Bicarbonate ion

cross_nutrient

Bicarbonate coadministration modifies the calcium response attributed to potassium salts.

endpoint

The bicarbonate-containing arms reduced calcium excretion relative to non-bicarbonate arms in the older-adult trial; a potassium main effect was not significant.

experimental-exposure

171 adults aged at least 50 randomized to placebo, KHCO3, NaHCO3, or KCl at 67.5 mmol/day for three months; 162 analyzed; all received calcium and vitamin D.

experimental_model

171 adults aged at least 50 randomized to placebo, KHCO3, NaHCO3, or KCl at 67.5 mmol/day for three months; 162 analyzed; all received calcium and vitamin D.

limitations

Pooled factorial comparison, calcium/vitamin D co-supplementation, three-month surrogate endpoint; not evidence of fracture prevention or universal potassium neutrality.

nutrient_topic

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

organism

Homo sapiens

plain_language

The calcium-loss effect tracked the alkali component rather than the presence of potassium in the salt.

primary_references

[dawson-hughes-2009-bicarbonate] Treatment with Potassium Bicarbonate Lowers Calcium Excretion and Bone Resorption in Older Men and Women (2009). https://pmc.ncbi.nlm.nih.gov/articles/PMC2630872/ DOI: 10.1210/jc.2008-1662

tissue_or_cell_type

kidney and urine

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1260–1272

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 171 adults aged at least 50 randomized to placebo, KHCO3, NaHCO3, or KCl at 67.5 mmol/day for three months; 162 analyzed; all received calcium and vitamin D. · source_derived_draft · unverified_draft

### bicarbonate-component-lowers-calciuria The bicarbonate-containing arms reduced calcium excretion relative to non-bicarbonate arms in the older-adult trial; a potassium main effect was not significant. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The calcium-loss effect tracked the alkali component rather than the presence of potassium in the salt. organism: Homo sapiens tissue_or_cell_type: kidney and urine experimental_model: 171 adults aged at least 50 randomized to placebo, KHCO3, NaHCO3, or KCl at 67.5 mmol/day for three months; 162 analyzed; all received calcium and vitamin D. limitations: Pooled factorial comparison, calcium/vitamin D co-supplementation, three-month surrogate endpoint; not evidence of fracture prevention or universal potassium neutrality. cross_nutrient: Bicarbonate coadministration modifies the calcium response attributed to potassium salts. experimental-exposure: 171 adults aged at least 50 randomized to placebo, KHCO3, NaHCO3, or KCl at 67.5 mmol/day for three months; 162 analyzed; all received calcium and vitamin D. endpoint: The bicarbonate-containing arms reduced calcium excretion relative to non-bicarbonate arms in the older-adult trial; a potassium main effect was not significant. [dawson-hughes-2009-bicarbonate] Treatment with Potassium Bicarbonate Lowers Calcium Excretion and Bone Resorption in Older Men and Women (2009). https://pmc.ncbi.nlm.nih.gov/articles/PMC2630872/ DOI: 10.1210/jc.2008-1662

evidence_access

Primary abstract

experimental_model

Reconstituted enzyme kinetics and bicarbonate-deprived human cell culture.

limitations

The culture manipulation is not a bicarbonate supplementation trial or a clinical intracellular threshold.

nutrient_topic

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

plain_language

An additional substrate can limit the threonine-dependent reaction.

primary_references

CO2-sensitive tRNA modification associated with human mitochondrial disease. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29760464/ · DOI 10.1038/s41467-018-04250-4

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 138–144

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Reconstituted enzyme kinetics and bicarbonate-deprived human cell culture. · source_derived_draft · unverified_draft

## l-threonine-bicarbonate-limitation An additional substrate can limit the threonine-dependent reaction. The measured bicarbonate/CO2 Km for t6A37 formation was 31 millimolar; human cells cultured without bicarbonate had less t6A37 in mitochondrial tRNAs. Model: Reconstituted enzyme kinetics and bicarbonate-deprived human cell culture. Limitations: The culture manipulation is not a bicarbonate supplementation trial or a clinical intracellular threshold. Evidence access: Primary abstract CO2-sensitive tRNA modification associated with human mitochondrial disease. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29760464/ · DOI 10.1038/s41467-018-04250-4

evidence_span

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experimental_model

Seven cryo-EM structures with uptake and computational analyses

exposure

Apo, bicarbonate-bound and inhibitor-bound states

limitations

Transport mechanism analysis; not a dietary chloride threshold.

nutrient_topic

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

organism

Human AE1

plain_language

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

primary_references

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

tissue_or_cell_type

Erythrocyte anion exchanger protein

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

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

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

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium and aldosterone-dependent sodium/acid handling jointly influence systemic bicarbonate.

endpoint

In adrenalectomized rats, low potassium combined with high aldosterone produced a larger serum-bicarbonate rise than either perturbation alone.

experimental-exposure

Glucocorticoid-replete adrenalectomized rats with varied dietary potassium and zero, physiological, or pharmacological aldosterone replacement.

experimental_model

Glucocorticoid-replete adrenalectomized rats with varied dietary potassium and zero, physiological, or pharmacological aldosterone replacement.

limitations

Endocrine replacement experiment, not ordinary dietary deficiency; H/K-ATPase and H-ATPase were regulated differently.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Potassium depletion and mineralocorticoid exposure can act together on renal acid handling.

primary_references

[eiam-1993-atpases] Regulation of collecting tubule adenosine triphosphatases by aldosterone and potassium (1993). https://pubmed.ncbi.nlm.nih.gov/8390478/ DOI: 10.1172/JCI116471

tissue_or_cell_type

collecting tubule and systemic blood

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1137–1149

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Glucocorticoid-replete adrenalectomized rats with varied dietary potassium and zero, physiological, or pharmacological aldosterone replacement. · source_derived_draft · unverified_draft

