm1. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The bone-related chloride transporter is a coupled exchanger, not a simple chloride pore. organism: Human and rat ClC-7; Xenopus oocytes and mammalian cells tissue_or_cell_type: Engineered plasma membrane experimental_model: Electrophysiology of plasma-membrane-targeted constructs limitations: Engineering enabled measurement outside lysosomes. Species checked in author manuscript https://edoc.mdc-berlin.de/id/eprint/11621/1/11621oa.pdf, Results; native direction depends on gradients. exposure: ClC-7 sorting-motif mutations and Ostm1 constructs evidence_span: {"source_cache": "artifacts/chloride-research/21527911.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1a83cfa67615e467858b2a56c2e6b6e1ae8414a28c553b8a645d7789987f53c5", "start_char": 0, "end_char": 1081, "text_sha256": "1a83cfa67615e467858b2a56c2e6b6e1ae8414a28c553b8a645d7789987f53c5"} [chloride-p21527911] ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1 for transport activity. (2011). https://pubmed.ncbi.nlm.nih.gov/21527911/ DOI: 10.1038/emboj.2011.137

evidence_span

{"source_cache": "artifacts/chloride-research/9930699.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6", "start_char": 0, "end_char": 1181, "text_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6"}

experimental_model

Developmental expression and antisense suppression

exposure

KCC2 expression during maturation; antisense inhibition

limitations

Neuronal gradient mechanism; dietary chloride restriction is not the intervention.

nutrient_topic

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

organism

Rat

plain_language

Potassium-coupled chloride removal helps mature neurons respond to GABA with inhibition.

primary_references

[chloride-p9930699] The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. (1999). https://pubmed.ncbi.nlm.nih.gov/9930699/ DOI: 10.1038/16697

tissue_or_cell_type

Hippocampal pyramidal neurons

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 393–404

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Developmental expression and antisense suppression · source_derived_draft · unverified_draft

### chloride-kcc2-cl-extrusion Developmental KCC2 expression accompanied the shift toward hyperpolarizing GABA-A responses. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium-coupled chloride removal helps mature neurons respond to GABA with inhibition. organism: Rat tissue_or_cell_type: Hippocampal pyramidal neurons experimental_model: Developmental expression and antisense suppression limitations: Neuronal gradient mechanism; dietary chloride restriction is not the intervention. exposure: KCC2 expression during maturation; antisense inhibition evidence_span: {"source_cache": "artifacts/chloride-research/9930699.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6", "start_char": 0, "end_char": 1181, "text_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6"} [chloride-p9930699] The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. (1999). https://pubmed.ncbi.nlm.nih.gov/9930699/ DOI: 10.1038/16697

evidence_span

{"source_cache": "artifacts/chloride-research/9359420.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0", "start_char": 0, "end_char": 1700, "text_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0"}

experimental_model

Purified-enzyme substrate kinetics

exposure

100 mM chloride with varying thiocyanate

limitations

Product chemistry under assay conditions; not a recommendation to raise chloride or thiocyanate intake.

nutrient_topic

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

organism

Human neutrophil enzyme

plain_language

An abundant chloride pool does not mean it is the enzyme’s only substrate.

primary_references

[chloride-p9359420] Thiocyanate and chloride as competing substrates for myeloperoxidase. (1997). https://pubmed.ncbi.nlm.nih.gov/9359420/ DOI: 10.1042/bj3270487

tissue_or_cell_type

Myeloperoxidase reaction mixture

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 627–638

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

### chloride-mpo-thiocyanate Myeloperoxidase favored thiocyanate kinetically and generated hypothiocyanite despite 100 mM chloride. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: An abundant chloride pool does not mean it is the enzyme’s only substrate. organism: Human neutrophil enzyme tissue_or_cell_type: Myeloperoxidase reaction mixture experimental_model: Purified-enzyme substrate kinetics limitations: Product chemistry under assay conditions; not a recommendation to raise chloride or thiocyanate intake. exposure: 100 mM chloride with varying thiocyanate evidence_span: {"source_cache": "artifacts/chloride-research/9359420.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0", "start_char": 0, "end_char": 1700, "text_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0"} [chloride-p9359420] Thiocyanate and chloride as competing substrates for myeloperoxidase. (1997). https://pubmed.ncbi.nlm.nih.gov/9359420/ DOI: 10.1042/bj3270487

evidence_span

{"source_cache": "artifacts/berberine-research/21747769.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4", "start_char": 0, "end_char": 1734, "text_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4"}

experimental_model

Ussing-chamber short-circuit current, patch clamp and kinase perturbation

exposure

Forskolin-stimulated secretion and berberine; IC50 about 80 micromolar

limitations

Intestinal cell mechanism, not proof of systemic potassium depletion. The observed channel complex differs from cardiac KCNQ1/KCNE1.

nutrient_topic

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

organism

Human T84 colonic cells

plain_language

Lower total chloride secretion did not require directly blocking the apical chloride conductance.

primary_references

[berberine-p21747769] Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels. (2011). https://pubmed.ncbi.nlm.nih.gov/21747769/ DOI: 10.3389/fphys.2011.00033

tissue_or_cell_type

Basolateral potassium recycling and chloride secretion

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 584–595

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ussing-chamber short-circuit current, patch clamp and kinase perturbation · source_derived_draft · unverified_draft

### berberine-apical-chloride-null Berberine did not affect apical chloride conductance in the permeabilized-cell experiments. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lower total chloride secretion did not require directly blocking the apical chloride conductance. organism: Human T84 colonic cells tissue_or_cell_type: Basolateral potassium recycling and chloride secretion experimental_model: Ussing-chamber short-circuit current, patch clamp and kinase perturbation limitations: Intestinal cell mechanism, not proof of systemic potassium depletion. The observed channel complex differs from cardiac KCNQ1/KCNE1. exposure: Forskolin-stimulated secretion and berberine; IC50 about 80 micromolar evidence_span: {"source_cache": "artifacts/berberine-research/21747769.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4", "start_char": 0, "end_char": 1734, "text_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4"} [berberine-p21747769] Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels. (2011). https://pubmed.ncbi.nlm.nih.gov/21747769/ DOI: 10.3389/fphys.2011.00033

cross_nutrient

true

experimental_model

Human pendrin expressed in Xenopus oocytes and Sf9 insect cells

exposure

PDS cRNA microinjection or recombinant baculovirus expression; concentrations not provided in abstract.

limitations

This demonstrates shared anion transport capability, not that dietary chloride deficiency blocks iodine repletion.

nutrient_topic

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

organism

Human protein in Xenopus laevis and Spodoptera frugiperda cells

plain_language

Pendrin handles chloride as well as iodide.

primary_references

[iodine-trans-pendrin-halides1999] The Pendred syndrome gene encodes a chloride-iodide transport protein. (1999). https://pubmed.ncbi.nlm.nih.gov/10192399/ DOI: 10.1038/7783

tissue_or_cell_type

Heterologous cell membranes

transport_effect

depends Pendrin is an anion exchanger and the record reports increased transport without naming its direction.

transport_pool

the cytosol across the plasma membrane Pendrin is an anion exchanger and the record reports increased transport without naming its direction.

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 310–321

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human pendrin expressed in Xenopus oocytes and Sf9 insect cells · source_derived_draft · unverified_draft

### iodine-trans-pendrin-chloride Expression of human pendrin increased chloride transport in Xenopus oocytes and Sf9 cells, alongside increased iodide transport. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Pendrin handles chloride as well as iodide. organism: Human protein in Xenopus laevis and Spodoptera frugiperda cells tissue_or_cell_type: Heterologous cell membranes experimental_model: Human pendrin expressed in Xenopus oocytes and Sf9 insect cells limitations: This demonstrates shared anion transport capability, not that dietary chloride deficiency blocks iodine repletion. exposure: PDS cRNA microinjection or recombinant baculovirus expression; concentrations not provided in abstract. cross_nutrient: true [iodine-trans-pendrin-halides1999] The Pendred syndrome gene encodes a chloride-iodide transport protein. (1999). https://pubmed.ncbi.nlm.nih.gov/10192399/ DOI: 10.1038/7783

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human transporter expressed in Xenopus oocytes.

limitations

Assay currents do not by themselves define a clinical electrolyte threshold or a universal coupling ratio for every substrate.

nutrient_topic

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

plain_language

Sodium dependence is different from chloride being a transported substrate.

primary_references

The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15090606/ · DOI 10.1113/jphysiol.2004.063859

trigger_kind

machinery_impairment Imported condition classification; unverified.

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 110–116

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human transporter expressed in Xenopus oocytes. · source_derived_draft · unverified_draft

## butyrate-smct1-sodium-loss Sodium dependence is different from chloride being a transported substrate. Human SMCT/SLC5A8 transport-associated currents depended on external sodium; chloride influenced part of the current but was not cotransported. Model: Human transporter expressed in Xenopus oocytes. Limitations: Assay currents do not by themselves define a clinical electrolyte threshold or a universal coupling ratio for every substrate. Evidence access: Primary abstract The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15090606/ · DOI 10.1113/jphysiol.2004.063859

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sodium-research/8096428.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7f7a7712c9e952343e279ae89e0d1051857c4188820819def597a430fdaf9e4c", "start_char": 0, "end_char": 1587, "text_sha256": "7f7a7712c9e952343e279ae89e0d1051857c4188820819def597a430fdaf9e4c"}

experimental_model

Sustained dDAVP-induced hyponatremia followed by withdrawal and tissue measurements

exposure

14 days hyponatremia; sodium rose from 104 to 139 mmol/L over 24 hours after withdrawal

limitations

Extreme experimental correction; records tissue reaccumulation, not a safe human correction rate or direct proof of myelin injury in this study.

nutrient_topic

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

organism

Rat

plain_language

The brain’s electrolyte content changed quickly after blood sodium rose.

primary_references

[sodium-p8096428] Rapid correction of hyponatremia produces differential effects on brain osmolyte and electrolyte reaccumulation in rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8096428/ DOI: 10.1016/0006-8993(93)91564-9

tissue_or_cell_type

Brain water, electrolytes and organic osmolytes

trigger_kind

biomarker_context Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 1019–1030

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sustained dDAVP-induced hyponatremia followed by withdrawal and tissue measurements · source_derived_draft · unverified_draft

### sodium-brain-electrolytes Brain sodium and chloride overshot normal control contents by 24 hours after rapid correction. Condition category: biomarker_context nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The brain’s electrolyte content changed quickly after blood sodium rose. organism: Rat tissue_or_cell_type: Brain water, electrolytes and organic osmolytes experimental_model: Sustained dDAVP-induced hyponatremia followed by withdrawal and tissue measurements limitations: Extreme experimental correction; records tissue reaccumulation, not a safe human correction rate or direct proof of myelin injury in this study. exposure: 14 days hyponatremia; sodium rose from 104 to 139 mmol/L over 24 hours after withdrawal evidence_span: {"source_cache": "artifacts/sodium-research/8096428.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7f7a7712c9e952343e279ae89e0d1051857c4188820819def597a430fdaf9e4c", "start_char": 0, "end_char": 1587, "text_sha256": "7f7a7712c9e952343e279ae89e0d1051857c4188820819def597a430fdaf9e4c"} [sodium-p8096428] Rapid correction of hyponatremia produces differential effects on brain osmolyte and electrolyte reaccumulation in rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8096428/ DOI: 10.1016/0006-8993(93)91564-9

evidence_span

{"source_cache": "artifacts/sodium-research/23467095.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d16bb4b4becde85238492e01054f360aeaf57ea90015cba99459cd155fa4251f", "start_char": 0, "end_char": 1913, "text_sha256": "d16bb4b4becde85238492e01054f360aeaf57ea90015cba99459cd155fa4251f"}

experimental_model

Cytokine-driven T-cell culture, gene silencing/inhibition and experimental autoimmune encephalomyelitis

exposure

Increased NaCl in culture or high-salt mouse diet

limitations

NaCl exposure includes both ions and osmotic context. Mouse EAE and cultured T cells do not establish that salt causes human multiple sclerosis.

nutrient_topic

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

organism

Human and mouse T cells; mouse disease model

plain_language

Salt conditions can change immune-cell differentiation in an experimental setting.

primary_references

[sodium-p23467095] Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23467095/ DOI: 10.1038/nature11868

tissue_or_cell_type

T-helper cells and experimental CNS autoimmunity

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 486–497

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cytokine-driven T-cell culture, gene silencing/inhibition and experimental autoimmune encephalomyelitis · source_derived_draft · unverified_draft

### sodium-salt-th17 Increased NaCl enhanced cytokine-induced TH17 differentiation in human and mouse T-cell cultures. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Salt conditions can change immune-cell differentiation in an experimental setting. organism: Human and mouse T cells; mouse disease model tissue_or_cell_type: T-helper cells and experimental CNS autoimmunity experimental_model: Cytokine-driven T-cell culture, gene silencing/inhibition and experimental autoimmune encephalomyelitis limitations: NaCl exposure includes both ions and osmotic context. Mouse EAE and cultured T cells do not establish that salt causes human multiple sclerosis. exposure: Increased NaCl in culture or high-salt mouse diet evidence_span: {"source_cache": "artifacts/sodium-research/23467095.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d16bb4b4becde85238492e01054f360aeaf57ea90015cba99459cd155fa4251f", "start_char": 0, "end_char": 1913, "text_sha256": "d16bb4b4becde85238492e01054f360aeaf57ea90015cba99459cd155fa4251f"} [sodium-p23467095] Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23467095/ DOI: 10.1038/nature11868

evidence_access

Primary abstract

experimental_model

Mouse ventrobasal thalamic neurons and recombinant receptor comparisons.

limitations

Bath concentration is not an oral dose; this does not establish treatment of human anxiety or insomnia.

nutrient_topic

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

plain_language

A low concentration changed neuronal firing in this mouse brain region.

primary_references

Taurine is a potent activator of extrasynaptic GABA(A) receptors in the thalamus. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18171928/ · DOI 10.1523/JNEUROSCI.3996-07.2008

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 433–439

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse ventrobasal thalamic neurons and recombinant receptor comparisons. · source_derived_draft · unverified_draft

## taurine-gabaa-tonic A low concentration changed neuronal firing in this mouse brain region. Taurine at 10–100 micromolar reduced excitability of mouse thalamocortical neurons and evoked tonic currents consistent with extrasynaptic alpha4beta2delta GABA-A receptors. Model: Mouse ventrobasal thalamic neurons and recombinant receptor comparisons. Limitations: Bath concentration is not an oral dose; this does not establish treatment of human anxiety or insomnia. Evidence access: Primary abstract Taurine is a potent activator of extrasynaptic GABA(A) receptors in the thalamus. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18171928/ · DOI 10.1523/JNEUROSCI.3996-07.2008

evidence_access

Primary abstract

experimental_model

Human receptor expressed in Xenopus oocytes or human cells; electrophysiology.

