Sodium ion

evidence_access

Primary full text

experimental_model

Everted mouse ileum; 1 mM L-isoleucine, five-minute uptake assay.

limitations

Does not imply extra dietary sodium improves absorption in sodium-replete people.

nutrient_topic

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

plain_language

An ion gradient helps the intestine take up this amino acid.

primary_references

Tissue-specific amino acid transporter partners ACE2 and collectrin differentially interact with hartnup mutations. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19185582/ · DOI 10.1053/j.gastro.2008.10.055

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 18–24

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Everted mouse ileum; 1 mM L-isoleucine, five-minute uptake assay. · source_derived_draft · unverified_draft

## isoleucine-intestinal-sodium An ion gradient helps the intestine take up this amino acid. Replacing sodium during mouse ileum uptake assays removed the sodium-dependent component of radiolabeled L-isoleucine uptake. Model: Everted mouse ileum; 1 mM L-isoleucine, five-minute uptake assay. Limitations: Does not imply extra dietary sodium improves absorption in sodium-replete people. Evidence access: Primary full text Tissue-specific amino acid transporter partners ACE2 and collectrin differentially interact with hartnup mutations. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19185582/ · DOI 10.1053/j.gastro.2008.10.055

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

evidence_span

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experimental_model

Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays

exposure

Acute hypoxia and inhibition of mitochondrial sodium/calcium exchange

limitations

Mechanistic research under hypoxia, including multiple preparations. Do not infer that dietary salt drives this chain, that every tissue responds identically, or that ROS here proves disease.

nutrient_topic

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

organism

Human and mouse cells; additional rat vascular experiments in the paper

plain_language

A sodium-linked membrane effect contributed to a mitochondrial redox signal.

primary_references

[sodium-p32728214] Na+ controls hypoxic signalling by the mitochondrial respiratory chain. (2020). https://pubmed.ncbi.nlm.nih.gov/32728214/ DOI: 10.1038/s41586-020-2551-y

tissue_or_cell_type

Mitochondrial matrix and inner membrane

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 811–822

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays · source_derived_draft · unverified_draft

### sodium-complex3-ros The pathway produced complex III superoxide; inhibiting mitochondrial sodium import blocked the response. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sodium-linked membrane effect contributed to a mitochondrial redox signal. organism: Human and mouse cells; additional rat vascular experiments in the paper tissue_or_cell_type: Mitochondrial matrix and inner membrane experimental_model: Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays limitations: Mechanistic research under hypoxia, including multiple preparations. Do not infer that dietary salt drives this chain, that every tissue responds identically, or that ROS here proves disease. exposure: Acute hypoxia and inhibition of mitochondrial sodium/calcium exchange evidence_span: {"source_cache": "artifacts/sodium-research/32728214.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2780431aa362c99c816f986e923fd65ed0c0324e8c8674af8ff2a2f9367762c1", "start_char": 0, "end_char": 1533, "text_sha256": "2780431aa362c99c816f986e923fd65ed0c0324e8c8674af8ff2a2f9367762c1"} [sodium-p32728214] Na+ controls hypoxic signalling by the mitochondrial respiratory chain. (2020). https://pubmed.ncbi.nlm.nih.gov/32728214/ DOI: 10.1038/s41586-020-2551-y

evidence_span

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experimental_model

Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays

exposure

Acute hypoxia and inhibition of mitochondrial sodium/calcium exchange

limitations

Mechanistic research under hypoxia, including multiple preparations. Do not infer that dietary salt drives this chain, that every tissue responds identically, or that ROS here proves disease.

nutrient_topic

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

organism

Human and mouse cells; additional rat vascular experiments in the paper

plain_language

Sodium changed the physical behavior of a mitochondrial membrane.

primary_references

[sodium-p32728214] Na+ controls hypoxic signalling by the mitochondrial respiratory chain. (2020). https://pubmed.ncbi.nlm.nih.gov/32728214/ DOI: 10.1038/s41586-020-2551-y

tissue_or_cell_type

Mitochondrial matrix and inner membrane

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 785–796

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays · source_derived_draft · unverified_draft

### sodium-membrane-fluidity Matrix sodium interacted with phospholipids and reduced inner-membrane fluidity in the study. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sodium changed the physical behavior of a mitochondrial membrane. organism: Human and mouse cells; additional rat vascular experiments in the paper tissue_or_cell_type: Mitochondrial matrix and inner membrane experimental_model: Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays limitations: Mechanistic research under hypoxia, including multiple preparations. Do not infer that dietary salt drives this chain, that every tissue responds identically, or that ROS here proves disease. exposure: Acute hypoxia and inhibition of mitochondrial sodium/calcium exchange evidence_span: {"source_cache": "artifacts/sodium-research/32728214.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2780431aa362c99c816f986e923fd65ed0c0324e8c8674af8ff2a2f9367762c1", "start_char": 0, "end_char": 1533, "text_sha256": "2780431aa362c99c816f986e923fd65ed0c0324e8c8674af8ff2a2f9367762c1"} [sodium-p32728214] Na+ controls hypoxic signalling by the mitochondrial respiratory chain. (2020). https://pubmed.ncbi.nlm.nih.gov/32728214/ DOI: 10.1038/s41586-020-2551-y

evidence_span

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experimental_model

Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays

exposure

Acute hypoxia and inhibition of mitochondrial sodium/calcium exchange

limitations

Mechanistic research under hypoxia, including multiple preparations. Do not infer that dietary salt drives this chain, that every tissue responds identically, or that ROS here proves disease.

nutrient_topic

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

organism

Human and mouse cells; additional rat vascular experiments in the paper

plain_language

The effect depended on how the respiratory machinery was organized.

primary_references

[sodium-p32728214] Na+ controls hypoxic signalling by the mitochondrial respiratory chain. (2020). https://pubmed.ncbi.nlm.nih.gov/32728214/ DOI: 10.1038/s41586-020-2551-y

tissue_or_cell_type

Mitochondrial matrix and inner membrane

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 798–809

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays · source_derived_draft · unverified_draft

### sodium-quinone-mobility The sodium-linked membrane change reduced free ubiquinone mobility between complexes II and III, while transport within supercomplexes was spared. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The effect depended on how the respiratory machinery was organized. organism: Human and mouse cells; additional rat vascular experiments in the paper tissue_or_cell_type: Mitochondrial matrix and inner membrane experimental_model: Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays limitations: Mechanistic research under hypoxia, including multiple preparations. Do not infer that dietary salt drives this chain, that every tissue responds identically, or that ROS here proves disease. exposure: Acute hypoxia and inhibition of mitochondrial sodium/calcium exchange evidence_span: {"source_cache": "artifacts/sodium-research/32728214.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2780431aa362c99c816f986e923fd65ed0c0324e8c8674af8ff2a2f9367762c1", "start_char": 0, "end_char": 1533, "text_sha256": "2780431aa362c99c816f986e923fd65ed0c0324e8c8674af8ff2a2f9367762c1"} [sodium-p32728214] Na+ controls hypoxic signalling by the mitochondrial respiratory chain. (2020). https://pubmed.ncbi.nlm.nih.gov/32728214/ DOI: 10.1038/s41586-020-2551-y

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_span

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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

Na+ 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 295–306

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-sodium Human CHT1-mediated choline uptake depended on Na+ in the oocyte assay. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Na+ 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

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experimental_model

Mouse knockout and cell transport experiments

exposure

LPC-bound versus unesterified DHA; sodium-dependent transport

limitations

LPC-DHA is a choline-containing lipid, not free choline. No claim that oral choline necessarily raises brain DHA.

nutrient_topic

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

organism

Mouse Mfsd2a and experimental expression system

plain_language

This lipid transport route also depends on an ion gradient.

primary_references

[choline-p24828044] Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. (2014). https://pubmed.ncbi.nlm.nih.gov/24828044/ DOI: 10.1038/nature13241

tissue_or_cell_type

Blood-brain-barrier endothelium

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 958–969

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse knockout and cell transport experiments · source_derived_draft · unverified_draft

### choline-mfsd2a-sodium Mfsd2a-mediated LPC transport was sodium-dependent. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This lipid transport route also depends on an ion gradient. organism: Mouse Mfsd2a and experimental expression system tissue_or_cell_type: Blood-brain-barrier endothelium experimental_model: Mouse knockout and cell transport experiments limitations: LPC-DHA is a choline-containing lipid, not free choline. No claim that oral choline necessarily raises brain DHA. exposure: LPC-bound versus unesterified DHA; sodium-dependent transport evidence_span: {"source_cache": "artifacts/choline-research/24828044.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695", "start_char": 0, "end_char": 1689, "text_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695"} [choline-p24828044] Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. (2014). https://pubmed.ncbi.nlm.nih.gov/24828044/ DOI: 10.1038/nature13241

evidence_access

Primary abstract

experimental_model

Dog kidney enzyme binding assay.

limitations

No human dietary sodium recommendation follows.

nutrient_topic

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

plain_language

The ionic environment changes how vanadate interacts with the pump.

primary_references

Vanadate binding to the (Na + K)-ATPase. · 1981 · https://pubmed.ncbi.nlm.nih.gov/6277881/ · DOI 10.1007/BF00743200

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 246–252

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Dog kidney enzyme binding assay. · source_derived_draft · unverified_draft

## vanadium-pump-sodium The ionic environment changes how vanadate interacts with the pump. Sodium decreased vanadate binding in magnesium-containing medium, whereas sodium and potassium had little effect in the manganese condition. Model: Dog kidney enzyme binding assay. Limitations: No human dietary sodium recommendation follows. Evidence access: Primary abstract Vanadate binding to the (Na + K)-ATPase. · 1981 · https://pubmed.ncbi.nlm.nih.gov/6277881/ · DOI 10.1007/BF00743200

evidence_access

Primary abstract

experimental_model

Human OCTN2 structures in ligand-free, carnitine/sodium-bound and ipratropium-bound conformations; 2025 primary study.

limitations

Structural coupling does not show that more sodium intake increases transport.

nutrient_topic

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

plain_language

Sodium supports transport through a separate coupled binding site.

primary_references

Structural basis of sodium ion-dependent carnitine transport by OCTN2. · 2025 · https://pubmed.ncbi.nlm.nih.gov/41318751/ · DOI 10.1038/s41467-025-66867-6

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 490–496

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human OCTN2 structures in ligand-free, carnitine/sodium-bound and ipratropium-bound conformations; 2025 primary study. · source_derived_draft · unverified_draft

## l-carnitine-octn2-structure Sodium supports transport through a separate coupled binding site. Human OCTN2 cryo-EM structures identified a sodium-binding cavity separate from the carnitine site, with allosteric coupling supported by electrophysiology. Model: Human OCTN2 structures in ligand-free, carnitine/sodium-bound and ipratropium-bound conformations; 2025 primary study. Limitations: Structural coupling does not show that more sodium intake increases transport. Evidence access: Primary abstract Structural basis of sodium ion-dependent carnitine transport by OCTN2. · 2025 · https://pubmed.ncbi.nlm.nih.gov/41318751/ · DOI 10.1038/s41467-025-66867-6

experimental_model

Human airway epithelial cells at an air–liquid interface; transepithelial radiotracer transport.

exposure_category

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

limitations

The proposed apical CFTR route was inferred pharmacologically, not proven by this experiment. This is iodide biology, not a KI-specific counter-ion effect.

nutrient_topic

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

plain_language

Sodium-dependent delivery supplies the airway defence system.

primary_references

Transcellular thiocyanate transport by human airway epithelia. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15345749/ · DOI 10.1113/jphysiol.2004.071548

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 152–158

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Human airway epithelial cells at an air–liquid interface; transepithelial radiotracer transport. · source_derived_draft · unverified_draft

## ki-air-sodium Sodium-dependent delivery supplies the airway defence system. Thiocyanate transport required basolateral sodium and concentrated thiocyanate tenfold apically. Model: Human airway epithelial cells at an air–liquid interface; transepithelial radiotracer transport. Limitations: The proposed apical CFTR route was inferred pharmacologically, not proven by this experiment. This is iodide biology, not a KI-specific counter-ion effect. Evidence location: Primary abstract Transcellular thiocyanate transport by human airway epithelia. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15345749/ · DOI 10.1113/jphysiol.2004.071548

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/theanine-research/18293419.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c94471071feadec8a04eafa7e9d53999dd9756b7f1d5dc1f351152b9b5f4b5d3", "start_char": 0, "end_char": 1751, "text_sha256": "c94471071feadec8a04eafa7e9d53999dd9756b7f1d5dc1f351152b9b5f4b5d3"}

experimental_model

Radiotracer uptake in synaptosomes and cultured neural cells

exposure

Theanine 0.1-10 millimolar in uptake assays; sustained 10 millimolar for glutamate release

limitations

High cell concentrations; 10 mM is far above the approximately 25 micromolar plasma peak in the separate human 100 mg study. Different cells from the system L screen; no claim all routes are sodium-dependent.

nutrient_topic

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

organism

Rat neurons and astroglia

plain_language

This particular transport system required its normal ionic environment.

primary_references

[theanine-p18293419] Theanine, an ingredient of green tea, inhibits [3H]glutamine transport in neurons and astroglia in rat brain. (2008). https://pubmed.ncbi.nlm.nih.gov/18293419/ DOI: 10.1002/jnr.21637

tissue_or_cell_type

Glutamine transport and extracellular glutamate

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Theanine: metabolism, neural signaling, nutrient connections and human outcomes (2026-09-17) · lines 276–287

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiotracer uptake in synaptosomes and cultured neural cells · source_derived_draft · unverified_draft

### theanine-sodium-replacement Replacing sodium chloride with choline chloride reduced theanine and glutamine accumulation in rat brain preparations. Condition category: machinery_impairment nutrient_topic: L-Theanine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This particular transport system required its normal ionic environment. organism: Rat neurons and astroglia tissue_or_cell_type: Glutamine transport and extracellular glutamate experimental_model: Radiotracer uptake in synaptosomes and cultured neural cells limitations: High cell concentrations; 10 mM is far above the approximately 25 micromolar plasma peak in the separate human 100 mg study. Different cells from the system L screen; no claim all routes are sodium-dependent. exposure: Theanine 0.1-10 millimolar in uptake assays; sustained 10 millimolar for glutamate release evidence_span: {"source_cache": "artifacts/theanine-research/18293419.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c94471071feadec8a04eafa7e9d53999dd9756b7f1d5dc1f351152b9b5f4b5d3", "start_char": 0, "end_char": 1751, "text_sha256": "c94471071feadec8a04eafa7e9d53999dd9756b7f1d5dc1f351152b9b5f4b5d3"} [theanine-p18293419] Theanine, an ingredient of green tea, inhibits [3H]glutamine transport in neurons and astroglia in rat brain. (2008). https://pubmed.ncbi.nlm.nih.gov/18293419/ DOI: 10.1002/jnr.21637

evidence_access

Primary abstract

experimental_model

Jejunum from male castrated Pietrain × Danbred pigs receiving different methionine supplements.

limitations

Tissue flux integrates several transporters; it does not identify one exclusive threonine carrier.

nutrient_topic

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

plain_language

An ion gradient contributes to intestinal amino-acid movement.

primary_references

Transport of Neutral Amino Acids in the Jejunum of Pigs with Special Consideration of L-Methionine. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39408384/ · DOI 10.3390/nu16193418

L-Threonine: translation, intestinal barrier, metabolism 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 · Jejunum from male castrated Pietrain × Danbred pigs receiving different methionine supplements. · source_derived_draft · unverified_draft

## l-threonine-pig-sodium-uptake An ion gradient contributes to intestinal amino-acid movement. Ex vivo pig jejunal L-threonine flux was sodium dependent in assays using 50 micromolar and 5 millimolar amino-acid concentrations. Model: Jejunum from male castrated Pietrain × Danbred pigs receiving different methionine supplements. Limitations: Tissue flux integrates several transporters; it does not identify one exclusive threonine carrier. Evidence access: Primary abstract Transport of Neutral Amino Acids in the Jejunum of Pigs with Special Consideration of L-Methionine. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39408384/ · DOI 10.3390/nu16193418

evidence_span

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experimental_model

Apical transport kinetics and transporter knockdown

exposure

Citrulline uptake on permeable supports; SLC6A19 or SLC7A9 silencing

limitations

Renal evidence must not be relabeled as a demonstrated human intestinal transport mechanism.

nutrient_topic

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

organism

Human HK-2 cells; rat cultures studied separately

plain_language

Sodium dependence applies to part of the transport system, not every citrulline transporter.

primary_references

[citrulline-p19322909] Transport characteristics of L-citrulline in renal apical membrane of proximal tubular cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19322909/ DOI: 10.1002/bdd.653

tissue_or_cell_type

Renal proximal tubular epithelium

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 424–435

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

### citrulline-renal-sodium HK-2 citrulline uptake included two sodium-dependent saturable components and one sodium-independent component. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sodium dependence applies to part of the transport system, not every citrulline transporter. organism: Human HK-2 cells; rat cultures studied separately tissue_or_cell_type: Renal proximal tubular epithelium experimental_model: Apical transport kinetics and transporter knockdown limitations: Renal evidence must not be relabeled as a demonstrated human intestinal transport mechanism. exposure: Citrulline uptake on permeable supports; SLC6A19 or SLC7A9 silencing evidence_span: {"source_cache": "artifacts/citrulline-research/19322909.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f466fcced77ee9fe7a97f010112a035332d513382d13e6187d10bc02be152ece", "start_char": 0, "end_char": 1531, "text_sha256": "f466fcced77ee9fe7a97f010112a035332d513382d13e6187d10bc02be152ece"} [citrulline-p19322909] Transport characteristics of L-citrulline in renal apical membrane of proximal tubular cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19322909/ DOI: 10.1002/bdd.653

cross_nutrient

true

experimental_model

Rat and mouse intestinal localization, intestinal brush-border vesicles and IEC-6 cells

exposure

Sodium-dependent vesicle uptake with perchlorate inhibition; concentrations not verified from abstract.

limitations

The abstract does not assign every vesicle experiment to one rodent species; the claim preserves the rodent scope and does not attribute the protein to humans.

nutrient_topic

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

organism

Rodent intestinal preparation; rat and mouse study

plain_language

Intestinal iodide uptake can use the sodium gradient.

primary_references

[iodine-trans-intestine2009] The Na+/I- symporter mediates active iodide uptake in the intestine. (2009). https://pubmed.ncbi.nlm.nih.gov/19052257/ DOI: 10.1152/ajpcell.00509.2008

tissue_or_cell_type

Intestinal brush-border membrane vesicles

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 258–269

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat and mouse intestinal localization, intestinal brush-border vesicles and IEC-6 cells · source_derived_draft · unverified_draft

### iodine-trans-intestinal-sodium-uptake Rodent intestinal brush-border membrane vesicles accumulated iodide in a sodium-dependent, perchlorate-sensitive manner. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Intestinal iodide uptake can use the sodium gradient. organism: Rodent intestinal preparation; rat and mouse study tissue_or_cell_type: Intestinal brush-border membrane vesicles experimental_model: Rat and mouse intestinal localization, intestinal brush-border vesicles and IEC-6 cells limitations: The abstract does not assign every vesicle experiment to one rodent species; the claim preserves the rodent scope and does not attribute the protein to humans. exposure: Sodium-dependent vesicle uptake with perchlorate inhibition; concentrations not verified from abstract. cross_nutrient: true [iodine-trans-intestine2009] The Na+/I- symporter mediates active iodide uptake in the intestine. (2009). https://pubmed.ncbi.nlm.nih.gov/19052257/ DOI: 10.1152/ajpcell.00509.2008

cross_nutrient

true

experimental_model

Endogenous rat NIS in IEC-6 intestinal epithelial cells; initial-rate transport and statistical thermodynamic fitting

exposure

Initial-rate iodide uptake at 5, 10, 20 or 60 micromolar iodide with 0–260 mM sodium; two-minute incubations; constant osmolarity.

limitations

Kd values depend on the authors’ transport model; the finding does not show that eating extra salt improves iodine status.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Sodium binding makes NIS bind iodide more readily.

primary_references

[iodine-trans-sodium-affinity2014] Physiological sodium concentrations enhance the iodide affinity of the Na+/I- symporter. (2014). https://pubmed.ncbi.nlm.nih.gov/24888603/ DOI: 10.1038/ncomms4948

tissue_or_cell_type

IEC-6 intestinal epithelial cells

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 180–191

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Endogenous rat NIS in IEC-6 intestinal epithelial cells; initial-rate transport and statistical thermodynamic fitting · source_derived_draft · unverified_draft

### iodine-trans-sodium-affinity Thermodynamic fits to rat IEC-6 NIS transport data estimated an iodide Kd of 224 micromolar without sodium binding and 22.4 micromolar in the sodium-bound state. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sodium binding makes NIS bind iodide more readily. organism: Rattus norvegicus tissue_or_cell_type: IEC-6 intestinal epithelial cells experimental_model: Endogenous rat NIS in IEC-6 intestinal epithelial cells; initial-rate transport and statistical thermodynamic fitting limitations: Kd values depend on the authors’ transport model; the finding does not show that eating extra salt improves iodine status. exposure: Initial-rate iodide uptake at 5, 10, 20 or 60 micromolar iodide with 0–260 mM sodium; two-minute incubations; constant osmolarity. cross_nutrient: true [iodine-trans-sodium-affinity2014] Physiological sodium concentrations enhance the iodide affinity of the Na+/I- symporter. (2014). https://pubmed.ncbi.nlm.nih.gov/24888603/ DOI: 10.1038/ncomms4948

evidence_span

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experimental_model

Voltage clamp and kinetic model fitting

exposure

Sodium and voltage manipulations

limitations

Cooperative sodium binding and turnover were model-derived; this is not a clinical sodium recommendation.

nutrient_topic

Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)

organism

Human SMIT2 in Xenopus oocytes

plain_language

The sodium gradient is part of the transport machinery, rather than inositol moving independently of ions.

primary_references

[ino-p24944204] The transport mechanism of the human sodium/myo-inositol transporter 2 (SMIT2/SGLT6), a member of the LeuT structural family. (2014). https://pubmed.ncbi.nlm.nih.gov/24944204/ DOI: 10.1152/ajpcell.00054.2014

tissue_or_cell_type

Heterologous membrane transport

Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 340–351

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Voltage clamp and kinetic model fitting · source_derived_draft · unverified_draft

### ino-smit2-sodium A fitted five-state model of human SMIT2 currents included cooperative Na+ binding and a likely rate-limiting return of empty transporter. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The sodium gradient is part of the transport machinery, rather than inositol moving independently of ions. organism: Human SMIT2 in Xenopus oocytes tissue_or_cell_type: Heterologous membrane transport experimental_model: Voltage clamp and kinetic model fitting limitations: Cooperative sodium binding and turnover were model-derived; this is not a clinical sodium recommendation. exposure: Sodium and voltage manipulations evidence_span: {"source_cache": "artifacts/inositol-research/24944204.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12216ce12672706d91e22c9fbc1ebc5dbe77444e9869048f8a0d456f621cb41e", "start_char": 0, "end_char": 1647, "text_sha256": "12216ce12672706d91e22c9fbc1ebc5dbe77444e9869048f8a0d456f621cb41e"} [ino-p24944204] The transport mechanism of the human sodium/myo-inositol transporter 2 (SMIT2/SGLT6), a member of the LeuT structural family. (2014). https://pubmed.ncbi.nlm.nih.gov/24944204/ DOI: 10.1152/ajpcell.00054.2014

cross_nutrient

true

experimental_model

Isolated rabbit renal brush-border membrane vesicles with controlled ion gradients and membrane potentials

exposure

Inward NaCl gradient under voltage clamp; potassium, rubidium, lithium, ammonium and choline could not substitute for sodium.

limitations

Rabbit isolated-membrane experiment; this predates molecular identification of SMVT and does not independently assign the effect to human SLC5A6 or establish a human renal clearance threshold.

nutrient_topic

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

organism

Oryctolagus cuniculus

plain_language

Sodium provides energy for pantothenate uptake at the rabbit kidney brush border.

primary_references

[b5-trans-renal1986] Pantothenate-sodium cotransport in renal brush-border membranes. (1986). https://pubmed.ncbi.nlm.nih.gov/3771539/ DOI: 10.1016/s0021-9258(18)66891-7

tissue_or_cell_type

Renal brush-border membrane vesicles

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 236–247

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated rabbit renal brush-border membrane vesicles with controlled ion gradients and membrane potentials · source_derived_draft · unverified_draft

### b5-trans-renal-sodium-gradient An inward sodium gradient drove transient pantothenate accumulation against its concentration gradient in voltage-clamped rabbit renal brush-border vesicles. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sodium provides energy for pantothenate uptake at the rabbit kidney brush border. organism: Oryctolagus cuniculus tissue_or_cell_type: Renal brush-border membrane vesicles experimental_model: Isolated rabbit renal brush-border membrane vesicles with controlled ion gradients and membrane potentials limitations: Rabbit isolated-membrane experiment; this predates molecular identification of SMVT and does not independently assign the effect to human SLC5A6 or establish a human renal clearance threshold. exposure: Inward NaCl gradient under voltage clamp; potassium, rubidium, lithium, ammonium and choline could not substitute for sodium. cross_nutrient: true [b5-trans-renal1986] Pantothenate-sodium cotransport in renal brush-border membranes. (1986). https://pubmed.ncbi.nlm.nih.gov/3771539/ DOI: 10.1016/s0021-9258(18)66891-7

cross_nutrient

true

experimental_model

Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes

exposure

Sodium concentration-response of cloned human SMVT-mediated vitamin uptake.

limitations

Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition. The ratio is inferred from transport kinetics, rather than direct counting of individual cotransport events.

nutrient_topic

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

organism

Homo sapiens

plain_language

Two sodium ions accompany each pantothenate molecule in the reported SMVT transport model.

primary_references

[b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

tissue_or_cell_type

HRPE cell plasma membrane

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 197–208

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes · source_derived_draft · unverified_draft

### b5-trans-two-sodium-pantothenate Sodium-dependence kinetics of human SLC5A6-mediated pantothenate uptake supported a 2:1 sodium:pantothenate coupling ratio. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two sodium ions accompany each pantothenate molecule in the reported SMVT transport model. organism: Homo sapiens tissue_or_cell_type: HRPE cell plasma membrane experimental_model: Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes limitations: Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition. The ratio is inferred from transport kinetics, rather than direct counting of individual cotransport events. exposure: Sodium concentration-response of cloned human SMVT-mediated vitamin uptake. cross_nutrient: true [b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

evidence_span

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experimental_model

Cryo-EM reconstruction at 3.2 angstrom resolution

exposure

Purified Nav1.4–beta1 structure

limitations

Structural support for permeation and inactivation; this experiment did not test dietary sodium or clinical supplementation.

nutrient_topic

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

organism

Human channel complex

plain_language

A dedicated sodium-channel protein helps electrically excitable cells generate signals.

primary_references

[sodium-p30190309] Structure of the human voltage-gated sodium channel Nav1.4 in complex with β1. (2018). https://pubmed.ncbi.nlm.nih.gov/30190309/ DOI: 10.1126/science.aau2486

tissue_or_cell_type

Skeletal-muscle Nav1.4 with beta1

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 343–354

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM reconstruction at 3.2 angstrom resolution · source_derived_draft · unverified_draft

### sodium-nav14-pore The human Nav1.4–beta1 structure resolved its pore and voltage-sensing domains, supporting a molecular account of sodium permeation. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A dedicated sodium-channel protein helps electrically excitable cells generate signals. organism: Human channel complex tissue_or_cell_type: Skeletal-muscle Nav1.4 with beta1 experimental_model: Cryo-EM reconstruction at 3.2 angstrom resolution limitations: Structural support for permeation and inactivation; this experiment did not test dietary sodium or clinical supplementation. exposure: Purified Nav1.4–beta1 structure evidence_span: {"source_cache": "artifacts/sodium-research/30190309.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2c9e7fceab1407740b539362913e9f97227515a9a7d9439ce57113545d2f7436", "start_char": 0, "end_char": 876, "text_sha256": "2c9e7fceab1407740b539362913e9f97227515a9a7d9439ce57113545d2f7436"} [sodium-p30190309] Structure of the human voltage-gated sodium channel Nav1.4 in complex with β1. (2018). https://pubmed.ncbi.nlm.nih.gov/30190309/ DOI: 10.1126/science.aau2486

evidence_span

{"source_cache": "artifacts/biotin-research/9814986.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7cc679e31b95ae919c15fadf0d56933d2ed8074664e11cd80a96e910181857be", "start_char": 0, "end_char": 1676, "text_sha256": "7cc679e31b95ae919c15fadf0d56933d2ed8074664e11cd80a96e910181857be"}

experimental_model

Transport and inhibitor experiments in human NCM460 colonic epithelial cells

exposure

Radiolabeled biotin with sodium replacement, pantothenate and kinase modulators

limitations

Cell-line kinetics do not quantify microbiome contributions or demonstrate competition at ordinary dietary intakes.

