Proton

cross_nutrient

false

experimental_model

Wild-type human ZnT1 cryo-EM, biochemical assays and molecular dynamics

exposure

Cryo-EM preparations with 1 mM zinc at pH 6.0 or pH 7.5.

limitations

Conformational snapshots and simulations do not directly quantify coupled proton flux or establish that calcium cannot couple transport. This record preserves observations and labels the interpretation.

nutrient_topic

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

organism

Homo sapiens protein

plain_language

Acidity changed the shapes captured for human ZnT1, informing one proposed export mechanism.

primary_references

[zinc-trans-39390258] Structural insights into human zinc transporter ZnT1 mediated Zn2+ efflux. (2024). https://pubmed.ncbi.nlm.nih.gov/39390258/ DOI: 10.1038/s44319-024-00287-3

tissue_or_cell_type

Detergent-solubilized purified membrane protein

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 297–308

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type human ZnT1 cryo-EM, biochemical assays and molecular dynamics · source_derived_draft · unverified_draft

### zinc-trans-znt1-low-ph-conformations Human ZnT1 purified with zinc at pH 6.0 yielded inward-facing, outward-facing and mixed dimers, whereas the pH 7.5 zinc-bound structure was outward-facing; the authors interpreted structures and simulations as supporting proton-dependent zinc release. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Acidity changed the shapes captured for human ZnT1, informing one proposed export mechanism. organism: Homo sapiens protein tissue_or_cell_type: Detergent-solubilized purified membrane protein experimental_model: Wild-type human ZnT1 cryo-EM, biochemical assays and molecular dynamics limitations: Conformational snapshots and simulations do not directly quantify coupled proton flux or establish that calcium cannot couple transport. This record preserves observations and labels the interpretation. exposure: Cryo-EM preparations with 1 mM zinc at pH 6.0 or pH 7.5. cross_nutrient: false [zinc-trans-39390258] Structural insights into human zinc transporter ZnT1 mediated Zn2+ efflux. (2024). https://pubmed.ncbi.nlm.nih.gov/39390258/ DOI: 10.1038/s44319-024-00287-3

evidence_span

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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

experimental_model

Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor

exposure

Addition and withdrawal of 0.4 mM pyruvate; neutral pH; Figure 3E reports n=11 and P<0.05. Methods: 2 microgram pyronic and 2 microgram transporter/empty-vector plasmid, transfected 24 hours after plating on coverslips 72 hours before assay.

limitations

Selected primary main-text results, figure legend and methods reviewed through indexed PMC passages; supplements not independently reviewed. Difference was observed at neutral pH, not at acidic pH. This is not a K562 experiment and does not establish the mechanism of the genetic interaction. SLC16A11 has intracellular and cell-surface pools; pyruvate transport direction depends on gradients.

organism

Human

primary_locator

Results: SLC16A11 is a H+-coupled monocarboxylate transporter; Figure 3D-E; pyruvate transport methods.

primary_references

https://doi.org/10.1016/j.cell.2017.06.011

SLC16A11 and mitochondrial glutathione: published screen connection and transport evidence · lines 51–57

Primary sources 2022 and 2017, plus labelled descriptive reanalysis on 2026-09-20. · supports · Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor · source_derived_draft · unverified_draft

HEK293T cells expressing reference SLC16A11 showed approximately 45 percent higher pyruvate efflux rate than empty-vector controls in the reported assay. primary_references: https://doi.org/10.1016/j.cell.2017.06.011 primary_locator: Results: SLC16A11 is a H+-coupled monocarboxylate transporter; Figure 3D-E; pyruvate transport methods. organism: Human experimental_model: Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor exposure: Addition and withdrawal of 0.4 mM pyruvate; neutral pH; Figure 3E reports n=11 and P<0.05. Methods: 2 microgram pyronic and 2 microgram transporter/empty-vector plasmid, transfected 24 hours after plating on coverslips 72 hours before assay. limitations: Selected primary main-text results, figure legend and methods reviewed through indexed PMC passages; supplements not independently reviewed. Difference was observed at neutral pH, not at acidic pH. This is not a K562 experiment and does not establish the mechanism of the genetic interaction. SLC16A11 has intracellular and cell-surface pools; pyruvate transport direction depends on gradients.

experimental_model

Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor

exposure

Addition and withdrawal of 0.4 mM pyruvate; neutral pH; Figure 3E reports n=11 and P<0.05. Methods: 2 microgram pyronic and 2 microgram transporter/empty-vector plasmid, transfected 24 hours after plating on coverslips 72 hours before assay.

limitations

Selected primary main-text results, figure legend and methods reviewed through indexed PMC passages; supplements not independently reviewed. Difference was observed at neutral pH, not at acidic pH. This is not a K562 experiment and does not establish the mechanism of the genetic interaction. SLC16A11 has intracellular and cell-surface pools; pyruvate transport direction depends on gradients.