limitations

Not a clinical sedative effect; chloride gradient and receptor composition shape cellular response.

nutrient_topic

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

plain_language

Taurine can activate a receptor named for glycine.

primary_references

Activation of human alpha1 and alpha2 homomeric glycine receptors by taurine and GABA. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11559772/ · DOI 10.1111/j.1469-7793.2001.t01-1-00741.x

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 417–423

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human receptor expressed in Xenopus oocytes or human cells; electrophysiology. · source_derived_draft · unverified_draft

## taurine-glycine-receptor-alpha1 Taurine can activate a receptor named for glycine. Applied taurine activated recombinant human alpha1 homomeric glycine receptors in oocytes and HEK293 cells; its potency and efficacy varied with the experimental receptor response. Model: Human receptor expressed in Xenopus oocytes or human cells; electrophysiology. Limitations: Not a clinical sedative effect; chloride gradient and receptor composition shape cellular response. Evidence access: Primary abstract Activation of human alpha1 and alpha2 homomeric glycine receptors by taurine and GABA. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11559772/ · DOI 10.1111/j.1469-7793.2001.t01-1-00741.x

evidence_access

Primary abstract

experimental_model

Recombinant human alpha2 receptor electrophysiology.

limitations

Avoid labeling taurine a universally weak or full agonist.

nutrient_topic

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

plain_language

The receptor subtype and cell setting change the strength of taurine signaling.

primary_references

Activation of human alpha1 and alpha2 homomeric glycine receptors by taurine and GABA. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11559772/ · DOI 10.1111/j.1469-7793.2001.t01-1-00741.x

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 425–431

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human alpha2 receptor electrophysiology. · source_derived_draft · unverified_draft

## taurine-glycine-receptor-alpha2 The receptor subtype and cell setting change the strength of taurine signaling. Applied taurine also activated human alpha2 homomeric glycine receptors, with efficacy varying from weak to full agonism across tested conditions. Model: Recombinant human alpha2 receptor electrophysiology. Limitations: Avoid labeling taurine a universally weak or full agonist. Evidence access: Primary abstract Activation of human alpha1 and alpha2 homomeric glycine receptors by taurine and GABA. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11559772/ · DOI 10.1111/j.1469-7793.2001.t01-1-00741.x

evidence_access

Primary abstract

experimental_model

Purified human MPO system and stimulated human neutrophils.

limitations

Taurine chloramine remains an oxidant; free taurine is not equivalent to every chloramine effect.

nutrient_topic

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

plain_language

An immune-cell oxidant reacts with taurine to make a different active molecule.

primary_references

Chlorination of taurine by human neutrophils. Evidence for hypochlorous acid generation. · 1982 · https://pubmed.ncbi.nlm.nih.gov/6286728/ · DOI 10.1172/jci110652

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 361–367

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Purified human MPO system and stimulated human neutrophils. · source_derived_draft · unverified_draft

## taurine-mpo-chlorination An immune-cell oxidant reacts with taurine to make a different active molecule. Purified myeloperoxidase plus hydrogen peroxide, chloride and taurine generated taurine chloramine; removing chloride or peroxide, or inhibiting MPO, blocked generation. Model: Purified human MPO system and stimulated human neutrophils. Limitations: Taurine chloramine remains an oxidant; free taurine is not equivalent to every chloramine effect. Evidence access: Primary abstract Chlorination of taurine by human neutrophils. Evidence for hypochlorous acid generation. · 1982 · https://pubmed.ncbi.nlm.nih.gov/6286728/ · DOI 10.1172/jci110652

evidence_access

Primary abstract

experimental_model

Human placental brush-border proteins reconstituted in proteoliposomes.

limitations

This was not purified SLC6A6 alone; the coupling estimate is assay-specific, not a reason to consume more sodium.

nutrient_topic

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

plain_language

The sodium gradient helps power taurine entry.

primary_references

Solubilization and functional reconstitution of the human placental taurine transporter. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8431457/ · DOI 10.1016/0005-2736(93)90296-c

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 113–119

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human placental brush-border proteins reconstituted in proteoliposomes. · source_derived_draft · unverified_draft

## taurine-placental-sodium The sodium gradient helps power taurine entry. Replacing sodium strongly reduced taurine uptake in reconstituted human placental membranes; uptake kinetics supported two sodium ions per taurine. Model: Human placental brush-border proteins reconstituted in proteoliposomes. Limitations: This was not purified SLC6A6 alone; the coupling estimate is assay-specific, not a reason to consume more sodium. Evidence access: Primary abstract Solubilization and functional reconstitution of the human placental taurine transporter. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8431457/ · DOI 10.1016/0005-2736(93)90296-c

evidence_access

Primary abstract

experimental_model

Human SLC6A6 cryo-EM structures plus biochemical transport assays.

limitations

Transport activity is distinct from oral absorption, blood concentration and tissue sufficiency.

nutrient_topic

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

plain_language

Cells need a transporter to accumulate taurine.

primary_references

Molecular basis of human taurine transporter uptake and inhibition. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40789850/ · DOI 10.1038/s41467-025-62857-w

transport_effect

raises Uptake assays characterised sodium- and chloride-dependent taurine transport.

transport_pool

the expressing cell Uptake assays characterised sodium- and chloride-dependent taurine transport.

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 105–111

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human SLC6A6 cryo-EM structures plus biochemical transport assays. · source_derived_draft · unverified_draft

## taurine-taut-uptake Cells need a transporter to accumulate taurine. Human TauT structures and uptake assays characterized sodium- and chloride-dependent taurine transport and substrate recognition. Model: Human SLC6A6 cryo-EM structures plus biochemical transport assays. Limitations: Transport activity is distinct from oral absorption, blood concentration and tissue sufficiency. Evidence access: Primary abstract Molecular basis of human taurine transporter uptake and inhibition. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40789850/ · DOI 10.1038/s41467-025-62857-w

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human erythrocytes; DIDS pharmacological intervention.

limitations

DIDS is an inhibitor, not itself an exchanger; pharmacology does not establish a unique SLC4A1 transport substrate or route.

nutrient_topic

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

plain_language

Membrane transport can gate the redox response.

primary_references

Efflux of glutathione and glutathione complexes from human erythrocytes in response to vanadate. · 2013 · https://pubmed.ncbi.nlm.nih.gov/22824382/ · DOI 10.1016/j.bcmd.2012.07.001

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 166–172

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human erythrocytes; DIDS pharmacological intervention. · source_derived_draft · unverified_draft

## vanadium-anion-exchanger-block Membrane transport can gate the redox response. DIDS inhibited the intracellular thiol decrease and extracellular increase during vanadate exposure, supporting an anion-transport-dependent step. Model: Human erythrocytes; DIDS pharmacological intervention. Limitations: DIDS is an inhibitor, not itself an exchanger; pharmacology does not establish a unique SLC4A1 transport substrate or route. Evidence access: Primary abstract Efflux of glutathione and glutathione complexes from human erythrocytes in response to vanadate. · 2013 · https://pubmed.ncbi.nlm.nih.gov/22824382/ · DOI 10.1016/j.bcmd.2012.07.001

evidence_span

{"source_cache": "artifacts/creatine-research/8473283.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10a3e9e18054bc80e38fe289f59ba358853482082e69c87af0844ac90a6da5c7", "start_char": 0, "end_char": 1330, "text_sha256": "10a3e9e18054bc80e38fe289f59ba358853482082e69c87af0844ac90a6da5c7"}

experimental_model

Rabbit transporter cloning and heterologous uptake assay

exposure

Radiolabeled creatine uptake with ion dependence and substrate analogues

limitations

Rabbit expression assay; neither human ion stoichiometry nor a benefit from extra dietary salt is inferred.

nutrient_topic

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

organism

Rabbit transporter expressed in COS-7 cells

plain_language

Creatine uptake used both sodium and chloride in this transport experiment.

primary_references

[creatine-p8473283] A Na(+)-dependent creatine transporter in rabbit brain, muscle, heart, and kidney. cDNA cloning and functional expression. (1993). https://pubmed.ncbi.nlm.nih.gov/8473283/ DOI: 10.1016/s0021-9258(18)52891-x

tissue_or_cell_type

Cell plasma membrane

transport_effect

raises Sodium- and chloride-dependent creatine uptake with an apparent Km near 35 micromolar.

transport_pool

the expressing cell Sodium- and chloride-dependent creatine uptake with an apparent Km near 35 micromolar.

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 412–423

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rabbit transporter cloning and heterologous uptake assay · source_derived_draft · unverified_draft

### creatine-rabbit-sodium-chloride The cloned rabbit creatine transporter mediated sodium- and chloride-dependent creatine uptake, with an apparent Km of approximately 35 micromolar. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Creatine uptake used both sodium and chloride in this transport experiment. organism: Rabbit transporter expressed in COS-7 cells tissue_or_cell_type: Cell plasma membrane experimental_model: Rabbit transporter cloning and heterologous uptake assay limitations: Rabbit expression assay; neither human ion stoichiometry nor a benefit from extra dietary salt is inferred. exposure: Radiolabeled creatine uptake with ion dependence and substrate analogues evidence_span: {"source_cache": "artifacts/creatine-research/8473283.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10a3e9e18054bc80e38fe289f59ba358853482082e69c87af0844ac90a6da5c7", "start_char": 0, "end_char": 1330, "text_sha256": "10a3e9e18054bc80e38fe289f59ba358853482082e69c87af0844ac90a6da5c7"} [creatine-p8473283] A Na(+)-dependent creatine transporter in rabbit brain, muscle, heart, and kidney. cDNA cloning and functional expression. (1993). https://pubmed.ncbi.nlm.nih.gov/8473283/ DOI: 10.1016/s0021-9258(18)52891-x

evidence_span

{"source_cache": "artifacts/chloride-research/37679563.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8330a7df77cf5fed0d32a5623d7e0531cacb4306d3e4356b4fcbdb591501d3ef", "start_char": 0, "end_char": 1012, "text_sha256": "8330a7df77cf5fed0d32a5623d7e0531cacb4306d3e4356b4fcbdb591501d3ef"}

experimental_model

Seven cryo-EM structures with uptake and computational analyses

exposure

Apo, bicarbonate-bound and inhibitor-bound states

limitations

Transport mechanism analysis; not a dietary chloride threshold.

nutrient_topic

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

organism

Human AE1

plain_language

Red cells use a dedicated anion exchanger in the system that carries carbon dioxide between tissues and lungs.

primary_references

[chloride-p37679563] Substrate binding and inhibition of the anion exchanger 1 transporter. (2023). https://pubmed.ncbi.nlm.nih.gov/37679563/ DOI: 10.1038/s41594-023-01085-6

tissue_or_cell_type

Erythrocyte anion exchanger protein

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 302–313

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Seven cryo-EM structures with uptake and computational analyses · source_derived_draft · unverified_draft

### chloride-ae1-bicarbonate Cryo-EM resolved bicarbonate-bound human AE1 and identified substrate-recognition features. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Red cells use a dedicated anion exchanger in the system that carries carbon dioxide between tissues and lungs. organism: Human AE1 tissue_or_cell_type: Erythrocyte anion exchanger protein experimental_model: Seven cryo-EM structures with uptake and computational analyses limitations: Transport mechanism analysis; not a dietary chloride threshold. exposure: Apo, bicarbonate-bound and inhibitor-bound states evidence_span: {"source_cache": "artifacts/chloride-research/37679563.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8330a7df77cf5fed0d32a5623d7e0531cacb4306d3e4356b4fcbdb591501d3ef", "start_char": 0, "end_char": 1012, "text_sha256": "8330a7df77cf5fed0d32a5623d7e0531cacb4306d3e4356b4fcbdb591501d3ef"} [chloride-p37679563] Substrate binding and inhibition of the anion exchanger 1 transporter. (2023). https://pubmed.ncbi.nlm.nih.gov/37679563/ DOI: 10.1038/s41594-023-01085-6

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chloride-research/15123620.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2625c35640cf2ef20c066d3b628a000b6d37756e1245624670c45bc247468ab", "start_char": 0, "end_char": 1416, "text_sha256": "e2625c35640cf2ef20c066d3b628a000b6d37756e1245624670c45bc247468ab"}

experimental_model

Targeted Slc4a2 deletion

exposure

AE2-null versus control mice

limitations

Whole-gene loss affects membrane development as well as transport; not dietary chloride depletion.

nutrient_topic

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

organism

Mouse

plain_language

Stomach acid production requires functioning chloride-handling machinery.

primary_references

[chloride-p15123620] Mice with a targeted disruption of the AE2 Cl-/HCO3- exchanger are achlorhydric. (2004). https://pubmed.ncbi.nlm.nih.gov/15123620/ DOI: 10.1074/jbc.m403779200

tissue_or_cell_type

Gastric parietal cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 172–183

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted Slc4a2 deletion · source_derived_draft · unverified_draft

### chloride-ae2-acid AE2-null mice failed to secrete gastric acid. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Stomach acid production requires functioning chloride-handling machinery. organism: Mouse tissue_or_cell_type: Gastric parietal cells experimental_model: Targeted Slc4a2 deletion limitations: Whole-gene loss affects membrane development as well as transport; not dietary chloride depletion. exposure: AE2-null versus control mice evidence_span: {"source_cache": "artifacts/chloride-research/15123620.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2625c35640cf2ef20c066d3b628a000b6d37756e1245624670c45bc247468ab", "start_char": 0, "end_char": 1416, "text_sha256": "e2625c35640cf2ef20c066d3b628a000b6d37756e1245624670c45bc247468ab"} [chloride-p15123620] Mice with a targeted disruption of the AE2 Cl-/HCO3- exchanger are achlorhydric. (2004). https://pubmed.ncbi.nlm.nih.gov/15123620/ DOI: 10.1074/jbc.m403779200

evidence_span

{"source_cache": "artifacts/chloride-research/1718606.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a66a28a6b6c5d2abfee4d416aeddca8f38a48e343d2715f599c8c05998943f67", "start_char": 0, "end_char": 925, "text_sha256": "a66a28a6b6c5d2abfee4d416aeddca8f38a48e343d2715f599c8c05998943f67"}

experimental_model

Phosphorylated CFTR channel nucleotide assays

exposure

Hydrolyzable nucleotides, analogues and Mg-free ATP

limitations

Records the measured Mg/nucleotide dependence, not the paper’s historical assignment of opening to NBD1 hydrolysis.

nutrient_topic

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

organism

Human CFTR in expression preparations

plain_language

Magnesium and ATP are part of the working channel system; chloride alone is insufficient.

primary_references

[chloride-p1718606] Nucleoside triphosphates are required to open the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1718606/ DOI: 10.1016/0092-8674(91)90072-7

tissue_or_cell_type

Cytosolic channel face

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 250–261

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phosphorylated CFTR channel nucleotide assays · source_derived_draft · unverified_draft