nutrient_topic

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

organism

Homo sapiens

plain_language

Colon cells can take up free biotin through a saturable transport process.

primary_references

[b7-p9814986] Biotin uptake by human colonic epithelial NCM460 cells: a carrier-mediated process shared with pantothenic acid. (1998). https://pubmed.ncbi.nlm.nih.gov/9814986/ DOI: 10.1152/ajpcell.1998.275.5.c1365

tissue_or_cell_type

Colonic epithelium; NCM460 culture

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 182–193

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transport and inhibitor experiments in human NCM460 colonic epithelial cells · source_derived_draft · unverified_draft

### b7-colon-sodium Biotin uptake in human NCM460 cells was saturable, energy dependent and sodium dependent, with apparent Km 19.7 micromolar. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Colon cells can take up free biotin through a saturable transport process. organism: Homo sapiens tissue_or_cell_type: Colonic epithelium; NCM460 culture experimental_model: Transport and inhibitor experiments in human NCM460 colonic epithelial cells limitations: Cell-line kinetics do not quantify microbiome contributions or demonstrate competition at ordinary dietary intakes. exposure: Radiolabeled biotin with sodium replacement, pantothenate and kinase modulators evidence_span: {"source_cache": "artifacts/biotin-research/9814986.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7cc679e31b95ae919c15fadf0d56933d2ed8074664e11cd80a96e910181857be", "start_char": 0, "end_char": 1676, "text_sha256": "7cc679e31b95ae919c15fadf0d56933d2ed8074664e11cd80a96e910181857be"} [b7-p9814986] Biotin uptake by human colonic epithelial NCM460 cells: a carrier-mediated process shared with pantothenic acid. (1998). https://pubmed.ncbi.nlm.nih.gov/9814986/ DOI: 10.1152/ajpcell.1998.275.5.c1365

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Ace2-null mouse intestine; expression, interaction and uptake assays.

limitations

Kidney accessory-protein dependence differs; not evidence that every change in ACE2 produces dietary isoleucine deficiency.

nutrient_topic

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

plain_language

A working transporter also needs its accessory protein in this tissue.

primary_references

Tissue-specific amino acid transporter partners ACE2 and collectrin differentially interact with hartnup mutations. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19185582/ · DOI 10.1053/j.gastro.2008.10.055

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Isoleucine: transport, translation, catabolism 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 · Ace2-null mouse intestine; expression, interaction and uptake assays. · source_derived_draft · unverified_draft

## isoleucine-intestinal-ace2 A working transporter also needs its accessory protein in this tissue. Ace2 deletion removed intestinal B0AT1 expression and abolished sodium-dependent isoleucine uptake in mouse ileum segments. Model: Ace2-null mouse intestine; expression, interaction and uptake assays. Limitations: Kidney accessory-protein dependence differs; not evidence that every change in ACE2 produces dietary isoleucine deficiency. Evidence access: Primary full text Tissue-specific amino acid transporter partners ACE2 and collectrin differentially interact with hartnup mutations. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19185582/ · DOI 10.1053/j.gastro.2008.10.055

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

TAL electrical selectivity participates in magnesium and calcium conservation; no dietary synergy is implied.

evidence-system

Renal RNAi and isolated TAL electrophysiology

experimental_model

Renal RNAi and isolated TAL electrophysiology

limitations

Selectivity evidence is not proof claudin-16 alone forms a specifically magnesium-selective pore.

nutrient_topic

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

organism

Mouse

plain_language

The junction lost part of its preference for positively charged ions, changing the conditions that support mineral recovery.

primary_references

[hou-2007-cldn16] Transgenic RNAi depletion of claudin-16 and the renal handling of magnesium. (2007). https://pubmed.ncbi.nlm.nih.gov/17442678/ DOI: 10.1074/jbc.M700632200

tissue

Renal thick ascending limb

tissue_or_cell_type

Renal thick ascending limb

trigger_kind

machinery_impairment Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1097–1109

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Renal RNAi and isolated TAL electrophysiology · source_derived_draft · unverified_draft

### cldn16-depletion-selectivity Claudin-16 RNAi reduced paracellular cation selectivity in isolated mouse thick ascending limbs. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The junction lost part of its preference for positively charged ions, changing the conditions that support mineral recovery. organism: Mouse tissue_or_cell_type: Renal thick ascending limb experimental_model: Renal RNAi and isolated TAL electrophysiology limitations: Selectivity evidence is not proof claudin-16 alone forms a specifically magnesium-selective pore. cross_nutrient: TAL electrical selectivity participates in magnesium and calcium conservation; no dietary synergy is implied. evidence-system: Renal RNAi and isolated TAL electrophysiology tissue: Renal thick ascending limb [hou-2007-cldn16] Transgenic RNAi depletion of claudin-16 and the renal handling of magnesium. (2007). https://pubmed.ncbi.nlm.nih.gov/17442678/ DOI: 10.1074/jbc.M700632200

cross_nutrient

Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration.

experimental_model

Partially purified pig-kidney pump; sodium-22 occlusion, EGCg quench-flow, ATP/Mg manipulations.

limitations

Equilibrium and Na-ATPase conditions; full Na/K exchange and systemic Mg deficiency were not tested.

nutrient_topic

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

organism

Sus scrofa

plain_language

Magnesium can oppose sodium binding as well as support ATP chemistry.

primary_references

[faraj-2023-nka] Measurements of Na+-occluded intermediates during the catalytic cycle of the Na+/K+-ATPase provide novel insights into the mechanism of Na+ transport (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC9860123/ DOI: 10.1016/j.jbc.2022.102811

tissue_or_cell_type

Kidney enzyme membrane preparation

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 857–867

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Partially purified pig-kidney pump; sodium-22 occlusion, EGCg quench-flow, ATP/Mg manipulations. · source_derived_draft · unverified_draft

### mg-nka-free-mg-sodium-occlusion Free Mg reduced apparent sodium affinity in pig-kidney pump sodium-22 occlusion experiments. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium can oppose sodium binding as well as support ATP chemistry. organism: Sus scrofa tissue_or_cell_type: Kidney enzyme membrane preparation experimental_model: Partially purified pig-kidney pump; sodium-22 occlusion, EGCg quench-flow, ATP/Mg manipulations. limitations: Equilibrium and Na-ATPase conditions; full Na/K exchange and systemic Mg deficiency were not tested. cross_nutrient: Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration. [faraj-2023-nka] Measurements of Na+-occluded intermediates during the catalytic cycle of the Na+/K+-ATPase provide novel insights into the mechanism of Na+ transport (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC9860123/ DOI: 10.1016/j.jbc.2022.102811

cross_nutrient

Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration.

experimental_model

Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP.

limitations

Measured stoichiometry applies to specified ionic conditions; no Mg titration was performed.

nutrient_topic

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

organism

Homo sapiens

plain_language

ATP turnover was directly linked to outward sodium pumping in a magnesium-containing preparation.

primary_references

[garrahan-1967-nka] The stoicheiometry of the sodium pump (1967). https://doi.org/10.1113/jphysiol.1967.sp008297 DOI: 10.1113/jphysiol.1967.sp008297

tissue_or_cell_type

Resealed erythrocyte ghosts

transport_direction

Sodium: intracellular ghost compartment to external medium.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 819–830

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP. · source_derived_draft · unverified_draft

### mg-nka-isotope-atp-sodium-coupling In Mg-loaded human red-cell ghosts, ouabain-sensitive hydrolysis of one ATP accompanied loss of about three sodium ions. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP turnover was directly linked to outward sodium pumping in a magnesium-containing preparation. organism: Homo sapiens tissue_or_cell_type: Resealed erythrocyte ghosts experimental_model: Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP. limitations: Measured stoichiometry applies to specified ionic conditions; no Mg titration was performed. cross_nutrient: Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration. transport_direction: Sodium: intracellular ghost compartment to external medium. [garrahan-1967-nka] The stoicheiometry of the sodium pump (1967). https://doi.org/10.1113/jphysiol.1967.sp008297 DOI: 10.1113/jphysiol.1967.sp008297

cross_nutrient

Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration.

experimental_model

Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP.

limitations

This experiment found unequal fluxes but did not itself measure an exact 3:2 ratio.

nutrient_topic

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

organism

Homo sapiens

plain_language

The pump moves the two nutrient ions in opposite directions.

primary_references

[garrahan-1967-nka] The stoicheiometry of the sodium pump (1967). https://doi.org/10.1113/jphysiol.1967.sp008297 DOI: 10.1113/jphysiol.1967.sp008297

tissue_or_cell_type

Erythrocytes

transport_direction

Sodium outward; potassium inward.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 832–843

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP. · source_derived_draft · unverified_draft

### mg-nka-isotope-opposed-flux Sodium-24 and potassium-42 experiments demonstrated ouabain-sensitive sodium efflux and potassium influx in human red cells. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pump moves the two nutrient ions in opposite directions. organism: Homo sapiens tissue_or_cell_type: Erythrocytes experimental_model: Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP. limitations: This experiment found unequal fluxes but did not itself measure an exact 3:2 ratio. cross_nutrient: Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration. transport_direction: Sodium outward; potassium inward. [garrahan-1967-nka] The stoicheiometry of the sodium pump (1967). https://doi.org/10.1113/jphysiol.1967.sp008297 DOI: 10.1113/jphysiol.1967.sp008297

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

magnesium -> sodium -> potassium

experimental_model

Dietary restriction in C57BL/6J mice with renal transport assays

limitations

Cleaved subunits and amiloride response support ENaC inhibition; the molecular cause was unresolved.

nutrient_topic

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

organism

Mus musculus

plain_language

With less dietary Mg, these kidneys reduced the sodium entry pathway that normally helps drive potassium secretion.

primary_references

[maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704

tissue_or_cell_type

Kidney distal nephron

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 154–164

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary restriction in C57BL/6J mice with renal transport assays · source_derived_draft · unverified_draft

### mg-restriction-reduces-enac-activity Mg restriction reduced cleaved alpha/gamma ENaC abundance and blunted amiloride-induced sodium excretion in mice. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: With less dietary Mg, these kidneys reduced the sodium entry pathway that normally helps drive potassium secretion. organism: Mus musculus tissue_or_cell_type: Kidney distal nephron experimental_model: Dietary restriction in C57BL/6J mice with renal transport assays limitations: Cleaved subunits and amiloride response support ENaC inhibition; the molecular cause was unresolved. cross_nutrient: magnesium -> sodium -> potassium [maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

magnesium -> sodium -> potassium

experimental_model

Dietary restriction in C57BL/6J mice with renal transport assays

limitations

Integrated mechanism supported across experiments; enhanced distal Na delivery was not demonstrated and is not required by these data.

nutrient_topic

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

organism

Mus musculus

plain_language

Sodium entry changes the electrical conditions for potassium exit; lifting the Mg brake on ROMK matters when that driving force is available.

primary_references

[maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704 [yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617

spatial_transport_direction

Na+: tubular lumen to cell via ENaC; K+: cell to lumen via ROMK.

tissue_or_cell_type

Kidney distal nephron

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 203–215

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary restriction in C57BL/6J mice with renal transport assays · source_derived_draft · unverified_draft

### mg-romk-enac-conditional-k-secretory-chain The mouse findings support a model in which sustained ENaC sodium entry and higher ROMK conductance jointly favor potassium secretion during combined Na/Mg restriction. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sodium entry changes the electrical conditions for potassium exit; lifting the Mg brake on ROMK matters when that driving force is available. organism: Mus musculus tissue_or_cell_type: Kidney distal nephron experimental_model: Dietary restriction in C57BL/6J mice with renal transport assays limitations: Integrated mechanism supported across experiments; enhanced distal Na delivery was not demonstrated and is not required by these data. cross_nutrient: magnesium -> sodium -> potassium spatial_transport_direction: Na+: tubular lumen to cell via ENaC; K+: cell to lumen via ROMK. [maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704 [yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617

cross_nutrient

Sodium availability affected measured magnesium export in this assay; coupling is contested.

evidence-system

Human construct overexpression; mag-fura-2; extracellular Na replacement

experimental_model

Human construct overexpression; mag-fura-2; extracellular Na replacement

limitations

Indirect free-ion assay and overexpression; conflicts with sodium-independent isotope flux in a different construct/protocol.

nutrient_topic

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

organism

Human protein and human-derived cells

plain_language

This experiment supported sodium-coupled export of magnesium.

primary_references

[kolisek-2012-slc41a1] Human gene SLC41A1 encodes for the Na+/Mg2+ exchanger (2012). https://pubmed.ncbi.nlm.nih.gov/22031603/ DOI: 10.1152/ajpcell.00289.2011

tissue

HEK293 cells

tissue_or_cell_type

HEK293 cells

transport_direction

Mg2+ from cytosol toward extracellular solution.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1165–1178

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human construct overexpression; mag-fura-2; extracellular Na replacement · source_derived_draft · unverified_draft

### slc41a1-sodium-dependent-efflux Human SLC41A1-associated Mg efflux in HEK293 cells fell sharply when extracellular sodium was replaced in the Kolisek assay. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This experiment supported sodium-coupled export of magnesium. organism: Human protein and human-derived cells tissue_or_cell_type: HEK293 cells experimental_model: Human construct overexpression; mag-fura-2; extracellular Na replacement limitations: Indirect free-ion assay and overexpression; conflicts with sodium-independent isotope flux in a different construct/protocol. cross_nutrient: Sodium availability affected measured magnesium export in this assay; coupling is contested. transport_direction: Mg2+ from cytosol toward extracellular solution. evidence-system: Human construct overexpression; mag-fura-2; extracellular Na replacement tissue: HEK293 cells [kolisek-2012-slc41a1] Human gene SLC41A1 encodes for the Na+/Mg2+ exchanger (2012). https://pubmed.ncbi.nlm.nih.gov/22031603/ DOI: 10.1152/ajpcell.00289.2011

cross_nutrient

This assay challenges obligatory sodium dependence of SLC41A1-associated magnesium extrusion.

evidence-system

Mouse SLC41A1 construct; stable-isotope 25Mg measurements

experimental_model

Mouse SLC41A1 construct; stable-isotope 25Mg measurements

limitations

Different ortholog, loading and readout from the sodium-dependent report; physiological coupling remains unresolved.

nutrient_topic

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

organism

Mouse protein; human-derived cells

plain_language

A different experiment found magnesium export that did not require sodium.

primary_references

[arjona-2019-slc41a1] SLC41A1 is essential for magnesium homeostasis in vivo (2019). https://pubmed.ncbi.nlm.nih.gov/30417250/ DOI: 10.1007/s00424-018-2234-9

tissue

HEK293 cells

tissue_or_cell_type

HEK293 cells

transport_direction

Mg2+ from cytosol toward extracellular solution.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1180–1193

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse SLC41A1 construct; stable-isotope 25Mg measurements · source_derived_draft · unverified_draft

### slc41a1-sodium-independent-efflux Mouse SLC41A1 expressed in HEK293 cells supported Mg extrusion without extracellular sodium in the Arjona isotope assay. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A different experiment found magnesium export that did not require sodium. organism: Mouse protein; human-derived cells tissue_or_cell_type: HEK293 cells experimental_model: Mouse SLC41A1 construct; stable-isotope 25Mg measurements limitations: Different ortholog, loading and readout from the sodium-dependent report; physiological coupling remains unresolved. cross_nutrient: This assay challenges obligatory sodium dependence of SLC41A1-associated magnesium extrusion. transport_direction: Mg2+ from cytosol toward extracellular solution. evidence-system: Mouse SLC41A1 construct; stable-isotope 25Mg measurements tissue: HEK293 cells [arjona-2019-slc41a1] SLC41A1 is essential for magnesium homeostasis in vivo (2019). https://pubmed.ncbi.nlm.nih.gov/30417250/ DOI: 10.1007/s00424-018-2234-9

evidence_access

Primary abstract

experimental_model

Human colonic-cell exposure experiments.

limitations

The separate pectin-fed rat arm is not an isolated human butyrate intervention or proof of net whole-body sodium retention.

nutrient_topic

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

plain_language

It changed machinery that supports intestinal sodium absorption.

primary_references

SCFA increase intestinal Na absorption by induction of NHE3 in rat colon and human intestinal C2/bbe cells. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11254495/ · DOI 10.1152/ajpgi.2001.280.4.G687

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 150–156

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human colonic-cell exposure experiments. · source_derived_draft · unverified_draft

## butyrate-nhe3-sodium It changed machinery that supports intestinal sodium absorption. Butyrate increased apical NHE3 protein and sodium/hydrogen exchange activity in human C2/bbe monolayers, while NHE2 did not increase. Model: Human colonic-cell exposure experiments. Limitations: The separate pectin-fed rat arm is not an isolated human butyrate intervention or proof of net whole-body sodium retention. Evidence access: Primary abstract SCFA increase intestinal Na absorption by induction of NHE3 in rat colon and human intestinal C2/bbe cells. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11254495/ · DOI 10.1152/ajpgi.2001.280.4.G687

evidence_access

Primary full text, intervention methods and primary results

experimental_model

Double-blind randomized trial after supervised antihypertensive washout; sodium chloride placebo matched the sodium load.

limitations

Small short trial; do not infer the increase was simply unmatched sodium or advise medication changes.

nutrient_topic

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

plain_language

An oral human trial found higher blood pressure.

primary_references

Effects of Oral Butyrate on Blood Pressure in Patients With Hypertension: A Randomized, Placebo-Controlled Trial. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39034917/ · DOI 10.1161/HYPERTENSIONAHA.123.22437

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 582–588

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Double-blind randomized trial after supervised antihypertensive washout; sodium chloride placebo matched the sodium load. · source_derived_draft · unverified_draft

## butyrate-oral-bp-increase An oral human trial found higher blood pressure. In 23 hypertensive adults, 3.9 g/day oral sodium butyrate for four weeks increased daytime systolic pressure by 9.63 mmHg and diastolic pressure by 5.08 mmHg versus sodium-matched placebo. Model: Double-blind randomized trial after supervised antihypertensive washout; sodium chloride placebo matched the sodium load. Limitations: Small short trial; do not infer the increase was simply unmatched sodium or advise medication changes. Evidence access: Primary full text, intervention methods and primary results Effects of Oral Butyrate on Blood Pressure in Patients With Hypertension: A Randomized, Placebo-Controlled Trial. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39034917/ · DOI 10.1161/HYPERTENSIONAHA.123.22437

evidence_access

Primary abstract

experimental_model

Human SLC5A8 expressed in frog oocytes; radiotracer and voltage-clamp assays.

limitations

Expression host is not the protein species. This does not establish that extra dietary sodium improves uptake.

nutrient_topic

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

plain_language

A human transporter can concentrate butyrate using a sodium gradient.

primary_references

Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na(+)-coupled transporter for short-chain fatty acids. · 2004 · https://pubmed.ncbi.nlm.nih.gov/14966140/ · DOI 10.1074/jbc.C400059200

transport_effect

raises Expression increased butyrate uptake and generated sodium-dependent inward currents.

transport_pool

the expressing cell Expression increased butyrate uptake and generated sodium-dependent inward currents.

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 102–108

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human SLC5A8 expressed in frog oocytes; radiotracer and voltage-clamp assays. · source_derived_draft · unverified_draft

## butyrate-smct1-uptake A human transporter can concentrate butyrate using a sodium gradient. Expressing human intestinal SLC5A8 in Xenopus oocytes increased butyrate uptake and generated sodium-dependent inward currents. Model: Human SLC5A8 expressed in frog oocytes; radiotracer and voltage-clamp assays. Limitations: Expression host is not the protein species. This does not establish that extra dietary sodium improves uptake. Evidence access: Primary abstract Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na(+)-coupled transporter for short-chain fatty acids. · 2004 · https://pubmed.ncbi.nlm.nih.gov/14966140/ · DOI 10.1074/jbc.C400059200

evidence_access

Primary full text

experimental_model

Normal and IPF human lung fibroblast transporter experiments.

limitations

Dual transport does not by itself prove clinically relevant competition at ordinary plasma concentrations.

nutrient_topic

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

plain_language

A shared importer links access to two amino acids.

primary_references

TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 504–510

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Normal and IPF human lung fibroblast transporter experiments. · source_derived_draft · unverified_draft

## alanine-fibroblast-transporter A shared importer links access to two amino acids. SLC38A2 mediated alanine and glutamine uptake in human lung fibroblasts and increased with TGF-beta exposure or alanine deprivation. Model: Normal and IPF human lung fibroblast transporter experiments. Limitations: Dual transport does not by itself prove clinically relevant competition at ordinary plasma concentrations. Evidence access: Primary full text TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449

evidence_access

Primary abstract

experimental_model

Human Caco-2 substrate challenges and expression/inhibitor measurements.

limitations

No blanket claim that all amino acids compete or that one oral mixture improves absorption.

nutrient_topic

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

plain_language

Shared transport can produce rapid nutrient interactions without making new transporter protein.

primary_references

Posttranslational alanine trans-stimulation of zwitterionic amino acid transport systems in human intestinal Caco-2 cells. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11971679/ · DOI 10.1006/jsre.2002.6406

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 480–486

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human Caco-2 substrate challenges and expression/inhibitor measurements. · source_derived_draft · unverified_draft

## alanine-intestinal-other-substrates Shared transport can produce rapid nutrient interactions without making new transporter protein. Other substrates of System B or L increased alanine uptake, whereas nonsubstrates did not; cycloheximide/actinomycin did not block acute activation and ATB0 mRNA did not change. Model: Human Caco-2 substrate challenges and expression/inhibitor measurements. Limitations: No blanket claim that all amino acids compete or that one oral mixture improves absorption. Evidence access: Primary abstract Posttranslational alanine trans-stimulation of zwitterionic amino acid transport systems in human intestinal Caco-2 cells. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11971679/ · DOI 10.1006/jsre.2002.6406

evidence_access

Primary full text

experimental_model

Pig jejunum/ileum Ussing chambers; alanine challenge.

limitations

Current is a functional proxy; associated AMPK/PKA changes were not established as the cause. No human malabsorption conclusion follows.

nutrient_topic

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

plain_language

A second compound altered the electrical transport response to alanine.

primary_references

Resveratrol Inhibits Porcine Intestinal Glucose and Alanine Transport: Potential Roles of Na⁺/K⁺-ATPase Activity, Protein Kinase A, AMP-Activated Protein Kinase and the Association of Selected Nutrient Transport Proteins with Detergent Resistant Membranes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29510506/ · DOI 10.3390/nu10030302

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 488–494

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pig jejunum/ileum Ussing chambers; alanine challenge. · source_derived_draft · unverified_draft

## alanine-intestinal-resveratrol A second compound altered the electrical transport response to alanine. Resveratrol at 300 micromolar for 30 minutes reduced alanine-evoked short-circuit current in isolated porcine intestinal preparations. Model: Pig jejunum/ileum Ussing chambers; alanine challenge. Limitations: Current is a functional proxy; associated AMPK/PKA changes were not established as the cause. No human malabsorption conclusion follows. Evidence access: Primary full text Resveratrol Inhibits Porcine Intestinal Glucose and Alanine Transport: Potential Roles of Na⁺/K⁺-ATPase Activity, Protein Kinase A, AMP-Activated Protein Kinase and the Association of Selected Nutrient Transport Proteins with Detergent Resistant Membranes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29510506/ · DOI 10.3390/nu10030302

evidence_access

Primary abstract

experimental_model

Human Caco-2 monolayers; sodium-dependent and sodium-independent transport assays.

limitations

Historical functional systems are not assigned to one modern transporter gene without direct evidence.

nutrient_topic

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

plain_language

What is already inside an intestinal cell can change how quickly amino acids cross its membrane.

primary_references

Posttranslational alanine trans-stimulation of zwitterionic amino acid transport systems in human intestinal Caco-2 cells. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11971679/ · DOI 10.1006/jsre.2002.6406

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 472–478

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human Caco-2 monolayers; sodium-dependent and sodium-independent transport assays. · source_derived_draft · unverified_draft

## alanine-intestinal-transstimulation What is already inside an intestinal cell can change how quickly amino acids cross its membrane. Alanine add-back increased apical System B and System L uptake within five minutes in depleted Caco-2 cells, increasing both apparent Km and Vmax. Model: Human Caco-2 monolayers; sodium-dependent and sodium-independent transport assays. Limitations: Historical functional systems are not assigned to one modern transporter gene without direct evidence. Evidence access: Primary abstract Posttranslational alanine trans-stimulation of zwitterionic amino acid transport systems in human intestinal Caco-2 cells. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11971679/ · DOI 10.1006/jsre.2002.6406

evidence_access

Primary abstract

experimental_model

Normal rat islets; radiocalcium uptake.

limitations

This does not identify a unique sodium transporter or calcium-channel isoform.

nutrient_topic

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

plain_language

Amino-acid exposure can affect the ion signal used for secretion.

primary_references

The stimulus-secretion coupling of amino acid-induced insulin release. Insulinotropic action of L-alanine. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12383948/ · DOI 10.1016/s0304-4165(02)00337-9

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 384–390

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Normal rat islets; radiocalcium uptake. · source_derived_draft · unverified_draft

## alanine-islet-calcium Amino-acid exposure can affect the ion signal used for secretion. Alanine stimulated calcium-45 uptake in rat islets without another exogenous nutrient. Model: Normal rat islets; radiocalcium uptake. Limitations: This does not identify a unique sodium transporter or calcium-channel isoform. Evidence access: Primary abstract The stimulus-secretion coupling of amino acid-induced insulin release. Insulinotropic action of L-alanine. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12383948/ · DOI 10.1016/s0304-4165(02)00337-9

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human PDAC genetic transporter perturbation and stable-isotope flux assays.

limitations

Tissue-specific transporter dependence; not every cell uses SLC38A2 as its dominant route.

nutrient_topic

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

plain_language

An intact uptake system can be as important as having alanine outside the cell.

primary_references

Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 184–190

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

## alanine-pdac-snat2 An intact uptake system can be as important as having alanine outside the cell. Loss of SLC38A2 prevented human PDAC cells from effectively taking up and concentrating environmental alanine. Model: Human PDAC genetic transporter perturbation and stable-isotope flux assays. Limitations: Tissue-specific transporter dependence; not every cell uses SLC38A2 as its dominant route. Evidence access: Primary full text Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959

evidence_access

Primary full text

experimental_model

Human PSC transporter and flux experiments.

limitations

SLC1A4 was not the sole alanine exporter and exchange is not equivalent to an irreversible one-way pump.

nutrient_topic

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

plain_language

An exchanger helps neighboring cells share alanine.

primary_references

Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 176–182

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

## alanine-psc-exchanger An exchanger helps neighboring cells share alanine. SLC1A4 perturbation and isotope-flux studies supported a role for SLC1A4, alongside other transporters, in rapid alanine exchange by human pancreatic stellate cells. Model: Human PSC transporter and flux experiments. Limitations: SLC1A4 was not the sole alanine exporter and exchange is not equivalent to an irreversible one-way pump. Evidence access: Primary full text Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959

cross_nutrient

Potassium/sodium-B6 enzyme kinetics.

evidence_location

Full text: Metal binding and enzyme activity; Figure 1

experimental_model

Purified recombinant human PDXK kinetics and crystallography.

exposure

Kinetic assays at pH 7.3.

limitations

Lower Km is not a direct binding constant; results do not define dietary sodium/potassium effects.

nutrient_topic

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

organism

Homo sapiens

plain_language

Potassium and sodium affect different kinetic properties.