organism

Human

primary_locator

Results: SLC16A11 is a H+-coupled monocarboxylate transporter; Figure 3D-E; pyruvate transport methods.

primary_references

https://doi.org/10.1016/j.cell.2017.06.011

SLC16A11 and mitochondrial glutathione: published screen connection and transport evidence · lines 42–48

Primary sources 2022 and 2017, plus labelled descriptive reanalysis on 2026-09-20. · supports · Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor · source_derived_draft · unverified_draft

HEK293T cells expressing reference SLC16A11 showed approximately 45 percent higher pyruvate influx rate than empty-vector controls in the reported assay. primary_references: https://doi.org/10.1016/j.cell.2017.06.011 primary_locator: Results: SLC16A11 is a H+-coupled monocarboxylate transporter; Figure 3D-E; pyruvate transport methods. organism: Human experimental_model: Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor exposure: Addition and withdrawal of 0.4 mM pyruvate; neutral pH; Figure 3E reports n=11 and P<0.05. Methods: 2 microgram pyronic and 2 microgram transporter/empty-vector plasmid, transfected 24 hours after plating on coverslips 72 hours before assay. limitations: Selected primary main-text results, figure legend and methods reviewed through indexed PMC passages; supplements not independently reviewed. Difference was observed at neutral pH, not at acidic pH. This is not a K562 experiment and does not establish the mechanism of the genetic interaction. SLC16A11 has intracellular and cell-surface pools; pyruvate transport direction depends on gradients.

compartment_description

Sealed extracellular resorption lacuna

experimental_model

Acridine-orange localization and reversible pH perturbation

limitations

This study localizes acidification; it does not identify a particular modern proton-pump subunit or measure whole-body calcium flux.

nutrient_topic

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

organism

Gallus gallus

plain_language

Bone-resorbing cells create a locally acidic space against bone.

primary_references

[baron1985] Cell-mediated extracellular acidification and bone resorption: evidence for a low pH in resorbing lacunae and localization of a 100-kD lysosomal membrane protein at the osteoclast ruffled border (1985). https://rupress.org/jcb/article/101/6/2210/21648/Cell-mediated-extracellular-acidification-and-bone DOI: 10.1083/jcb.101.6.2210

tissue_or_cell_type

Osteoclast-bone interface

Calcium: mechanism-first literature curation (2026-09-17) · lines 1081–1091

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acridine-orange localization and reversible pH perturbation · source_derived_draft · unverified_draft

### osteoclast-lacuna-acidification Resorbing osteoclasts acidified the extracellular compartment beneath their ruffled border and reacidified it after ammonium chloride washout. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Bone-resorbing cells create a locally acidic space against bone. organism: Gallus gallus tissue_or_cell_type: Osteoclast-bone interface experimental_model: Acridine-orange localization and reversible pH perturbation limitations: This study localizes acidification; it does not identify a particular modern proton-pump subunit or measure whole-body calcium flux. compartment_description: Sealed extracellular resorption lacuna [baron1985] Cell-mediated extracellular acidification and bone resorption: evidence for a low pH in resorbing lacunae and localization of a 100-kD lysosomal membrane protein at the osteoclast ruffled border (1985). https://rupress.org/jcb/article/101/6/2210/21648/Cell-mediated-extracellular-acidification-and-bone DOI: 10.1083/jcb.101.6.2210

cross_nutrient

false

experimental_model

Human CA6 purified from pooled saliva or breast milk; stopped-flow enzymology

exposure

Stopped-flow CO2 hydration assay of proteins purified from pooled human saliva and milk.

limitations

Protein kinetic measurements; no test of dietary zinc treatment or infant health outcomes. Table values characterize the isolated preparations.

nutrient_topic

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

organism

Homo sapiens

plain_language

Secreted CA6 accelerates conversion of carbon dioxide and water into bicarbonate.

primary_references

[zinc-enz-ca6-2022] Biochemical and Biophysical Characterization of Carbonic Anhydrase VI from Human Milk and Saliva. (2022). https://pubmed.ncbi.nlm.nih.gov/35947329/ DOI: 10.1007/s10930-022-10070-9

tissue_or_cell_type

Human saliva and breast milk; purified enzyme assay

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 664–675

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CA6 purified from pooled saliva or breast milk; stopped-flow enzymology · source_derived_draft · unverified_draft

### zinc-enz-ca6-hydration Purified human salivary and milk CA6 catalyzed CO2 hydration, with reported kcat values of 3.3×10^5 and 2.3×10^5 s−1, respectively. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Secreted CA6 accelerates conversion of carbon dioxide and water into bicarbonate. organism: Homo sapiens tissue_or_cell_type: Human saliva and breast milk; purified enzyme assay experimental_model: Human CA6 purified from pooled saliva or breast milk; stopped-flow enzymology limitations: Protein kinetic measurements; no test of dietary zinc treatment or infant health outcomes. Table values characterize the isolated preparations. exposure: Stopped-flow CO2 hydration assay of proteins purified from pooled human saliva and milk. cross_nutrient: false [zinc-enz-ca6-2022] Biochemical and Biophysical Characterization of Carbonic Anhydrase VI from Human Milk and Saliva. (2022). https://pubmed.ncbi.nlm.nih.gov/35947329/ DOI: 10.1007/s10930-022-10070-9

evidence_access

Primary full text

experimental_model

Reconstituted purified human transporter.