### chloride-cftr-mgatp Phosphorylated CFTR channels opened with ATP but not Mg-free ATP in this preparation. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium and ATP are part of the working channel system; chloride alone is insufficient. organism: Human CFTR in expression preparations tissue_or_cell_type: Cytosolic channel face experimental_model: Phosphorylated CFTR channel nucleotide assays limitations: Records the measured Mg/nucleotide dependence, not the paper’s historical assignment of opening to NBD1 hydrolysis. exposure: Hydrolyzable nucleotides, analogues and Mg-free ATP evidence_span: {"source_cache": "artifacts/chloride-research/1718606.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a66a28a6b6c5d2abfee4d416aeddca8f38a48e343d2715f599c8c05998943f67", "start_char": 0, "end_char": 925, "text_sha256": "a66a28a6b6c5d2abfee4d416aeddca8f38a48e343d2715f599c8c05998943f67"} [chloride-p1718606] Nucleoside triphosphates are required to open the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1718606/ DOI: 10.1016/0092-8674(91)90072-7

evidence_span

{"source_cache": "artifacts/chloride-research/16034421.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a437e5233f3bb917ef5bbfee37e6eaed1745baf86fd4f35c85d8ad509dfa0f0", "start_char": 0, "end_char": 1359, "text_sha256": "3a437e5233f3bb917ef5bbfee37e6eaed1745baf86fd4f35c85d8ad509dfa0f0"}

experimental_model

Voltage and proton-flux measurements

exposure

Positive voltage and pore-glutamate mutation

limitations

Heterologous measurements; intracellular physiological direction depends on gradients.

nutrient_topic

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

organism

Mammalian ClC constructs in expression systems

plain_language

The related ClC-4 protein is separately represented as an exchanger.

primary_references

[chloride-p16034421] Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5. (2005). https://pubmed.ncbi.nlm.nih.gov/16034421/ DOI: 10.1038/nature03720

tissue_or_cell_type

Plasma-membrane-expressed transport proteins

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 653–664

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Voltage and proton-flux measurements · source_derived_draft · unverified_draft

### chloride-clc4-exchange ClC-4 also supported secondary active proton transport in the expression assay. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The related ClC-4 protein is separately represented as an exchanger. organism: Mammalian ClC constructs in expression systems tissue_or_cell_type: Plasma-membrane-expressed transport proteins experimental_model: Voltage and proton-flux measurements limitations: Heterologous measurements; intracellular physiological direction depends on gradients. exposure: Positive voltage and pore-glutamate mutation evidence_span: {"source_cache": "artifacts/chloride-research/16034421.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a437e5233f3bb917ef5bbfee37e6eaed1745baf86fd4f35c85d8ad509dfa0f0", "start_char": 0, "end_char": 1359, "text_sha256": "3a437e5233f3bb917ef5bbfee37e6eaed1745baf86fd4f35c85d8ad509dfa0f0"} [chloride-p16034421] Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5. (2005). https://pubmed.ncbi.nlm.nih.gov/16034421/ DOI: 10.1038/nature03720

evidence_span

{"source_cache": "artifacts/chloride-research/16034421.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a437e5233f3bb917ef5bbfee37e6eaed1745baf86fd4f35c85d8ad509dfa0f0", "start_char": 0, "end_char": 1359, "text_sha256": "3a437e5233f3bb917ef5bbfee37e6eaed1745baf86fd4f35c85d8ad509dfa0f0"}

experimental_model

Voltage and proton-flux measurements

exposure

Positive voltage and pore-glutamate mutation

limitations

Heterologous measurements; intracellular physiological direction depends on gradients.

nutrient_topic

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

organism

Mammalian ClC constructs in expression systems

plain_language

Some proteins historically called chloride channels are coupled chloride/proton exchangers.

primary_references

[chloride-p16034421] Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5. (2005). https://pubmed.ncbi.nlm.nih.gov/16034421/ DOI: 10.1038/nature03720

tissue_or_cell_type

Plasma-membrane-expressed transport proteins

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 640–651

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Voltage and proton-flux measurements · source_derived_draft · unverified_draft

### chloride-clc5-exchange ClC-5 transported protons against their electrochemical gradient in coupling with anion transport. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some proteins historically called chloride channels are coupled chloride/proton exchangers. organism: Mammalian ClC constructs in expression systems tissue_or_cell_type: Plasma-membrane-expressed transport proteins experimental_model: Voltage and proton-flux measurements limitations: Heterologous measurements; intracellular physiological direction depends on gradients. exposure: Positive voltage and pore-glutamate mutation evidence_span: {"source_cache": "artifacts/chloride-research/16034421.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a437e5233f3bb917ef5bbfee37e6eaed1745baf86fd4f35c85d8ad509dfa0f0", "start_char": 0, "end_char": 1359, "text_sha256": "3a437e5233f3bb917ef5bbfee37e6eaed1745baf86fd4f35c85d8ad509dfa0f0"} [chloride-p16034421] Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5. (2005). https://pubmed.ncbi.nlm.nih.gov/16034421/ DOI: 10.1038/nature03720

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chloride-research/11207362.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e10ae61257fa402ab9e10d55af44013139462a9d85236b75f5b52bdea0c7b5a", "start_char": 0, "end_char": 821, "text_sha256": "5e10ae61257fa402ab9e10d55af44013139462a9d85236b75f5b52bdea0c7b5a"}

experimental_model

Clcn7 knockout and human mutation identification

exposure

ClC-7 loss

limitations

Historical title calls ClC-7 a channel; current exchanger classification does not change the reported knockout phenotype. Not a dietary chloride study.

nutrient_topic

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

organism

Mouse; human infantile osteopetrosis patient

plain_language

Chloride-handling machinery supports the acidic compartment used to resorb bone.

primary_references

[chloride-p11207362] Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. (2001). https://pubmed.ncbi.nlm.nih.gov/11207362/ DOI: 10.1016/s0092-8674(01)00206-9

tissue_or_cell_type

Osteoclast ruffled border

trigger_kind

machinery_impairment Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (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 · Clcn7 knockout and human mutation identification · source_derived_draft · unverified_draft

### chloride-clc7-acidification Clcn7-null osteoclasts failed to acidify the resorption lacuna. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride-handling machinery supports the acidic compartment used to resorb bone. organism: Mouse; human infantile osteopetrosis patient tissue_or_cell_type: Osteoclast ruffled border experimental_model: Clcn7 knockout and human mutation identification limitations: Historical title calls ClC-7 a channel; current exchanger classification does not change the reported knockout phenotype. Not a dietary chloride study. exposure: ClC-7 loss evidence_span: {"source_cache": "artifacts/chloride-research/11207362.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e10ae61257fa402ab9e10d55af44013139462a9d85236b75f5b52bdea0c7b5a", "start_char": 0, "end_char": 821, "text_sha256": "5e10ae61257fa402ab9e10d55af44013139462a9d85236b75f5b52bdea0c7b5a"} [chloride-p11207362] Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. (2001). https://pubmed.ncbi.nlm.nih.gov/11207362/ DOI: 10.1016/s0092-8674(01)00206-9

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chloride-research/1379744.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbf542bf788774a420bad7ab2caa8bb57c09da9c31a285c06e9bc6ece9e1c320", "start_char": 0, "end_char": 867, "text_sha256": "bbf542bf788774a420bad7ab2caa8bb57c09da9c31a285c06e9bc6ece9e1c320"}

experimental_model

Linkage and sequence analysis

exposure

Dominant/recessive myotonia pedigrees

limitations

Early genetic report; different variants have different channel effects.

nutrient_topic

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

organism

Human

plain_language

Muscle stiffness can arise from faulty chloride channels despite adequate nutrient supply.

primary_references

[chloride-p1379744] The skeletal muscle chloride channel in dominant and recessive human myotonia. (1992). https://pubmed.ncbi.nlm.nih.gov/1379744/ DOI: 10.1126/science.1379744

tissue_or_cell_type

Skeletal muscle; German families

trigger_kind

machinery_impairment Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 458–469

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

### chloride-clcn1-myotonia CLCN1 linkage and a disease-associated substitution implicated the muscle chloride channel in inherited myotonia. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Muscle stiffness can arise from faulty chloride channels despite adequate nutrient supply. organism: Human tissue_or_cell_type: Skeletal muscle; German families experimental_model: Linkage and sequence analysis limitations: Early genetic report; different variants have different channel effects. exposure: Dominant/recessive myotonia pedigrees evidence_span: {"source_cache": "artifacts/chloride-research/1379744.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbf542bf788774a420bad7ab2caa8bb57c09da9c31a285c06e9bc6ece9e1c320", "start_char": 0, "end_char": 867, "text_sha256": "bbf542bf788774a420bad7ab2caa8bb57c09da9c31a285c06e9bc6ece9e1c320"} [chloride-p1379744] The skeletal muscle chloride channel in dominant and recessive human myotonia. (1992). https://pubmed.ncbi.nlm.nih.gov/1379744/ DOI: 10.1126/science.1379744

evidence_span

{"source_cache": "artifacts/chloride-research/27335120.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0a0a14e0cc6fd76c451f92665dfed0255edcaf0355b46414f91c74d977f5d6b3", "start_char": 0, "end_char": 1432, "text_sha256": "0a0a14e0cc6fd76c451f92665dfed0255edcaf0355b46414f91c74d977f5d6b3"}

experimental_model

Clcnk2 knockout and nephron patch clamp

exposure

Gene deletion; furosemide/thiazide responses

limitations

Mouse ortholog; not a claim of dietary chloride deficiency.

nutrient_topic

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

organism

Mouse

plain_language

Chloride needs a route out of the back of kidney cells as well as a route in.

primary_references

[chloride-p27335120] The ClC-K2 Chloride Channel Is Critical for Salt Handling in the Distal Nephron. (2017). https://pubmed.ncbi.nlm.nih.gov/27335120/ DOI: 10.1681/asn.2016010085

tissue_or_cell_type

Thick ascending limb and distal nephron

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 913–924

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clcnk2 knockout and nephron patch clamp · source_derived_draft · unverified_draft

### chloride-clcnk2-basolateral Knockout patch-clamp studies identified ClC-K2 as a major basolateral chloride channel in the tested nephron segments. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride needs a route out of the back of kidney cells as well as a route in. organism: Mouse tissue_or_cell_type: Thick ascending limb and distal nephron experimental_model: Clcnk2 knockout and nephron patch clamp limitations: Mouse ortholog; not a claim of dietary chloride deficiency. exposure: Gene deletion; furosemide/thiazide responses evidence_span: {"source_cache": "artifacts/chloride-research/27335120.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0a0a14e0cc6fd76c451f92665dfed0255edcaf0355b46414f91c74d977f5d6b3", "start_char": 0, "end_char": 1432, "text_sha256": "0a0a14e0cc6fd76c451f92665dfed0255edcaf0355b46414f91c74d977f5d6b3"} [chloride-p27335120] The ClC-K2 Chloride Channel Is Critical for Salt Handling in the Distal Nephron. (2017). https://pubmed.ncbi.nlm.nih.gov/27335120/ DOI: 10.1681/asn.2016010085

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chloride-research/9326936.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "80ade45b4ae654e5aa13b671daebab418640aa033aca3a74cae4ccf52d4e279e", "start_char": 0, "end_char": 1227, "text_sha256": "80ade45b4ae654e5aa13b671daebab418640aa033aca3a74cae4ccf52d4e279e"}

experimental_model

Genetics in seventeen kindreds

exposure

Loss-of-function CLCNKB variants

limitations

This cohort had normal magnesium and variable calciuria; do not universalize the full phenotype.

nutrient_topic

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

organism

Human

plain_language

A chloride-channel defect can drive loss of other electrolytes.

primary_references

[chloride-p9326936] Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III. (1997). https://pubmed.ncbi.nlm.nih.gov/9326936/ DOI: 10.1038/ng1097-171

tissue_or_cell_type

Renal salt handling

trigger_kind

machinery_impairment Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 887–898

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

### chloride-clcnkb-salt CLCNKB loss-of-function variants caused renal salt-wasting hypokalemic alkalosis in the studied families. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A chloride-channel defect can drive loss of other electrolytes. organism: Human tissue_or_cell_type: Renal salt handling experimental_model: Genetics in seventeen kindreds limitations: This cohort had normal magnesium and variable calciuria; do not universalize the full phenotype. exposure: Loss-of-function CLCNKB variants evidence_span: {"source_cache": "artifacts/chloride-research/9326936.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "80ade45b4ae654e5aa13b671daebab418640aa033aca3a74cae4ccf52d4e279e", "start_char": 0, "end_char": 1227, "text_sha256": "80ade45b4ae654e5aa13b671daebab418640aa033aca3a74cae4ccf52d4e279e"} [chloride-p9326936] Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III. (1997). https://pubmed.ncbi.nlm.nih.gov/9326936/ DOI: 10.1038/ng1097-171

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chloride-research/8896562.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7883032c511e388e8c37bf64651bb2e9b19ef65fee624c0e8c31359894fe9e64", "start_char": 0, "end_char": 1272, "text_sha256": "7883032c511e388e8c37bf64651bb2e9b19ef65fee624c0e8c31359894fe9e64"}

experimental_model

Genetic mapping in 32 Finnish and four Polish patients

exposure

Inherited DRA variants

limitations

Human transport disease; does not imply low dietary intake or a dietary cure.

nutrient_topic

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

organism

Human

plain_language

A defective intestinal exchanger can cause chloride-rich diarrhea even when chloride is consumed.

primary_references

[chloride-p8896562] Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea. (1996). https://pubmed.ncbi.nlm.nih.gov/8896562/ DOI: 10.1038/ng1196-316

tissue_or_cell_type

Intestinal epithelium

trigger_kind

machinery_impairment Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 159–170

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic mapping in 32 Finnish and four Polish patients · source_derived_draft · unverified_draft

### chloride-dra-loss DRA variants segregated with congenital chloride diarrhea in the studied families. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A defective intestinal exchanger can cause chloride-rich diarrhea even when chloride is consumed. organism: Human tissue_or_cell_type: Intestinal epithelium experimental_model: Genetic mapping in 32 Finnish and four Polish patients limitations: Human transport disease; does not imply low dietary intake or a dietary cure. exposure: Inherited DRA variants evidence_span: {"source_cache": "artifacts/chloride-research/8896562.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7883032c511e388e8c37bf64651bb2e9b19ef65fee624c0e8c31359894fe9e64", "start_char": 0, "end_char": 1272, "text_sha256": "7883032c511e388e8c37bf64651bb2e9b19ef65fee624c0e8c31359894fe9e64"} [chloride-p8896562] Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea. (1996). https://pubmed.ncbi.nlm.nih.gov/8896562/ DOI: 10.1038/ng1196-316