primary_references

[safo2007] Crystal Structure of human pyridoxal kinase: structural basis of M(+) and M(2+) activation. (2007). https://pubmed.ncbi.nlm.nih.gov/17766369/ DOI: 10.1110/ps.073022107

tissue_or_cell_type

Purified human enzyme

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 203–215

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

### b6-transport-pdxk-k-na Human PDXK showed lower substrate Km with potassium than sodium, whereas sodium supported over twice the maximal activity. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium and sodium affect different kinetic properties. organism: Homo sapiens tissue_or_cell_type: Purified human enzyme experimental_model: Purified recombinant human PDXK kinetics and crystallography. limitations: Lower Km is not a direct binding constant; results do not define dietary sodium/potassium effects. exposure: Kinetic assays at pH 7.3. evidence_location: Full text: Metal binding and enzyme activity; Figure 1 cross_nutrient: Potassium/sodium-B6 enzyme kinetics. [safo2007] Crystal Structure of human pyridoxal kinase: structural basis of M(+) and M(2+) activation. (2007). https://pubmed.ncbi.nlm.nih.gov/17766369/ DOI: 10.1110/ps.073022107

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Human family genetics and transfected COS-cell transport assays

exposure

L243P, T262M and double-mutant constructs

limitations

Family-specific genetic disease; loss of bile-acid transport was tested, whereas individual fat-soluble-vitamin deficiencies were not.

nutrient_topic

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

organism

Human SLC10A2

plain_language

A sodium-coupled transporter helps recycle bile acids; mutations can break that route.

primary_references

[sodium-p9109432] Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2). (1997). https://pubmed.ncbi.nlm.nih.gov/9109432/ DOI: 10.1172/jci119355

tissue_or_cell_type

Ileal bile-acid transporter

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 642–653

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human family genetics and transfected COS-cell transport assays · source_derived_draft · unverified_draft

### sodium-asbt-loss L243P, T262M and the double mutant abolished taurocholate and other bile-acid transport in transfected cells. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sodium-coupled transporter helps recycle bile acids; mutations can break that route. organism: Human SLC10A2 tissue_or_cell_type: Ileal bile-acid transporter experimental_model: Human family genetics and transfected COS-cell transport assays limitations: Family-specific genetic disease; loss of bile-acid transport was tested, whereas individual fat-soluble-vitamin deficiencies were not. exposure: L243P, T262M and double-mutant constructs evidence_span: {"source_cache": "artifacts/sodium-research/9109432.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "019508b2d05ec7e21a73ff66bdea9a0b09c6c7e7d8e404de3db49b2a0825ebbe", "start_char": 0, "end_char": 1389, "text_sha256": "019508b2d05ec7e21a73ff66bdea9a0b09c6c7e7d8e404de3db49b2a0825ebbe"} [sodium-p9109432] Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2). (1997). https://pubmed.ncbi.nlm.nih.gov/9109432/ DOI: 10.1172/jci119355

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sodium-research/15286788.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "72277489510231d6da07dacf086404f5f069094a47d7a1a2de9a8392556c3a14", "start_char": 0, "end_char": 1040, "text_sha256": "72277489510231d6da07dacf086404f5f069094a47d7a1a2de9a8392556c3a14"}

experimental_model

Human genetic mapping and heterologous transport-function tests

exposure

Hartnup-associated variants versus normal transporter

limitations

Not every clinical feature of Hartnup disorder was explained; no direct test here of niacin supplementation or sodium shortage.

nutrient_topic

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

organism

Human SLC6A19

plain_language

Even with sodium and food present, a damaged transporter can limit nutrient transport.

primary_references

[sodium-p15286788] Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19. (2004). https://pubmed.ncbi.nlm.nih.gov/15286788/ DOI: 10.1038/ng1406

tissue_or_cell_type

Kidney/intestine transporter; expression assays

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 603–614

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human genetic mapping and heterologous transport-function tests · source_derived_draft · unverified_draft

### sodium-b0at1-loss Tested Hartnup-associated SLC6A19 variants reduced neutral amino acid transport in vitro. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Even with sodium and food present, a damaged transporter can limit nutrient transport. organism: Human SLC6A19 tissue_or_cell_type: Kidney/intestine transporter; expression assays experimental_model: Human genetic mapping and heterologous transport-function tests limitations: Not every clinical feature of Hartnup disorder was explained; no direct test here of niacin supplementation or sodium shortage. exposure: Hartnup-associated variants versus normal transporter evidence_span: {"source_cache": "artifacts/sodium-research/15286788.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "72277489510231d6da07dacf086404f5f069094a47d7a1a2de9a8392556c3a14", "start_char": 0, "end_char": 1040, "text_sha256": "72277489510231d6da07dacf086404f5f069094a47d7a1a2de9a8392556c3a14"} [sodium-p15286788] Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19. (2004). https://pubmed.ncbi.nlm.nih.gov/15286788/ DOI: 10.1038/ng1406

evidence_span

{"source_cache": "artifacts/sodium-research/15286788.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "72277489510231d6da07dacf086404f5f069094a47d7a1a2de9a8392556c3a14", "start_char": 0, "end_char": 1040, "text_sha256": "72277489510231d6da07dacf086404f5f069094a47d7a1a2de9a8392556c3a14"}

experimental_model

Human genetic mapping and heterologous transport-function tests

exposure

Hartnup-associated variants versus normal transporter

limitations

Not every clinical feature of Hartnup disorder was explained; no direct test here of niacin supplementation or sodium shortage.

nutrient_topic

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

organism

Human SLC6A19

plain_language

Sodium coupling is also used to absorb or recover some amino acids.

primary_references

[sodium-p15286788] Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19. (2004). https://pubmed.ncbi.nlm.nih.gov/15286788/ DOI: 10.1038/ng1406

tissue_or_cell_type

Kidney/intestine transporter; expression assays

transport_effect

raises Sodium-dependent neutral amino acid transport, which is inward.

transport_pool

the expressing cell Sodium-dependent neutral amino acid transport, which is inward.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 590–601

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human genetic mapping and heterologous transport-function tests · source_derived_draft · unverified_draft

### sodium-b0at1-transport SLC6A19 functioned as a sodium-dependent, chloride-independent neutral amino acid transporter. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sodium coupling is also used to absorb or recover some amino acids. organism: Human SLC6A19 tissue_or_cell_type: Kidney/intestine transporter; expression assays experimental_model: Human genetic mapping and heterologous transport-function tests limitations: Not every clinical feature of Hartnup disorder was explained; no direct test here of niacin supplementation or sodium shortage. exposure: Hartnup-associated variants versus normal transporter evidence_span: {"source_cache": "artifacts/sodium-research/15286788.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "72277489510231d6da07dacf086404f5f069094a47d7a1a2de9a8392556c3a14", "start_char": 0, "end_char": 1040, "text_sha256": "72277489510231d6da07dacf086404f5f069094a47d7a1a2de9a8392556c3a14"} [sodium-p15286788] Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19. (2004). https://pubmed.ncbi.nlm.nih.gov/15286788/ DOI: 10.1038/ng1406

evidence_span

{"source_cache": "artifacts/sodium-research/13575523.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ee58d9f6c640fec095876c15e7ddf6fe8bf539cb972c74841db02d2640eebbe2", "start_char": 54337, "end_char": 56036, "text_sha256": "29b3a155f7b33a8b86aa9e30182063d71f5af3c60910a237794c1310094a4c39"}

experimental_model

Simultaneous isotope-dilution and serum measurements, including serial observations

exposure

Observed variation in body composition

limitations

Historical observational regression; serum-water sodium and exchangeable pools are not interchangeable with current clinical plasma measurements or all body sodium. Not an individual correction calculator.

nutrient_topic

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

organism

Human patients with chronic illnesses

plain_language

Blood sodium reflects a relationship between body cations and water, rather than a simple count of how much sodium was eaten.

primary_references

[sodium-p13575523] Interrelations between serum sodium concentration, serum osmolarity and total exchangeable sodium, total exchangeable potassium and total body water. (1958). https://pubmed.ncbi.nlm.nih.gov/13575523/ DOI: 10.1172/jci103712

tissue_or_cell_type

Whole-body water and exchangeable cations

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 265–276

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Simultaneous isotope-dilution and serum measurements, including serial observations · source_derived_draft · unverified_draft

### sodium-body-water-ratio Serum-water sodium correlated strongly with (exchangeable sodium + exchangeable potassium)/total body water in the studied patients. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blood sodium reflects a relationship between body cations and water, rather than a simple count of how much sodium was eaten. organism: Human patients with chronic illnesses tissue_or_cell_type: Whole-body water and exchangeable cations experimental_model: Simultaneous isotope-dilution and serum measurements, including serial observations limitations: Historical observational regression; serum-water sodium and exchangeable pools are not interchangeable with current clinical plasma measurements or all body sodium. Not an individual correction calculator. exposure: Observed variation in body composition evidence_span: {"source_cache": "artifacts/sodium-research/13575523.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ee58d9f6c640fec095876c15e7ddf6fe8bf539cb972c74841db02d2640eebbe2", "start_char": 54337, "end_char": 56036, "text_sha256": "29b3a155f7b33a8b86aa9e30182063d71f5af3c60910a237794c1310094a4c39"} [sodium-p13575523] Interrelations between serum sodium concentration, serum osmolarity and total exchangeable sodium, total exchangeable potassium and total body water. (1958). https://pubmed.ncbi.nlm.nih.gov/13575523/ DOI: 10.1172/jci103712

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/7945388.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f936121279583ab698555d2a318900a9dc5a42ecbf294619ee3abcc95c9a2f0", "start_char": 0, "end_char": 910, "text_sha256": "4f936121279583ab698555d2a318900a9dc5a42ecbf294619ee3abcc95c9a2f0"}

experimental_model

Cloning and functional expression

exposure

Radiolabeled creatine uptake

limitations

This primary abstract establishes sodium dependence; no chloride stoichiometry or clinical benefit is inferred.

nutrient_topic

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

organism

Human SLC6A8 in COS-7 cells

plain_language

Creatine entry has its own sodium-coupled transporter.

primary_references

[sodium-p7945388] The cloning and expression of a human creatine transporter. (1994). https://pubmed.ncbi.nlm.nih.gov/7945388/ DOI: 10.1006/bbrc.1994.2475

tissue_or_cell_type

Cell plasma membrane

transport_effect

raises Expression conferred sodium-dependent creatine uptake.

transport_pool

the expressing cell Expression conferred sodium-dependent creatine uptake.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 629–640

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

### sodium-creatine-transport Human creatine-transporter expression conferred sodium-dependent creatine uptake with Km 14.9 ± 3.0 micromolar in five experiments. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Creatine entry has its own sodium-coupled transporter. organism: Human SLC6A8 in COS-7 cells tissue_or_cell_type: Cell plasma membrane experimental_model: Cloning and functional expression limitations: This primary abstract establishes sodium dependence; no chloride stoichiometry or clinical benefit is inferred. exposure: Radiolabeled creatine uptake evidence_span: {"source_cache": "artifacts/sodium-research/7945388.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f936121279583ab698555d2a318900a9dc5a42ecbf294619ee3abcc95c9a2f0", "start_char": 0, "end_char": 910, "text_sha256": "4f936121279583ab698555d2a318900a9dc5a42ecbf294619ee3abcc95c9a2f0"} [sodium-p7945388] The cloning and expression of a human creatine transporter. (1994). https://pubmed.ncbi.nlm.nih.gov/7945388/ DOI: 10.1006/bbrc.1994.2475

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sodium-research/8589714.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c85f54f2086e1dc34cabaa8e4521a157bfeb5512b7882ca214ddfa2597b9bc4e", "start_char": 0, "end_char": 696, "text_sha256": "c85f54f2086e1dc34cabaa8e4521a157bfeb5512b7882ca214ddfa2597b9bc4e"}

experimental_model

Human family genetics and sodium-channel functional testing

exposure

Loss-of-function alpha- or beta-subunit variants in five kindreds

limitations

Autosomal recessive pseudohypoaldosteronism; not ordinary dietary sodium deficiency and not proof that additional aldosterone can repair the channel.

nutrient_topic

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

organism

Human

plain_language

The sodium entry channel itself can fail.

primary_references

[sodium-p8589714] Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. (1996). https://pubmed.ncbi.nlm.nih.gov/8589714/ DOI: 10.1038/ng0396-248

tissue_or_cell_type

ENaC-dependent epithelia and systemic electrolyte phenotype

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 928–939

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human family genetics and sodium-channel functional testing · source_derived_draft · unverified_draft

### sodium-enac-loss-current The alpha- or beta-subunit variants identified in affected families caused loss of channel activity. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The sodium entry channel itself can fail. organism: Human tissue_or_cell_type: ENaC-dependent epithelia and systemic electrolyte phenotype experimental_model: Human family genetics and sodium-channel functional testing limitations: Autosomal recessive pseudohypoaldosteronism; not ordinary dietary sodium deficiency and not proof that additional aldosterone can repair the channel. exposure: Loss-of-function alpha- or beta-subunit variants in five kindreds evidence_span: {"source_cache": "artifacts/sodium-research/8589714.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c85f54f2086e1dc34cabaa8e4521a157bfeb5512b7882ca214ddfa2597b9bc4e", "start_char": 0, "end_char": 696, "text_sha256": "c85f54f2086e1dc34cabaa8e4521a157bfeb5512b7882ca214ddfa2597b9bc4e"} [sodium-p8589714] Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. (1996). https://pubmed.ncbi.nlm.nih.gov/8589714/ DOI: 10.1038/ng0396-248

evidence_span

{"source_cache": "artifacts/sodium-research/9822723.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064", "start_char": 0, "end_char": 1740, "text_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064"}

experimental_model

Whole-cell current reversal measurements

exposure

Ion substitution, intracellular sodium/glutamate and extracellular potassium

limitations

Stoichiometry inferred from reversal potentials; the predicted ischemic extracellular glutamate concentration is not an in-vivo result.

nutrient_topic

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

organism

Mammalian GLT-1 expressed in Chinese hamster ovary cells

plain_language

Changing the ion gradients can reverse a transporter that normally clears glutamate.

primary_references

[sodium-p9822723] Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. (1998). https://pubmed.ncbi.nlm.nih.gov/9822723/ DOI: 10.1523/jneurosci.18-23-09620.1998

tissue_or_cell_type

Plasma membrane

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 382–393

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

### sodium-glt1-reversal Increasing extracellular potassium around cells loaded with sodium and glutamate evoked an outward, blocker-sensitive reversed transport current. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing the ion gradients can reverse a transporter that normally clears glutamate. organism: Mammalian GLT-1 expressed in Chinese hamster ovary cells tissue_or_cell_type: Plasma membrane experimental_model: Whole-cell current reversal measurements limitations: Stoichiometry inferred from reversal potentials; the predicted ischemic extracellular glutamate concentration is not an in-vivo result. exposure: Ion substitution, intracellular sodium/glutamate and extracellular potassium evidence_span: {"source_cache": "artifacts/sodium-research/9822723.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064", "start_char": 0, "end_char": 1740, "text_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064"} [sodium-p9822723] Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. (1998). https://pubmed.ncbi.nlm.nih.gov/9822723/ DOI: 10.1523/jneurosci.18-23-09620.1998

evidence_span

{"source_cache": "artifacts/sodium-research/9822723.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064", "start_char": 0, "end_char": 1740, "text_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064"}

experimental_model

Whole-cell current reversal measurements

exposure

Ion substitution, intracellular sodium/glutamate and extracellular potassium

limitations

Stoichiometry inferred from reversal potentials; the predicted ischemic extracellular glutamate concentration is not an in-vivo result.

nutrient_topic

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

organism

Mammalian GLT-1 expressed in Chinese hamster ovary cells

plain_language

Glutamate clearance uses sodium, potassium and proton gradients together.

primary_references

[sodium-p9822723] Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. (1998). https://pubmed.ncbi.nlm.nih.gov/9822723/ DOI: 10.1523/jneurosci.18-23-09620.1998

tissue_or_cell_type

Plasma membrane

transport_effect

raises Uptake of one glutamate anion with three sodium ions and one proton.

transport_pool

the expressing cell Uptake of one glutamate anion with three sodium ions and one proton.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 369–380

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

### sodium-glt1-stoichiometry Current reversal measurements supported uptake of one glutamate anion with three sodium ions and one proton, coupled to outward movement of one potassium ion. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutamate clearance uses sodium, potassium and proton gradients together. organism: Mammalian GLT-1 expressed in Chinese hamster ovary cells tissue_or_cell_type: Plasma membrane experimental_model: Whole-cell current reversal measurements limitations: Stoichiometry inferred from reversal potentials; the predicted ischemic extracellular glutamate concentration is not an in-vivo result. exposure: Ion substitution, intracellular sodium/glutamate and extracellular potassium evidence_span: {"source_cache": "artifacts/sodium-research/9822723.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064", "start_char": 0, "end_char": 1740, "text_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064"} [sodium-p9822723] Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. (1998). https://pubmed.ncbi.nlm.nih.gov/9822723/ DOI: 10.1523/jneurosci.18-23-09620.1998

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sodium-research/8524790.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "31f8bb4c6f32108b9d6042db6ec60ed8c77b21af322621a2cb0fd9c2aa7236a1", "start_char": 0, "end_char": 1598, "text_sha256": "31f8bb4c6f32108b9d6042db6ec60ed8c77b21af322621a2cb0fd9c2aa7236a1"}

experimental_model

Human kindred analysis and oocyte channel-expression comparison

exposure

P616L as numbered in the paper

limitations

Gain-of-function genetic disease; no implication that this mutation is caused by salt intake.

nutrient_topic

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

organism

Human variant in Xenopus oocytes

plain_language

A mutation can make sodium entry excessive even without a defective sodium supply.

primary_references

[sodium-p8524790] A de novo missense mutation of the beta subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity. (1995). https://pubmed.ncbi.nlm.nih.gov/8524790/ DOI: 10.1073/pnas.92.25.11495

tissue_or_cell_type

ENaC beta-subunit regulatory tail

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 954–965

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human kindred analysis and oocyte channel-expression comparison · source_derived_draft · unverified_draft

### sodium-liddle-current The beta-subunit P616L mutant increased amiloride-sensitive sodium current 8.8-fold versus normal subunits in oocytes. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A mutation can make sodium entry excessive even without a defective sodium supply. organism: Human variant in Xenopus oocytes tissue_or_cell_type: ENaC beta-subunit regulatory tail experimental_model: Human kindred analysis and oocyte channel-expression comparison limitations: Gain-of-function genetic disease; no implication that this mutation is caused by salt intake. exposure: P616L as numbered in the paper evidence_span: {"source_cache": "artifacts/sodium-research/8524790.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "31f8bb4c6f32108b9d6042db6ec60ed8c77b21af322621a2cb0fd9c2aa7236a1", "start_char": 0, "end_char": 1598, "text_sha256": "31f8bb4c6f32108b9d6042db6ec60ed8c77b21af322621a2cb0fd9c2aa7236a1"} [sodium-p8524790] A de novo missense mutation of the beta subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity. (1995). https://pubmed.ncbi.nlm.nih.gov/8524790/ DOI: 10.1073/pnas.92.25.11495

evidence_span

{"source_cache": "artifacts/sodium-research/32728214.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2780431aa362c99c816f986e923fd65ed0c0324e8c8674af8ff2a2f9367762c1", "start_char": 0, "end_char": 1533, "text_sha256": "2780431aa362c99c816f986e923fd65ed0c0324e8c8674af8ff2a2f9367762c1"}

experimental_model

Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays

exposure

Acute hypoxia and inhibition of mitochondrial sodium/calcium exchange

limitations

Mechanistic research under hypoxia, including multiple preparations. Do not infer that dietary salt drives this chain, that every tissue responds identically, or that ROS here proves disease.

nutrient_topic

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

organism

Human and mouse cells; additional rat vascular experiments in the paper

plain_language

Calcium handling can bring sodium into the mitochondrion.

primary_references

[sodium-p32728214] Na+ controls hypoxic signalling by the mitochondrial respiratory chain. (2020). https://pubmed.ncbi.nlm.nih.gov/32728214/ DOI: 10.1038/s41586-020-2551-y

tissue_or_cell_type

Mitochondrial matrix and inner membrane

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 772–783

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays · source_derived_draft · unverified_draft

### sodium-matrix-sodium Activation of mitochondrial sodium/calcium exchange promoted sodium import into the matrix during the hypoxic pathway. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium handling can bring sodium into the mitochondrion. organism: Human and mouse cells; additional rat vascular experiments in the paper tissue_or_cell_type: Mitochondrial matrix and inner membrane experimental_model: Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays limitations: Mechanistic research under hypoxia, including multiple preparations. Do not infer that dietary salt drives this chain, that every tissue responds identically, or that ROS here proves disease. exposure: Acute hypoxia and inhibition of mitochondrial sodium/calcium exchange evidence_span: {"source_cache": "artifacts/sodium-research/32728214.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2780431aa362c99c816f986e923fd65ed0c0324e8c8674af8ff2a2f9367762c1", "start_char": 0, "end_char": 1533, "text_sha256": "2780431aa362c99c816f986e923fd65ed0c0324e8c8674af8ff2a2f9367762c1"} [sodium-p32728214] Na+ controls hypoxic signalling by the mitochondrial respiratory chain. (2020). https://pubmed.ncbi.nlm.nih.gov/32728214/ DOI: 10.1038/s41586-020-2551-y

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sodium-research/16358215.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb", "start_char": 0, "end_char": 1515, "text_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb"}

experimental_model

Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria

exposure

SLC34A3 disease-associated mutations in five families

limitations

Genotype–phenotype evidence supports a primary renal defect; downstream calcitriol/calcium pattern is observed, not a dietary sodium intervention.

nutrient_topic

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

organism

Human

plain_language

The kidney’s sodium/phosphate transporter is important for retaining phosphate.

primary_references

[sodium-p16358215] Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. (2006). https://pubmed.ncbi.nlm.nih.gov/16358215/ DOI: 10.1086/499410

tissue_or_cell_type

Renal proximal tubule and systemic mineral phenotype

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 668–679

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria · source_derived_draft · unverified_draft

### sodium-napi2c-phosphate SLC34A3 mutations segregated with renal phosphate wasting and hypophosphatemic rickets in the studied families. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidney’s sodium/phosphate transporter is important for retaining phosphate. organism: Human tissue_or_cell_type: Renal proximal tubule and systemic mineral phenotype experimental_model: Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria limitations: Genotype–phenotype evidence supports a primary renal defect; downstream calcitriol/calcium pattern is observed, not a dietary sodium intervention. exposure: SLC34A3 disease-associated mutations in five families evidence_span: {"source_cache": "artifacts/sodium-research/16358215.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb", "start_char": 0, "end_char": 1515, "text_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb"} [sodium-p16358215] Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. (2006). https://pubmed.ncbi.nlm.nih.gov/16358215/ DOI: 10.1086/499410

evidence_span

{"source_cache": "artifacts/sodium-research/17408578.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5df7ccac391e94f2688ccacf287fda852b7a52e5279d1488ef48f0f52a3c6265", "start_char": 0, "end_char": 953, "text_sha256": "5df7ccac391e94f2688ccacf287fda852b7a52e5279d1488ef48f0f52a3c6265"}

experimental_model

Protein interaction, glial metabolism and SFO neuronal recordings

exposure

Elevated sodium; Nax knockout; lactate exposure

limitations

Brain salt-sensing pathway in experimental preparations; not a human sodium-intake threshold.

nutrient_topic

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

organism

Mouse SFO and mammalian cell preparations

plain_language

Glial cells turn a sodium signal into a metabolic signal carried by lactate.

primary_references

[sodium-p17408578] Glial Nax channels control lactate signaling to neurons for brain [Na+] sensing. (2007). https://pubmed.ncbi.nlm.nih.gov/17408578/ DOI: 10.1016/j.neuron.2007.03.014

tissue_or_cell_type

Glial cells and GABAergic neurons of the subfornical organ

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 460–471

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein interaction, glial metabolism and SFO neuronal recordings · source_derived_draft · unverified_draft

### sodium-nax-lactate The sodium-associated increase in SFO lactate production occurred in wild-type but not Nax-knockout mice. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glial cells turn a sodium signal into a metabolic signal carried by lactate. organism: Mouse SFO and mammalian cell preparations tissue_or_cell_type: Glial cells and GABAergic neurons of the subfornical organ experimental_model: Protein interaction, glial metabolism and SFO neuronal recordings limitations: Brain salt-sensing pathway in experimental preparations; not a human sodium-intake threshold. exposure: Elevated sodium; Nax knockout; lactate exposure evidence_span: {"source_cache": "artifacts/sodium-research/17408578.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5df7ccac391e94f2688ccacf287fda852b7a52e5279d1488ef48f0f52a3c6265", "start_char": 0, "end_char": 953, "text_sha256": "5df7ccac391e94f2688ccacf287fda852b7a52e5279d1488ef48f0f52a3c6265"} [sodium-p17408578] Glial Nax channels control lactate signaling to neurons for brain [Na+] sensing. (2007). https://pubmed.ncbi.nlm.nih.gov/17408578/ DOI: 10.1016/j.neuron.2007.03.014

evidence_span

{"source_cache": "artifacts/sodium-research/17408578.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5df7ccac391e94f2688ccacf287fda852b7a52e5279d1488ef48f0f52a3c6265", "start_char": 0, "end_char": 953, "text_sha256": "5df7ccac391e94f2688ccacf287fda852b7a52e5279d1488ef48f0f52a3c6265"}

experimental_model

Protein interaction, glial metabolism and SFO neuronal recordings

exposure

Elevated sodium; Nax knockout; lactate exposure

limitations

Brain salt-sensing pathway in experimental preparations; not a human sodium-intake threshold.

nutrient_topic

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

organism

Mouse SFO and mammalian cell preparations

plain_language

A sodium-sensing channel can connect sodium detection to the cell’s energy use.

primary_references

[sodium-p17408578] Glial Nax channels control lactate signaling to neurons for brain [Na+] sensing. (2007). https://pubmed.ncbi.nlm.nih.gov/17408578/ DOI: 10.1016/j.neuron.2007.03.014

tissue_or_cell_type

Glial cells and GABAergic neurons of the subfornical organ

Sodium: gradients, nutrient transport, fluid regulation and loss states (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 · Protein interaction, glial metabolism and SFO neuronal recordings · source_derived_draft · unverified_draft

### sodium-nax-pump Nax directly interacted with sodium/potassium-pump alpha subunits in the study. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sodium-sensing channel can connect sodium detection to the cell’s energy use. organism: Mouse SFO and mammalian cell preparations tissue_or_cell_type: Glial cells and GABAergic neurons of the subfornical organ experimental_model: Protein interaction, glial metabolism and SFO neuronal recordings limitations: Brain salt-sensing pathway in experimental preparations; not a human sodium-intake threshold. exposure: Elevated sodium; Nax knockout; lactate exposure evidence_span: {"source_cache": "artifacts/sodium-research/17408578.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5df7ccac391e94f2688ccacf287fda852b7a52e5279d1488ef48f0f52a3c6265", "start_char": 0, "end_char": 953, "text_sha256": "5df7ccac391e94f2688ccacf287fda852b7a52e5279d1488ef48f0f52a3c6265"} [sodium-p17408578] Glial Nax channels control lactate signaling to neurons for brain [Na+] sensing. (2007). https://pubmed.ncbi.nlm.nih.gov/17408578/ DOI: 10.1016/j.neuron.2007.03.014

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sodium-research/18441326.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ca538a7ecb046a47f9246778b3dede99c503a45c6048f75541612c8db37448c", "start_char": 0, "end_char": 1213, "text_sha256": "3ca538a7ecb046a47f9246778b3dede99c503a45c6048f75541612c8db37448c"}

experimental_model

Homology modeling and site-directed mutagenesis with oocyte transport assays

exposure

E91 and R298 mutations and charge-reversal construct

limitations

Structure model plus functional assay; charge rescue does not establish clinical treatment or dietary sodium responsiveness.

nutrient_topic

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

organism

Human kidney NBCe1 in Xenopus oocytes

plain_language

Acid–base regulation depends on the protein’s structure as well as available sodium.