limitations

Not a measurement of brain exposure after an oral supplement.

nutrient_topic

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

plain_language

Vesicles use a proton gradient to store polyamines.

primary_references

Identification of a mammalian vesicular polyamine transporter. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25355561/ · DOI 10.1038/srep06836

transport_effect

raises Recorded as transport of spermidine into proteoliposomes by proton exchange.

transport_pool

the secretory-vesicle lumen Recorded as transport of spermidine into proteoliposomes by proton exchange.

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 142–148

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

## spermidine-vesicle-transport Vesicles use a proton gradient to store polyamines. Purified human SLC18B1 transported spermidine into proteoliposomes by proton exchange. Model: Reconstituted purified human transporter. Limitations: Not a measurement of brain exposure after an oral supplement. Evidence access: Primary full text Identification of a mammalian vesicular polyamine transporter. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25355561/ · DOI 10.1038/srep06836

experimental_model

E. coli inducible lysine decarboxylase structural and acid-stress experiments.

limitations

Bacterial pathway. Cadaverine exposure or health effects in a human cannot be inferred from this culture mechanism.

organism

Escherichia coli

plain_language

Some bacteria use lysine to buffer acidic conditions.

primary_references

[cada-2011] Linkage between the bacterial acid stress and stringent responses: the structure of the inducible lysine decarboxylase (2011). https://pubmed.ncbi.nlm.nih.gov/21278708/ DOI: 10.1038/emboj.2011.5

tissue_or_cell_type

Not specified as a whole tissue; see experimental model.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 618–626

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · E. coli inducible lysine decarboxylase structural and acid-stress experiments. · source_derived_draft · unverified_draft

### bacterial-cada-decarboxylation E. coli CadA converts lysine to cadaverine and CO2 while consuming a proton during acid stress. Plain language: Some bacteria use lysine to buffer acidic conditions. Condition category: normal organism: Escherichia coli tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: E. coli inducible lysine decarboxylase structural and acid-stress experiments. limitations: Bacterial pathway. Cadaverine exposure or health effects in a human cannot be inferred from this culture mechanism. [cada-2011] Linkage between the bacterial acid stress and stringent responses: the structure of the inducible lysine decarboxylase (2011). https://pubmed.ncbi.nlm.nih.gov/21278708/ DOI: 10.1038/emboj.2011.5

evidence_span

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experimental_model

Cloning and functional expression of DCT1/DMT1

exposure

Metal-ion uptake, membrane potential and iron-deficient feeding

limitations

Original broad substrate profile; later substrate-specific studies and species differences must be retained. Competition in an assay is not a universal dietary interaction.

nutrient_topic

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

organism

Rat transporter

plain_language

The uptake protein uses an electrochemical gradient to bring ferrous iron into cells.

primary_references

[iron-p9242408] Cloning and characterization of a mammalian proton-coupled metal-ion transporter. (1997). https://pubmed.ncbi.nlm.nih.gov/9242408/ DOI: 10.1038/41343

tissue_or_cell_type

Transport assay and duodenal expression

transport_effect

raises Proton-coupled and membrane-potential-dependent Fe(II) transport, which is inward.

transport_pool

the expressing cell Proton-coupled and membrane-potential-dependent Fe(II) transport, which is inward.

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 394–405

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning and functional expression of DCT1/DMT1 · source_derived_draft · unverified_draft

### iron-dmt-proton-transport Rat DCT1/DMT1 mediated proton-coupled Fe(II) transport that depended on membrane potential. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The uptake protein uses an electrochemical gradient to bring ferrous iron into cells. organism: Rat transporter tissue_or_cell_type: Transport assay and duodenal expression experimental_model: Cloning and functional expression of DCT1/DMT1 limitations: Original broad substrate profile; later substrate-specific studies and species differences must be retained. Competition in an assay is not a universal dietary interaction. exposure: Metal-ion uptake, membrane potential and iron-deficient feeding evidence_span: {"source_cache": "artifacts/iron-research/9242408.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0b5241ac49e6de4e273c91f36387357c9bd76ce602e44defffc3b8b42191fe52", "start_char": 0, "end_char": 1203, "text_sha256": "0b5241ac49e6de4e273c91f36387357c9bd76ce602e44defffc3b8b42191fe52"} [iron-p9242408] Cloning and characterization of a mammalian proton-coupled metal-ion transporter. (1997). https://pubmed.ncbi.nlm.nih.gov/9242408/ DOI: 10.1038/41343