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chloride-research/9930699.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6", "start_char": 0, "end_char": 1181, "text_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6"}

experimental_model

Developmental expression and antisense suppression

exposure

KCC2 expression during maturation; antisense inhibition

limitations

Neuronal gradient mechanism; dietary chloride restriction is not the intervention.

nutrient_topic

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

organism

Rat

plain_language

GABA’s electrical effect depends on the chloride gradient maintained by the cell.

primary_references

[chloride-p9930699] The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. (1999). https://pubmed.ncbi.nlm.nih.gov/9930699/ DOI: 10.1038/16697

tissue_or_cell_type

Hippocampal pyramidal neurons

trigger_kind

machinery_impairment Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 406–417

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Developmental expression and antisense suppression · source_derived_draft · unverified_draft

### chloride-kcc2-gaba-loss Suppressing KCC2 shifted the GABA-A reversal potential in a positive direction in mature neurons. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: GABA’s electrical effect depends on the chloride gradient maintained by the cell. organism: Rat tissue_or_cell_type: Hippocampal pyramidal neurons experimental_model: Developmental expression and antisense suppression limitations: Neuronal gradient mechanism; dietary chloride restriction is not the intervention. exposure: KCC2 expression during maturation; antisense inhibition evidence_span: {"source_cache": "artifacts/chloride-research/9930699.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6", "start_char": 0, "end_char": 1181, "text_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6"} [chloride-p9930699] The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. (1999). https://pubmed.ncbi.nlm.nih.gov/9930699/ DOI: 10.1038/16697

evidence_span

{"source_cache": "artifacts/chloride-research/24790029.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9fc0ba50276b74ac5cd7aa29c4c8af4917132a43259b45363b5c16a19b775334", "start_char": 0, "end_char": 896, "text_sha256": "9fc0ba50276b74ac5cd7aa29c4c8af4917132a43259b45363b5c16a19b775334"}

experimental_model

Genome-wide screen, gene disruption and rescue

exposure

LRRC8 knockout and isoform coexpression

limitations

Channel composition and cellular volume response; no dietary intervention.

nutrient_topic

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

organism

Human cell lines

plain_language

A swelling-responsive anion channel is a protein assembly, not one interchangeable subunit.

primary_references

[chloride-p24790029] Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC. (2014). https://pubmed.ncbi.nlm.nih.gov/24790029/ DOI: 10.1126/science.1252826

tissue_or_cell_type

Plasma membrane

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 471–482

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genome-wide screen, gene disruption and rescue · source_derived_draft · unverified_draft

### chloride-lrrc8a-vrac Deleting LRRC8A abolished VRAC currents; reconstitution required LRRC8A with another LRRC8 isoform. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A swelling-responsive anion channel is a protein assembly, not one interchangeable subunit. organism: Human cell lines tissue_or_cell_type: Plasma membrane experimental_model: Genome-wide screen, gene disruption and rescue limitations: Channel composition and cellular volume response; no dietary intervention. exposure: LRRC8 knockout and isoform coexpression evidence_span: {"source_cache": "artifacts/chloride-research/24790029.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9fc0ba50276b74ac5cd7aa29c4c8af4917132a43259b45363b5c16a19b775334", "start_char": 0, "end_char": 896, "text_sha256": "9fc0ba50276b74ac5cd7aa29c4c8af4917132a43259b45363b5c16a19b775334"} [chloride-p24790029] Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC. (2014). https://pubmed.ncbi.nlm.nih.gov/24790029/ DOI: 10.1126/science.1252826

evidence_span

{"source_cache": "artifacts/chloride-research/27507113.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "978879bf8054ce7c99ef939133966e618cc8030cb7bd624e250ce32002455927", "start_char": 0, "end_char": 2050, "text_sha256": "978879bf8054ce7c99ef939133966e618cc8030cb7bd624e250ce32002455927"}

experimental_model

Observational cohort and separate uncontrolled pilot

exposure

162-person cohort; ten-person pilot, lysine chloride 115 mmol/day for three days

limitations

Association does not establish causality; the small pilot did not prove clinical benefit or survival improvement.

nutrient_topic

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

organism

Human heart failure patients

plain_language

The study tested a way to supply chloride without sodium; benefit remains unresolved.

primary_references

[chloride-p27507113] Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights. (2016). https://pubmed.ncbi.nlm.nih.gov/27507113/ DOI: 10.1161/circheartfailure.116.003180

tissue_or_cell_type

Blood and renal diuretic response

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 952–963

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Observational cohort and separate uncontrolled pilot · source_derived_draft · unverified_draft

### chloride-lysine-chloride The pilot reported a mean serum chloride rise of 2.2 mmol/L after sodium-free lysine chloride supplementation. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The study tested a way to supply chloride without sodium; benefit remains unresolved. organism: Human heart failure patients tissue_or_cell_type: Blood and renal diuretic response experimental_model: Observational cohort and separate uncontrolled pilot limitations: Association does not establish causality; the small pilot did not prove clinical benefit or survival improvement. exposure: 162-person cohort; ten-person pilot, lysine chloride 115 mmol/day for three days evidence_span: {"source_cache": "artifacts/chloride-research/27507113.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "978879bf8054ce7c99ef939133966e618cc8030cb7bd624e250ce32002455927", "start_char": 0, "end_char": 2050, "text_sha256": "978879bf8054ce7c99ef939133966e618cc8030cb7bd624e250ce32002455927"} [chloride-p27507113] Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights. (2016). https://pubmed.ncbi.nlm.nih.gov/27507113/ DOI: 10.1161/circheartfailure.116.003180

evidence_span

{"source_cache": "artifacts/chloride-research/2012204.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac", "start_char": 0, "end_char": 1695, "text_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac"}

experimental_model

Perfused isolated juxtaglomerular apparatus

exposure

Luminal ion substitutions and 1 µM bumetanide

limitations

Pharmacological evidence for macula-densa Na-K-2Cl transport; molecular NKCC2 was not genetically tested in this experiment.

nutrient_topic

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

organism

Rabbit

plain_language

The chloride must engage the transport system to produce the usual signal.

primary_references

[chloride-p2012204] Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport. (1991). https://pubmed.ncbi.nlm.nih.gov/2012204/ DOI: 10.1152/ajprenal.1991.260.4.f486

tissue_or_cell_type

Macula densa and renin-secreting apparatus

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 575–586

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Perfused isolated juxtaglomerular apparatus · source_derived_draft · unverified_draft

### chloride-macula-transport-renin Luminal bumetanide increased renin release during high-NaCl perfusion, supporting cotransporter-dependent sensing. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The chloride must engage the transport system to produce the usual signal. organism: Rabbit tissue_or_cell_type: Macula densa and renin-secreting apparatus experimental_model: Perfused isolated juxtaglomerular apparatus limitations: Pharmacological evidence for macula-densa Na-K-2Cl transport; molecular NKCC2 was not genetically tested in this experiment. exposure: Luminal ion substitutions and 1 µM bumetanide evidence_span: {"source_cache": "artifacts/chloride-research/2012204.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac", "start_char": 0, "end_char": 1695, "text_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac"} [chloride-p2012204] Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport. (1991). https://pubmed.ncbi.nlm.nih.gov/2012204/ DOI: 10.1152/ajprenal.1991.260.4.f486

evidence_span

{"source_cache": "artifacts/chloride-research/9359420.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0", "start_char": 0, "end_char": 1700, "text_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0"}

experimental_model

Purified-enzyme substrate kinetics

exposure

100 mM chloride with varying thiocyanate

limitations

Product chemistry under assay conditions; not a recommendation to raise chloride or thiocyanate intake.

nutrient_topic

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

organism

Human neutrophil enzyme

plain_language

Immune chemistry can convert chloride into a reactive antimicrobial oxidant.

primary_references

[chloride-p9359420] Thiocyanate and chloride as competing substrates for myeloperoxidase. (1997). https://pubmed.ncbi.nlm.nih.gov/9359420/ DOI: 10.1042/bj3270487

tissue_or_cell_type

Myeloperoxidase reaction mixture

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 614–625

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

### chloride-mpo-hocl Myeloperoxidase used hydrogen peroxide to oxidize chloride to hypochlorous acid. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Immune chemistry can convert chloride into a reactive antimicrobial oxidant. organism: Human neutrophil enzyme tissue_or_cell_type: Myeloperoxidase reaction mixture experimental_model: Purified-enzyme substrate kinetics limitations: Product chemistry under assay conditions; not a recommendation to raise chloride or thiocyanate intake. exposure: 100 mM chloride with varying thiocyanate evidence_span: {"source_cache": "artifacts/chloride-research/9359420.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0", "start_char": 0, "end_char": 1700, "text_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0"} [chloride-p9359420] Thiocyanate and chloride as competing substrates for myeloperoxidase. (1997). https://pubmed.ncbi.nlm.nih.gov/9359420/ DOI: 10.1042/bj3270487

evidence_span

{"source_cache": "artifacts/chloride-research/20389022.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e38f38d6be0ba6db309bcc35de163f9dd6db62963c41864ca0b7fe6c24a31ddb", "start_char": 0, "end_char": 1550, "text_sha256": "e38f38d6be0ba6db309bcc35de163f9dd6db62963c41864ca0b7fe6c24a31ddb"}

experimental_model

Gene deletion and perfused collecting ducts

exposure

Slc4a8, NCC and ENaC perturbations

limitations

Mouse electroneutral transport; thiazide sensitivity alone does not identify NCC.

nutrient_topic

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

organism

Mouse

plain_language

Sodium and chloride can be reabsorbed through a coupled exchanger system beyond NCC.

primary_references

[chloride-p20389022] The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice. (2010). https://pubmed.ncbi.nlm.nih.gov/20389022/ DOI: 10.1172/jci40145

tissue_or_cell_type

Cortical collecting duct

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 536–547

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene deletion and perfused collecting ducts · source_derived_draft · unverified_draft

### chloride-ndcbe-sodium Slc4a8 deletion abolished the thiazide-sensitive NaCl absorption measured in cortical collecting ducts. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sodium and chloride can be reabsorbed through a coupled exchanger system beyond NCC. organism: Mouse tissue_or_cell_type: Cortical collecting duct experimental_model: Gene deletion and perfused collecting ducts limitations: Mouse electroneutral transport; thiazide sensitivity alone does not identify NCC. exposure: Slc4a8, NCC and ENaC perturbations evidence_span: {"source_cache": "artifacts/chloride-research/20389022.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e38f38d6be0ba6db309bcc35de163f9dd6db62963c41864ca0b7fe6c24a31ddb", "start_char": 0, "end_char": 1550, "text_sha256": "e38f38d6be0ba6db309bcc35de163f9dd6db62963c41864ca0b7fe6c24a31ddb"} [chloride-p20389022] The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice. (2010). https://pubmed.ncbi.nlm.nih.gov/20389022/ DOI: 10.1172/jci40145

evidence_span

{"source_cache": "artifacts/chloride-research/19295148.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "55bc6d4f9cf1d9a44f4d6c851dabd587bb2ffb7a337f67c5f9e7bfe8aefa870f", "start_char": 0, "end_char": 982, "text_sha256": "55bc6d4f9cf1d9a44f4d6c851dabd587bb2ffb7a337f67c5f9e7bfe8aefa870f"}

experimental_model

Nkcc1 knockout and neuronal activity measurements

exposure

Nkcc1 deletion

limitations

Developmental hippocampal model; does not generalize to every immature neuron.

nutrient_topic

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

organism

Mouse

plain_language

Chloride loading can help GABA excite developing neurons in this specific circuit.

primary_references

[chloride-p19295148] NKCC1-dependent GABAergic excitation drives synaptic network maturation during early hippocampal development. (2009). https://pubmed.ncbi.nlm.nih.gov/19295148/ DOI: 10.1523/jneurosci.1377-08.2009

tissue_or_cell_type

Early postnatal hippocampal CA1 network

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 419–430

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nkcc1 knockout and neuronal activity measurements · source_derived_draft · unverified_draft

### chloride-nkcc1-gaba Nkcc1 deletion attenuated GABA-triggered depolarization and calcium transients during early hippocampal development. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride loading can help GABA excite developing neurons in this specific circuit. organism: Mouse tissue_or_cell_type: Early postnatal hippocampal CA1 network experimental_model: Nkcc1 knockout and neuronal activity measurements limitations: Developmental hippocampal model; does not generalize to every immature neuron. exposure: Nkcc1 deletion evidence_span: {"source_cache": "artifacts/chloride-research/19295148.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "55bc6d4f9cf1d9a44f4d6c851dabd587bb2ffb7a337f67c5f9e7bfe8aefa870f", "start_char": 0, "end_char": 982, "text_sha256": "55bc6d4f9cf1d9a44f4d6c851dabd587bb2ffb7a337f67c5f9e7bfe8aefa870f"} [chloride-p19295148] NKCC1-dependent GABAergic excitation drives synaptic network maturation during early hippocampal development. (2009). https://pubmed.ncbi.nlm.nih.gov/19295148/ DOI: 10.1523/jneurosci.1377-08.2009

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chloride-research/20375274.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ddda637993b80b24351aefe0451312d849175bd3ec2f3af23b72b50f7439953", "start_char": 0, "end_char": 1797, "text_sha256": "8ddda637993b80b24351aefe0451312d849175bd3ec2f3af23b72b50f7439953"}

experimental_model

Pendrin knockout and isolated collecting-duct perfusion

exposure

Slc26a4 deletion

limitations

Residual exchange remained; baseline urine chloride excretion was unchanged.

nutrient_topic

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

organism

Mouse

plain_language

The kidney uses chloride exchange to help dispose of bicarbonate.

primary_references

[chloride-p20375274] Deletion of the anion exchanger Slc26a4 (pendrin) decreases apical Cl(-)/HCO3(-) exchanger activity and impairs bicarbonate secretion in kidney collecting duct. (2010). https://pubmed.ncbi.nlm.nih.gov/20375274/ DOI: 10.1152/ajpcell.00033.2010

tissue_or_cell_type

Non-acid-secreting intercalated cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 510–521

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pendrin knockout and isolated collecting-duct perfusion · source_derived_draft · unverified_draft