primary_references

[sodium-p18441326] Entry to "formula tunnel" revealed by SLC4A4 human mutation and structural model. (2008). https://pubmed.ncbi.nlm.nih.gov/18441326/ DOI: 10.1074/jbc.m709819200

tissue_or_cell_type

Sodium/bicarbonate transporter N-terminal domain

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 707–718

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Homology modeling and site-directed mutagenesis with oocyte transport assays · source_derived_draft · unverified_draft

### sodium-nbce1-mutation Mutagenesis of NBCe1 residues E91 or R298 reduced transport function in the expression assay. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Acid–base regulation depends on the protein’s structure as well as available sodium. organism: Human kidney NBCe1 in Xenopus oocytes tissue_or_cell_type: Sodium/bicarbonate transporter N-terminal domain experimental_model: Homology modeling and site-directed mutagenesis with oocyte transport assays limitations: Structure model plus functional assay; charge rescue does not establish clinical treatment or dietary sodium responsiveness. exposure: E91 and R298 mutations and charge-reversal construct evidence_span: {"source_cache": "artifacts/sodium-research/18441326.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ca538a7ecb046a47f9246778b3dede99c503a45c6048f75541612c8db37448c", "start_char": 0, "end_char": 1213, "text_sha256": "3ca538a7ecb046a47f9246778b3dede99c503a45c6048f75541612c8db37448c"} [sodium-p18441326] Entry to "formula tunnel" revealed by SLC4A4 human mutation and structural model. (2008). https://pubmed.ncbi.nlm.nih.gov/18441326/ DOI: 10.1074/jbc.m709819200

evidence_span

{"source_cache": "artifacts/sodium-research/20018762.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8594465b44cbb04ed3a631d5dae19959e7c0494a86537d6a60d33d6db1821831", "start_char": 0, "end_char": 1085, "text_sha256": "8594465b44cbb04ed3a631d5dae19959e7c0494a86537d6a60d33d6db1821831"}

experimental_model

Overexpression, siRNA, rescue, mutant and fluorescent ion-imaging experiments

exposure

NCLX abundance, inactive mutant and ion substitutions

limitations

Supports molecular identification in these assays. Protein species and construct details must be taken from the original methods; not evidence for raising dietary sodium.

nutrient_topic

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

organism

Mammalian cultured-cell preparations

plain_language

A mitochondrial exchanger connects sodium movement with calcium removal.

primary_references

[sodium-p20018762] NCLX is an essential component of mitochondrial Na+/Ca2+ exchange. (2010). https://pubmed.ncbi.nlm.nih.gov/20018762/ DOI: 10.1073/pnas.0908099107

tissue_or_cell_type

Mitochondrial cristae

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 733–744

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Overexpression, siRNA, rescue, mutant and fluorescent ion-imaging experiments · source_derived_draft · unverified_draft

### sodium-nclx-efflux NCLX overexpression increased sodium-dependent mitochondrial calcium efflux; silencing reduced it and heterologous rescue restored it. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A mitochondrial exchanger connects sodium movement with calcium removal. organism: Mammalian cultured-cell preparations tissue_or_cell_type: Mitochondrial cristae experimental_model: Overexpression, siRNA, rescue, mutant and fluorescent ion-imaging experiments limitations: Supports molecular identification in these assays. Protein species and construct details must be taken from the original methods; not evidence for raising dietary sodium. exposure: NCLX abundance, inactive mutant and ion substitutions evidence_span: {"source_cache": "artifacts/sodium-research/20018762.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8594465b44cbb04ed3a631d5dae19959e7c0494a86537d6a60d33d6db1821831", "start_char": 0, "end_char": 1085, "text_sha256": "8594465b44cbb04ed3a631d5dae19959e7c0494a86537d6a60d33d6db1821831"} [sodium-p20018762] NCLX is an essential component of mitochondrial Na+/Ca2+ exchange. (2010). https://pubmed.ncbi.nlm.nih.gov/20018762/ DOI: 10.1073/pnas.0908099107

evidence_span

{"source_cache": "artifacts/sodium-research/9685390.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08cdedaad32299795a52b81183d565d2b476b7a190b2af7b950c829f8c11ddf6", "start_char": 0, "end_char": 1549, "text_sha256": "08cdedaad32299795a52b81183d565d2b476b7a190b2af7b950c829f8c11ddf6"}

experimental_model

Cloning and functional expression

exposure

Radiolabeled carnitine uptake and sodium dependence

limitations

Expression assay; dietary sodium intake, mitochondrial fatty-acid oxidation and clinical supplementation were not directly tested.

nutrient_topic

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

organism

Human OCTN2 in HEK293 cells

plain_language

The sodium gradient helps bring carnitine into cells.

primary_references

[sodium-p9685390] Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. (1998). https://pubmed.ncbi.nlm.nih.gov/9685390/ DOI: 10.1074/jbc.273.32.20378

tissue_or_cell_type

Cell plasma membrane

transport_effect

raises Expression increased sodium-dependent carnitine uptake.

transport_pool

the expressing cell Expression increased sodium-dependent carnitine uptake.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 616–627

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

### sodium-octn2-carnitine Human OCTN2 expression increased sodium-dependent carnitine uptake with an apparent Km of 4.34 micromolar. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The sodium gradient helps bring carnitine into cells. organism: Human OCTN2 in HEK293 cells tissue_or_cell_type: Cell plasma membrane experimental_model: Cloning and functional expression limitations: Expression assay; dietary sodium intake, mitochondrial fatty-acid oxidation and clinical supplementation were not directly tested. exposure: Radiolabeled carnitine uptake and sodium dependence evidence_span: {"source_cache": "artifacts/sodium-research/9685390.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08cdedaad32299795a52b81183d565d2b476b7a190b2af7b950c829f8c11ddf6", "start_char": 0, "end_char": 1549, "text_sha256": "08cdedaad32299795a52b81183d565d2b476b7a190b2af7b950c829f8c11ddf6"} [sodium-p9685390] Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. (1998). https://pubmed.ncbi.nlm.nih.gov/9685390/ DOI: 10.1074/jbc.273.32.20378

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sodium-research/10440307.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd7239d3f0a151f53930364ba35b974cd938a67bc4282e4b67a02e24f68e9969", "start_char": 0, "end_char": 2141, "text_sha256": "cd7239d3f0a151f53930364ba35b974cd938a67bc4282e4b67a02e24f68e9969"}

experimental_model

Randomized double-blind comparison in 300 adults with severe cholera

exposure

Reduced-osmolarity versus then-standard WHO oral rehydration solution

limitations

Historical formulation comparison; not a current formulation recommendation. Both sodium and other solution properties changed; no isolated sodium effect.

nutrient_topic

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

organism

Human

plain_language

Replacing fluid is not just replacing water: solution composition affected blood sodium.

primary_references

[sodium-p10440307] Efficacy and safety of oral rehydration solution with reduced osmolarity in adults with cholera: a randomised double-blind clinical trial. CHOICE study group. (1999). https://pubmed.ncbi.nlm.nih.gov/10440307/ DOI: 10.1016/s0140-6736(98)09332-5

tissue_or_cell_type

Intestinal fluid loss and serum sodium

trigger_kind

biomarker_context Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 1045–1056

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind comparison in 300 adults with severe cholera · source_derived_draft · unverified_draft

### sodium-ors-sodium Hyponatremia below 130 mmol/L occurred in 29/142 versus 16/150 participants receiving reduced-osmolarity versus standard ORS; affected participants were symptom-free. Condition category: biomarker_context nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacing fluid is not just replacing water: solution composition affected blood sodium. organism: Human tissue_or_cell_type: Intestinal fluid loss and serum sodium experimental_model: Randomized double-blind comparison in 300 adults with severe cholera limitations: Historical formulation comparison; not a current formulation recommendation. Both sodium and other solution properties changed; no isolated sodium effect. exposure: Reduced-osmolarity versus then-standard WHO oral rehydration solution evidence_span: {"source_cache": "artifacts/sodium-research/10440307.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd7239d3f0a151f53930364ba35b974cd938a67bc4282e4b67a02e24f68e9969", "start_char": 0, "end_char": 2141, "text_sha256": "cd7239d3f0a151f53930364ba35b974cd938a67bc4282e4b67a02e24f68e9969"} [sodium-p10440307] Efficacy and safety of oral rehydration solution with reduced osmolarity in adults with cholera: a randomised double-blind clinical trial. CHOICE study group. (1999). https://pubmed.ncbi.nlm.nih.gov/10440307/ DOI: 10.1016/s0140-6736(98)09332-5

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_span

{"source_cache": "artifacts/sodium-research/10358046.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d53e3e8ce41bb21d5cac2a5bfe6a6abdc702d0870add9c0a002e58ac374a97b", "start_char": 0, "end_char": 1343, "text_sha256": "7d53e3e8ce41bb21d5cac2a5bfe6a6abdc702d0870add9c0a002e58ac374a97b"}

experimental_model

Immediate-early gene induction and channel coexpression

exposure

Aldosterone exposure; receptor dependence and protein-synthesis tests

limitations

Cell and oocyte mechanism; the study does not imply that dietary sodium directly activates SGK1 in every tissue.

nutrient_topic

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

organism

Rabbit/mouse collecting-duct preparations; mouse SGK in Xenopus oocytes

plain_language

The kinase can increase sodium flow through ENaC.

primary_references

[sodium-p10358046] sgk is an aldosterone-induced kinase in the renal collecting duct. Effects on epithelial na+ channels. (1999). https://pubmed.ncbi.nlm.nih.gov/10358046/ DOI: 10.1074/jbc.274.24.16973

tissue_or_cell_type

Cortical collecting duct and expression system

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 408–419

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Immediate-early gene induction and channel coexpression · source_derived_draft · unverified_draft

### sodium-sgk-enac Coexpression of mouse sgk with the three ENaC subunits increased sodium current in Xenopus oocytes. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kinase can increase sodium flow through ENaC. organism: Rabbit/mouse collecting-duct preparations; mouse SGK in Xenopus oocytes tissue_or_cell_type: Cortical collecting duct and expression system experimental_model: Immediate-early gene induction and channel coexpression limitations: Cell and oocyte mechanism; the study does not imply that dietary sodium directly activates SGK1 in every tissue. exposure: Aldosterone exposure; receptor dependence and protein-synthesis tests evidence_span: {"source_cache": "artifacts/sodium-research/10358046.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d53e3e8ce41bb21d5cac2a5bfe6a6abdc702d0870add9c0a002e58ac374a97b", "start_char": 0, "end_char": 1343, "text_sha256": "7d53e3e8ce41bb21d5cac2a5bfe6a6abdc702d0870add9c0a002e58ac374a97b"} [sodium-p10358046] sgk is an aldosterone-induced kinase in the renal collecting duct. Effects on epithelial na+ channels. (1999). https://pubmed.ncbi.nlm.nih.gov/10358046/ DOI: 10.1074/jbc.274.24.16973

evidence_span

{"source_cache": "artifacts/sodium-research/2008213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba4e32dc5111895acfe9e109cf57a7e07bc3c4e07e82ad3b4f7715cfaf10af74", "start_char": 0, "end_char": 1357, "text_sha256": "ba4e32dc5111895acfe9e109cf57a7e07bc3c4e07e82ad3b4f7715cfaf10af74"}

experimental_model

Family segregation and Xenopus oocyte transport assay

exposure

Disease-associated SGLT1 missense variant versus normal transporter

limitations

A genetic transporter defect is not sodium dietary deficiency; the sugar-malabsorption phenotype must not be presented as a reason to add salt.

nutrient_topic

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

organism

Human SGLT1 expressed in frog oocytes

plain_language

A sodium gradient helps intestinal cells take up glucose.

primary_references

[sodium-p2008213] Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. (1991). https://pubmed.ncbi.nlm.nih.gov/2008213/ DOI: 10.1038/350354a0

tissue_or_cell_type

Intestinal brush border

transport_effect

raises Couples glucose entry to the inward sodium electrochemical gradient.

transport_pool

the enterocyte interior Couples glucose entry to the inward sodium electrochemical gradient.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 291–302

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Family segregation and Xenopus oocyte transport assay · source_derived_draft · unverified_draft

### sodium-sglt1-gradient Normal intestinal SGLT1 couples glucose entry to the inward sodium electrochemical gradient. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sodium gradient helps intestinal cells take up glucose. organism: Human SGLT1 expressed in frog oocytes tissue_or_cell_type: Intestinal brush border experimental_model: Family segregation and Xenopus oocyte transport assay limitations: A genetic transporter defect is not sodium dietary deficiency; the sugar-malabsorption phenotype must not be presented as a reason to add salt. exposure: Disease-associated SGLT1 missense variant versus normal transporter evidence_span: {"source_cache": "artifacts/sodium-research/2008213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba4e32dc5111895acfe9e109cf57a7e07bc3c4e07e82ad3b4f7715cfaf10af74", "start_char": 0, "end_char": 1357, "text_sha256": "ba4e32dc5111895acfe9e109cf57a7e07bc3c4e07e82ad3b4f7715cfaf10af74"} [sodium-p2008213] Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. (1991). https://pubmed.ncbi.nlm.nih.gov/2008213/ DOI: 10.1038/350354a0

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sodium-research/2008213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba4e32dc5111895acfe9e109cf57a7e07bc3c4e07e82ad3b4f7715cfaf10af74", "start_char": 0, "end_char": 1357, "text_sha256": "ba4e32dc5111895acfe9e109cf57a7e07bc3c4e07e82ad3b4f7715cfaf10af74"}

experimental_model

Family segregation and Xenopus oocyte transport assay

exposure

Disease-associated SGLT1 missense variant versus normal transporter

limitations

A genetic transporter defect is not sodium dietary deficiency; the sugar-malabsorption phenotype must not be presented as a reason to add salt.

nutrient_topic

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

organism

Human SGLT1 expressed in frog oocytes

plain_language

The transport protein itself can be the limiting step.

primary_references

[sodium-p2008213] Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. (1991). https://pubmed.ncbi.nlm.nih.gov/2008213/ DOI: 10.1038/350354a0

tissue_or_cell_type

Intestinal brush border

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 304–315

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Family segregation and Xenopus oocyte transport assay · source_derived_draft · unverified_draft

### sodium-sglt1-loss The familial SGLT1 missense variant abolished sodium-dependent glucose transport in injected oocytes. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The transport protein itself can be the limiting step. organism: Human SGLT1 expressed in frog oocytes tissue_or_cell_type: Intestinal brush border experimental_model: Family segregation and Xenopus oocyte transport assay limitations: A genetic transporter defect is not sodium dietary deficiency; the sugar-malabsorption phenotype must not be presented as a reason to add salt. exposure: Disease-associated SGLT1 missense variant versus normal transporter evidence_span: {"source_cache": "artifacts/sodium-research/2008213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba4e32dc5111895acfe9e109cf57a7e07bc3c4e07e82ad3b4f7715cfaf10af74", "start_char": 0, "end_char": 1357, "text_sha256": "ba4e32dc5111895acfe9e109cf57a7e07bc3c4e07e82ad3b4f7715cfaf10af74"} [sodium-p2008213] Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. (1991). https://pubmed.ncbi.nlm.nih.gov/2008213/ DOI: 10.1038/350354a0

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sodium-research/20616166.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0596ceea07c063931780bf6128a238c81622461ed65dd5b0d382f0202e1626f9", "start_char": 0, "end_char": 1704, "text_sha256": "0596ceea07c063931780bf6128a238c81622461ed65dd5b0d382f0202e1626f9"}

experimental_model

Sglt2-null mice, localization, clearance and micropuncture

exposure

Genetic Slc5a2 deletion

limitations

Renal glucose reabsorption and water output changed, but the knockout did not show the measured signs of volume depletion. Genetic deletion is not a dietary experiment.

nutrient_topic

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

organism

Mouse

plain_language

The early kidney tubule uses a specific sodium/glucose transporter to reclaim filtered glucose.

primary_references

[sodium-p20616166] SGLT2 mediates glucose reabsorption in the early proximal tubule. (2011). https://pubmed.ncbi.nlm.nih.gov/20616166/ DOI: 10.1681/asn.2010030246

tissue_or_cell_type

Renal early proximal tubule

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 317–328

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sglt2-null mice, localization, clearance and micropuncture · source_derived_draft · unverified_draft

### sodium-sglt2-early Early proximal glucose reabsorption was 78 ± 6% in wild-type mice and absent in Sglt2-null mice. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The early kidney tubule uses a specific sodium/glucose transporter to reclaim filtered glucose. organism: Mouse tissue_or_cell_type: Renal early proximal tubule experimental_model: Sglt2-null mice, localization, clearance and micropuncture limitations: Renal glucose reabsorption and water output changed, but the knockout did not show the measured signs of volume depletion. Genetic deletion is not a dietary experiment. exposure: Genetic Slc5a2 deletion evidence_span: {"source_cache": "artifacts/sodium-research/20616166.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0596ceea07c063931780bf6128a238c81622461ed65dd5b0d382f0202e1626f9", "start_char": 0, "end_char": 1704, "text_sha256": "0596ceea07c063931780bf6128a238c81622461ed65dd5b0d382f0202e1626f9"} [sodium-p20616166] SGLT2 mediates glucose reabsorption in the early proximal tubule. (2011). https://pubmed.ncbi.nlm.nih.gov/20616166/ DOI: 10.1681/asn.2010030246

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_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

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Abstract: reported experimental results

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays

exposure

Intraperitoneal calcitriol once daily for 2 days; dose not specified in the retrieved abstract.

limitations

Stimulation was segment-specific: increased transporter protein in ileum did not establish the same active-flux response there. No human dietary-dose inference.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

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

organism

Mus musculus

plain_language

Active vitamin D increased the intestine’s sodium-coupled phosphate uptake in the responsive segment.

primary_references

[vdm-hernando2021] 1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine. (2021). https://pubmed.ncbi.nlm.nih.gov/33200827/ DOI: 10.1113/jp280345

tissue_or_cell_type

Jejunum

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 665–679

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays · source_derived_draft · unverified_draft

### vdm-calcitriol-increases-jejunal-phosphate-transport Two daily calcitriol injections increased active phosphate transport in wild-type mouse jejunum. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Active vitamin D increased the intestine’s sodium-coupled phosphate uptake in the responsive segment. organism: Mus musculus tissue_or_cell_type: Jejunum experimental_model: Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays limitations: Stimulation was segment-specific: increased transporter protein in ileum did not establish the same active-flux response there. No human dietary-dose inference. exposure: Intraperitoneal calcitriol once daily for 2 days; dose not specified in the retrieved abstract. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-hernando2021] 1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine. (2021). https://pubmed.ncbi.nlm.nih.gov/33200827/ DOI: 10.1113/jp280345

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Abstract: reported experimental results

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays

exposure

Intraperitoneal calcitriol once daily for 2 days; dose not specified in the retrieved abstract.

limitations

A negative result for this assay and regimen does not exclude other doses, durations, species or intestinal segments.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

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

organism

Mus musculus

plain_language

The measured phosphate response involved transport through cells; the route between cells did not show the same increase.

primary_references

[vdm-hernando2021] 1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine. (2021). https://pubmed.ncbi.nlm.nih.gov/33200827/ DOI: 10.1113/jp280345

tissue_or_cell_type

Intestinal epithelium

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 681–695

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays · source_derived_draft · unverified_draft

### vdm-calcitriol-no-detected-paracellular-phosphate-response The two-day calcitriol regimen did not detectably increase paracellular phosphate flux in the mouse intestine. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured phosphate response involved transport through cells; the route between cells did not show the same increase. organism: Mus musculus tissue_or_cell_type: Intestinal epithelium experimental_model: Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays limitations: A negative result for this assay and regimen does not exclude other doses, durations, species or intestinal segments. exposure: Intraperitoneal calcitriol once daily for 2 days; dose not specified in the retrieved abstract. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-hernando2021] 1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine. (2021). https://pubmed.ncbi.nlm.nih.gov/33200827/ DOI: 10.1113/jp280345

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Abstract: reported experimental results

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Single recombinant FGF23 injection in rodents; renal transcript/protein and serum phosphate measurements

exposure

Single recombinant FGF23 injection; serum phosphate reduction was first observed at 9 hours; dose not recovered in the primary abstract.

limitations

Transporter abundance is not itself a flux measurement. Lack of a PTH rise and parathyroidectomized-rat responses support a PTH-independent action in this experiment.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

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

organism

Mus musculus; Rattus norvegicus

plain_language

FGF23 reduced a kidney transporter that normally helps retain phosphate.

primary_references

[vdm-shimada2004] FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. (2004). https://pubmed.ncbi.nlm.nih.gov/15040831/ DOI: 10.1359/jbmr.0301264

tissue_or_cell_type

Kidney

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 745–759

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single recombinant FGF23 injection in rodents; renal transcript/protein and serum phosphate measurements · source_derived_draft · unverified_draft

### vdm-fgf23-reduces-renal-napi2a Recombinant FGF23 reduced renal NaPi-IIa mRNA and protein abundance in the acute rodent injection study. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: FGF23 reduced a kidney transporter that normally helps retain phosphate. organism: Mus musculus; Rattus norvegicus tissue_or_cell_type: Kidney experimental_model: Single recombinant FGF23 injection in rodents; renal transcript/protein and serum phosphate measurements limitations: Transporter abundance is not itself a flux measurement. Lack of a PTH rise and parathyroidectomized-rat responses support a PTH-independent action in this experiment. exposure: Single recombinant FGF23 injection; serum phosphate reduction was first observed at 9 hours; dose not recovered in the primary abstract. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-shimada2004] FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. (2004). https://pubmed.ncbi.nlm.nih.gov/15040831/ DOI: 10.1359/jbmr.0301264

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Abstract: reported experimental results

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays

exposure

Intraperitoneal calcitriol once daily for 2 days; dose not specified in the retrieved abstract.

limitations

Conditional transporter loss removes the measured hormonal increment; it does not prove that all baseline phosphate absorption is absent.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

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

organism

Mus musculus

plain_language

Without this intestinal transporter, active vitamin D failed to produce its usual phosphate-uptake increment.

primary_references

[vdm-hernando2021] 1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine. (2021). https://pubmed.ncbi.nlm.nih.gov/33200827/ DOI: 10.1113/jp280345

tissue_or_cell_type

Intestinal epithelium

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 697–711

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays · source_derived_draft · unverified_draft

### vdm-slc34a2-deletion-removes-calcitriol-phosphate-increment Intestine-specific Slc34a2 deletion eliminated the phosphate-transport increase induced by the tested calcitriol regimen. Condition category: machinery_impairment nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Without this intestinal transporter, active vitamin D failed to produce its usual phosphate-uptake increment. organism: Mus musculus tissue_or_cell_type: Intestinal epithelium experimental_model: Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays limitations: Conditional transporter loss removes the measured hormonal increment; it does not prove that all baseline phosphate absorption is absent. exposure: Intraperitoneal calcitriol once daily for 2 days; dose not specified in the retrieved abstract. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-hernando2021] 1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine. (2021). https://pubmed.ncbi.nlm.nih.gov/33200827/ DOI: 10.1113/jp280345

evidence_span

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experimental_model

Mouse knockout and cell transport experiments

exposure

LPC-bound versus unesterified DHA; sodium-dependent transport

limitations

LPC-DHA is a choline-containing lipid, not free choline. No claim that oral choline necessarily raises brain DHA.

nutrient_topic

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

organism

Mouse Mfsd2a and experimental expression system

plain_language

The chemical package used to carry DHA mattered.

primary_references

[choline-p24828044] Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. (2014). https://pubmed.ncbi.nlm.nih.gov/24828044/ DOI: 10.1038/nature13241

tissue_or_cell_type

Blood-brain-barrier endothelium

transport_effect

raises Mfsd2a is recorded as the influx route carrying DHA as lysophosphatidylcholine.

transport_pool

the brain-endothelial cell interior Mfsd2a is recorded as the influx route carrying DHA as lysophosphatidylcholine.

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 945–956

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse knockout and cell transport experiments · source_derived_draft · unverified_draft

### choline-mfsd2a-lpc Mfsd2a transported DHA carried by lysophosphatidylcholine rather than unesterified DHA in the tested system. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The chemical package used to carry DHA mattered. organism: Mouse Mfsd2a and experimental expression system tissue_or_cell_type: Blood-brain-barrier endothelium experimental_model: Mouse knockout and cell transport experiments limitations: LPC-DHA is a choline-containing lipid, not free choline. No claim that oral choline necessarily raises brain DHA. exposure: LPC-bound versus unesterified DHA; sodium-dependent transport evidence_span: {"source_cache": "artifacts/choline-research/24828044.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695", "start_char": 0, "end_char": 1689, "text_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695"} [choline-p24828044] Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. (2014). https://pubmed.ncbi.nlm.nih.gov/24828044/ DOI: 10.1038/nature13241

compartment_description

Plasma membrane

experimental_model

Human cardiac NCX1; cryo-EM and functional exchange assays

limitations

Net direction depends on electrochemical gradients and voltage; NCX1 is not an ATP-hydrolyzing pump.

nutrient_topic

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

organism

Homo sapiens

plain_language

NCX1 couples calcium movement to sodium moving the other way.

primary_references

[ca-xue2023] Structural mechanisms of the human cardiac sodium-calcium exchanger NCX1 (2023). https://pubmed.ncbi.nlm.nih.gov/37794011/ DOI: 10.1038/s41467-023-41885-4

research_relationship_category

transport

tissue_or_cell_type

Cardiac NCX1 expression system

transport_effect

depends Reversible exchange: forward mode extrudes calcium and reverse mode admits it, which the record states.

transport_or_reaction_direction

Reversible Na+/Ca2+ exchange; forward calcium extrusion or reverse calcium entry

transport_pool

cytosolic calcium Reversible exchange: forward mode extrudes calcium and reverse mode admits it, which the record states.

Calcium: mechanism-first literature curation (2026-09-17) · lines 625–637

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cardiac NCX1; cryo-EM and functional exchange assays · source_derived_draft · unverified_draft

### ca-ncx1-calcium-sodium-exchange Human cardiac NCX1 exchanges calcium and sodium in opposing directions across the membrane. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: NCX1 couples calcium movement to sodium moving the other way. organism: Homo sapiens tissue_or_cell_type: Cardiac NCX1 expression system experimental_model: Human cardiac NCX1; cryo-EM and functional exchange assays limitations: Net direction depends on electrochemical gradients and voltage; NCX1 is not an ATP-hydrolyzing pump. research_relationship_category: transport transport_or_reaction_direction: Reversible Na+/Ca2+ exchange; forward calcium extrusion or reverse calcium entry compartment_description: Plasma membrane [ca-xue2023] Structural mechanisms of the human cardiac sodium-calcium exchanger NCX1 (2023). https://pubmed.ncbi.nlm.nih.gov/37794011/ DOI: 10.1038/s41467-023-41885-4

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

cross_nutrient

Diuresis links vitamin loss with renal electrolyte management.

experimental_model

Timed crossover physiologic measurements.

exposure

Single intravenous furosemide doses 1, 3 and 10 mg, and a separate 750 mL saline infusion; acute physiologic study exposures.

limitations

Acute small study; cannot predict chronic deficiency for every diuretic user or infer a universal flow threshold.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

Producing more urine can increase B1 loss even without a unique drug-specific mechanism.

primary_references

[b1-rieck1999] Urinary loss of thiamine is increased by low doses of furosemide in healthy volunteers (1999). https://pubmed.ncbi.nlm.nih.gov/10482308/ DOI: 10.1016/s0022-2143(99)90203-2

tissue_or_cell_type

Urine

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1720–1731

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

### b1-diuresis-urinary-loss Furosemide and saline interventions increased urinary thiamine loss in six volunteers; excretion tracked urine flow without an additional intervention-type effect. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Producing more urine can increase B1 loss even without a unique drug-specific mechanism. organism: Homo sapiens tissue_or_cell_type: Urine experimental_model: Timed crossover physiologic measurements. limitations: Acute small study; cannot predict chronic deficiency for every diuretic user or infer a universal flow threshold. cross_nutrient: Diuresis links vitamin loss with renal electrolyte management. exposure: Single intravenous furosemide doses 1, 3 and 10 mg, and a separate 750 mL saline infusion; acute physiologic study exposures. [b1-rieck1999] Urinary loss of thiamine is increased by low doses of furosemide in healthy volunteers (1999). https://pubmed.ncbi.nlm.nih.gov/10482308/ DOI: 10.1016/s0022-2143(99)90203-2

evidence-scope

HeLa cells

evidence_locator

Abstract

evidence_spans

[{"source_document": "artifacts/thiamine_transport_sources/dutta-1999-slc19a2-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1275}]

experimental_model

Human placental cDNA expressed in HeLa cells; radiotracer uptake.

limitations

Does not establish an exact proton stoichiometry.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

B1 entry in this assay depended on proton conditions without sodium cotransport.

primary_references

[dutta-1999-slc19a2] Cloning of the human thiamine transporter, a member of the folate transporter family (1999). https://pubmed.ncbi.nlm.nih.gov/10542220/ DOI: 10.1074/jbc.274.45.31925

tissue_or_cell_type

HeLa cells

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 135–147

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human placental cDNA expressed in HeLa cells; radiotracer uptake. · source_derived_draft · unverified_draft

### b1-slc19a2-sodium-independence SLC19A2-mediated uptake did not require extracellular sodium and increased with an outward proton gradient. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 entry in this assay depended on proton conditions without sodium cotransport. organism: Homo sapiens tissue_or_cell_type: HeLa cells experimental_model: Human placental cDNA expressed in HeLa cells; radiotracer uptake. limitations: Does not establish an exact proton stoichiometry. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/dutta-1999-slc19a2-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1275}] evidence_locator: Abstract evidence-scope: HeLa cells [dutta-1999-slc19a2] Cloning of the human thiamine transporter, a member of the folate transporter family (1999). https://pubmed.ncbi.nlm.nih.gov/10542220/ DOI: 10.1074/jbc.274.45.31925

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chloride-research/11099045.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca", "start_char": 0, "end_char": 1218, "text_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca"}

experimental_model

Clcn5 knockout and uptake measurements

exposure

Clcn5 disruption

limitations

The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated.

nutrient_topic

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

organism

Mouse

plain_language

The sodium/hydrogen exchanger changed location too.

primary_references

[chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597

tissue_or_cell_type

Proximal renal tubule

trigger_kind

machinery_impairment Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 731–742

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clcn5 knockout and uptake measurements · source_derived_draft · unverified_draft

### chloride-clc5-nhe3 NHE3 also redistributed toward intracellular vesicles at steady state despite slower internalization. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The sodium/hydrogen exchanger changed location too. organism: Mouse tissue_or_cell_type: Proximal renal tubule experimental_model: Clcn5 knockout and uptake measurements limitations: The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated. exposure: Clcn5 disruption evidence_span: {"source_cache": "artifacts/chloride-research/11099045.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca", "start_char": 0, "end_char": 1218, "text_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca"} [chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597

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/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

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

Two separately modeled exchangers cooperate in the proposed route.

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 549–560

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-pendrin-ndcbe Isolated-duct results supported parallel pendrin and NDCBE action in electroneutral NaCl absorption. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two separately modeled exchangers cooperate in the proposed route. 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/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_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

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium deficiency changes sodium-phosphate transport machinery in an isoform-specific manner.

endpoint

Potassium deficiency increased brush-border NaPi-IIa abundance in the studied rat experiments despite reduced total sodium-dependent phosphate transport.

experimental-exposure

Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses.

experimental_model

Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses.

limitations

Isoform abundance and localization do not apportion total phosphate flux; transporter-specific contributions and initiating signal remain unresolved.

nutrient_topic

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

organism

Rattus norvegicus; Mus musculus where specified

plain_language

More of one transporter did not mean greater overall phosphate recovery.

primary_references

[breusegem-2009-phosphate] Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency (2009). https://pubmed.ncbi.nlm.nih.gov/19493963/ DOI: 10.1152/ajprenal.90765.2008

tissue_or_cell_type

renal proximal-tubule brush border

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1372–1384

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. · source_derived_draft · unverified_draft

### k-deficiency-napi2a-abundance Potassium deficiency increased brush-border NaPi-IIa abundance in the studied rat experiments despite reduced total sodium-dependent phosphate transport. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: More of one transporter did not mean greater overall phosphate recovery. organism: Rattus norvegicus; Mus musculus where specified tissue_or_cell_type: renal proximal-tubule brush border experimental_model: Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. limitations: Isoform abundance and localization do not apportion total phosphate flux; transporter-specific contributions and initiating signal remain unresolved. cross_nutrient: Potassium deficiency changes sodium-phosphate transport machinery in an isoform-specific manner. experimental-exposure: Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. endpoint: Potassium deficiency increased brush-border NaPi-IIa abundance in the studied rat experiments despite reduced total sodium-dependent phosphate transport. [breusegem-2009-phosphate] Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency (2009). https://pubmed.ncbi.nlm.nih.gov/19493963/ DOI: 10.1152/ajprenal.90765.2008

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium deficiency changes sodium-phosphate transport machinery in an isoform-specific manner.

endpoint

Dietary potassium deficiency decreased proximal-tubule brush-border NaPi-IIc protein abundance in rats and mice.

experimental-exposure

Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses.

experimental_model

Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses.

limitations

Isoform abundance and localization do not apportion total phosphate flux; transporter-specific contributions and initiating signal remain unresolved.

nutrient_topic

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

organism

Rattus norvegicus; Mus musculus where specified

plain_language

A sodium-phosphate uptake protein was depleted from the membrane.

primary_references

[breusegem-2009-phosphate] Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency (2009). https://pubmed.ncbi.nlm.nih.gov/19493963/ DOI: 10.1152/ajprenal.90765.2008

tissue_or_cell_type

renal proximal-tubule brush border

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1344–1356

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. · source_derived_draft · unverified_draft

### k-deficiency-napi2c-abundance Dietary potassium deficiency decreased proximal-tubule brush-border NaPi-IIc protein abundance in rats and mice. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sodium-phosphate uptake protein was depleted from the membrane. organism: Rattus norvegicus; Mus musculus where specified tissue_or_cell_type: renal proximal-tubule brush border experimental_model: Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. limitations: Isoform abundance and localization do not apportion total phosphate flux; transporter-specific contributions and initiating signal remain unresolved. cross_nutrient: Potassium deficiency changes sodium-phosphate transport machinery in an isoform-specific manner. experimental-exposure: Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. endpoint: Dietary potassium deficiency decreased proximal-tubule brush-border NaPi-IIc protein abundance in rats and mice. [breusegem-2009-phosphate] Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency (2009). https://pubmed.ncbi.nlm.nih.gov/19493963/ DOI: 10.1152/ajprenal.90765.2008

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium deficiency changes sodium-phosphate transport machinery in an isoform-specific manner.

endpoint

Dietary potassium deficiency decreased proximal-tubule brush-border PiT-2 abundance in rats and mice.

experimental-exposure

Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses.

experimental_model

Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses.

limitations

Isoform abundance and localization do not apportion total phosphate flux; transporter-specific contributions and initiating signal remain unresolved.

nutrient_topic

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

organism

Rattus norvegicus; Mus musculus where specified

plain_language

A second, distinct sodium-phosphate transporter declined.

primary_references

[breusegem-2009-phosphate] Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency (2009). https://pubmed.ncbi.nlm.nih.gov/19493963/ DOI: 10.1152/ajprenal.90765.2008

tissue_or_cell_type

renal proximal-tubule brush border

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1358–1370

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. · source_derived_draft · unverified_draft

### k-deficiency-pit2-abundance Dietary potassium deficiency decreased proximal-tubule brush-border PiT-2 abundance in rats and mice. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second, distinct sodium-phosphate transporter declined. organism: Rattus norvegicus; Mus musculus where specified tissue_or_cell_type: renal proximal-tubule brush border experimental_model: Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. limitations: Isoform abundance and localization do not apportion total phosphate flux; transporter-specific contributions and initiating signal remain unresolved. cross_nutrient: Potassium deficiency changes sodium-phosphate transport machinery in an isoform-specific manner. experimental-exposure: Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. endpoint: Dietary potassium deficiency decreased proximal-tubule brush-border PiT-2 abundance in rats and mice. [breusegem-2009-phosphate] Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency (2009). https://pubmed.ncbi.nlm.nih.gov/19493963/ DOI: 10.1152/ajprenal.90765.2008

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium/sodium balance -> pressure.

experimental_model

Same cohort and intervention.

limitations

Not an independent replication or proof of one molecular mediator.

nutrient_topic

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

organism

Homo sapiens

plain_language

In this setting, lowering potassium raised blood pressure.

primary_references

[k-krishna1991] Potassium depletion exacerbates essential hypertension (1991). https://pubmed.ncbi.nlm.nih.gov/2058867/ DOI: 10.7326/0003-4819-115-2-77

tissue_or_cell_type

Systemic circulation

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1522–1532

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

### k-depletion-human-pressure Low potassium increased systolic/diastolic pressure by about 7/6 mmHg in the same crossover. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this setting, lowering potassium raised blood pressure. organism: Homo sapiens tissue_or_cell_type: Systemic circulation experimental_model: Same cohort and intervention. limitations: Not an independent replication or proof of one molecular mediator. cross_nutrient: Potassium/sodium balance -> pressure. [k-krishna1991] Potassium depletion exacerbates essential hypertension (1991). https://pubmed.ncbi.nlm.nih.gov/2058867/ DOI: 10.7326/0003-4819-115-2-77

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium -> sodium balance.

experimental_model

12 hypertensive adults; ten-day periods.

exposure

16 versus 96 mmol/day K; sodium 120 mmol/day.

limitations

Supports retention physiology; the human study did not measure the Kir4.1-WNK-NCC chain.

nutrient_topic

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

organism

Homo sapiens

plain_language

A potassium shortage changed how the kidney handled sodium.

primary_references

[k-krishna1991] Potassium depletion exacerbates essential hypertension (1991). https://pubmed.ncbi.nlm.nih.gov/2058867/ DOI: 10.7326/0003-4819-115-2-77

tissue_or_cell_type

Kidney and urine

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1509–1520

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 12 hypertensive adults; ten-day periods. · source_derived_draft · unverified_draft

### k-depletion-human-sodium-retention At fixed sodium intake, potassium depletion reduced urinary sodium from 110 to 83 mmol/day in this crossover. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A potassium shortage changed how the kidney handled sodium. organism: Homo sapiens tissue_or_cell_type: Kidney and urine experimental_model: 12 hypertensive adults; ten-day periods. limitations: Supports retention physiology; the human study did not measure the Kir4.1-WNK-NCC chain. cross_nutrient: Potassium -> sodium balance. exposure: 16 versus 96 mmol/day K; sodium 120 mmol/day. [k-krishna1991] Potassium depletion exacerbates essential hypertension (1991). https://pubmed.ncbi.nlm.nih.gov/2058867/ DOI: 10.7326/0003-4819-115-2-77

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium depletion regulates a sodium-dependent organic-anion transport process relevant to calcium-stone chemistry.

endpoint

Fourteen days of potassium depletion increased maximal sodium-dependent citrate transport in rat renal brush-border vesicles.

experimental-exposure

Rats given low-potassium diet for 14 days; urine citrate and renal cortical brush-border membrane vesicle transport kinetics.

experimental_model

Rats given low-potassium diet for 14 days; urine citrate and renal cortical brush-border membrane vesicle transport kinetics.

limitations

Vesicle transport capacity is not a direct in-vivo flux measurement; molecular isoform identity was not tested.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

The proximal-tubule uptake system could reclaim citrate faster, linking potassium depletion to sodium-coupled citrate handling.

primary_references

[levi-1991-citrate] Chronic K depletion stimulates rat renal brush-border membrane Na-citrate cotransporter (1991). https://pubmed.ncbi.nlm.nih.gov/1683169/ DOI: 10.1152/ajprenal.1991.261.5.F767

tissue_or_cell_type

renal proximal-tubule apical membrane

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1190–1202

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats given low-potassium diet for 14 days; urine citrate and renal cortical brush-border membrane vesicle transport kinetics. · source_derived_draft · unverified_draft

### k-depletion-increases-na-citrate-transport Fourteen days of potassium depletion increased maximal sodium-dependent citrate transport in rat renal brush-border vesicles. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The proximal-tubule uptake system could reclaim citrate faster, linking potassium depletion to sodium-coupled citrate handling. organism: Rattus norvegicus tissue_or_cell_type: renal proximal-tubule apical membrane experimental_model: Rats given low-potassium diet for 14 days; urine citrate and renal cortical brush-border membrane vesicle transport kinetics. limitations: Vesicle transport capacity is not a direct in-vivo flux measurement; molecular isoform identity was not tested. cross_nutrient: Potassium depletion regulates a sodium-dependent organic-anion transport process relevant to calcium-stone chemistry. experimental-exposure: Rats given low-potassium diet for 14 days; urine citrate and renal cortical brush-border membrane vesicle transport kinetics. endpoint: Fourteen days of potassium depletion increased maximal sodium-dependent citrate transport in rat renal brush-border vesicles. [levi-1991-citrate] Chronic K depletion stimulates rat renal brush-border membrane Na-citrate cotransporter (1991). https://pubmed.ncbi.nlm.nih.gov/1683169/ DOI: 10.1152/ajprenal.1991.261.5.F767

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium status alters machinery that also controls sodium transport.

experimental_model

Rat/mouse soleus and extensor digitorum longus; K-free diet, diuretic or K-binding-resin depletion models.

limitations

Diet, diuretic and resin models differ; abstract does not provide each regimen duration.

nutrient_topic

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

organism

Rat and mouse

plain_language

Depleted muscle had fewer functional sodium-potassium pumps.

primary_references

[norgaard-1981-muscle] Potassium depletion decreases the number of 3H-ouabain binding sites and the active Na-K transport in skeletal muscle (1981). https://www.nature.com/articles/293739a0 DOI: 10.1038/293739a0

tissue_or_cell_type

Soleus/extensor digitorum longus

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 739–749

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat/mouse soleus and extensor digitorum longus; K-free diet, diuretic or K-binding-resin depletion models. · source_derived_draft · unverified_draft

### k-depletion-muscle-pump-loss Rodent potassium depletion reversibly reduced muscle ouabain-binding sites and pump-mediated potassium uptake capacity. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Depleted muscle had fewer functional sodium-potassium pumps. organism: Rat and mouse tissue_or_cell_type: Soleus/extensor digitorum longus experimental_model: Rat/mouse soleus and extensor digitorum longus; K-free diet, diuretic or K-binding-resin depletion models. limitations: Diet, diuretic and resin models differ; abstract does not provide each regimen duration. cross_nutrient: Potassium status alters machinery that also controls sodium transport. [norgaard-1981-muscle] Potassium depletion decreases the number of 3H-ouabain binding sites and the active Na-K transport in skeletal muscle (1981). https://www.nature.com/articles/293739a0 DOI: 10.1038/293739a0

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium deprivation changes glutamine nitrogen metabolism and sodium-coupled glutamine transport; these experiments did not manipulate dietary protein adequacy.

endpoint

Potassium deprivation increased renal SNAT3/SN1 expression in the rat time course.

experimental-exposure

Rats on control or potassium-deficient diets for up to 6 days; NH4Cl co-loading and NRK52E/LLC-PK1 cell experiments.

experimental_model

Rats on control or potassium-deficient diets for up to 6 days; NH4Cl co-loading and NRK52E/LLC-PK1 cell experiments.

limitations

Dietary deprivation precedes detectable hypokalemia here; protein expression does not independently establish transport flux or quantify net bicarbonate generation.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

More glutamine transporter was detected in the kidney, supporting substrate delivery to the ammonia pathway.

primary_references

[hossain-2011-k-ammoniagenesis] Cellular and molecular basis of increased ammoniagenesis in potassium deprivation (2011). https://journals.physiology.org/doi/full/10.1152/ajprenal.00010.2011 DOI: 10.1152/ajprenal.00010.2011

tissue_or_cell_type

renal proximal tubule and whole-kidney excretion

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 972–984

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats on control or potassium-deficient diets for up to 6 days; NH4Cl co-loading and NRK52E/LLC-PK1 cell experiments. · source_derived_draft · unverified_draft

### k-deprivation-snat3 Potassium deprivation increased renal SNAT3/SN1 expression in the rat time course. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: More glutamine transporter was detected in the kidney, supporting substrate delivery to the ammonia pathway. organism: Rattus norvegicus tissue_or_cell_type: renal proximal tubule and whole-kidney excretion experimental_model: Rats on control or potassium-deficient diets for up to 6 days; NH4Cl co-loading and NRK52E/LLC-PK1 cell experiments. limitations: Dietary deprivation precedes detectable hypokalemia here; protein expression does not independently establish transport flux or quantify net bicarbonate generation. cross_nutrient: Potassium deprivation changes glutamine nitrogen metabolism and sodium-coupled glutamine transport; these experiments did not manipulate dietary protein adequacy. experimental-exposure: Rats on control or potassium-deficient diets for up to 6 days; NH4Cl co-loading and NRK52E/LLC-PK1 cell experiments. endpoint: Potassium deprivation increased renal SNAT3/SN1 expression in the rat time course. [hossain-2011-k-ammoniagenesis] Cellular and molecular basis of increased ammoniagenesis in potassium deprivation (2011). https://journals.physiology.org/doi/full/10.1152/ajprenal.00010.2011 DOI: 10.1152/ajprenal.00010.2011

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium deprivation regulates sodium-bicarbonate transport machinery.

endpoint

Four days of potassium-free diet increased cortical proximal-tubule NBCe1-A expression in wild-type mice.

experimental-exposure

NBCe1-A-selective knockout mice and wild-type littermates on control or potassium-free diets; four-day response.

experimental_model

NBCe1-A-selective knockout mice and wild-type littermates on control or potassium-free diets; four-day response.

limitations

Expression was measured; this record does not assign a bicarbonate transport stoichiometry or measure its flux.

nutrient_topic

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

organism

Mus musculus

plain_language

A sodium-bicarbonate transporter adapted during potassium conservation.

primary_references

[lee-2020-nbce1a] NBCe1-A is required for the renal ammonia and K+ response to hypokalemia (2020). https://pubmed.ncbi.nlm.nih.gov/31841393/ DOI: 10.1152/ajprenal.00481.2019

tissue_or_cell_type

cortical proximal tubule

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1068–1080

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · NBCe1-A-selective knockout mice and wild-type littermates on control or potassium-free diets; four-day response. · source_derived_draft · unverified_draft

### k-free-diet-increases-nbce1a Four days of potassium-free diet increased cortical proximal-tubule NBCe1-A expression in wild-type mice. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sodium-bicarbonate transporter adapted during potassium conservation. organism: Mus musculus tissue_or_cell_type: cortical proximal tubule experimental_model: NBCe1-A-selective knockout mice and wild-type littermates on control or potassium-free diets; four-day response. limitations: Expression was measured; this record does not assign a bicarbonate transport stoichiometry or measure its flux. cross_nutrient: Potassium deprivation regulates sodium-bicarbonate transport machinery. experimental-exposure: NBCe1-A-selective knockout mice and wild-type littermates on control or potassium-free diets; four-day response. endpoint: Four days of potassium-free diet increased cortical proximal-tubule NBCe1-A expression in wild-type mice. [lee-2020-nbce1a] NBCe1-A is required for the renal ammonia and K+ response to hypokalemia (2020). https://pubmed.ncbi.nlm.nih.gov/31841393/ DOI: 10.1152/ajprenal.00481.2019

cross_nutrient

Hormonal stimulation coordinates sodium extrusion and potassium entry.

experimental_model

Rat soleus in 85 mM Na/9 mM K.

limitations

Ex vivo rescue is not a clinical intervention recommendation.

nutrient_topic

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

organism

Rat

plain_language

Stimulating the shared sodium-potassium pump improved muscle responses.

primary_references

[overgaard-1999-muscle] Relations between excitability and contractility in rat soleus muscle: role of the Na+-K+ pump and Na+/K+ gradients (1999). https://pubmed.ncbi.nlm.nih.gov/10373703/ DOI: 10.1111/j.1469-7793.1999.0215r.x

tissue_or_cell_type

Soleus muscle

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 727–737

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat soleus in 85 mM Na/9 mM K. · source_derived_draft · unverified_draft

### k-insulin-muscle-pump-rescue Insulin stimulation of active Na-K transport restored M-wave area and force in the reduced-gradient soleus preparation. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Stimulating the shared sodium-potassium pump improved muscle responses. organism: Rat tissue_or_cell_type: Soleus muscle experimental_model: Rat soleus in 85 mM Na/9 mM K. limitations: Ex vivo rescue is not a clinical intervention recommendation. cross_nutrient: Hormonal stimulation coordinates sodium extrusion and potassium entry. [overgaard-1999-muscle] Relations between excitability and contractility in rat soleus muscle: role of the Na+-K+ pump and Na+/K+ gradients (1999). https://pubmed.ncbi.nlm.nih.gov/10373703/ DOI: 10.1111/j.1469-7793.1999.0215r.x

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Low extracellular potassium changes sodium-channel availability in this cell population.

experimental_model

Rat atrial electrophysiology and modeling.

limitations

Distinct from the calcium-overload route in tubulated cells.

nutrient_topic

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

organism

Rat

plain_language

Some atrial cells became unstable through sodium-channel behavior.

primary_references

[tazmini-2020-cardiac] Hypokalemia Promotes Arrhythmia by Distinct Mechanisms in Atrial and Ventricular Myocytes (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC7098435/ DOI: 10.1161/CIRCRESAHA.119.315641

tissue_or_cell_type

Untubulated atrial myocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 681–691

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

### k-low-atrial-sodium-reactivation Untubulated atrial cells developed low-K early afterdepolarizations associated with sodium-current reactivation, hyperpolarization and brief action potentials. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some atrial cells became unstable through sodium-channel behavior. organism: Rat tissue_or_cell_type: Untubulated atrial myocytes experimental_model: Rat atrial electrophysiology and modeling. limitations: Distinct from the calcium-overload route in tubulated cells. cross_nutrient: Low extracellular potassium changes sodium-channel availability in this cell population. [tazmini-2020-cardiac] Hypokalemia Promotes Arrhythmia by Distinct Mechanisms in Atrial and Ventricular Myocytes (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC7098435/ DOI: 10.1161/CIRCRESAHA.119.315641

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium-to-sodium-to-calcium coupling is experimentally supported; dietary effect magnitude is untested.

experimental_model

Rat ventricular ion assays plus modeling.

limitations

NCX microdomain interpretation; source ouabain units differ between methods and figure legends.

nutrient_topic

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

organism

Rat

plain_language

Potassium-dependent sodium pumping helps the exchanger remove calcium.

primary_references

[aronsen-2015-cardiac] Hypokalaemia induces Ca2+ overload and Ca2+ waves in ventricular myocytes by reducing Na+,K+-ATPase alpha2 activity (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4376427/ DOI: 10.1113/jphysiol.2014.279893

tissue_or_cell_type

Ventricular myocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 622–632

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat ventricular ion assays plus modeling. · source_derived_draft · unverified_draft

### k-low-cardiac-ncx-calcium Pump inhibition during low-K exposure increased sodium sensed by NCX and favored cellular calcium loading. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium-dependent sodium pumping helps the exchanger remove calcium. organism: Rat tissue_or_cell_type: Ventricular myocytes experimental_model: Rat ventricular ion assays plus modeling. limitations: NCX microdomain interpretation; source ouabain units differ between methods and figure legends. cross_nutrient: Potassium-to-sodium-to-calcium coupling is experimentally supported; dietary effect magnitude is untested. [aronsen-2015-cardiac] Hypokalaemia induces Ca2+ overload and Ca2+ waves in ventricular myocytes by reducing Na+,K+-ATPase alpha2 activity (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4376427/ DOI: 10.1113/jphysiol.2014.279893

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Low extracellular potassium compromises sodium extrusion.

experimental_model

Rat ventricular patch clamp/Na fluorescence.

limitations

Acute bath manipulation; not dietary depletion.

nutrient_topic

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

organism

Rat

plain_language

With less extracellular potassium, sodium extrusion slowed.

primary_references

[aronsen-2015-cardiac] Hypokalaemia induces Ca2+ overload and Ca2+ waves in ventricular myocytes by reducing Na+,K+-ATPase alpha2 activity (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4376427/ DOI: 10.1113/jphysiol.2014.279893

tissue_or_cell_type

Ventricular myocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 610–620

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat ventricular patch clamp/Na fluorescence. · source_derived_draft · unverified_draft

### k-low-cardiac-pump-current Lowering bath K from 5.0 to 2.7 mM reduced ventricular pump current and increased intracellular sodium. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: With less extracellular potassium, sodium extrusion slowed. organism: Rat tissue_or_cell_type: Ventricular myocytes experimental_model: Rat ventricular patch clamp/Na fluorescence. limitations: Acute bath manipulation; not dietary depletion. cross_nutrient: Low extracellular potassium compromises sodium extrusion. [aronsen-2015-cardiac] Hypokalaemia induces Ca2+ overload and Ca2+ waves in ventricular myocytes by reducing Na+,K+-ATPase alpha2 activity (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4376427/ DOI: 10.1113/jphysiol.2014.279893

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Sodium entry and calcium loading interact during low extracellular potassium.

experimental_model

Low-K cardiac inhibition experiments and computational model.

limitations

The complete feedback sequence is model-supported, not every step directly measured.

nutrient_topic

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

organism

Rabbit/rat and mathematical model

plain_language

Persistent sodium entry helped sustain low-potassium electrical instability.

primary_references

[pezhouman-2015-camkii] Molecular Basis of Hypokalemia-Induced Ventricular Fibrillation (2015). https://pubmed.ncbi.nlm.nih.gov/26269574/ DOI: 10.1161/CIRCULATIONAHA.115.016217

tissue_or_cell_type

Ventricular myocardium

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 657–667

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Low-K cardiac inhibition experiments and computational model. · source_derived_draft · unverified_draft

### k-low-late-sodium-feedback GS-967 suppressed hypokalemic early afterdepolarizations; simulations implicated CaMKII-enhanced late sodium current in a sodium/calcium feedback loop. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Persistent sodium entry helped sustain low-potassium electrical instability. organism: Rabbit/rat and mathematical model tissue_or_cell_type: Ventricular myocardium experimental_model: Low-K cardiac inhibition experiments and computational model. limitations: The complete feedback sequence is model-supported, not every step directly measured. cross_nutrient: Sodium entry and calcium loading interact during low extracellular potassium. [pezhouman-2015-camkii] Molecular Basis of Hypokalemia-Induced Ventricular Fibrillation (2015). https://pubmed.ncbi.nlm.nih.gov/26269574/ DOI: 10.1161/CIRCULATIONAHA.115.016217

cross_nutrient

Reduced sodium and elevated potassium jointly impair excitability.

experimental_model

Isolated rat soleus, combined bath-ion perturbation.

limitations

Combined perturbation cannot be attributed to potassium alone; not dietary excess.

nutrient_topic

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

organism

Rat

plain_language

Both sodium and potassium gradients matter for muscle activation.

primary_references

[overgaard-1999-muscle] Relations between excitability and contractility in rat soleus muscle: role of the Na+-K+ pump and Na+/K+ gradients (1999). https://pubmed.ncbi.nlm.nih.gov/10373703/ DOI: 10.1111/j.1469-7793.1999.0215r.x

tissue_or_cell_type

Soleus muscle

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 715–725

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated rat soleus, combined bath-ion perturbation. · source_derived_draft · unverified_draft

### k-na-gradients-muscle-excitability The combined 85 mM Na/9 mM K bath reduced M-wave area and tetanic force versus 147 mM Na/4 mM K. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Both sodium and potassium gradients matter for muscle activation. organism: Rat tissue_or_cell_type: Soleus muscle experimental_model: Isolated rat soleus, combined bath-ion perturbation. limitations: Combined perturbation cannot be attributed to potassium alone; not dietary excess. cross_nutrient: Reduced sodium and elevated potassium jointly impair excitability. [overgaard-1999-muscle] Relations between excitability and contractility in rat soleus muscle: role of the Na+-K+ pump and Na+/K+ gradients (1999). https://pubmed.ncbi.nlm.nih.gov/10373703/ DOI: 10.1111/j.1469-7793.1999.0215r.x

cross_nutrient

Potassium transport depends jointly on sodium and magnesium-supported ATP chemistry.