### chloride-pendrin-bicarbonate Pendrin-null collecting ducts had reduced apical chloride/bicarbonate exchange and impaired bicarbonate secretion. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidney uses chloride exchange to help dispose of bicarbonate. organism: Mouse tissue_or_cell_type: Non-acid-secreting intercalated cells experimental_model: Pendrin knockout and isolated collecting-duct perfusion limitations: Residual exchange remained; baseline urine chloride excretion was unchanged. exposure: Slc26a4 deletion evidence_span: {"source_cache": "artifacts/chloride-research/20375274.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ddda637993b80b24351aefe0451312d849175bd3ec2f3af23b72b50f7439953", "start_char": 0, "end_char": 1797, "text_sha256": "8ddda637993b80b24351aefe0451312d849175bd3ec2f3af23b72b50f7439953"} [chloride-p20375274] Deletion of the anion exchanger Slc26a4 (pendrin) decreases apical Cl(-)/HCO3(-) exchanger activity and impairs bicarbonate secretion in kidney collecting duct. (2010). https://pubmed.ncbi.nlm.nih.gov/20375274/ DOI: 10.1152/ajpcell.00033.2010

evidence_span

{"source_cache": "artifacts/chloride-research/1716180.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5", "start_char": 0, "end_char": 961, "text_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5"}

experimental_model

PKA phosphorylation and CFTR mutagenesis

exposure

Serines 660, 737, 795 and 813

limitations

Early site mapping; do not imply these are the only regulatory sites or endorse the historical gating model.

nutrient_topic

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

organism

Human CFTR in cells

plain_language

A kinase switches the channel into a state that can respond to stimulation.

primary_references

[chloride-p1716180] Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1716180/ DOI: 10.1016/0092-8674(91)90446-6

tissue_or_cell_type

CFTR regulatory domain

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 237–248

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · PKA phosphorylation and CFTR mutagenesis · source_derived_draft · unverified_draft

### chloride-pka-cftr PKA phosphorylated CFTR regulatory-domain serines; combined mutation of the four tested sites abolished the cAMP-responsive chloride signal. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A kinase switches the channel into a state that can respond to stimulation. organism: Human CFTR in cells tissue_or_cell_type: CFTR regulatory domain experimental_model: PKA phosphorylation and CFTR mutagenesis limitations: Early site mapping; do not imply these are the only regulatory sites or endorse the historical gating model. exposure: Serines 660, 737, 795 and 813 evidence_span: {"source_cache": "artifacts/chloride-research/1716180.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5", "start_char": 0, "end_char": 961, "text_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5"} [chloride-p1716180] Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1716180/ DOI: 10.1016/0092-8674(91)90446-6

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chloride-research/2450456.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7", "start_char": 0, "end_char": 1348, "text_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7"}

experimental_model

Human depletion–repletion balance experiment

exposure

Furosemide plus restricted NaCl; oral KCl repletion over 36 hours

limitations

Loss-associated depletion; KCl supplies potassium too. Mechanism does not imply self-treatment or apply to every alkalosis.

nutrient_topic

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

organism

Human men

plain_language

Restoring volume was not necessary for correction in this experiment.

primary_references

[chloride-p2450456] On the mechanism by which chloride corrects metabolic alkalosis in man. (1988). https://pubmed.ncbi.nlm.nih.gov/2450456/ DOI: 10.1016/0002-9343(88)90265-3

tissue_or_cell_type

Kidney and systemic acid–base balance

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 835–846

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human depletion–repletion balance experiment · source_derived_draft · unverified_draft

### chloride-repletion-alkalosis Oral KCl corrected induced chloride-depletion alkalosis while plasma volume, body weight and filtration remained reduced. Condition category: nutrient_deficiency nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring volume was not necessary for correction in this experiment. organism: Human men tissue_or_cell_type: Kidney and systemic acid–base balance experimental_model: Human depletion–repletion balance experiment limitations: Loss-associated depletion; KCl supplies potassium too. Mechanism does not imply self-treatment or apply to every alkalosis. exposure: Furosemide plus restricted NaCl; oral KCl repletion over 36 hours evidence_span: {"source_cache": "artifacts/chloride-research/2450456.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7", "start_char": 0, "end_char": 1348, "text_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7"} [chloride-p2450456] On the mechanism by which chloride corrects metabolic alkalosis in man. (1988). https://pubmed.ncbi.nlm.nih.gov/2450456/ DOI: 10.1016/0002-9343(88)90265-3

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chloride-research/19004773.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ed1a2033c883ec9b4eeab6a9c0bae03d1f478adf66913c3d5e8c43879a836d3e", "start_char": 0, "end_char": 1342, "text_sha256": "ed1a2033c883ec9b4eeab6a9c0bae03d1f478adf66913c3d5e8c43879a836d3e"}

experimental_model

Slc26a9 deletion and heterologous transport assays

exposure

Knockout at five weeks; expression assays

limitations

Different assays showed conductance or exchange; do not assign one universal stoichiometry.

nutrient_topic

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

organism

Mouse protein; oocytes and cultured cells

plain_language

A second chloride-handling protein is needed for normal acid secretion in this model.

primary_references

[chloride-p19004773] Deletion of the chloride transporter Slc26a9 causes loss of tubulovesicles in parietal cells and impairs acid secretion in the stomach. (2008). https://pubmed.ncbi.nlm.nih.gov/19004773/ DOI: 10.1073/pnas.0800616105

tissue_or_cell_type

Gastric parietal cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 198–209

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc26a9 deletion and heterologous transport assays · source_derived_draft · unverified_draft

### chloride-slc26a9-acid Slc26a9-null mice lost gastric acid secretion at five weeks. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second chloride-handling protein is needed for normal acid secretion in this model. organism: Mouse protein; oocytes and cultured cells tissue_or_cell_type: Gastric parietal cells experimental_model: Slc26a9 deletion and heterologous transport assays limitations: Different assays showed conductance or exchange; do not assign one universal stoichiometry. exposure: Knockout at five weeks; expression assays evidence_span: {"source_cache": "artifacts/chloride-research/19004773.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ed1a2033c883ec9b4eeab6a9c0bae03d1f478adf66913c3d5e8c43879a836d3e", "start_char": 0, "end_char": 1342, "text_sha256": "ed1a2033c883ec9b4eeab6a9c0bae03d1f478adf66913c3d5e8c43879a836d3e"} [chloride-p19004773] Deletion of the chloride transporter Slc26a9 causes loss of tubulovesicles in parietal cells and impairs acid secretion in the stomach. (2008). https://pubmed.ncbi.nlm.nih.gov/19004773/ DOI: 10.1073/pnas.0800616105

evidence_span

{"source_cache": "artifacts/chloride-research/30742493.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1ff038684ceacd46ad1e237d0cf13337924ec0f611d00a373cd3cbeeeb31864a", "start_char": 0, "end_char": 1882, "text_sha256": "1ff038684ceacd46ad1e237d0cf13337924ec0f611d00a373cd3cbeeeb31864a"}

experimental_model

Primary epithelial cultures and native tissue

exposure

IL-4 induction and pendrin knockdown

limitations

Inflamed surface epithelium differs from Calu-3; no universal airway assignment.

nutrient_topic

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

organism

Human nasal and bronchial epithelia

plain_language

Different airway cells can use a different balance of the same transport proteins.

primary_references

[chloride-p30742493] Pendrin Mediates Bicarbonate Secretion and Enhances Cystic Fibrosis Transmembrane Conductance Regulator Function in Airway Surface Epithelia. (2019). https://pubmed.ncbi.nlm.nih.gov/30742493/ DOI: 10.1165/rcmb.2018-0158oc

tissue_or_cell_type

Ciliated airway surface

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 1056–1067

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary epithelial cultures and native tissue · source_derived_draft · unverified_draft

### chloride-surface-pendrin IL-4-induced pendrin supported chloride/bicarbonate exchange in primary airway surface cultures. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different airway cells can use a different balance of the same transport proteins. organism: Human nasal and bronchial epithelia tissue_or_cell_type: Ciliated airway surface experimental_model: Primary epithelial cultures and native tissue limitations: Inflamed surface epithelium differs from Calu-3; no universal airway assignment. exposure: IL-4 induction and pendrin knockdown evidence_span: {"source_cache": "artifacts/chloride-research/30742493.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1ff038684ceacd46ad1e237d0cf13337924ec0f611d00a373cd3cbeeeb31864a", "start_char": 0, "end_char": 1882, "text_sha256": "1ff038684ceacd46ad1e237d0cf13337924ec0f611d00a373cd3cbeeeb31864a"} [chloride-p30742493] Pendrin Mediates Bicarbonate Secretion and Enhances Cystic Fibrosis Transmembrane Conductance Regulator Function in Airway Surface Epithelia. (2019). https://pubmed.ncbi.nlm.nih.gov/30742493/ DOI: 10.1165/rcmb.2018-0158oc

evidence_access

Primary abstract

experimental_model

Human alpha1 receptor, rapid agonist application and patch recording.

limitations

Homomeric experimental receptor differs from native heteromeric receptor mixtures; chloride gradient determines current consequences.

nutrient_topic

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

plain_language

Glycine can directly open a receptor channel.

primary_references

Kinetic determinants of agonist action at the recombinant human glycine receptor. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12679369/ · DOI 10.1113/jphysiol.2002.037796

Glycine: supply, one-carbon allocation, receptors and cross-nutrient mechanisms (2026-09-19) · lines 194–200

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human alpha1 receptor, rapid agonist application and patch recording. · source_derived_draft · unverified_draft

## glycine-glyr-opening Glycine can directly open a receptor channel. Glycine opened recombinant human alpha1 homomeric glycine receptors in HEK293 cells; rapid-application and single-channel assays resolved activation kinetics. Model: Human alpha1 receptor, rapid agonist application and patch recording. Limitations: Homomeric experimental receptor differs from native heteromeric receptor mixtures; chloride gradient determines current consequences. Evidence access: Primary abstract Kinetic determinants of agonist action at the recombinant human glycine receptor. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12679369/ · DOI 10.1113/jphysiol.2002.037796

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human disease-associated receptor constructs in frog oocytes; concentration-response and single-channel recording.

limitations

Modeling implicated impaired gating rather than simply loss of ligand binding; not dietary glycine deficiency.

nutrient_topic

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

plain_language

The receptor can respond poorly even when its ligand is supplied.

primary_references

Properties of human glycine receptors containing the hyperekplexia mutation alpha1(K276E), expressed in Xenopus oocytes. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9490812/ · DOI 10.1111/j.1469-7793.1998.025bu.x

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors and cross-nutrient mechanisms (2026-09-19) · lines 210–216

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human disease-associated receptor constructs in frog oocytes; concentration-response and single-channel recording. · source_derived_draft · unverified_draft

## glycine-glyr-variant The receptor can respond poorly even when its ligand is supplied. Human alpha1(K276E)/beta receptors expressed in Xenopus oocytes were about 29-fold less glycine-sensitive than wild type and had shorter channel openings. Model: Human disease-associated receptor constructs in frog oocytes; concentration-response and single-channel recording. Limitations: Modeling implicated impaired gating rather than simply loss of ligand binding; not dietary glycine deficiency. Evidence access: Primary abstract Properties of human glycine receptors containing the hyperekplexia mutation alpha1(K276E), expressed in Xenopus oocytes. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9490812/ · DOI 10.1111/j.1469-7793.1998.025bu.x

evidence_access

Primary full text

experimental_model

Human GlyT1/GlyT2 voltage-clamp measurements and kinetic models.

limitations

Binding-order models are interpretations constrained by currents, not direct structures of every transport state.

nutrient_topic

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

plain_language

Raising one intracellular ion did not simply switch these transporters off.

primary_references

A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31270129/ · DOI 10.1085/jgp.201912318

Glycine: supply, one-carbon allocation, receptors 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 GlyT1/GlyT2 voltage-clamp measurements and kinetic models. · source_derived_draft · unverified_draft

## glycine-glyt-ion-cooperativity Raising one intracellular ion did not simply switch these transporters off. GlyT1 and GlyT2 maintained forward transport under the tested elevated intracellular sodium or chloride conditions, consistent with cooperative ion/substrate binding. Model: Human GlyT1/GlyT2 voltage-clamp measurements and kinetic models. Limitations: Binding-order models are interpretations constrained by currents, not direct structures of every transport state. Evidence access: Primary full text A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31270129/ · DOI 10.1085/jgp.201912318

evidence_access

Primary full text

experimental_model

Human transporter in nonhuman COS-7 host cells; whole-cell electrophysiology, usually 1 mM glycine.

limitations

The stoichiometry is established background incorporated into this primary kinetic study; no dietary salt intervention. Human protein and host-cell species differ.

nutrient_topic

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

plain_language

Glycine uptake draws on ion gradients, not just the amount of amino acid outside.

primary_references

A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31270129/ · DOI 10.1085/jgp.201912318

transport_effect

raises Sodium- and chloride-coupled glycine transport, which is inward.

transport_pool

the expressing cell Sodium- and chloride-coupled glycine transport, which is inward.

Glycine: supply, one-carbon allocation, receptors and cross-nutrient mechanisms (2026-09-19) · lines 26–32

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human transporter in nonhuman COS-7 host cells; whole-cell electrophysiology, usually 1 mM glycine. · source_derived_draft · unverified_draft

## glycine-glyt1-transport Glycine uptake draws on ion gradients, not just the amount of amino acid outside. Human GlyT1 expressed in COS-7 cells transported glycine with sodium and chloride; the kinetic analysis used the established 2 Na+:1 Cl-:1 glycine coupling. Model: Human transporter in nonhuman COS-7 host cells; whole-cell electrophysiology, usually 1 mM glycine. Limitations: The stoichiometry is established background incorporated into this primary kinetic study; no dietary salt intervention. Human protein and host-cell species differ. Evidence access: Primary full text A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31270129/ · DOI 10.1085/jgp.201912318

evidence_access

Primary full text

experimental_model

Human recombinant GlyT2, voltage clamp and kinetic modeling.

limitations

Methods refer to GlyT2a and a purchased GlyT2b plasmid; this record stays at gene level rather than resolving that isoform discrepancy by guesswork.

nutrient_topic

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

plain_language

A second transporter uses a different ion coupling to accumulate the same substrate.

primary_references

A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31270129/ · DOI 10.1085/jgp.201912318

transport_effect

raises Recorded as sodium/chloride-coupled glycine uptake.

transport_pool

the expressing cell Recorded as sodium/chloride-coupled glycine uptake.