experimental_model

Resealed human erythrocyte ghosts; sided ion substitutions.

limitations

Sided activation adds to existing catalog flux/phosphorylation records; MgATP-only binding is not asserted.

nutrient_topic

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

organism

Human

plain_language

Potassium outside and sodium inside activate complementary sides of the pump.

primary_references

[garrahan-1967-pump] The stoicheiometry of the sodium pump (1967). https://pmc.ncbi.nlm.nih.gov/articles/PMC1365482/ DOI: 10.1113/jphysiol.1967.sp008297

tissue_or_cell_type

Erythrocyte membrane

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 575–585

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Resealed human erythrocyte ghosts; sided ion substitutions. · source_derived_draft · unverified_draft

### k-pump-extracellular-activation External potassium supported ouabain-sensitive ATP hydrolysis when erythrocyte ghosts contained sodium, ATP and magnesium. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium outside and sodium inside activate complementary sides of the pump. organism: Human tissue_or_cell_type: Erythrocyte membrane experimental_model: Resealed human erythrocyte ghosts; sided ion substitutions. limitations: Sided activation adds to existing catalog flux/phosphorylation records; MgATP-only binding is not asserted. cross_nutrient: Potassium transport depends jointly on sodium and magnesium-supported ATP chemistry. [garrahan-1967-pump] The stoicheiometry of the sodium pump (1967). https://pmc.ncbi.nlm.nih.gov/articles/PMC1365482/ DOI: 10.1113/jphysiol.1967.sp008297

cross_nutrient

Sodium export couples to potassium-supported pump cycling and magnesium-dependent energy use.

experimental_model

Radiotracer sodium and ATP-hydrolysis assay.

limitations

This measurement does not itself establish an exact two-potassium ratio.

nutrient_topic

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

organism

Human

plain_language

ATP consumption pays for sodium extrusion while potassium is available externally.

primary_references

[garrahan-1967-pump] The stoicheiometry of the sodium pump (1967). https://pmc.ncbi.nlm.nih.gov/articles/PMC1365482/ DOI: 10.1113/jphysiol.1967.sp008297

tissue_or_cell_type

Erythrocyte membrane

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 587–597

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiotracer sodium and ATP-hydrolysis assay. · source_derived_draft · unverified_draft

### k-pump-sodium-atp-coupling Ouabain-sensitive extrusion was approximately three sodium ions per ATP hydrolyzed in resealed erythrocyte ghosts. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP consumption pays for sodium extrusion while potassium is available externally. organism: Human tissue_or_cell_type: Erythrocyte membrane experimental_model: Radiotracer sodium and ATP-hydrolysis assay. limitations: This measurement does not itself establish an exact two-potassium ratio. cross_nutrient: Sodium export couples to potassium-supported pump cycling and magnesium-dependent energy use. [garrahan-1967-pump] The stoicheiometry of the sodium pump (1967). https://pmc.ncbi.nlm.nih.gov/articles/PMC1365482/ DOI: 10.1113/jphysiol.1967.sp008297

cross_nutrient

Combined sodium reduction/potassium increase; not potassium-alone molecular causation.

experimental_model

Cluster-randomized trial; mean 4.74-year follow-up.

limitations

Both sodium and potassium changed, so their effects cannot be separated. Serious kidney disease and potassium-sparing drugs/supplements were excluded; no serial serum-potassium surveillance.

nutrient_topic

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

organism

Homo sapiens

plain_language

Replacing part of sodium chloride with potassium chloride improved a clinical outcome in the studied population.

primary_references

[k-neal2021] Effect of Salt Substitution on Cardiovascular Events and Death (2021). https://pubmed.ncbi.nlm.nih.gov/34459569/ DOI: 10.1056/nejmoa2105675

tissue_or_cell_type

Clinical cerebrovascular outcome

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1697–1707

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cluster-randomized trial; mean 4.74-year follow-up. · source_derived_draft · unverified_draft

### k-sodium-potassium-salt-stroke-trial The 75% NaCl/25% KCl salt substitute reduced stroke incidence versus ordinary salt in SSaSS (rate ratio 0.86). Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacing part of sodium chloride with potassium chloride improved a clinical outcome in the studied population. organism: Homo sapiens tissue_or_cell_type: Clinical cerebrovascular outcome experimental_model: Cluster-randomized trial; mean 4.74-year follow-up. limitations: Both sodium and potassium changed, so their effects cannot be separated. Serious kidney disease and potassium-sparing drugs/supplements were excluded; no serial serum-potassium surveillance. cross_nutrient: Combined sodium reduction/potassium increase; not potassium-alone molecular causation. [k-neal2021] Effect of Salt Substitution on Cardiovascular Events and Death (2021). https://pubmed.ncbi.nlm.nih.gov/34459569/ DOI: 10.1056/nejmoa2105675

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Sodium-bicarbonate transport machinery is required for the full potassium-responsive ammonia adaptation.

endpoint

NBCe1-A deletion blunted the urinary ammonia-excretion response to potassium-free feeding.

experimental-exposure

NBCe1-A-selective knockout mice and wild-type littermates on control or potassium-free diets; four-day response.

experimental_model

NBCe1-A-selective knockout mice and wild-type littermates on control or potassium-free diets; four-day response.

limitations

Assay reports total ammonia. Knockout also causes acidosis and outer-medullary compensation; the exact signal is unresolved.

nutrient_topic

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

organism

Mus musculus

plain_language

A sodium-bicarbonate transporter was needed for the full kidney ammonia response to potassium deprivation.

primary_references

[lee-2020-nbce1a] NBCe1-A is required for the renal ammonia and K+ response to hypokalemia (2020). https://pubmed.ncbi.nlm.nih.gov/31841393/ DOI: 10.1152/ajprenal.00481.2019

tissue_or_cell_type

cortical proximal tubule and urinary ammonia output

trigger_kind

machinery_impairment Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1082–1094

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · NBCe1-A-selective knockout mice and wild-type littermates on control or potassium-free diets; four-day response. · source_derived_draft · unverified_draft

### nbce1a-loss-blunts-k-ammonia-response NBCe1-A deletion blunted the urinary ammonia-excretion response to potassium-free feeding. Condition category: machinery_impairment nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sodium-bicarbonate transporter was needed for the full kidney ammonia response to potassium deprivation. organism: Mus musculus tissue_or_cell_type: cortical proximal tubule and urinary ammonia output experimental_model: NBCe1-A-selective knockout mice and wild-type littermates on control or potassium-free diets; four-day response. limitations: Assay reports total ammonia. Knockout also causes acidosis and outer-medullary compensation; the exact signal is unresolved. cross_nutrient: Sodium-bicarbonate transport machinery is required for the full potassium-responsive ammonia adaptation. experimental-exposure: NBCe1-A-selective knockout mice and wild-type littermates on control or potassium-free diets; four-day response. endpoint: NBCe1-A deletion blunted the urinary ammonia-excretion response to potassium-free feeding. [lee-2020-nbce1a] NBCe1-A is required for the renal ammonia and K+ response to hypokalemia (2020). https://pubmed.ncbi.nlm.nih.gov/31841393/ DOI: 10.1152/ajprenal.00481.2019

cross_nutrient

Sodium transport through ENaC supports potassium secretion.

evidence_location

Figure 7 and associated Results.

experimental_model

Benzamil pretreatment and flow increase

limitations

Other species/segments can show ENaC-independent components; no universal requirement claimed.

nutrient_topic

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

organism

Oryctolagus cuniculus

plain_language

Sodium entry through ENaC supports potassium secretion in this perfused segment.

primary_references

[liu-2007-calcium-flow] Ca2+ dependence of flow-stimulated K secretion in the mammalian cortical collecting duct (2007). https://journals.physiology.org/doi/10.1152/ajprenal.00057.2007 DOI: 10.1152/ajprenal.00057.2007

tissue_or_cell_type

Cortical collecting duct

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 382–393

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

### renal-enac-supports-rabbit-flow-k-secretion Benzamil inhibition of sodium absorption abolished the flow-stimulated increase in K secretion in rabbit CCDs. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sodium entry through ENaC supports potassium secretion in this perfused segment. organism: Oryctolagus cuniculus tissue_or_cell_type: Cortical collecting duct experimental_model: Benzamil pretreatment and flow increase limitations: Other species/segments can show ENaC-independent components; no universal requirement claimed. cross_nutrient: Sodium transport through ENaC supports potassium secretion. evidence_location: Figure 7 and associated Results. [liu-2007-calcium-flow] Ca2+ dependence of flow-stimulated K secretion in the mammalian cortical collecting duct (2007). https://journals.physiology.org/doi/10.1152/ajprenal.00057.2007 DOI: 10.1152/ajprenal.00057.2007

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

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

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium restriction changes sodium handling through NCC.

evidence_location

Figure 2A-C.

experimental_model

Wild-type versus Slc12a3-null dietary study

limitations

Knockout tests pathway contribution, not exclusive control of pressure.

nutrient_topic

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

organism

Mus musculus

plain_language

Potassium scarcity can make sodium retention easier through NCC.

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

Kidney

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 112–123

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type versus Slc12a3-null dietary study · source_derived_draft · unverified_draft

### renal-low-k-ncc-salt-retention Low-potassium feeding on high salt reduced sodium excretion; NCC deletion blunted the blood-pressure response. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium scarcity can make sodium retention easier through NCC. organism: Mus musculus tissue_or_cell_type: Kidney experimental_model: Wild-type versus Slc12a3-null dietary study limitations: Knockout tests pathway contribution, not exclusive control of pressure. cross_nutrient: Potassium restriction changes sodium handling through NCC. evidence_location: Figure 2A-C. [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

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

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Defective sodium-channel regulation compromises K balance.

evidence_location

Abstract; Results Figures 1 and 5.

experimental_model

Inducible renal MR deletion

limitations

NCC remained activatable by K restriction; receptor effects on NCC are not assumed to be direct.

nutrient_topic

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

organism

Mus musculus

plain_language

The mineralocorticoid receptor helps maintain the sodium-channel machinery needed for normal potassium balance.

primary_references

[terker-2016-mineralocorticoid] Direct and Indirect Mineralocorticoid Effects Determine Distal Salt Transport (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4978056/ DOI: 10.1681/ASN.2015070815

tissue_or_cell_type

Aldosterone-sensitive distal nephron

trigger_kind

machinery_impairment Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 395–406

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

### renal-mr-supports-enac-processing Nephron-wide MR deletion impaired apical ENaC orientation/cleavage and produced hyperkalemia with salt wasting in adult mice. Condition category: machinery_impairment nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mineralocorticoid receptor helps maintain the sodium-channel machinery needed for normal potassium balance. organism: Mus musculus tissue_or_cell_type: Aldosterone-sensitive distal nephron experimental_model: Inducible renal MR deletion limitations: NCC remained activatable by K restriction; receptor effects on NCC are not assumed to be direct. cross_nutrient: Defective sodium-channel regulation compromises K balance. evidence_location: Abstract; Results Figures 1 and 5. [terker-2016-mineralocorticoid] Direct and Indirect Mineralocorticoid Effects Determine Distal Salt Transport (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4978056/ DOI: 10.1681/ASN.2015070815

cross_nutrient

K loading can increase sodium excretion through NCC regulation.

evidence_location

Primary abstract; NCC-deficient natriuresis comparison.

experimental_model

NCC knockout and control K gavage

limitations

This does not establish that increased distal sodium delivery alone explains all kaliuresis.

nutrient_topic

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

organism

Mus musculus

plain_language

Turning NCC down contributes to the sodium loss caused by potassium loading.

primary_references

[sorensen-2013-oral-k-ncc] Rapid dephosphorylation of the renal sodium chloride cotransporter in response to oral potassium intake in mice (2013). https://pubmed.ncbi.nlm.nih.gov/23447069/ DOI: 10.1038/ki.2013.14

tissue_or_cell_type

Kidney

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 307–318

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · NCC knockout and control K gavage · source_derived_draft · unverified_draft

### renal-ncc-loss-blunts-k-natriuresis NCC-deficient mice showed markedly less sodium excretion after the acute oral K load than controls. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Turning NCC down contributes to the sodium loss caused by potassium loading. organism: Mus musculus tissue_or_cell_type: Kidney experimental_model: NCC knockout and control K gavage limitations: This does not establish that increased distal sodium delivery alone explains all kaliuresis. cross_nutrient: K loading can increase sodium excretion through NCC regulation. evidence_location: Primary abstract; NCC-deficient natriuresis comparison. [sorensen-2013-oral-k-ncc] Rapid dephosphorylation of the renal sodium chloride cotransporter in response to oral potassium intake in mice (2013). https://pubmed.ncbi.nlm.nih.gov/23447069/ DOI: 10.1038/ki.2013.14

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

cross_nutrient

Higher sodium-channel availability can support the secretory machinery used for K balance.

evidence_location

Figures 3-5; interaction and anti-FLAG surface-labeling experiments.

experimental_model

Oocyte binding, current and surface-labeling assays

limitations

Molecular sufficiency does not establish exclusive control in intact kidneys.

nutrient_topic

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

organism

Xenopus laevis

plain_language

Phosphorylation weakens the sodium-channel removal signal, leaving more channels at the surface.

primary_references

[debonneville-2001-sgk-nedd4] Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression (2001). https://pubmed.ncbi.nlm.nih.gov/11742982/ DOI: 10.1093/emboj/20.24.7052

tissue_or_cell_type

Oocytes

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 421–432

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oocyte binding, current and surface-labeling assays · source_derived_draft · unverified_draft

### renal-phospho-nedd4l-releases-enac SGK-dependent Nedd4-2 phosphorylation reduced its ENaC interaction and increased ENaC surface expression in oocytes. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Phosphorylation weakens the sodium-channel removal signal, leaving more channels at the surface. organism: Xenopus laevis tissue_or_cell_type: Oocytes experimental_model: Oocyte binding, current and surface-labeling assays limitations: Molecular sufficiency does not establish exclusive control in intact kidneys. cross_nutrient: Higher sodium-channel availability can support the secretory machinery used for K balance. evidence_location: Figures 3-5; interaction and anti-FLAG surface-labeling experiments. [debonneville-2001-sgk-nedd4] Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression (2001). https://pubmed.ncbi.nlm.nih.gov/11742982/ DOI: 10.1093/emboj/20.24.7052

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

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human high-dose oral loading, with versus without carbohydrate.

limitations

Small acute study; not a fixed conversion fraction for foods or a brain measurement.

nutrient_topic

Monosodium Glutamate (MSG) collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Monosodium L-glutamate

plain_language

Carbohydrate changed how much glutamate appeared in blood.

primary_references

Effect of carbohydrate on plasma and erythrocyte glutamate levels in humans ingesting large doses of monosodium L-glutamate in water. · 1983 · https://pubmed.ncbi.nlm.nih.gov/6133445/ · DOI 10.1093/ajcn/37.6.961

trigger_kind

biomarker_context Imported condition classification; unverified.

Monosodium Glutamate (MSG): taste, gut sensing, exposure and cross-nutrient mechanisms (2026-09-20) · lines 26–32

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human high-dose oral loading, with versus without carbohydrate. · source_derived_draft · unverified_draft

## monosodium-glutamate-carbohydrate-exposure Carbohydrate changed how much glutamate appeared in blood. In eight adults receiving 150 mg/kg MSG in water, adding 1.1 g/kg hydrolyzed corn starch lowered mean peak plasma glutamate from 59.4 to 7.18 micromol/dL. Model: Human high-dose oral loading, with versus without carbohydrate. Limitations: Small acute study; not a fixed conversion fraction for foods or a brain measurement. Evidence access: Primary abstract Effect of carbohydrate on plasma and erythrocyte glutamate levels in humans ingesting large doses of monosodium L-glutamate in water. · 1983 · https://pubmed.ncbi.nlm.nih.gov/6133445/ · DOI 10.1093/ajcn/37.6.961

evidence_access

Primary full text; background and test samples

experimental_model

Chemical identity and ingredient design in the primary sensory study.

limitations

This is background chemistry, not a measurement of absorption or tissue delivery.

nutrient_topic

Monosodium Glutamate (MSG) collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Monosodium L-glutamate

plain_language

The ingredient contributes both glutamate and sodium.

primary_references

Validation of preferred salt concentration in soup based on a randomized blinded experiment in multiple regions in Japan-influence of umami (L-glutamate) on saltiness and palatability of low-salt solutions. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31996813/ · DOI 10.1038/s41440-020-0397-1

Monosodium Glutamate (MSG): taste, gut sensing, exposure and cross-nutrient mechanisms (2026-09-20) · lines 18–24

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Chemical identity and ingredient design in the primary sensory study. · source_derived_draft · unverified_draft

## monosodium-glutamate-salt-identity The ingredient contributes both glutamate and sodium. MSG is the sodium salt of L-glutamate; the sensory study treats added MSG and NaCl as separate ingredients. Model: Chemical identity and ingredient design in the primary sensory study. Limitations: This is background chemistry, not a measurement of absorption or tissue delivery. Evidence access: Primary full text; background and test samples Validation of preferred salt concentration in soup based on a randomized blinded experiment in multiple regions in Japan-influence of umami (L-glutamate) on saltiness and palatability of low-salt solutions. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31996813/ · DOI 10.1038/s41440-020-0397-1

evidence_access

Primary full text

experimental_model

Randomized blinded tasting across nineteen Japanese regions.

limitations

MSG itself adds sodium; net reduction requires NaCl replacement. No long-term sodium intake or blood-pressure effect was measured. Three authors were Ajinomoto employees.

nutrient_topic

Monosodium Glutamate (MSG) collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Monosodium L-glutamate

plain_language

Flavor enhancement may help a lower-salt recipe remain acceptable.

primary_references

Validation of preferred salt concentration in soup based on a randomized blinded experiment in multiple regions in Japan-influence of umami (L-glutamate) on saltiness and palatability of low-salt solutions. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31996813/ · DOI 10.1038/s41440-020-0397-1

Monosodium Glutamate (MSG): taste, gut sensing, exposure and cross-nutrient mechanisms (2026-09-20) · lines 250–256

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Randomized blinded tasting across nineteen Japanese regions. · source_derived_draft · unverified_draft

## monosodium-glutamate-sodium-substitution Flavor enhancement may help a lower-salt recipe remain acceptable. In 584 participants, adding 0.3% MSG improved palatability ratings at tested 0.3%, 0.6% and 0.9% NaCl concentrations. Model: Randomized blinded tasting across nineteen Japanese regions. Limitations: MSG itself adds sodium; net reduction requires NaCl replacement. No long-term sodium intake or blood-pressure effect was measured. Three authors were Ajinomoto employees. Evidence access: Primary full text Validation of preferred salt concentration in soup based on a randomized blinded experiment in multiple regions in Japan-influence of umami (L-glutamate) on saltiness and palatability of low-salt solutions. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31996813/ · DOI 10.1038/s41440-020-0397-1

evidence_access

Primary abstract

experimental_model

Human B0AT1 structural and transport study; established physiological role described in abstract.

limitations

Transporter identity does not specify a universal saturation threshold.

nutrient_topic

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

plain_language

The gut and kidney transport machinery helps determine phenylalanine availability.

primary_references

Structure-guided development of a potent human B0AT1 inhibitor effective in a mouse model of phenylketonuria. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42350764/ · DOI 10.1038/s42003-026-10535-y

transport_effect

raises Recorded as acting during intestinal absorption and renal reuptake, both of which are inward.

transport_pool

the enterocyte and tubule cell interior Recorded as acting during intestinal absorption and renal reuptake, both of which are inward.

L-Phenylalanine: transport, protein synthesis, cofactor recycling 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 B0AT1 structural and transport study; established physiological role described in abstract. · source_derived_draft · unverified_draft

## l-phenylalanine-renal-transporter The gut and kidney transport machinery helps determine phenylalanine availability. B0AT1/SLC6A19 transports neutral amino acids including phenylalanine during intestinal absorption and renal reuptake. Model: Human B0AT1 structural and transport study; established physiological role described in abstract. Limitations: Transporter identity does not specify a universal saturation threshold. Evidence access: Primary abstract Structure-guided development of a potent human B0AT1 inhibitor effective in a mouse model of phenylketonuria. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42350764/ · DOI 10.1038/s42003-026-10535-y

evidence_access

Primary abstract

experimental_model

Mouse STC-1 cell transport, membrane-potential and secretion assays.

limitations

The accessed abstract does not identify a specific transporter isoform; B0AT1 is not assigned by inference.

nutrient_topic

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

plain_language

Amino-acid transport can supply an electrical signal as well as a nutrient.

primary_references

Identification of a regulatory pathway of L-phenylalanine-induced GLP-1 secretion in the enteroendocrine L cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34953208/ · DOI 10.1016/j.bbrc.2021.12.043

L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 318–324

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse STC-1 cell transport, membrane-potential and secretion assays. · source_derived_draft · unverified_draft

## l-phenylalanine-stc-sodium Amino-acid transport can supply an electrical signal as well as a nutrient. Sodium-dependent phenylalanine uptake contributed to depolarization and GLP-1 secretion in STC-1 cells. Model: Mouse STC-1 cell transport, membrane-potential and secretion assays. Limitations: The accessed abstract does not identify a specific transporter isoform; B0AT1 is not assigned by inference. Evidence access: Primary abstract Identification of a regulatory pathway of L-phenylalanine-induced GLP-1 secretion in the enteroendocrine L cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34953208/ · DOI 10.1016/j.bbrc.2021.12.043

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Cultured human cells challenged with oxidant generators or high glucose.

limitations

Transport dependence does not locate ergothioneine inside mitochondria.

nutrient_topic

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

plain_language

Protection depended on getting the compound inside.

primary_references

Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049

trigger_kind

machinery_impairment Imported condition classification; unverified.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 280–286

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured human cells challenged with oxidant generators or high glucose. · source_derived_draft · unverified_draft

## ergothioneine-endothelial-entry-loss Protection depended on getting the compound inside. SLC22A4 siRNA reduced ergothioneine uptake and abolished its cytoprotection in human brain microvascular endothelial cells. Model: Cultured human cells challenged with oxidant generators or high glucose. Limitations: Transport dependence does not locate ergothioneine inside mitochondria. Evidence access: Primary abstract Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049

evidence_access

Primary abstract

experimental_model

Metabolomic screening and uptake assays in transfected human cells.

limitations

Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures.

nutrient_topic

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

plain_language

An additional carrier connects carnitine to the transport network.

primary_references

Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

transport_effect

raises Expression enabled uptake in HEK293 substrate assays.

transport_pool

the expressing cell Expression enabled uptake in HEK293 substrate assays.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 64–70

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Metabolomic screening and uptake assays in transfected human cells. · source_derived_draft · unverified_draft

## ergothioneine-slc22a15-carnitine An additional carrier connects carnitine to the transport network. Human SLC22A15 expression enabled uptake of carnitine in HEK293 substrate assays. Model: Metabolomic screening and uptake assays in transfected human cells. Limitations: Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures. Evidence access: Primary abstract Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

evidence_access

Primary abstract

experimental_model

Metabolomic screening and uptake assays in transfected human cells.

limitations

Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures.

nutrient_topic

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

plain_language

An additional carrier connects carnosine to the transport network.

primary_references

Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

transport_effect

raises Expression enabled uptake in HEK293 substrate assays.

transport_pool

the expressing cell Expression enabled uptake in HEK293 substrate assays.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 56–62

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Metabolomic screening and uptake assays in transfected human cells. · source_derived_draft · unverified_draft

## ergothioneine-slc22a15-carnosine An additional carrier connects carnosine to the transport network. Human SLC22A15 expression enabled uptake of carnosine in HEK293 substrate assays. Model: Metabolomic screening and uptake assays in transfected human cells. Limitations: Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures. Evidence access: Primary abstract Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

evidence_access

Primary abstract

experimental_model

Metabolomic screening and uptake assays in transfected human cells.

limitations

Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures.

nutrient_topic

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

plain_language

An additional carrier connects ergothioneine to the transport network.

primary_references

Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

transport_effect

raises Expression enabled uptake in HEK293 substrate assays.

transport_pool

the expressing cell Expression enabled uptake in HEK293 substrate assays.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 48–54

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Metabolomic screening and uptake assays in transfected human cells. · source_derived_draft · unverified_draft

## ergothioneine-slc22a15-ergo An additional carrier connects ergothioneine to the transport network. Human SLC22A15 expression enabled uptake of ergothioneine in HEK293 substrate assays. Model: Metabolomic screening and uptake assays in transfected human cells. Limitations: Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures. Evidence access: Primary abstract Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

evidence_access

Primary abstract

experimental_model

Metabolomic screening and uptake assays in transfected human cells.

limitations

Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures.

nutrient_topic

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

plain_language

An additional carrier connects thiamine to the transport network.

primary_references

Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

transport_effect

raises Expression enabled uptake in HEK293 substrate assays.

transport_pool

the expressing cell Expression enabled uptake in HEK293 substrate assays.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 72–78

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Metabolomic screening and uptake assays in transfected human cells. · source_derived_draft · unverified_draft

## ergothioneine-slc22a15-thiamine An additional carrier connects thiamine to the transport network. Human SLC22A15 expression enabled uptake of thiamine in HEK293 substrate assays. Model: Metabolomic screening and uptake assays in transfected human cells. Limitations: Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures. Evidence access: Primary abstract Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

evidence_access

Primary abstract

experimental_model

Human transporter expressed in HEK293 cells.

limitations

Expression experiments do not quantify uptake in every human tissue.

nutrient_topic

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

plain_language

A specific carrier lets cells build an ergothioneine pool.

primary_references

Discovery of the ergothioneine transporter. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15795384/ · DOI 10.1073/pnas.0408624102

transport_effect

raises Sodium-dependent ergothioneine uptake with intracellular retention.

transport_pool

the expressing cell Sodium-dependent ergothioneine uptake with intracellular retention.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 16–22

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human transporter expressed in HEK293 cells. · source_derived_draft · unverified_draft

## ergothioneine-slc22a4-uptake A specific carrier lets cells build an ergothioneine pool. Expression of human SLC22A4 in HEK293 cells produced efficient, sodium-dependent ergothioneine uptake and intracellular retention. Model: Human transporter expressed in HEK293 cells. Limitations: Expression experiments do not quantify uptake in every human tissue. Evidence access: Primary abstract Discovery of the ergothioneine transporter. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15795384/ · DOI 10.1073/pnas.0408624102

evidence_access

Primary abstract

experimental_model

Rat transporter in HEK293 cells; uptake also examined in rat PC12 cells.

limitations

Rat measurements; no demonstrated benefit from increasing dietary salt.

nutrient_topic

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

plain_language

The carrier couples entry to sodium.

primary_references

Functional characterization of ergothioneine transport by rat organic cation/carnitine transporter Octn1 (slc22a4). · 2008 · https://pubmed.ncbi.nlm.nih.gov/18670092/ · DOI 10.1248/bpb.31.1580

transport_effect

raises Saturable, pH-sensitive, sodium-dependent ergothioneine uptake.

transport_pool

the expressing cell Saturable, pH-sensitive, sodium-dependent ergothioneine uptake.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 24–30

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat transporter in HEK293 cells; uptake also examined in rat PC12 cells. · source_derived_draft · unverified_draft

## ergothioneine-sodium-coupling-rat The carrier couples entry to sodium. Rat Slc22a4-mediated ergothioneine uptake was saturable, pH-sensitive and sodium-dependent, with approximately 1:1 sodium:substrate stoichiometry. Model: Rat transporter in HEK293 cells; uptake also examined in rat PC12 cells. Limitations: Rat measurements; no demonstrated benefit from increasing dietary salt. Evidence access: Primary abstract Functional characterization of ergothioneine transport by rat organic cation/carnitine transporter Octn1 (slc22a4). · 2008 · https://pubmed.ncbi.nlm.nih.gov/18670092/ · DOI 10.1248/bpb.31.1580

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

Human SIT1 heterologous expression in the mammalian transporter identification study.

limitations

Rat concentration-response and ion-substitution details are recorded separately rather than assumed identical in humans.

nutrient_topic

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

plain_language

Cell entry depends on transport machinery and ion gradients.

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 Functioned as a sodium-dependent proline transporter, which is inward.

transport_pool

the expressing cell Functioned as a sodium-dependent proline transporter, which is inward.

L-Proline: synthesis, collagen processing, redox metabolism 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 SIT1 heterologous expression in the mammalian transporter identification study. · source_derived_draft · unverified_draft

## l-proline-sit1-uptake Cell entry depends on transport machinery and ion gradients. Human SIT1/SLC6A20 functioned as a sodium-dependent proline transporter when expressed for functional testing. Model: Human SIT1 heterologous expression in the mammalian transporter identification study. Limitations: Rat concentration-response and ion-substitution details are recorded separately rather than assumed identical in humans. 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

Hamster enzyme and membrane-vesicle controls.

limitations

Negative controls narrow the interpretation; they do not rule out every ion-transport effect.

nutrient_topic

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

plain_language

Reduced whole-tissue absorption did not identify a direct sodium-pump or brush-border transport block.

primary_references

Inhibitory effect of steviol, a metabolite of stevioside, on glucose absorption in everted hamster intestine in vitro. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7482583/ · DOI 10.1016/0378-4274(95)03391-w

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 354–360

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Hamster enzyme and membrane-vesicle controls. · source_derived_draft · unverified_draft

## stevia-hamster-pump-control Reduced whole-tissue absorption did not identify a direct sodium-pump or brush-border transport block. Steviol did not inhibit intestinal sodium-potassium ATPase activity or brush-border-vesicle glucose uptake in the hamster experiment. Model: Hamster enzyme and membrane-vesicle controls. Limitations: Negative controls narrow the interpretation; they do not rule out every ion-transport effect. Evidence access: Primary abstract Inhibitory effect of steviol, a metabolite of stevioside, on glucose absorption in everted hamster intestine in vitro. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7482583/ · DOI 10.1016/0378-4274(95)03391-w

evidence_access

Primary full text; Figure 1 and patch-clamp methods

experimental_model

Whole-cell patch clamp with 1 micromolar free intracellular calcium.

limitations

Human host-cell origin does not establish construct species; that uncertainty is explicit in the channel node.

nutrient_topic

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

plain_language

It strengthens an existing ion-channel response rather than supplying the calcium signal.

primary_references

Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28361903/ · DOI 10.1038/ncomms14733

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 170–176

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Whole-cell patch clamp with 1 micromolar free intracellular calcium. · source_derived_draft · unverified_draft

## stevia-trpm5-stev It strengthens an existing ion-channel response rather than supplying the calcium signal. Stevioside increased calcium-activated TRPM5 currents in transfected HEK293T cells; the effect reversed with washout. Model: Whole-cell patch clamp with 1 micromolar free intracellular calcium. Limitations: Human host-cell origin does not establish construct species; that uncertainty is explicit in the channel node. Evidence access: Primary full text; Figure 1 and patch-clamp methods Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28361903/ · DOI 10.1038/ncomms14733

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_access

Primary abstract

experimental_model

Human OCTN2 in HEK293 cells.

limitations

A kinetic constant is not a treatment target.

nutrient_topic

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

plain_language

The transporter also carries the acetylated form.

primary_references

Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10525100/

transport_effect

raises Sodium-dependent acetylcarnitine transport with a measured Km of 8.5 micromolar.

transport_pool

the expressing cell Sodium-dependent acetylcarnitine transport with a measured Km of 8.5 micromolar.

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 50–56

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human OCTN2 in HEK293 cells. · source_derived_draft · unverified_draft

## l-carnitine-octn2-acetyl The transporter also carries the acetylated form. Expressed human OCTN2 transported acetyl-L-carnitine in a sodium-dependent manner with a measured Km of 8.5 micromolar. Model: Human OCTN2 in HEK293 cells. Limitations: A kinetic constant is not a treatment target. Evidence access: Primary abstract Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10525100/

evidence_access

Primary abstract

experimental_model

Human OCTN2 expressed in HEK293 cells.

limitations

Does not imply that eating more salt improves carnitine uptake.

nutrient_topic

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

plain_language

Cell entry depends on a sodium-coupled transporter.

primary_references

Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10525100/

transport_effect

raises Sodium-coupled, with about one sodium ion accompanying each carnitine molecule inward.

transport_pool

the expressing cell Sodium-coupled, with about one sodium ion accompanying each carnitine molecule inward.

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 42–48

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human OCTN2 expressed in HEK293 cells. · source_derived_draft · unverified_draft

## l-carnitine-octn2-sodium Cell entry depends on a sodium-coupled transporter. Human OCTN2 transport measurements were consistent with approximately one sodium ion accompanying each carnitine molecule. Model: Human OCTN2 expressed in HEK293 cells. Limitations: Does not imply that eating more salt improves carnitine uptake. Evidence access: Primary abstract Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10525100/

evidence_access

Primary abstract

experimental_model

Defined receptor assay solutions.

limitations

Voltage and ionic conditions are essential; no general claim that spermidine bypasses all NMDA magnesium block.

nutrient_topic

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

plain_language

A magnesium block is not identical for every permeating species.

primary_references

Spermidine and Ca(2+), but not Na(+), can permeate NMDA receptors consisting of GluN1 and GluN2A or GluN2B in the presence of Mg(2+). · 2015 · https://pubmed.ncbi.nlm.nih.gov/26086092/ · DOI 10.1016/j.bbrc.2015.06.081

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 470–476

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Defined receptor assay solutions. · source_derived_draft · unverified_draft

## spermidine-nmda-magnesium A magnesium block is not identical for every permeating species. Spermidine and calcium influx persisted under magnesium conditions that strongly inhibited sodium influx. Model: Defined receptor assay solutions. Limitations: Voltage and ionic conditions are essential; no general claim that spermidine bypasses all NMDA magnesium block. Evidence access: Primary abstract Spermidine and Ca(2+), but not Na(+), can permeate NMDA receptors consisting of GluN1 and GluN2A or GluN2B in the presence of Mg(2+). · 2015 · https://pubmed.ncbi.nlm.nih.gov/26086092/ · DOI 10.1016/j.bbrc.2015.06.081

evidence_span

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experimental_model

Cell uptake and stable human-transporter expression

exposure

Radiolabeled theanine with leucine/BCH competition and sodium replacement

limitations

Human transporter identity confirmed in the public primary PDF methods. Engineered cells do not prove which transporter dominates human blood-brain-barrier flux or a clinical meal interaction.

nutrient_topic

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

organism

Mammalian cell lines; human LAT1 and LAT2 expressed in mouse S2 cells

plain_language

Sodium dependence varies with the transport system and cell model.

primary_references

[theanine-p23221699] The involvement of L-type amino acid transporters in theanine transport. (2012). https://pubmed.ncbi.nlm.nih.gov/23221699/ DOI: 10.1271/bbb.120519

tissue_or_cell_type

System L amino acid transport

L-Theanine: metabolism, neural signaling, nutrient connections and human outcomes (2026-09-17) · lines 211–222

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell uptake and stable human-transporter expression · source_derived_draft · unverified_draft

### theanine-sodium-independent-system-l Theanine uptake was mostly sodium independent in the cell-line screen supporting system L transport. Condition category: normal nutrient_topic: L-Theanine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sodium dependence varies with the transport system and cell model. organism: Mammalian cell lines; human LAT1 and LAT2 expressed in mouse S2 cells tissue_or_cell_type: System L amino acid transport experimental_model: Cell uptake and stable human-transporter expression limitations: Human transporter identity confirmed in the public primary PDF methods. Engineered cells do not prove which transporter dominates human blood-brain-barrier flux or a clinical meal interaction. exposure: Radiolabeled theanine with leucine/BCH competition and sodium replacement evidence_span: {"source_cache": "artifacts/theanine-research/23221699.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f79abd668759eccd12f86ec895af75dadf94f6412c29d51a2b6cfde712f9372", "start_char": 0, "end_char": 1143, "text_sha256": "0f79abd668759eccd12f86ec895af75dadf94f6412c29d51a2b6cfde712f9372"} [theanine-p23221699] The involvement of L-type amino acid transporters in theanine transport. (2012). https://pubmed.ncbi.nlm.nih.gov/23221699/ DOI: 10.1271/bbb.120519

evidence_access

Primary abstract

experimental_model

Cloned human liver-cell SN2 in mammalian expression assays.

limitations

Transporter kinetics do not supply a dietary sodium or histidine target.

nutrient_topic

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

plain_language

A second uptake system depends on the ionic and pH environment.

primary_references

Structure, function, and tissue expression pattern of human SN2, a subtype of the amino acid transport system N. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11243884/ · DOI 10.1006/bbrc.2001.4504

transport_effect

raises Sodium-dependent histidine transport with a measured Km of 0.6 mM.

transport_pool

the expressing cell Sodium-dependent histidine transport with a measured Km of 0.6 mM.

L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 74–80

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cloned human liver-cell SN2 in mammalian expression assays. · source_derived_draft · unverified_draft

## histidine-sn2-uptake A second uptake system depends on the ionic and pH environment. Expressed human SN2 transported histidine with sodium dependence and strong pH sensitivity; the measured histidine Km was 0.6 +/- 0.1 mM. Model: Cloned human liver-cell SN2 in mammalian expression assays. Limitations: Transporter kinetics do not supply a dietary sodium or histidine target. Evidence access: Primary abstract Structure, function, and tissue expression pattern of human SN2, a subtype of the amino acid transport system N. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11243884/ · DOI 10.1006/bbrc.2001.4504

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 tagged unglycosylated rat NIS expressed in human 293F cells; cryo-EM and functional comparison

exposure

Tagged N225Q/N485Q/N497Q rat NIS; iodide-bound structure at 3.12 Å.

limitations

Structural ion assignments and engineered construct support a binding mechanism; they do not alone measure physiological transport rates.

nutrient_topic

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

organism

Rat protein produced in human 293F cells

plain_language

The NIS structure shows where iodide and its two sodium partners bind.

primary_references

[iodine-trans-nis-structure2022] Structural insights into the mechanism of the sodium/iodide symporter. (2022). https://pubmed.ncbi.nlm.nih.gov/36517601/ DOI: 10.1038/s41586-022-05530-2

tissue_or_cell_type

Purified detergent-solubilized membrane protein

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 193–204

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified tagged unglycosylated rat NIS expressed in human 293F cells; cryo-EM and functional comparison · source_derived_draft · unverified_draft

### iodine-trans-nis-bound-ions The iodide-bound cryo-EM structure of engineered rat NIS contained density assigned to one iodide and two sodium ions in the substrate-binding cavity. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The NIS structure shows where iodide and its two sodium partners bind. organism: Rat protein produced in human 293F cells tissue_or_cell_type: Purified detergent-solubilized membrane protein experimental_model: Purified tagged unglycosylated rat NIS expressed in human 293F cells; cryo-EM and functional comparison limitations: Structural ion assignments and engineered construct support a binding mechanism; they do not alone measure physiological transport rates. exposure: Tagged N225Q/N485Q/N497Q rat NIS; iodide-bound structure at 3.12 Å. cross_nutrient: true [iodine-trans-nis-structure2022] Structural insights into the mechanism of the sodium/iodide symporter. (2022). https://pubmed.ncbi.nlm.nih.gov/36517601/ DOI: 10.1038/s41586-022-05530-2

cross_nutrient

true

experimental_model

Rat NIS expressed in Xenopus laevis oocytes; electrophysiology and tracer uptake

exposure

Tracer uptake and electrophysiology; apparent sodium affinity 28 ± 3 mM and iodide affinity 33 ± 9 micromolar.

limitations

Rat-protein assay parameters are not dietary sodium requirements or human iodide thresholds.

nutrient_topic

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

organism

Rat protein in Xenopus laevis oocytes

plain_language

NIS uses sodium movement to carry iodide into cells.

primary_references

[iodine-trans-stoichiometry1997] Thyroid Na+/I- symporter. Mechanism, stoichiometry, and specificity. (1997). https://pubmed.ncbi.nlm.nih.gov/9341168/ DOI: 10.1074/jbc.272.43.27230

tissue_or_cell_type

Oocyte plasma membrane

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 167–178

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat NIS expressed in Xenopus laevis oocytes; electrophysiology and tracer uptake · source_derived_draft · unverified_draft

### iodine-trans-sodium-coupling Rat NIS expressed in Xenopus oocytes transported iodide with two sodium ions per anion and generated inward electrogenic transport. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: NIS uses sodium movement to carry iodide into cells. organism: Rat protein in Xenopus laevis oocytes tissue_or_cell_type: Oocyte plasma membrane experimental_model: Rat NIS expressed in Xenopus laevis oocytes; electrophysiology and tracer uptake limitations: Rat-protein assay parameters are not dietary sodium requirements or human iodide thresholds. exposure: Tracer uptake and electrophysiology; apparent sodium affinity 28 ± 3 mM and iodide affinity 33 ± 9 micromolar. cross_nutrient: true [iodine-trans-stoichiometry1997] Thyroid Na+/I- symporter. Mechanism, stoichiometry, and specificity. (1997). https://pubmed.ncbi.nlm.nih.gov/9341168/ DOI: 10.1074/jbc.272.43.27230

evidence_access

Primary abstract

experimental_model

Bovine capillary RNA, membrane protein analysis and transport kinetics; aggregate apparent Km 14 micromolar at −61 mV.

limitations

The panel is not a physical three-protein complex; transport assays do not measure whole human brain exposure after food intake.

nutrient_topic

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

plain_language

The brain-facing barrier membrane participates in removing extracellular glutamate.

primary_references

Na(+)-dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) of the blood-brain barrier. A mechanism for glutamate removal. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10542215/ · DOI 10.1074/jbc.274.45.31891

L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 106–112

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Bovine capillary RNA, membrane protein analysis and transport kinetics; aggregate apparent Km 14 micromolar at −61 mV. · source_derived_draft · unverified_draft

## glutamate-bbb-clearance The brain-facing barrier membrane participates in removing extracellular glutamate. Bovine brain-capillary membrane preparations contained EAAT1/2/3 on the abluminal side and showed voltage- and potassium-dependent glutamate uptake. Model: Bovine capillary RNA, membrane protein analysis and transport kinetics; aggregate apparent Km 14 micromolar at −61 mV. Limitations: The panel is not a physical three-protein complex; transport assays do not measure whole human brain exposure after food intake. Evidence access: Primary abstract Na(+)-dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) of the blood-brain barrier. A mechanism for glutamate removal. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10542215/ · DOI 10.1074/jbc.274.45.31891

evidence_access

Primary full text

experimental_model

Anesthetized rats; 2 mL intragastric infusion at 1 mL/min, nerve discharge assessed after infusion.

limitations

MSG was the exposure; human food intake and subjective effects were not tested.

nutrient_topic

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

plain_language

Glutamate in the stomach can signal through nerves without first acting at a brain glutamate receptor.

primary_references

Effects of intragastric infusion of inosine monophosphate and L: -glutamate on vagal gastric afferent activity and subsequent autonomic reflexes. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21132420/ · DOI 10.1007/s12576-010-0121-z

L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 66–72

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Anesthetized rats; 2 mL intragastric infusion at 1 mL/min, nerve discharge assessed after infusion. · source_derived_draft · unverified_draft

## glutamate-gastric-vagal Glutamate in the stomach can signal through nerves without first acting at a brain glutamate receptor. Intragastric 150 mM MSG increased gastric vagal afferent discharge in anesthetized rats. Model: Anesthetized rats; 2 mL intragastric infusion at 1 mL/min, nerve discharge assessed after infusion. Limitations: MSG was the exposure; human food intake and subjective effects were not tested. Evidence access: Primary full text Effects of intragastric infusion of inosine monophosphate and L: -glutamate on vagal gastric afferent activity and subsequent autonomic reflexes. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21132420/ · DOI 10.1007/s12576-010-0121-z

evidence_access

Primary abstract

experimental_model

Randomized placebo-controlled crossover; six-week periods.

limitations

Small trial; reduced lithium entry was inferred, not directly measured in patient kidney cells.

nutrient_topic

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

plain_language

Blocking a sodium channel improved the measured water response.

primary_references

Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18596116/ · DOI 10.2215/CJN.01640408

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 344–350

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Randomized placebo-controlled crossover; six-week periods. · source_derived_draft · unverified_draft

## lithium-amiloride-human Blocking a sodium channel improved the measured water response. Amiloride increased maximal urine osmolality and AQP2 excretion in an eleven-patient crossover trial during lithium therapy. Model: Randomized placebo-controlled crossover; six-week periods. Limitations: Small trial; reduced lithium entry was inferred, not directly measured in patient kidney cells. Evidence access: Primary abstract Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18596116/ · DOI 10.2215/CJN.01640408

evidence_access

Official prescribing information

experimental_model

Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.

limitations

Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.

nutrient_topic

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

plain_language

Fluid loss can amplify exposure.

primary_references

Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 568–574

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft

## lithium-dehydration Fluid loss can amplify exposure. Dehydration can promote lithium retention and toxicity. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

evidence_access

Official prescribing information

experimental_model

Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.

limitations

Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.

nutrient_topic

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

plain_language

Sodium loss can slow lithium removal.

primary_references

Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 576–582

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft

## lithium-diuretic-sodium Sodium loss can slow lithium removal. Diuretic-associated sodium loss can reduce lithium clearance. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Collecting-duct-specific mouse knockout and chronic lithium treatment.

limitations

Protection supports ENaC-mediated entry; connecting-tubule expression remained intact.

nutrient_topic

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

plain_language

A sodium channel helps lithium reach vulnerable kidney cells.

primary_references

alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21051735/ · DOI 10.1681/ASN.2010070734

trigger_kind

machinery_impairment Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 320–326

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Collecting-duct-specific mouse knockout and chronic lithium treatment. · source_derived_draft · unverified_draft

## lithium-enac-entry A sodium channel helps lithium reach vulnerable kidney cells. Collecting-duct Scnn1a deletion protected lithium-treated mice against polyuria and loss of urine concentration. Model: Collecting-duct-specific mouse knockout and chronic lithium treatment. Limitations: Protection supports ENaC-mediated entry; connecting-tubule expression remained intact. Evidence access: Primary abstract alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21051735/ · DOI 10.1681/ASN.2010070734

evidence_access

Primary abstract

experimental_model

Cloned human transporter kinetic analysis.

limitations

Net flux depends on citrate and ion concentrations; not unconditional stimulation at every substrate level.

nutrient_topic

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

plain_language

A stronger apparent response can coexist with a lower maximum rate.

primary_references

Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 288–294

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cloned human transporter kinetic analysis. · source_derived_draft · unverified_draft

## lithium-nact-affinity A stronger apparent response can coexist with a lower maximum rate. Lithium shifted human NaCT toward higher substrate affinity and lower transport capacity. Model: Cloned human transporter kinetic analysis. Limitations: Net flux depends on citrate and ion concentrations; not unconditional stimulation at every substrate level. Evidence access: Primary abstract Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523

evidence_access

Primary abstract

experimental_model

Expressed human transporter and human liver-cell experiments.

limitations

Not evidence that trace lithium has the same effect or that citrate salt ingestion determines the response.

nutrient_topic

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

plain_language

A sodium-coupled carrier links lithium to carbon metabolism.

primary_references

Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12826022/ · DOI 10.1042/BJ20030827

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 264–270

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Expressed human transporter and human liver-cell experiments. · source_derived_draft · unverified_draft

## lithium-nact-human A sodium-coupled carrier links lithium to carbon metabolism. Lithium stimulated human NaCT-mediated citrate transport at concentrations relevant to prescription exposure. Model: Expressed human transporter and human liver-cell experiments. Limitations: Not evidence that trace lithium has the same effect or that citrate salt ingestion determines the response. Evidence access: Primary abstract Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12826022/ · DOI 10.1042/BJ20030827

evidence_access

Primary abstract

experimental_model

Human liver-cell tracer/transport study.

limitations

Does not establish that this pathway explains clinical weight change.

nutrient_topic

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

plain_language

Transported citrate can enter lipid-building pathways.

primary_references

Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12826022/ · DOI 10.1042/BJ20030827

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 272–278

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human liver-cell tracer/transport study. · source_derived_draft · unverified_draft

## lithium-nact-lipids Transported citrate can enter lipid-building pathways. Lithium increased NaCT-mediated use of extracellular citrate for lipid synthesis in human liver cells. Model: Human liver-cell tracer/transport study. Limitations: Does not establish that this pathway explains clinical weight change. Evidence access: Primary abstract Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12826022/ · DOI 10.1042/BJ20030827

evidence_access

Primary abstract

experimental_model

Transporters cloned from eight species.

limitations

Explicit species difference; no contradiction between correctly scoped records.

nutrient_topic

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

plain_language

The human result cannot be assumed in rodents.

primary_references

Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 280–286

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Transporters cloned from eight species. · source_derived_draft · unverified_draft

## lithium-nact-rat The human result cannot be assumed in rodents. Lithium inhibited rat NaCT while stimulating primate transporters in the same comparative study. Model: Transporters cloned from eight species. Limitations: Explicit species difference; no contradiction between correctly scoped records. Evidence access: Primary abstract Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523

evidence_access

Official prescribing information

experimental_model

Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.

limitations

Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.

nutrient_topic

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

plain_language

Kidney handling controls removal.

primary_references

Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 608–614

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft

## lithium-renal-elimination Kidney handling controls removal. Lithium is not metabolized and is eliminated primarily through the kidneys. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

evidence_access

Official prescribing information

experimental_model

Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.

limitations

Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.

nutrient_topic

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

plain_language

Not all renal drug interactions increase exposure.

primary_references

Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 592–598

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft

## lithium-sglt2-interaction Not all renal drug interactions increase exposure. SGLT2 inhibitors may lower serum lithium. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

evidence_access

Primary abstract

experimental_model

15 healthy volunteers; randomized blinded crossover and fixed sodium/potassium intake.

limitations

Salt doses describe the experiment, not dosing advice; a test dose can perturb a clearance measurement.

nutrient_topic

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

plain_language

Lithium exposure can change sodium balance.

primary_references

Effect of a single test dose of lithium carbonate on sodium and potassium excretion in man. · 1991 · https://pubmed.ncbi.nlm.nih.gov/1649725/ · DOI 10.1042/cs0810059

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 352–358

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 15 healthy volunteers; randomized blinded crossover and fixed sodium/potassium intake. · source_derived_draft · unverified_draft

## lithium-sodium-excretion Lithium exposure can change sodium balance. Single 300- and 600-mg lithium-carbonate doses increased 24-hour sodium excretion by about 17 and 48 mmol, respectively. Model: 15 healthy volunteers; randomized blinded crossover and fixed sodium/potassium intake. Limitations: Salt doses describe the experiment, not dosing advice; a test dose can perturb a clearance measurement. Evidence access: Primary abstract Effect of a single test dose of lithium carbonate on sodium and potassium excretion in man. · 1991 · https://pubmed.ncbi.nlm.nih.gov/1649725/ · DOI 10.1042/cs0810059

evidence_access

Primary abstract

experimental_model

200 versus 40 mmol/day sodium; reabsorption 71 to 75% and 75 to 81%, respectively.

limitations

Not a recommendation to change salt intake; lithium clearance was not a universally pure proximal-tubule marker.

nutrient_topic

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

plain_language

Sodium intake changes the setting for a drug interaction.

primary_references

Indomethacin increases renal lithium reabsorption in man. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2494594/

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 368–374

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 200 versus 40 mmol/day sodium; reabsorption 71 to 75% and 75 to 81%, respectively. · source_derived_draft · unverified_draft

## lithium-sodium-renal-context Sodium intake changes the setting for a drug interaction. Indomethacin increased fractional lithium reabsorption on both high- and low-sodium diets in seven volunteers. Model: 200 versus 40 mmol/day sodium; reabsorption 71 to 75% and 75 to 81%, respectively. Limitations: Not a recommendation to change salt intake; lithium clearance was not a universally pure proximal-tubule marker. Evidence access: Primary abstract Indomethacin increases renal lithium reabsorption in man. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2494594/

dose

Glucose or alpha-methylglucose with sodium and phlorizin

duration

Acute transport assay

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human SGLT2 expressed in Xenopus oocytes

limitations

Oocyte transport identifies function but does not define human oral phlorizin exposure or renal selectivity in vivo.

nutrient_topic

Phlorizin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Phlorizin

organism

Human SGLT2 expressed in Xenopus oocytes

plain_language

Human SGLT2 expressed in Xenopus oocytes transported glucose with a 1:1 sodium-to-glucose ratio and was phlorizin-sensitive.

primary_references

The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. (1994). https://pubmed.ncbi.nlm.nih.gov/8282810/ DOI: 10.1172/JCI116972

route

In vitro

tissue

Radiotracer uptake and voltage-clamp current

Phlorizin: mechanism of action and interactions (2026-09-20) · lines 11–20

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Human SGLT2 expressed in Xenopus oocytes · source_derived_draft · unverified_draft

## phlorizin-human-sglt2-identification Human SGLT2 expressed in Xenopus oocytes transported glucose with a 1:1 sodium-to-glucose ratio and was phlorizin-sensitive. Model/species: Human SGLT2 expressed in Xenopus oocytes Tissue/system: Radiotracer uptake and voltage-clamp current Exposure: Glucose or alpha-methylglucose with sodium and phlorizin Route: In vitro Duration: Acute transport assay Limits: Oocyte transport identifies function but does not define human oral phlorizin exposure or renal selectivity in vivo. Primary reference: The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. (1994). https://pubmed.ncbi.nlm.nih.gov/8282810/ DOI: 10.1172/JCI116972 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

availability_state

machinery_impairment Imported condition classification; unverified.

dose

Phlorizin concentration-response

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

HEK293T cells expressing human SGLT2 or SGLT1

limitations

The indexed article has an erratum notice; the exact correction was not recovered in this curation and the numerical values require rechecking before quantitative reuse.

nutrient_topic

Phlorizin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Phlorizin

organism

HEK293T cells expressing human SGLT2 or SGLT1

plain_language

Phlorizin inhibited human SGLT2 more strongly than SGLT1 in HEK293T electrophysiology, with reported Ki values of 11 and 140 nM, respectively.

primary_references

Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2. (2011). https://pubmed.ncbi.nlm.nih.gov/20980548/ DOI: 10.1152/ajpcell.00388.2010

route

In vitro

tissue

Whole-cell sodium/glucose cotransport current

trigger_kind

machinery_impairment Imported condition classification; unverified.