Glycine: supply, one-carbon allocation, receptors and cross-nutrient mechanisms (2026-09-19) · lines 34–40

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant GlyT2, voltage clamp and kinetic modeling. · source_derived_draft · unverified_draft

## glycine-glyt2-transport A second transporter uses a different ion coupling to accumulate the same substrate. Human GlyT2 expressed in COS-7 cells supported sodium/chloride-coupled glycine uptake; the study modeled its established 3 Na+:1 Cl-:1 glycine stoichiometry. Model: Human recombinant GlyT2, voltage clamp and kinetic modeling. Limitations: Methods refer to GlyT2a and a purchased GlyT2b plasmid; this record stays at gene level rather than resolving that isoform discrepancy by guesswork. Evidence access: Primary full text A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31270129/ · DOI 10.1085/jgp.201912318

endpoint

HCl infusion causing acute mineral acidemia raised plasma potassium in the conscious-dog experiment.

experimental-exposure

Experimental acute mineral acidemia with hyperkalemia; not potassium deficiency or excessive potassium intake.

experimental_model

Twelve conscious dogs with portal/hepatic/systemic sampling; beta-hydroxybutyric acid 7 mEq/kg or HCl 3 mEq/kg infused over 30 minutes; additional anesthetized and obstructed-urinary-tract studies.

limitations

Acute HCl infusion, not every acidosis; portal glucagon rose and direct H/K exchange was not isolated.

nutrient_topic

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

organism

Canis lupus familiaris

plain_language

Acid type affected the potassium response; a rise in blood potassium did not imply excess potassium intake.

primary_references

[adrogue-1985-acid-infusion] Role of the endocrine pancreas in the kalemic response to acute metabolic acidosis in conscious dogs (1985). https://www.jci.org/articles/view/111775 DOI: 10.1172/JCI111775

tissue_or_cell_type

systemic and splanchnic circulation

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1151–1162

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve conscious dogs with portal/hepatic/systemic sampling; beta-hydroxybutyric acid 7 mEq/kg or HCl 3 mEq/kg infused over 30 minutes; additional anesthetized and obstructed-urinary-tract studies. · source_derived_draft · unverified_draft

### hcl-acidemia-raises-plasma-k HCl infusion causing acute mineral acidemia raised plasma potassium in the conscious-dog experiment. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Acid type affected the potassium response; a rise in blood potassium did not imply excess potassium intake. organism: Canis lupus familiaris tissue_or_cell_type: systemic and splanchnic circulation experimental_model: Twelve conscious dogs with portal/hepatic/systemic sampling; beta-hydroxybutyric acid 7 mEq/kg or HCl 3 mEq/kg infused over 30 minutes; additional anesthetized and obstructed-urinary-tract studies. limitations: Acute HCl infusion, not every acidosis; portal glucagon rose and direct H/K exchange was not isolated. experimental-exposure: Experimental acute mineral acidemia with hyperkalemia; not potassium deficiency or excessive potassium intake. endpoint: HCl infusion causing acute mineral acidemia raised plasma potassium in the conscious-dog experiment. [adrogue-1985-acid-infusion] Role of the endocrine pancreas in the kalemic response to acute metabolic acidosis in conscious dogs (1985). https://www.jci.org/articles/view/111775 DOI: 10.1172/JCI111775

cross_nutrient

Chloride salt/kidney context -> pressure.

experimental_model

Same five-day periods.

limitations

Context difference, not proof of a universal adverse potassium effect; molecular mediator unproven.

nutrient_topic

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

organism

Homo sapiens

plain_language

The pressure response differed from trials in people with better kidney function.

primary_references

[k-ckd-salts2026] Randomized Cross-Over Trial of Electrolyte, Acid-Base and Blood Pressure Effects of Salt Supplements in CKD (2026). https://pubmed.ncbi.nlm.nih.gov/42381762/ DOI: 10.1016/j.ekir.2026.106619

tissue_or_cell_type

Systemic circulation

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1685–1695

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same five-day periods. · source_derived_draft · unverified_draft

### k-ckd-chloride-salt-pressure Potassium chloride and sodium chloride increased home systolic pressure versus placebo in the CKD crossover. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pressure response differed from trials in people with better kidney function. organism: Homo sapiens tissue_or_cell_type: Systemic circulation experimental_model: Same five-day periods. limitations: Context difference, not proof of a universal adverse potassium effect; molecular mediator unproven. cross_nutrient: Chloride salt/kidney context -> pressure. [k-ckd-salts2026] Randomized Cross-Over Trial of Electrolyte, Acid-Base and Blood Pressure Effects of Salt Supplements in CKD (2026). https://pubmed.ncbi.nlm.nih.gov/42381762/ DOI: 10.1016/j.ekir.2026.106619

cross_nutrient

Potassium salt/chloride -> acid-base balance.

experimental_model

Same two-week CKD cohort.

limitations

No randomized comparator; no significant blood-pressure or eGFR change.

nutrient_topic

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

organism

Homo sapiens

plain_language

The chloride salt affected acid-base measurements as well as potassium.

primary_references

[k-gritter2022] Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD (2022). https://pubmed.ncbi.nlm.nih.gov/35609996/ DOI: 10.1681/asn.2022020147

tissue_or_cell_type

Plasma and urine

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1650–1660

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same two-week CKD cohort. · source_derived_draft · unverified_draft

### k-ckd-kcl-bicarbonate-response The same KCl run-in modestly lowered mean bicarbonate from 24.5 to 23.7 mmol/L and increased chloride; urinary ammonium did not increase. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The chloride salt affected acid-base measurements as well as potassium. organism: Homo sapiens tissue_or_cell_type: Plasma and urine experimental_model: Same two-week CKD cohort. limitations: No randomized comparator; no significant blood-pressure or eGFR change. cross_nutrient: Potassium salt/chloride -> acid-base balance. [k-gritter2022] Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD (2022). https://pubmed.ncbi.nlm.nih.gov/35609996/ DOI: 10.1681/asn.2022020147

availability_state

biomarker_context Imported condition classification; unverified.

cross_nutrient

Human biomarker evidence links increased KCl intake to altered NaCl-transporter regulation.

evidence_location

Primary abstract; randomized crossover uEV immunoblots.

experimental_model

Five-day crossover phases; 18 analyzed healthy participants; controlled high-Na/low-K diet

limitations

Vesicle cargo is an indirect renal readout; no dietary recommendation or direct transport-flux inference.

nutrient_topic

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

organism

Homo sapiens

plain_language

A human urine marker of the sodium-chloride transporter fell when potassium intake increased.

primary_references

[wu-2023-human-ncc] Randomized Trial on the Effect of Oral Potassium Chloride Supplementation on the Thiazide-Sensitive Sodium Chloride Cotransporter in Healthy Adults (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC10239795/ DOI: 10.1016/j.ekir.2023.03.011

tissue_or_cell_type

Urinary extracellular vesicles

trigger_kind

biomarker_context Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (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 · Five-day crossover phases; 18 analyzed healthy participants; controlled high-Na/low-K diet · source_derived_draft · unverified_draft

### renal-human-kcl-lowers-uev-ncc Supplementary KCl lowered total and phosphorylated NCC in urinary extracellular vesicles versus placebo in a randomized crossover study. Condition category: biomarker_context nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A human urine marker of the sodium-chloride transporter fell when potassium intake increased. organism: Homo sapiens tissue_or_cell_type: Urinary extracellular vesicles experimental_model: Five-day crossover phases; 18 analyzed healthy participants; controlled high-Na/low-K diet limitations: Vesicle cargo is an indirect renal readout; no dietary recommendation or direct transport-flux inference. cross_nutrient: Human biomarker evidence links increased KCl intake to altered NaCl-transporter regulation. evidence_location: Primary abstract; randomized crossover uEV immunoblots. [wu-2023-human-ncc] Randomized Trial on the Effect of Oral Potassium Chloride Supplementation on the Thiazide-Sensitive Sodium Chloride Cotransporter in Healthy Adults (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC10239795/ DOI: 10.1016/j.ekir.2023.03.011

cross_nutrient

Extracellular K controls the intracellular chloride signal.

evidence_location

Figure 6A-B; Figure S5.

experimental_model

Cell culture and Kir4.1 mutant comparisons

limitations

HEK chloride and WNK expression differ from native DCT.

nutrient_topic

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

organism

Homo sapiens; Mus musculus cell lines

plain_language

A change outside the cell can change chloride inside, connecting potassium sensing to salt transport.

primary_references

[terker-2015-k-voltage-chloride] Potassium Modulates Electrolyte Balance and Blood Pressure through Effects on Distal Cell Voltage and Chloride (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4332769/ DOI: 10.1016/j.cmet.2014.12.006

tissue_or_cell_type

HEK293 and mDCT cells

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 125–136

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell culture and Kir4.1 mutant comparisons · source_derived_draft · unverified_draft

### renal-low-external-k-lowers-cell-chloride Low-K medium lowered intracellular chloride in HEK293 and mDCT cells; depolarizing Kir4.1 mutants increased it. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A change outside the cell can change chloride inside, connecting potassium sensing to salt transport. organism: Homo sapiens; Mus musculus cell lines tissue_or_cell_type: HEK293 and mDCT cells experimental_model: Cell culture and Kir4.1 mutant comparisons limitations: HEK chloride and WNK expression differ from native DCT. cross_nutrient: Extracellular K controls the intracellular chloride signal. evidence_location: Figure 6A-B; Figure S5. [terker-2015-k-voltage-chloride] Potassium Modulates Electrolyte Balance and Blood Pressure through Effects on Distal Cell Voltage and Chloride (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4332769/ DOI: 10.1016/j.cmet.2014.12.006

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Low K availability increases signaling for sodium/chloride reabsorption.

evidence_location

Results; dietary NCC immunoblots.

experimental_model

Diet manipulation

limitations

pNCC is an activity-associated proxy; this is not a universal dietary threshold.

nutrient_topic

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

organism

Mus musculus

plain_language

With little dietary potassium, the kidney increases a sodium-chloride transporter signal.

primary_references

[terker-2015-k-voltage-chloride] Potassium Modulates Electrolyte Balance and Blood Pressure through Effects on Distal Cell Voltage and Chloride (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4332769/ DOI: 10.1016/j.cmet.2014.12.006

tissue_or_cell_type

Distal convoluted tubule

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 99–110

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

### renal-low-k-activates-ncc High-salt/low-potassium feeding increased renal NCC phosphorylation in mice. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: With little dietary potassium, the kidney increases a sodium-chloride transporter signal. organism: Mus musculus tissue_or_cell_type: Distal convoluted tubule experimental_model: Diet manipulation limitations: pNCC is an activity-associated proxy; this is not a universal dietary threshold. cross_nutrient: Low K availability increases signaling for sodium/chloride reabsorption. evidence_location: Results; dietary NCC immunoblots. [terker-2015-k-voltage-chloride] Potassium Modulates Electrolyte Balance and Blood Pressure through Effects on Distal Cell Voltage and Chloride (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4332769/ DOI: 10.1016/j.cmet.2014.12.006

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Low K increases urinary calcium output under the tested sodium background.

evidence_location

Primary abstract; final-week balance results.

experimental_model

Four-week 0.2% versus 4% K diet; both 8% NaCl

limitations

Weanling males; unusual salt/mineral diets; causal transport site and BP mediation unproven.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

In this high-salt setting, lower potassium intake increased calcium loss in urine.

primary_references

[wu-1995-k-calcium] Potassium depletion and salt-sensitive hypertension in Dahl rats: effect on calcium, magnesium, and phosphate excretions (1995). https://pubmed.ncbi.nlm.nih.gov/7581265/ DOI: 10.3109/10641969509033647

tissue_or_cell_type

Kidney/urine

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 510–521

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four-week 0.2% versus 4% K diet; both 8% NaCl · source_derived_draft · unverified_draft

### renal-low-k-increases-calcium-loss-high-salt Low versus high dietary K increased calcium excretion in both salt-sensitive and salt-resistant Dahl rats on high NaCl. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this high-salt setting, lower potassium intake increased calcium loss in urine. organism: Rattus norvegicus tissue_or_cell_type: Kidney/urine experimental_model: Four-week 0.2% versus 4% K diet; both 8% NaCl limitations: Weanling males; unusual salt/mineral diets; causal transport site and BP mediation unproven. cross_nutrient: Low K increases urinary calcium output under the tested sodium background. evidence_location: Primary abstract; final-week balance results. [wu-1995-k-calcium] Potassium depletion and salt-sensitive hypertension in Dahl rats: effect on calcium, magnesium, and phosphate excretions (1995). https://pubmed.ncbi.nlm.nih.gov/7581265/ DOI: 10.3109/10641969509033647

cross_nutrient

Luminal K availability supports coupled sodium/chloride reabsorption.

evidence_location

Primary abstract; ion-removal and conductance-blocking experiments.

experimental_model

Isolated perfused tubules; K removal and barium blockade

limitations

Electrical surrogate; the study predates molecular identification of NKCC2 and ROMK.

nutrient_topic

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

organism

Oryctolagus cuniculus

plain_language

Recycled luminal potassium supports sodium and chloride uptake in the thick ascending limb.

primary_references

[greger-1981-luminal-k] Presence of luminal K+, a prerequisite for active NaCl transport in the cortical thick ascending limb of Henle's loop of rabbit kidney (1981). https://pubmed.ncbi.nlm.nih.gov/7322839/ DOI: 10.1007/BF00584588

tissue_or_cell_type

Cortical thick ascending limb

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 447–458

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated perfused tubules; K removal and barium blockade · source_derived_draft · unverified_draft

### renal-luminal-k-enables-tal-salt-transport Removing luminal K reduced active transport current in rabbit cortical TAL; combining K removal with luminal barium nearly abolished it. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Recycled luminal potassium supports sodium and chloride uptake in the thick ascending limb. organism: Oryctolagus cuniculus tissue_or_cell_type: Cortical thick ascending limb experimental_model: Isolated perfused tubules; K removal and barium blockade limitations: Electrical surrogate; the study predates molecular identification of NKCC2 and ROMK. cross_nutrient: Luminal K availability supports coupled sodium/chloride reabsorption. evidence_location: Primary abstract; ion-removal and conductance-blocking experiments. [greger-1981-luminal-k] Presence of luminal K+, a prerequisite for active NaCl transport in the cortical thick ascending limb of Henle's loop of rabbit kidney (1981). https://pubmed.ncbi.nlm.nih.gov/7322839/ DOI: 10.1007/BF00584588

cross_nutrient

High K can suppress the sodium/chloride transporter through additional signaling.

evidence_location

Primary abstract; low extracellular chloride and DIDS experiments.

experimental_model

Perfused kidney and kidney slices

limitations

Pharmacological/ionic tests do not prove every chloride-sensitive step is absent.

nutrient_topic

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

organism

Mus musculus

plain_language

The rapid high-potassium response can persist when tested chloride movements are disrupted.

primary_references

[penton-2016-native-potassium-switch] Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl--dependent and independent mechanisms (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5088235/ DOI: 10.1113/JP272504

tissue_or_cell_type

Native DCT

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 229–240

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

### renal-native-high-k-cl-independent-ncc-off High-K-induced NCC dephosphorylation persisted during low extracellular chloride or chloride-channel blockade in mouse kidney preparations. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The rapid high-potassium response can persist when tested chloride movements are disrupted. organism: Mus musculus tissue_or_cell_type: Native DCT experimental_model: Perfused kidney and kidney slices limitations: Pharmacological/ionic tests do not prove every chloride-sensitive step is absent. cross_nutrient: High K can suppress the sodium/chloride transporter through additional signaling. evidence_location: Primary abstract; low extracellular chloride and DIDS experiments. [penton-2016-native-potassium-switch] Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl--dependent and independent mechanisms (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5088235/ DOI: 10.1113/JP272504

cross_nutrient

K concentration regulates sodium/chloride transport via chloride-sensitive signaling.

evidence_location

Abstract and Results; low chloride and DIDS comparisons.

experimental_model

Perfused kidney and kidney slices

limitations

Acute bath/perfusate manipulation is not whole-body potassium depletion.

nutrient_topic

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

organism

Mus musculus

plain_language

The low-potassium signal needs chloride movement to increase the transporter phosphate signal.

primary_references

[penton-2016-native-potassium-switch] Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl--dependent and independent mechanisms (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5088235/ DOI: 10.1113/JP272504

tissue_or_cell_type

Native DCT

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 216–227

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

### renal-native-low-k-requires-chloride-flux In native mouse kidney preparations, low extracellular K increased NCC phosphorylation through chloride-conductance-dependent SPAK/OSR1 signaling. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The low-potassium signal needs chloride movement to increase the transporter phosphate signal. organism: Mus musculus tissue_or_cell_type: Native DCT experimental_model: Perfused kidney and kidney slices limitations: Acute bath/perfusate manipulation is not whole-body potassium depletion. cross_nutrient: K concentration regulates sodium/chloride transport via chloride-sensitive signaling. evidence_location: Abstract and Results; low chloride and DIDS comparisons. [penton-2016-native-potassium-switch] Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl--dependent and independent mechanisms (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5088235/ DOI: 10.1113/JP272504

cross_nutrient

Potassium is a transported participant in this sodium/chloride entry mechanism.

evidence_location

Primary abstract; functional oocyte characterization.

experimental_model

Cloned renal cotransporter expression

limitations

Transport identity, not a dietary deficiency threshold; individual splice variants are not generalized.

nutrient_topic

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

organism

Mammalian proteins in Xenopus laevis oocytes

plain_language

NKCC2 moves potassium together with sodium and chloride; the related NCC transporter does not require potassium as cargo.

primary_references

[gamba-1994-nkcc2] Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney (1994). https://www.sciencedirect.com/science/article/pii/S0021925817324997 DOI: 10.1016/S0021-9258(17)32499-7

tissue_or_cell_type

Heterologous cell membrane

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 548–559

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloned renal cotransporter expression · source_derived_draft · unverified_draft

### renal-nkcc2-couples-potassium-to-salt-influx Cloned renal NKCC2 supported bumetanide-sensitive sodium-potassium-chloride cotransport in oocytes, distinct from NCC potassium-independent NaCl transport. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: NKCC2 moves potassium together with sodium and chloride; the related NCC transporter does not require potassium as cargo. organism: Mammalian proteins in Xenopus laevis oocytes tissue_or_cell_type: Heterologous cell membrane experimental_model: Cloned renal cotransporter expression limitations: Transport identity, not a dietary deficiency threshold; individual splice variants are not generalized. cross_nutrient: Potassium is a transported participant in this sodium/chloride entry mechanism. evidence_location: Primary abstract; functional oocyte characterization. [gamba-1994-nkcc2] Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney (1994). https://www.sciencedirect.com/science/article/pii/S0021925817324997 DOI: 10.1016/S0021-9258(17)32499-7

cross_nutrient

Defines the sodium/chloride transporter step of the potassium switch.

evidence_location

Primary abstract; phosphosite mapping, docking and Thr60Ala assays.

experimental_model

Recombinant phosphosite mapping and cell mutants

limitations

The dietary K response was not tested in this experiment.

nutrient_topic

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

organism

Human protein; HEK293/mpkDCT cells

plain_language

A kinase modifies the sodium-chloride transporter at regulatory sites.

primary_references

[richardson-2008-spak-osr1-ncc] Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1 (2008). https://pubmed.ncbi.nlm.nih.gov/18270262/ DOI: 10.1242/jcs.025312

tissue_or_cell_type

Biochemical assay and cultured kidney-derived cells

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 177–188

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant phosphosite mapping and cell mutants · source_derived_draft · unverified_draft

### renal-oxsr1-phosphorylates-ncc OSR1 phosphorylated human NCC at Thr46, Thr55 and Thr60; Thr60 mutation impaired chloride-depletion-induced NCC activation. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A kinase modifies the sodium-chloride transporter at regulatory sites. organism: Human protein; HEK293/mpkDCT cells tissue_or_cell_type: Biochemical assay and cultured kidney-derived cells experimental_model: Recombinant phosphosite mapping and cell mutants limitations: The dietary K response was not tested in this experiment. cross_nutrient: Defines the sodium/chloride transporter step of the potassium switch. evidence_location: Primary abstract; phosphosite mapping, docking and Thr60Ala assays. [richardson-2008-spak-osr1-ncc] Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1 (2008). https://pubmed.ncbi.nlm.nih.gov/18270262/ DOI: 10.1242/jcs.025312

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Loss of potassium-channel machinery impairs sodium/chloride recovery.

evidence_location

Lorenz primary abstract: micropuncture; Lu Results: TAL patch-clamp.

experimental_model

Pan-Romk deletion; micropuncture and companion patch-clamp studies

limitations

Hydronephrosis, developmental disease and compensatory transport complicate whole-kidney endpoints.

nutrient_topic

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

organism

Mus musculus

plain_language

ROMK-mediated potassium recycling supports loop salt recovery, while residual salt transport survives its deletion.

primary_references

[lorenz-2002-romk-tal] Impaired renal NaCl absorption in mice lacking the ROMK potassium channel, a model for type II Bartter's syndrome (2002). https://pubmed.ncbi.nlm.nih.gov/12122007/ DOI: 10.1074/jbc.M205627200 [lu-2002-romk-null] Absence of small conductance K+ channel (SK) activity in apical membranes of thick ascending limb and cortical collecting duct in ROMK (Bartter's) knockout mice (2002). https://pmc.ncbi.nlm.nih.gov/articles/PMC4426997/ DOI: 10.1074/jbc.M206644200

tissue_or_cell_type

Thick ascending limb

trigger_kind

machinery_impairment Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 561–573

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pan-Romk deletion; micropuncture and companion patch-clamp studies · source_derived_draft · unverified_draft

### renal-romk-supports-tal-salt-reabsorption Romk-null mice had reduced, but persisting, TAL NaCl absorption by micropuncture; the companion study demonstrated loss of native apical small-conductance K channels. Condition category: machinery_impairment nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: ROMK-mediated potassium recycling supports loop salt recovery, while residual salt transport survives its deletion. organism: Mus musculus tissue_or_cell_type: Thick ascending limb experimental_model: Pan-Romk deletion; micropuncture and companion patch-clamp studies limitations: Hydronephrosis, developmental disease and compensatory transport complicate whole-kidney endpoints. cross_nutrient: Loss of potassium-channel machinery impairs sodium/chloride recovery. evidence_location: Lorenz primary abstract: micropuncture; Lu Results: TAL patch-clamp. [lorenz-2002-romk-tal] Impaired renal NaCl absorption in mice lacking the ROMK potassium channel, a model for type II Bartter's syndrome (2002). https://pubmed.ncbi.nlm.nih.gov/12122007/ DOI: 10.1074/jbc.M205627200 [lu-2002-romk-null] Absence of small conductance K+ channel (SK) activity in apical membranes of thick ascending limb and cortical collecting duct in ROMK (Bartter's) knockout mice (2002). https://pmc.ncbi.nlm.nih.gov/articles/PMC4426997/ DOI: 10.1074/jbc.M206644200

cross_nutrient

Defines the sodium/chloride transporter step of the potassium switch.

evidence_location

Primary abstract; phosphosite mapping, docking and Thr60Ala assays.

experimental_model

Recombinant phosphosite mapping and cell mutants

limitations

The dietary K response was not tested in this experiment.

nutrient_topic

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

organism

Human protein; HEK293/mpkDCT cells

plain_language

A kinase modifies the sodium-chloride transporter at regulatory sites.

primary_references

[richardson-2008-spak-osr1-ncc] Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1 (2008). https://pubmed.ncbi.nlm.nih.gov/18270262/ DOI: 10.1242/jcs.025312

tissue_or_cell_type

Biochemical assay and cultured kidney-derived cells

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 164–175

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant phosphosite mapping and cell mutants · source_derived_draft · unverified_draft

### renal-stk39-phosphorylates-ncc SPAK phosphorylated human NCC at Thr46, Thr55 and Thr60; Thr60 mutation impaired chloride-depletion-induced NCC activation. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A kinase modifies the sodium-chloride transporter at regulatory sites. organism: Human protein; HEK293/mpkDCT cells tissue_or_cell_type: Biochemical assay and cultured kidney-derived cells experimental_model: Recombinant phosphosite mapping and cell mutants limitations: The dietary K response was not tested in this experiment. cross_nutrient: Defines the sodium/chloride transporter step of the potassium switch. evidence_location: Primary abstract; phosphosite mapping, docking and Thr60Ala assays. [richardson-2008-spak-osr1-ncc] Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1 (2008). https://pubmed.ncbi.nlm.nih.gov/18270262/ DOI: 10.1242/jcs.025312

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

A chloride-sensing defect disrupts K control of sodium transport.

evidence_location

Primary abstract; acute gavage NCC comparison.

experimental_model

Wnk4 LLFF knockin; oral K gavage

limitations

Constitutive kinase activation and longer-term K responses must be distinguished.

nutrient_topic

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

organism

Mus musculus

plain_language

Making WNK4 insensitive to chloride blocks the rapid potassium response in this mouse model.

primary_references

[chen-2019-wnk4-sensor] WNK4 kinase is a physiological intracellular chloride sensor (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6410802/ DOI: 10.1073/pnas.1817220116

tissue_or_cell_type

Kidney DCT

trigger_kind

machinery_impairment Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 242–253

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wnk4 LLFF knockin; oral K gavage · source_derived_draft · unverified_draft

### renal-wnk4-chloride-mutant-blocks-acute-k-off Acute oral potassium failed to suppress NCC in mice carrying chloride-insensitive WNK4, unlike wild-type controls. Condition category: machinery_impairment nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Making WNK4 insensitive to chloride blocks the rapid potassium response in this mouse model. organism: Mus musculus tissue_or_cell_type: Kidney DCT experimental_model: Wnk4 LLFF knockin; oral K gavage limitations: Constitutive kinase activation and longer-term K responses must be distinguished. cross_nutrient: A chloride-sensing defect disrupts K control of sodium transport. evidence_location: Primary abstract; acute gavage NCC comparison. [chen-2019-wnk4-sensor] WNK4 kinase is a physiological intracellular chloride sensor (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6410802/ DOI: 10.1073/pnas.1817220116

evidence_access

Primary abstract

experimental_model

Rat protein in Xenopus oocytes; alanine and lysine did not inhibit the reported proline transport.

limitations

This is not a human dietary sodium or chloride threshold.

nutrient_topic

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

plain_language

The driving ions and membrane voltage affect how this transporter works.

primary_references

Identification of mammalian proline transporter SIT1 (SLC6A20) with characteristics of classical system imino. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15632147/ · DOI 10.1074/jbc.M413027200

transport_effect

raises Sodium-dependent, chloride-stimulated, voltage-dependent proline transport, which is inward.

transport_pool

the expressing cell Sodium-dependent, chloride-stimulated, voltage-dependent proline transport, which is inward.

L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 174–180

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat protein in Xenopus oocytes; alanine and lysine did not inhibit the reported proline transport. · source_derived_draft · unverified_draft

## l-proline-rat-sit1-ion-coupling The driving ions and membrane voltage affect how this transporter works. Rat SIT1 expressed in Xenopus oocytes transported proline with apparent K0.5 about 0.2 mM; transport depended on sodium, was stimulated by chloride and depended on voltage. Model: Rat protein in Xenopus oocytes; alanine and lysine did not inhibit the reported proline transport. Limitations: This is not a human dietary sodium or chloride threshold. Evidence access: Primary abstract Identification of mammalian proline transporter SIT1 (SLC6A20) with characteristics of classical system imino. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15632147/ · DOI 10.1074/jbc.M413027200

evidence_access

Primary abstract

experimental_model

Canine kidney epithelial Ussing-chamber measurements; concentration-dependent bath exposure.

limitations

The source identifies CFTR-associated current; this is not a human dietary chloride-depletion mechanism.

nutrient_topic

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

plain_language

Chloride movement can determine fluid accumulation in a tissue model.

primary_references

Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23536832/ · DOI 10.1371/journal.pone.0058871

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 298–304

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Canine kidney epithelial Ussing-chamber measurements; concentration-dependent bath exposure. · source_derived_draft · unverified_draft

## stevia-cftr-current Chloride movement can determine fluid accumulation in a tissue model. Steviol acutely reduced forskolin-stimulated apical chloride current in canine MDCK epithelia. Model: Canine kidney epithelial Ussing-chamber measurements; concentration-dependent bath exposure. Limitations: The source identifies CFTR-associated current; this is not a human dietary chloride-depletion mechanism. Evidence access: Primary abstract Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23536832/ · DOI 10.1371/journal.pone.0058871

evidence_access

Primary abstract

experimental_model

Three-dimensional canine kidney cyst culture.

limitations

This does not show clinical treatment of human polycystic kidney disease.

nutrient_topic

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

plain_language

Reduced fluid-secretion-associated growth was separable from measured cell killing in this assay.

primary_references

Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23536832/ · DOI 10.1371/journal.pone.0058871

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 314–320

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Three-dimensional canine kidney cyst culture. · source_derived_draft · unverified_draft

## stevia-cyst-growth Reduced fluid-secretion-associated growth was separable from measured cell killing in this assay. Steviol at 100 micromolar reversibly inhibited MDCK cyst formation and growth; doses up to 200 micromolar did not alter measured cell viability, proliferation or apoptosis. Model: Three-dimensional canine kidney cyst culture. Limitations: This does not show clinical treatment of human polycystic kidney disease. Evidence access: Primary abstract Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23536832/ · DOI 10.1371/journal.pone.0058871

evidence_access

Primary abstract

experimental_model

Mouse colon transporter expressed in human retinal pigment epithelial cells and frog oocytes.

limitations

The transporter is mouse-derived even in a human host cell; dietary sodium/chloride effects were not tested.

nutrient_topic

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

plain_language

A second uptake route couples carnitine to both salt ions.

primary_references

Na+- and Cl--coupled active transport of carnitine by the amino acid transporter ATB(0,+) from mouse colon expressed in HRPE cells and Xenopus oocytes. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11306651/ · DOI 10.1111/j.1469-7793.2001.0297f.x

transport_effect

raises Carnitine transport requiring both sodium and chloride, which is inward.

transport_pool

the expressing cell Carnitine transport requiring both sodium and chloride, which is inward.