Phlorizin: mechanism of action and interactions (2026-09-20) · lines 22–31

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · HEK293T cells expressing human SGLT2 or SGLT1 · source_derived_draft · unverified_draft

## phlorizin-sglt1-sglt2-affinity Phlorizin inhibited human SGLT2 more strongly than SGLT1 in HEK293T electrophysiology, with reported Ki values of 11 and 140 nM, respectively. Model/species: HEK293T cells expressing human SGLT2 or SGLT1 Tissue/system: Whole-cell sodium/glucose cotransport current Exposure: Phlorizin concentration-response Route: In vitro Duration: Acute Limits: The indexed article has an erratum notice; the exact correction was not recovered in this curation and the numerical values require rechecking before quantitative reuse. Primary reference: Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2. (2011). https://pubmed.ncbi.nlm.nih.gov/20980548/ DOI: 10.1152/ajpcell.00388.2010 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Phlorizin and comparator synthetic inhibitors

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Purified human SGLT2-MAP17 complex

limitations

A bound structure explains inhibition but does not establish human pharmacokinetics; synthetic inhibitors used different outward-facing poses.

nutrient_topic

Phlorizin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Phlorizin

organism

Purified human SGLT2-MAP17 complex

plain_language

Cryo-EM placed phlorizin in an inward-facing human SGLT2-MAP17 complex, and biphasic kinetics suggested access from extracellular and intracellular sides.

primary_references

Transport and inhibition mechanism of the human SGLT2-MAP17 glucose transporter. (2024). https://pubmed.ncbi.nlm.nih.gov/38057552/ DOI: 10.1038/s41594-023-01134-0

route

Cell-free structural and transport analysis

tissue

Cryo-EM structures and inhibitor kinetics

Phlorizin: mechanism of action and interactions (2026-09-20) · lines 33–42

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Purified human SGLT2-MAP17 complex · source_derived_draft · unverified_draft

## phlorizin-sglt2-structure Cryo-EM placed phlorizin in an inward-facing human SGLT2-MAP17 complex, and biphasic kinetics suggested access from extracellular and intracellular sides. Model/species: Purified human SGLT2-MAP17 complex Tissue/system: Cryo-EM structures and inhibitor kinetics Exposure: Phlorizin and comparator synthetic inhibitors Route: Cell-free structural and transport analysis Duration: Acute Limits: A bound structure explains inhibition but does not establish human pharmacokinetics; synthetic inhibitors used different outward-facing poses. Primary reference: Transport and inhibition mechanism of the human SGLT2-MAP17 glucose transporter. (2024). https://pubmed.ncbi.nlm.nih.gov/38057552/ DOI: 10.1038/s41594-023-01134-0 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Human/mouse heterodimer expression and exchange assays

limitations

Neutral-substrate transport is sodium-dependent; lysine binding itself should not be mislabeled a sodium cotransport step.

organism

Homo sapiens

plain_language

This route helps lysine leave epithelial cells toward blood.

primary_references

[pfeiffer1999yl] Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family. (1999). https://pubmed.ncbi.nlm.nih.gov/9878049/ DOI: 10.1093/emboj/18.1.49

tissue_or_cell_type

Basolateral intestinal and renal epithelial membranes

transport_effect

lowers Exchanges intracellular cationic amino acids including lysine for extracellular neutral amino acids, so lysine leaves the cell.

transport_pool

the enterocyte interior Exchanges intracellular cationic amino acids including lysine for extracellular neutral amino acids, so lysine leaves the cell.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 34–42

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human/mouse heterodimer expression and exchange assays · source_derived_draft · unverified_draft

### basolateral-lysine-exchange SLC7A7-SLC3A2 exchanges intracellular cationic amino acids including lysine for extracellular neutral amino acids with sodium. Plain language: This route helps lysine leave epithelial cells toward blood. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Basolateral intestinal and renal epithelial membranes experimental_model: Human/mouse heterodimer expression and exchange assays limitations: Neutral-substrate transport is sodium-dependent; lysine binding itself should not be mislabeled a sodium cotransport step. [pfeiffer1999yl] Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family. (1999). https://pubmed.ncbi.nlm.nih.gov/9878049/ DOI: 10.1093/emboj/18.1.49

evidence_access

Primary abstract

experimental_model

Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL.

limitations

Insulin-clamp mechanism, not a fasting or refeeding-syndrome trial.

nutrient_topic

Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake

plain_language

Insulin changed kidney sodium retention.

primary_references

The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1120786/ · DOI 10.1172/JCI107996

Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 448–454

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL. · source_derived_draft · unverified_draft

## fast-insulin-sodium Insulin changed kidney sodium retention. Urinary sodium excretion fell from 401 to 213 microequivalents/min without changes in GFR, renal blood flow or aldosterone. Model: Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL. Limitations: Insulin-clamp mechanism, not a fasting or refeeding-syndrome trial. Evidence access: Primary abstract The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1120786/ · DOI 10.1172/JCI107996

cross_nutrient

true

experimental_model

Rat cDNA transporters expressed in Xenopus oocytes; mammalian tissue distribution

exposure

Heterologous cDNA expression and uptake assays

limitations

Primary abstract only; no inferred human kinetic constants.

nutrient_topic

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

organism

Rattus norvegicus protein in Xenopus laevis

plain_language

SVCT1 uses a sodium gradient to bring reduced vitamin C into cells.

primary_references

[tsukaguchi1999] A family of mammalian Na+-dependent L-ascorbic acid transporters. (1999). https://pubmed.ncbi.nlm.nih.gov/10331392/ DOI: 10.1038/19986

tissue_or_cell_type

Oocyte plasma membrane

transport_effect

raises Stereospecific concentrative uptake driven by the sodium electrochemical gradient.

transport_pool

the expressing cell Stereospecific concentrative uptake driven by the sodium electrochemical gradient.

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 104–115

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat cDNA transporters expressed in Xenopus oocytes; mammalian tissue distribution · source_derived_draft · unverified_draft

### vc-transport-svct1-uptake Rat SVCT1 expressed in Xenopus oocytes mediated stereospecific, concentrative uptake of reduced L-ascorbate driven by the sodium electrochemical gradient. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: SVCT1 uses a sodium gradient to bring reduced vitamin C into cells. organism: Rattus norvegicus protein in Xenopus laevis tissue_or_cell_type: Oocyte plasma membrane experimental_model: Rat cDNA transporters expressed in Xenopus oocytes; mammalian tissue distribution limitations: Primary abstract only; no inferred human kinetic constants. exposure: Heterologous cDNA expression and uptake assays cross_nutrient: true [tsukaguchi1999] A family of mammalian Na+-dependent L-ascorbic acid transporters. (1999). https://pubmed.ncbi.nlm.nih.gov/10331392/ DOI: 10.1038/19986

cross_nutrient

true

experimental_model

Rat cDNA transporters expressed in Xenopus oocytes; mammalian tissue distribution

exposure

Heterologous cDNA expression and uptake assays

limitations

Primary abstract only; no inferred human kinetic constants.

nutrient_topic

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

organism

Rattus norvegicus protein in Xenopus laevis

plain_language

SVCT2 uses a sodium gradient to bring reduced vitamin C into cells.

primary_references

[tsukaguchi1999] A family of mammalian Na+-dependent L-ascorbic acid transporters. (1999). https://pubmed.ncbi.nlm.nih.gov/10331392/ DOI: 10.1038/19986

tissue_or_cell_type

Oocyte plasma membrane

transport_effect

raises Stereospecific concentrative uptake driven by the sodium electrochemical gradient.

transport_pool

the expressing cell Stereospecific concentrative uptake driven by the sodium electrochemical gradient.

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 117–128

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat cDNA transporters expressed in Xenopus oocytes; mammalian tissue distribution · source_derived_draft · unverified_draft

### vc-transport-svct2-uptake Rat SVCT2 expressed in Xenopus oocytes mediated stereospecific, concentrative uptake of reduced L-ascorbate driven by the sodium electrochemical gradient. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: SVCT2 uses a sodium gradient to bring reduced vitamin C into cells. organism: Rattus norvegicus protein in Xenopus laevis tissue_or_cell_type: Oocyte plasma membrane experimental_model: Rat cDNA transporters expressed in Xenopus oocytes; mammalian tissue distribution limitations: Primary abstract only; no inferred human kinetic constants. exposure: Heterologous cDNA expression and uptake assays cross_nutrient: true [tsukaguchi1999] A family of mammalian Na+-dependent L-ascorbic acid transporters. (1999). https://pubmed.ncbi.nlm.nih.gov/10331392/ DOI: 10.1038/19986

experimental_model

Inside-out patch; cGMP EC50 about 30 micromolar

limitations

The historical experiment measured conductance before modern channel-subunit assignment.

nutrient_topic

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

organism

Rana temporaria

plain_language

cGMP directly keeps the rod cation channel open.

primary_references

[fesenko-1985] Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment (1985). https://pubmed.ncbi.nlm.nih.gov/2578616/ DOI: 10.1038/313310a0

tissue_or_cell_type

Rod outer-segment plasma membrane

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 938–947

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inside-out patch; cGMP EC50 about 30 micromolar · source_derived_draft · unverified_draft

### a-vision-cgmp-channel Cytoplasmic-side cGMP reversibly increased cation conductance in excised rod outer-segment patches without nucleoside triphosphates. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: cGMP directly keeps the rod cation channel open. organism: Rana temporaria tissue_or_cell_type: Rod outer-segment plasma membrane experimental_model: Inside-out patch; cGMP EC50 about 30 micromolar limitations: The historical experiment measured conductance before modern channel-subunit assignment. [fesenko-1985] Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment (1985). https://pubmed.ncbi.nlm.nih.gov/2578616/ DOI: 10.1038/313310a0

evidence_access

Primary abstract and primary methods/figure text

experimental_model

Mouse transporter/enzyme cDNAs; CHO-K1 and HEK293T cell experiments.

limitations

This is NAA transport, not proof that NaDC3 transports free L-aspartate in the tested assay.

nutrient_topic

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

plain_language

Transport of the intermediate can gate the next synthesis step.

primary_references

Molecular characterization of N-acetylaspartylglutamate synthetase. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20643647/ · DOI 10.1074/jbc.M110.111765

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 378–384

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse transporter/enzyme cDNAs; CHO-K1 and HEK293T cell experiments. · source_derived_draft · unverified_draft

## l-aspartate-naag-import-route Transport of the intermediate can gate the next synthesis step. Coexpression of the mouse NaDC3 transporter with Rimklb enabled supplied NAA to support NAAG synthesis in heterologous cells. Model: Mouse transporter/enzyme cDNAs; CHO-K1 and HEK293T cell experiments. Limitations: This is NAA transport, not proof that NaDC3 transports free L-aspartate in the tested assay. Evidence access: Primary abstract and primary methods/figure text Molecular characterization of N-acetylaspartylglutamate synthetase. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20643647/ · DOI 10.1074/jbc.M110.111765

evidence_span

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experimental_model

Hypertonic culture adaptation

exposure

Hypertonic exposure followed by isotonic recovery

limitations

Dog cell culture, not a human intake requirement.

nutrient_topic

Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)

organism

Canis familiaris

plain_language

Kidney-derived cells adjust inositol uptake as part of adaptation to concentrated surroundings.

primary_references

[ino-p8430828] Hypertonicity stimulates transcription of gene for Na(+)-myo-inositol cotransporter in MDCK cells. (1993). https://pubmed.ncbi.nlm.nih.gov/8430828/ DOI: 10.1152/ajprenal.1993.264.1.f20

tissue_or_cell_type

MDCK renal epithelial cells

Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 353–364

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

### ino-smit1-osmotic Hypertonic MDCK culture increased sodium/myo-inositol transporter transcription, mRNA and transport activity with different time courses. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Kidney-derived cells adjust inositol uptake as part of adaptation to concentrated surroundings. organism: Canis familiaris tissue_or_cell_type: MDCK renal epithelial cells experimental_model: Hypertonic culture adaptation limitations: Dog cell culture, not a human intake requirement. exposure: Hypertonic exposure followed by isotonic recovery evidence_span: {"source_cache": "artifacts/inositol-research/8430828.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0539c3e28460fcea154b9014b1d98f36bf5ee2b8b5a418f6951c9cf0ad92af8b", "start_char": 0, "end_char": 1156, "text_sha256": "0539c3e28460fcea154b9014b1d98f36bf5ee2b8b5a418f6951c9cf0ad92af8b"} [ino-p8430828] Hypertonicity stimulates transcription of gene for Na(+)-myo-inositol cotransporter in MDCK cells. (1993). https://pubmed.ncbi.nlm.nih.gov/8430828/ DOI: 10.1152/ajprenal.1993.264.1.f20

evidence_span

{"source_cache": "artifacts/inositol-research/19032932.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242", "start_char": 0, "end_char": 1164, "text_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242"}

experimental_model

Human SMIT2 overexpression and radiotracer uptake

exposure

Overexpression, glucose competition and insulin exposure

limitations

Overexpression is not normal transporter abundance. Insulin experiments used untransfected rat cells; changes in human diabetes are proposed, not demonstrated here.

nutrient_topic

Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)

organism

Human transporter in rat L6 myoblasts

plain_language

SMIT2 can bring free myo-inositol into cells.

primary_references

[ino-p19032932] Human sodium/inositol cotransporter 2 (SMIT2) transports inositols but not glucose in L6 cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19032932/ DOI: 10.1016/j.abb.2008.11.008

tissue_or_cell_type

Skeletal-muscle cell model

transport_effect

raises Expression increased myo-inositol uptake 37-fold against vector control.

transport_pool

the expressing cell Expression increased myo-inositol uptake 37-fold against vector control.

Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 288–299

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMIT2 overexpression and radiotracer uptake · source_derived_draft · unverified_draft

### ino-smit2-myo Human SMIT2 expression increased myo-inositol uptake 37-fold relative to vector control in rat L6 cells. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: SMIT2 can bring free myo-inositol into cells. organism: Human transporter in rat L6 myoblasts tissue_or_cell_type: Skeletal-muscle cell model experimental_model: Human SMIT2 overexpression and radiotracer uptake limitations: Overexpression is not normal transporter abundance. Insulin experiments used untransfected rat cells; changes in human diabetes are proposed, not demonstrated here. exposure: Overexpression, glucose competition and insulin exposure evidence_span: {"source_cache": "artifacts/inositol-research/19032932.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242", "start_char": 0, "end_char": 1164, "text_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242"} [ino-p19032932] Human sodium/inositol cotransporter 2 (SMIT2) transports inositols but not glucose in L6 cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19032932/ DOI: 10.1016/j.abb.2008.11.008

evidence_access

Primary abstract

experimental_model

Double-blind study, 12 caffeine and 12 placebo participants over six hours.

limitations

Proximal sodium-reabsorption inhibition was proposed from correlations, not directly measured; no osteoporosis outcome.

nutrient_topic

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

plain_language

High repeated exposure changed renal calcium clearance.

primary_references

The effect of high-dose, short-term caffeine intake on the renal clearance of calcium, sodium and creatinine in healthy adults. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33852164/ · DOI 10.1111/bcp.14856

Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18) · lines 356–362

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Double-blind study, 12 caffeine and 12 placebo participants over six hours. · source_derived_draft · unverified_draft

## caf-high-calcium High repeated exposure changed renal calcium clearance. An 800 mg total caffeine gum regimen increased renal calcium clearance by 77%; changes correlated with sodium clearance and urine volume. Model: Double-blind study, 12 caffeine and 12 placebo participants over six hours. Limitations: Proximal sodium-reabsorption inhibition was proposed from correlations, not directly measured; no osteoporosis outcome. Evidence access: Primary abstract The effect of high-dose, short-term caffeine intake on the renal clearance of calcium, sodium and creatinine in healthy adults. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33852164/ · DOI 10.1111/bcp.14856

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Awake mice; oral gavage and three-hour collection.

limitations

Evidence of receptor dependence, not a directly demonstrated human tubular segment.

nutrient_topic

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

plain_language

Removing A1 receptors removed the renal response in this animal model.

primary_references

Requirement of intact adenosine A1 receptors for the diuretic and natriuretic action of the methylxanthines theophylline and caffeine. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15590766/ · DOI 10.1124/jpet.104.080432

trigger_kind

machinery_impairment Imported condition classification; unverified.

Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18) · lines 364–370

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Awake mice; oral gavage and three-hour collection. · source_derived_draft · unverified_draft

## caf-renal-a1 Removing A1 receptors removed the renal response in this animal model. Caffeine 45 mg/kg caused diuresis and natriuresis in wild-type but not A1-knockout mice. Model: Awake mice; oral gavage and three-hour collection. Limitations: Evidence of receptor dependence, not a directly demonstrated human tubular segment. Evidence access: Primary abstract Requirement of intact adenosine A1 receptors for the diuretic and natriuretic action of the methylxanthines theophylline and caffeine. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15590766/ · DOI 10.1124/jpet.104.080432

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 316–322

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-na The acute urine measurement increased. Urinary sodium/creatinine rose from 3800 to 6200 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

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Human and monkey brain microvessel analyses; SLC5A6-siRNA experiments in human hCMEC/D3 endothelial cells

exposure

SLC5A6-specific siRNA and radiolabeled substrate uptake; tracer concentration not specified in the abstract.

limitations

Cellular luminal uptake is not itself a measurement of complete transendothelial delivery into brain tissue. Reported percentages apply to hCMEC/D3 under these assay conditions, not every human tissue.

nutrient_topic

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

organism

Homo sapiens

plain_language

SMVT supplied most measured biotin uptake in the human brain endothelial cell model.

primary_references

[b5-trans-brain2015] Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells. (2015). https://pubmed.ncbi.nlm.nih.gov/25809983/ DOI: 10.1111/jnc.13092

tissue_or_cell_type

hCMEC/D3 cerebral microvascular endothelial cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 288–299

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and monkey brain microvessel analyses; SLC5A6-siRNA experiments in human hCMEC/D3 endothelial cells · source_derived_draft · unverified_draft

### b5-trans-brain-biotin SLC5A6 knockdown analysis attributed 88.7% of total radiolabeled biotin uptake to SLC5A6 in human hCMEC/D3 brain endothelial cells. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: SMVT supplied most measured biotin uptake in the human brain endothelial cell model. organism: Homo sapiens tissue_or_cell_type: hCMEC/D3 cerebral microvascular endothelial cells experimental_model: Human and monkey brain microvessel analyses; SLC5A6-siRNA experiments in human hCMEC/D3 endothelial cells limitations: Cellular luminal uptake is not itself a measurement of complete transendothelial delivery into brain tissue. Reported percentages apply to hCMEC/D3 under these assay conditions, not every human tissue. exposure: SLC5A6-specific siRNA and radiolabeled substrate uptake; tracer concentration not specified in the abstract. cross_nutrient: true [b5-trans-brain2015] Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells. (2015). https://pubmed.ncbi.nlm.nih.gov/25809983/ DOI: 10.1111/jnc.13092

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Human and monkey brain microvessel analyses; SLC5A6-siRNA experiments in human hCMEC/D3 endothelial cells

exposure

SLC5A6-specific siRNA and radiolabeled substrate uptake; tracer concentration not specified in the abstract.

limitations

Cellular luminal uptake is not itself a measurement of complete transendothelial delivery into brain tissue. Reported percentages apply to hCMEC/D3 under these assay conditions, not every human tissue.

nutrient_topic

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

organism

Homo sapiens

plain_language

SMVT supplied most measured pantothenate uptake in the human brain endothelial cell model.

primary_references

[b5-trans-brain2015] Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells. (2015). https://pubmed.ncbi.nlm.nih.gov/25809983/ DOI: 10.1111/jnc.13092

tissue_or_cell_type

hCMEC/D3 cerebral microvascular endothelial cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 275–286

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and monkey brain microvessel analyses; SLC5A6-siRNA experiments in human hCMEC/D3 endothelial cells · source_derived_draft · unverified_draft

### b5-trans-brain-pantothenate SLC5A6 knockdown analysis attributed 98.6% of total radiolabeled pantothenate uptake to SLC5A6 in human hCMEC/D3 brain endothelial cells. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: SMVT supplied most measured pantothenate uptake in the human brain endothelial cell model. organism: Homo sapiens tissue_or_cell_type: hCMEC/D3 cerebral microvascular endothelial cells experimental_model: Human and monkey brain microvessel analyses; SLC5A6-siRNA experiments in human hCMEC/D3 endothelial cells limitations: Cellular luminal uptake is not itself a measurement of complete transendothelial delivery into brain tissue. Reported percentages apply to hCMEC/D3 under these assay conditions, not every human tissue. exposure: SLC5A6-specific siRNA and radiolabeled substrate uptake; tracer concentration not specified in the abstract. cross_nutrient: true [b5-trans-brain2015] Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells. (2015). https://pubmed.ncbi.nlm.nih.gov/25809983/ DOI: 10.1111/jnc.13092

cross_nutrient

true

experimental_model

Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes

exposure

Electrophysiology after human SMVT expression; pantothenate and extracellular sodium varied.

limitations

Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition.

nutrient_topic

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

organism

Homo sapiens (protein); Xenopus laevis (expression host)

plain_language

Pantothenate transport through human SMVT moves net positive charge inward.

primary_references

[b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

tissue_or_cell_type

Oocyte plasma membrane

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 210–221

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes · source_derived_draft · unverified_draft

### b5-trans-pantothenate-current Pantothenate evoked sodium-, concentration- and potential-dependent inward currents in Xenopus oocytes expressing human SLC5A6. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Pantothenate transport through human SMVT moves net positive charge inward. organism: Homo sapiens (protein); Xenopus laevis (expression host) tissue_or_cell_type: Oocyte plasma membrane experimental_model: Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes limitations: Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition. exposure: Electrophysiology after human SMVT expression; pantothenate and extracellular sodium varied. cross_nutrient: true [b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

cross_nutrient

true

experimental_model

Isolated rabbit renal brush-border membrane vesicles with controlled ion gradients and membrane potentials

exposure

Inside-negative membrane potential imposed with sodium present but no transmembrane sodium gradient.

limitations

Rabbit isolated-membrane experiment; this predates molecular identification of SMVT and does not independently assign the effect to human SLC5A6 or establish a human renal clearance threshold.

nutrient_topic

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

organism

Oryctolagus cuniculus

plain_language

Electrical potential also helps power renal pantothenate uptake.

primary_references

[b5-trans-renal1986] Pantothenate-sodium cotransport in renal brush-border membranes. (1986). https://pubmed.ncbi.nlm.nih.gov/3771539/ DOI: 10.1016/s0021-9258(18)66891-7

tissue_or_cell_type

Renal brush-border membrane vesicles

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 249–260

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated rabbit renal brush-border membrane vesicles with controlled ion gradients and membrane potentials · source_derived_draft · unverified_draft

### b5-trans-renal-membrane-potential An inside-negative membrane potential drove uphill pantothenate accumulation in rabbit renal brush-border vesicles when sodium was present even without a sodium concentration gradient. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Electrical potential also helps power renal pantothenate uptake. organism: Oryctolagus cuniculus tissue_or_cell_type: Renal brush-border membrane vesicles experimental_model: Isolated rabbit renal brush-border membrane vesicles with controlled ion gradients and membrane potentials limitations: Rabbit isolated-membrane experiment; this predates molecular identification of SMVT and does not independently assign the effect to human SLC5A6 or establish a human renal clearance threshold. exposure: Inside-negative membrane potential imposed with sodium present but no transmembrane sodium gradient. cross_nutrient: true [b5-trans-renal1986] Pantothenate-sodium cotransport in renal brush-border membranes. (1986). https://pubmed.ncbi.nlm.nih.gov/3771539/ DOI: 10.1016/s0021-9258(18)66891-7

cross_nutrient

true

experimental_model

Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes

exposure

Human SMVT cDNA expression; substrate concentrations not specified in the abstract.

limitations

Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition.

nutrient_topic

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

organism

Homo sapiens (protein and HRPE expression cells)

plain_language

SMVT carries biotin into cells using sodium-dependent transport.

primary_references

[b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

tissue_or_cell_type

HRPE cell plasma membrane

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 171–182

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes · source_derived_draft · unverified_draft

### b5-trans-smvt-biotin Expression of cloned human SLC5A6 in HRPE cells conferred sodium-dependent uptake of biotin. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: SMVT carries biotin into cells using sodium-dependent transport. organism: Homo sapiens (protein and HRPE expression cells) tissue_or_cell_type: HRPE cell plasma membrane experimental_model: Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes limitations: Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition. exposure: Human SMVT cDNA expression; substrate concentrations not specified in the abstract. cross_nutrient: true [b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

cross_nutrient

true

experimental_model

Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes

exposure

Human SMVT cDNA expression; substrate concentrations not specified in the abstract.

limitations

Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition.

nutrient_topic

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

organism

Homo sapiens (protein and HRPE expression cells)

plain_language

SMVT carries lipoate into cells using sodium-dependent transport.

primary_references

[b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

tissue_or_cell_type

HRPE cell plasma membrane

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 184–195

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes · source_derived_draft · unverified_draft

### b5-trans-smvt-lipoate Expression of cloned human SLC5A6 in HRPE cells conferred sodium-dependent uptake of lipoate. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: SMVT carries lipoate into cells using sodium-dependent transport. organism: Homo sapiens (protein and HRPE expression cells) tissue_or_cell_type: HRPE cell plasma membrane experimental_model: Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes limitations: Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition. exposure: Human SMVT cDNA expression; substrate concentrations not specified in the abstract. cross_nutrient: true [b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

cross_nutrient

true

experimental_model

Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes

exposure

Human SMVT cDNA expression; substrate concentrations not specified in the abstract.

limitations

Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition.

nutrient_topic

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

organism

Homo sapiens (protein and HRPE expression cells)

plain_language

SMVT carries pantothenate into cells using sodium-dependent transport.

primary_references

[b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

tissue_or_cell_type

HRPE cell plasma membrane

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 158–169

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes · source_derived_draft · unverified_draft

### b5-trans-smvt-pantothenate Expression of cloned human SLC5A6 in HRPE cells conferred sodium-dependent uptake of pantothenate. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: SMVT carries pantothenate into cells using sodium-dependent transport. organism: Homo sapiens (protein and HRPE expression cells) tissue_or_cell_type: HRPE cell plasma membrane experimental_model: Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes limitations: Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition. exposure: Human SMVT cDNA expression; substrate concentrations not specified in the abstract. cross_nutrient: true [b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

evidence_span

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experimental_model

Inducible Slc34a2 knockout, balance measurements and isolated ileum transport

exposure

Knockout versus wild type; low-P diet followed by an acute phosphate bolus

limitations

Fraction of active transport is not the fraction of total absorption in every diet or species. Normal serum phosphate can coexist with impaired intestinal entry because the kidney compensates.

nutrient_topic

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

organism

Mouse

plain_language

This transporter dominated the active route in that assay; passive absorption is a separate route.

primary_references

[phosphorus-p19729436] Intestinal npt2b plays a major role in phosphate absorption and homeostasis. (2009). https://pubmed.ncbi.nlm.nih.gov/19729436/ DOI: 10.1681/asn.2009050559

tissue_or_cell_type

Intestine and compensatory renal handling

Phosphorus: 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 · Inducible Slc34a2 knockout, balance measurements and isolated ileum transport · source_derived_draft · unverified_draft

### phosphorus-npt2b-active NaPi-IIb accounted for more than 90% of measured active phosphate absorption in isolated mouse ileum segments. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: This transporter dominated the active route in that assay; passive absorption is a separate route. organism: Mouse tissue_or_cell_type: Intestine and compensatory renal handling experimental_model: Inducible Slc34a2 knockout, balance measurements and isolated ileum transport limitations: Fraction of active transport is not the fraction of total absorption in every diet or species. Normal serum phosphate can coexist with impaired intestinal entry because the kidney compensates. exposure: Knockout versus wild type; low-P diet followed by an acute phosphate bolus evidence_span: {"source_cache": "artifacts/phosphorus-research/19729436.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d", "start_char": 0, "end_char": 1402, "text_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d"} [phosphorus-p19729436] Intestinal npt2b plays a major role in phosphate absorption and homeostasis. (2009). https://pubmed.ncbi.nlm.nih.gov/19729436/ DOI: 10.1681/asn.2009050559

evidence_span

{"source_cache": "artifacts/phosphorus-research/30158152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e", "start_char": 0, "end_char": 1701, "text_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e"}

experimental_model

Rodent physiology, human enteroid transport and healthy-volunteer intervention

exposure

Enteroid NHE3 perturbation; healthy volunteers 15 mg tenapanor twice daily for four days

limitations

Tenapanor inhibits NHE3 rather than binding phosphate. TEER is an epithelial assay measure, not a direct clinical permeability score.

nutrient_topic

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

organism

Human-derived intestinal epithelial system

plain_language

A sodium-handling protein can change how phosphate crosses the gut wall.

primary_references

[phosphorus-p30158152] Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. (2018). https://pubmed.ncbi.nlm.nih.gov/30158152/ DOI: 10.1126/scitranslmed.aam6474

tissue_or_cell_type

Intestinal epithelium; stool and urinary balance

Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 321–332

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rodent physiology, human enteroid transport and healthy-volunteer intervention · source_derived_draft · unverified_draft

### phosphorus-tenapanor-nhe3 Tenapanor inhibits intestinal NHE3, the sodium/hydrogen exchanger targeted in the phosphate-absorption study. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sodium-handling protein can change how phosphate crosses the gut wall. organism: Human-derived intestinal epithelial system tissue_or_cell_type: Intestinal epithelium; stool and urinary balance experimental_model: Rodent physiology, human enteroid transport and healthy-volunteer intervention limitations: Tenapanor inhibits NHE3 rather than binding phosphate. TEER is an epithelial assay measure, not a direct clinical permeability score. exposure: Enteroid NHE3 perturbation; healthy volunteers 15 mg tenapanor twice daily for four days evidence_span: {"source_cache": "artifacts/phosphorus-research/30158152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e", "start_char": 0, "end_char": 1701, "text_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e"} [phosphorus-p30158152] Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. (2018). https://pubmed.ncbi.nlm.nih.gov/30158152/ DOI: 10.1126/scitranslmed.aam6474