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 466–472

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse colon transporter expressed in human retinal pigment epithelial cells and frog oocytes. · source_derived_draft · unverified_draft

## l-carnitine-atb-carnitine A second uptake route couples carnitine to both salt ions. Expressing mouse ATB0,+ in HRPE cells enabled carnitine transport requiring both sodium and chloride; activation analysis was consistent with two sodium ions and one chloride ion. Model: Mouse colon transporter expressed in human retinal pigment epithelial cells and frog oocytes. Limitations: The transporter is mouse-derived even in a human host cell; dietary sodium/chloride effects were not tested. Evidence access: Primary abstract Na+- and Cl--coupled active transport of carnitine by the amino acid transporter ATB(0,+) from mouse colon expressed in HRPE cells and Xenopus oocytes. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11306651/ · DOI 10.1111/j.1469-7793.2001.0297f.x

evidence_span

{"source_cache": "artifacts/berberine-research/21747769.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4", "start_char": 0, "end_char": 1734, "text_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4"}

experimental_model

Ussing-chamber short-circuit current, patch clamp and kinase perturbation

exposure

Forskolin-stimulated secretion and berberine; IC50 about 80 micromolar

limitations

Intestinal cell mechanism, not proof of systemic potassium depletion. The observed channel complex differs from cardiac KCNQ1/KCNE1.

nutrient_topic

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

organism

Human T84 colonic cells

plain_language

The potassium-channel response is connected to movement of a different ion: chloride.

primary_references

[berberine-p21747769] Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels. (2011). https://pubmed.ncbi.nlm.nih.gov/21747769/ DOI: 10.3389/fphys.2011.00033

tissue_or_cell_type

Basolateral potassium recycling and chloride secretion

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 571–582

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ussing-chamber short-circuit current, patch clamp and kinase perturbation · source_derived_draft · unverified_draft

### berberine-chloride-secretion Berberine decreased forskolin-stimulated chloride secretion in T84 monolayers through a predominantly PKC-alpha-dependent pathway. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The potassium-channel response is connected to movement of a different ion: chloride. organism: Human T84 colonic cells tissue_or_cell_type: Basolateral potassium recycling and chloride secretion experimental_model: Ussing-chamber short-circuit current, patch clamp and kinase perturbation limitations: Intestinal cell mechanism, not proof of systemic potassium depletion. The observed channel complex differs from cardiac KCNQ1/KCNE1. exposure: Forskolin-stimulated secretion and berberine; IC50 about 80 micromolar evidence_span: {"source_cache": "artifacts/berberine-research/21747769.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4", "start_char": 0, "end_char": 1734, "text_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4"} [berberine-p21747769] Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels. (2011). https://pubmed.ncbi.nlm.nih.gov/21747769/ DOI: 10.3389/fphys.2011.00033

evidence_access

Primary full text

experimental_model

Rat pinealocytes and slices; electrogenic current assays.

limitations

Subtype assignment is pharmacological and supported by prior expression work, not a subtype-knockout demonstration.

nutrient_topic

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

plain_language

Transporting the amino acid can itself change the cell voltage.

primary_references

Glutamate transporter-mediated glutamate secretion in the mammalian pineal gland. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18945893/ · DOI 10.1523/JNEUROSCI.0894-08.2008

D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 152–158

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat pinealocytes and slices; electrogenic current assays. · source_derived_draft · unverified_draft

## d-aspartate-pineal-current Transporting the amino acid can itself change the cell voltage. D-aspartate elicited inward transporter-associated current in isolated rat pinealocytes; pharmacology favored GLT-1-type transport over ionotropic glutamate receptors. Model: Rat pinealocytes and slices; electrogenic current assays. Limitations: Subtype assignment is pharmacological and supported by prior expression work, not a subtype-knockout demonstration. Evidence access: Primary full text Glutamate transporter-mediated glutamate secretion in the mammalian pineal gland. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18945893/ · DOI 10.1523/JNEUROSCI.0894-08.2008

cross_nutrient

true

experimental_model

Purified human SLC26A7 cryo-EM; recombinant human SLC26A7 in HEK293T cells with whole-cell patch clamp

exposure

Apo and iodide-loaded cryo-EM structures at approximately 3.2 and 3.1 Å; Fig. 2.

limitations

Binding-site structures support transport capability but do not establish apical versus basolateral thyroid localization.

nutrient_topic

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

organism

Homo sapiens

plain_language

A recent structure directly supports iodide binding by human SLC26A7.

primary_references

[iodine-trans-slc26a7-structure2025] Structural basis for substrate recognition mechanism of human SLC26A7. (2025). https://pubmed.ncbi.nlm.nih.gov/40817112/ DOI: 10.1038/s41467-025-62792-w

tissue_or_cell_type

Purified membrane protein

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 453–464

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SLC26A7 cryo-EM; recombinant human SLC26A7 in HEK293T cells with whole-cell patch clamp · source_derived_draft · unverified_draft

### iodine-trans-a7-bound-iodide2025 Human SLC26A7 cryo-EM maps in the iodide-loaded state supported iodide assignments at a canonical site and a second site near the gate-domain interface. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A recent structure directly supports iodide binding by human SLC26A7. organism: Homo sapiens tissue_or_cell_type: Purified membrane protein experimental_model: Purified human SLC26A7 cryo-EM; recombinant human SLC26A7 in HEK293T cells with whole-cell patch clamp limitations: Binding-site structures support transport capability but do not establish apical versus basolateral thyroid localization. exposure: Apo and iodide-loaded cryo-EM structures at approximately 3.2 and 3.1 Å; Fig. 2. cross_nutrient: true [iodine-trans-slc26a7-structure2025] Structural basis for substrate recognition mechanism of human SLC26A7. (2025). https://pubmed.ncbi.nlm.nih.gov/40817112/ DOI: 10.1038/s41467-025-62792-w

cross_nutrient

true

experimental_model

Purified human SLC26A7 cryo-EM; recombinant human SLC26A7 in HEK293T cells with whole-cell patch clamp

exposure

Whole-cell patch clamp 24 hours after 2 micrograms plasmid transfection; 50/149 mM total halide conditions; voltage steps from −100 to +100 mV.

limitations

Halide concentrations greatly exceed physiological iodide; transport capacity does not settle net thyroid iodide flux, stoichiometry or localization.

nutrient_topic

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

organism

Homo sapiens

plain_language

Human SLC26A7 can carry both chloride and iodide under controlled laboratory conditions.

primary_references

[iodine-trans-slc26a7-structure2025] Structural basis for substrate recognition mechanism of human SLC26A7. (2025). https://pubmed.ncbi.nlm.nih.gov/40817112/ DOI: 10.1038/s41467-025-62792-w

tissue_or_cell_type

HEK293T plasma membrane

transport_effect

depends Recorded as a halide current that rose with bath halide concentration, so the direction follows the gradient.

transport_pool

the cytosol across the plasma membrane Recorded as a halide current that rose with bath halide concentration, so the direction follows the gradient.

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 466–477

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SLC26A7 cryo-EM; recombinant human SLC26A7 in HEK293T cells with whole-cell patch clamp · source_derived_draft · unverified_draft

### iodine-trans-a7-halide-current2025 Human SLC26A7 expression in HEK293T cells generated chloride and iodide currents that increased when bath halide concentrations rose from 50 to 149 mM. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human SLC26A7 can carry both chloride and iodide under controlled laboratory conditions. organism: Homo sapiens tissue_or_cell_type: HEK293T plasma membrane experimental_model: Purified human SLC26A7 cryo-EM; recombinant human SLC26A7 in HEK293T cells with whole-cell patch clamp limitations: Halide concentrations greatly exceed physiological iodide; transport capacity does not settle net thyroid iodide flux, stoichiometry or localization. exposure: Whole-cell patch clamp 24 hours after 2 micrograms plasmid transfection; 50/149 mM total halide conditions; voltage steps from −100 to +100 mV. cross_nutrient: true [iodine-trans-slc26a7-structure2025] Structural basis for substrate recognition mechanism of human SLC26A7. (2025). https://pubmed.ncbi.nlm.nih.gov/40817112/ DOI: 10.1038/s41467-025-62792-w

evidence_access

Primary full text

experimental_model

Rodent synaptic-vesicle acidification assays; glutamate compared with chloride.

limitations

The preparation does not show that glutamate supplements increase human dopamine.

nutrient_topic

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

plain_language

One transmitter can influence storage of another through shared vesicle chemistry.

primary_references

Vesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20223200/ · DOI 10.1016/j.neuron.2010.02.012

L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 314–320

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rodent synaptic-vesicle acidification assays; glutamate compared with chloride. · source_derived_draft · unverified_draft

## glutamate-glutamate-vesicle-acidification One transmitter can influence storage of another through shared vesicle chemistry. Glutamate co-entry increased vesicular acidification in the study, supporting the pH gradient used for monoamine storage. Model: Rodent synaptic-vesicle acidification assays; glutamate compared with chloride. Limitations: The preparation does not show that glutamate supplements increase human dopamine. Evidence access: Primary full text Vesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20223200/ · DOI 10.1016/j.neuron.2010.02.012

evidence_access

Primary full text

experimental_model

Purified rat transporter; controlled chloride/acetoacetate concentrations and washout.

limitations

This mechanism alone does not establish the effects of fasting or a ketogenic diet in humans.

nutrient_topic

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

plain_language

A metabolic fuel-related molecule altered transmitter packaging in a biochemical system.

primary_references

Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002

L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 282–288

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified rat transporter; controlled chloride/acetoacetate concentrations and washout. · source_derived_draft · unverified_draft

## glutamate-vglut2-acetoacetate A metabolic fuel-related molecule altered transmitter packaging in a biochemical system. Acetoacetate reversibly inhibited reconstituted rat VGLUT2 uptake with a chloride-dependent shift consistent with competition at allosteric regulation. Model: Purified rat transporter; controlled chloride/acetoacetate concentrations and washout. Limitations: This mechanism alone does not establish the effects of fasting or a ketogenic diet in humans. Evidence access: Primary full text Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002

dose

Micromolar substrates; concentration-dependent chlorination assays

duration

Rapid kinetic measurements at 25 degrees C; pH 7.0 and pH 5.0

evidence_access

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

evidence_scope

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

experimental_model

Purified human myeloperoxidase; cell-free chemistry

limitations

MPO substrates can stimulate or inhibit chlorination depending on conditions; not a universal MPO inhibitor.

nutrient_topic

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

organism

Purified human myeloperoxidase; cell-free chemistry

plain_language

Betanin stimulated or inhibited MPO chlorination at neutral pH depending on concentration; at pH 5 only inhibition was observed.

primary_references

Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid. (2005). https://pubmed.ncbi.nlm.nih.gov/15913556/ DOI: 10.1016/j.bbrc.2005.05.031

route

In vitro reagent addition

tissue

MPO redox cycle and HOCl solution

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 137–145

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Purified human myeloperoxidase; cell-free chemistry · source_derived_draft · unverified_draft

## betalains-betanin-chlorination Betanin stimulated or inhibited MPO chlorination at neutral pH depending on concentration; at pH 5 only inhibition was observed. Model/species: Purified human myeloperoxidase; cell-free chemistry Tissue: MPO redox cycle and HOCl solution Exposure: Micromolar substrates; concentration-dependent chlorination assays Route: In vitro reagent addition Duration: Rapid kinetic measurements at 25 degrees C; pH 7.0 and pH 5.0 Limits: MPO substrates can stimulate or inhibit chlorination depending on conditions; not a universal MPO inhibitor. Primary reference: Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid. (2005). https://pubmed.ncbi.nlm.nih.gov/15913556/ DOI: 10.1016/j.bbrc.2005.05.031

dose

Micromolar substrates; concentration-dependent chlorination assays

duration

Rapid kinetic measurements at 25 degrees C; pH 7.0 and pH 5.0

evidence_access

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

evidence_scope

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

experimental_model

Purified human myeloperoxidase; cell-free chemistry

limitations

MPO substrates can stimulate or inhibit chlorination depending on conditions; not a universal MPO inhibitor.

nutrient_topic

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

organism

Purified human myeloperoxidase; cell-free chemistry

plain_language

Indicaxanthin stimulated or inhibited MPO chlorination at neutral pH depending on concentration; at pH 5 only inhibition was observed.

primary_references

Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid. (2005). https://pubmed.ncbi.nlm.nih.gov/15913556/ DOI: 10.1016/j.bbrc.2005.05.031

route

In vitro reagent addition

tissue

MPO redox cycle and HOCl solution

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 177–185

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Purified human myeloperoxidase; cell-free chemistry · source_derived_draft · unverified_draft

## betalains-indicaxanthin-chlorination Indicaxanthin stimulated or inhibited MPO chlorination at neutral pH depending on concentration; at pH 5 only inhibition was observed. Model/species: Purified human myeloperoxidase; cell-free chemistry Tissue: MPO redox cycle and HOCl solution Exposure: Micromolar substrates; concentration-dependent chlorination assays Route: In vitro reagent addition Duration: Rapid kinetic measurements at 25 degrees C; pH 7.0 and pH 5.0 Limits: MPO substrates can stimulate or inhibit chlorination depending on conditions; not a universal MPO inhibitor. Primary reference: Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid. (2005). https://pubmed.ncbi.nlm.nih.gov/15913556/ DOI: 10.1016/j.bbrc.2005.05.031

evidence_access

Primary abstract

experimental_model

37 women, age 31–78; decaffeinated beverage with or without caffeine 6 mg/kg lean body mass; two-hour urine collection.

limitations

Acute renal handling. The exact tubular mechanism was unresolved; no long-term deficiency, bone loss or replacement requirement measured.

nutrient_topic

Caffeine collection; salts, coffee, species and coexposure contexts retain their identities. · Caffeine

plain_language

The acute urine measurement increased.

primary_references

Effects of dietary caffeine on renal handling of minerals in adult women. · 1990 · https://pubmed.ncbi.nlm.nih.gov/2402180/ · DOI 10.1016/0024-3205(90)90616-y

Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18) · lines 324–330

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · 37 women, age 31–78; decaffeinated beverage with or without caffeine 6 mg/kg lean body mass; two-hour urine collection. · source_derived_draft · unverified_draft

## caf-urine-cl The acute urine measurement increased. Urinary chloride/creatinine rose from 9200 to 14800 mg/g. Model: 37 women, age 31–78; decaffeinated beverage with or without caffeine 6 mg/kg lean body mass; two-hour urine collection. Limitations: Acute renal handling. The exact tubular mechanism was unresolved; no long-term deficiency, bone loss or replacement requirement measured. Evidence access: Primary abstract Effects of dietary caffeine on renal handling of minerals in adult women. · 1990 · https://pubmed.ncbi.nlm.nih.gov/2402180/ · DOI 10.1016/0024-3205(90)90616-y