### k-aldosterone-joint-bicarbonate In adrenalectomized rats, low potassium combined with high aldosterone produced a larger serum-bicarbonate rise than either perturbation alone. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium depletion and mineralocorticoid exposure can act together on renal acid handling. organism: Rattus norvegicus tissue_or_cell_type: collecting tubule and systemic blood experimental_model: Glucocorticoid-replete adrenalectomized rats with varied dietary potassium and zero, physiological, or pharmacological aldosterone replacement. limitations: Endocrine replacement experiment, not ordinary dietary deficiency; H/K-ATPase and H-ATPase were regulated differently. cross_nutrient: Potassium and aldosterone-dependent sodium/acid handling jointly influence systemic bicarbonate. experimental-exposure: Glucocorticoid-replete adrenalectomized rats with varied dietary potassium and zero, physiological, or pharmacological aldosterone replacement. endpoint: In adrenalectomized rats, low potassium combined with high aldosterone produced a larger serum-bicarbonate rise than either perturbation alone. [eiam-1993-atpases] Regulation of collecting tubule adenosine triphosphatases by aldosterone and potassium (1993). https://pubmed.ncbi.nlm.nih.gov/8390478/ DOI: 10.1172/JCI116471

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_span

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experimental_model

Cryo-EM of endogenous and recombinant human ACC1 filaments

exposure

Inactive substrate-containing and dephosphorylated/citrate-treated states

limitations

Filament presence alone does not mean enzyme activation; the paper resolved both active and inactive arrangements.

nutrient_topic

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

organism

Homo sapiens

plain_language

ACC1 makes a building block used in fatty-acid synthesis.

primary_references

[b7-p39383219] Filament structures unveil the dynamic organization of human acetyl-CoA carboxylase. (2024). https://pubmed.ncbi.nlm.nih.gov/39383219/ DOI: 10.1126/sciadv.ado4880

tissue_or_cell_type

Purified human ACC1

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 637–648

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM of endogenous and recombinant human ACC1 filaments · source_derived_draft · unverified_draft

### b7-acc1-reaction Human ACC1 uses biotin-dependent carboxylation of acetyl-CoA to generate malonyl-CoA. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ACC1 makes a building block used in fatty-acid synthesis. organism: Homo sapiens tissue_or_cell_type: Purified human ACC1 experimental_model: Cryo-EM of endogenous and recombinant human ACC1 filaments limitations: Filament presence alone does not mean enzyme activation; the paper resolved both active and inactive arrangements. exposure: Inactive substrate-containing and dephosphorylated/citrate-treated states evidence_span: {"source_cache": "artifacts/biotin-research/39383219.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5f7d3cd6a5865a03b8dc9c510f60249ee2c9f6516773780e5d7b4aef0a9b2db8", "start_char": 0, "end_char": 309, "text_sha256": "b094342ce091c8f919d065311ecd04ddd0c6b9b2824ba8adedd5768424a81a71"} [b7-p39383219] Filament structures unveil the dynamic organization of human acetyl-CoA carboxylase. (2024). https://pubmed.ncbi.nlm.nih.gov/39383219/ DOI: 10.1126/sciadv.ado4880

evidence_span

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experimental_model

Steady-state kinetics of purified recombinant human ACC2; LC-MS/MS malonyl-CoA assay

exposure

Bicarbonate, ATP, acetyl-CoA and citrate concentration matrices

limitations

Kinetic constants are assay properties; they do not define a dietary biotin or B5 threshold.

nutrient_topic

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

organism

Homo sapiens

plain_language

ACC2 makes the same carbon product as ACC1 but serves a distinct enzyme context.

primary_references

[b7-p19236960] Characterization of recombinant human acetyl-CoA carboxylase-2 steady-state kinetics. (2009). https://pubmed.ncbi.nlm.nih.gov/19236960/ DOI: 10.1016/j.bbapap.2009.02.004

tissue_or_cell_type

Purified human ACC2

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 676–687

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Steady-state kinetics of purified recombinant human ACC2; LC-MS/MS malonyl-CoA assay · source_derived_draft · unverified_draft

### b7-acc2-reaction Purified human ACC2 formed malonyl-CoA from acetyl-CoA in assays varying bicarbonate and ATP. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ACC2 makes the same carbon product as ACC1 but serves a distinct enzyme context. organism: Homo sapiens tissue_or_cell_type: Purified human ACC2 experimental_model: Steady-state kinetics of purified recombinant human ACC2; LC-MS/MS malonyl-CoA assay limitations: Kinetic constants are assay properties; they do not define a dietary biotin or B5 threshold. exposure: Bicarbonate, ATP, acetyl-CoA and citrate concentration matrices evidence_span: {"source_cache": "artifacts/biotin-research/19236960.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bedd791235b10ff5942ef7177b54bca5b2243883da02fb24572691aaf5975be5", "start_char": 0, "end_char": 896, "text_sha256": "bedd791235b10ff5942ef7177b54bca5b2243883da02fb24572691aaf5975be5"} [b7-p19236960] Characterization of recombinant human acetyl-CoA carboxylase-2 steady-state kinetics. (2009). https://pubmed.ncbi.nlm.nih.gov/19236960/ DOI: 10.1016/j.bbapap.2009.02.004

evidence_span

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experimental_model

Time-resolved cryo-EM and biochemical analysis of human PC

exposure

Pyruvate, ATP and acetyl-CoA catalytic conditions

limitations

Purified-enzyme regulation is not evidence that consuming B5 or biotin stimulates this pathway in every tissue.

nutrient_topic

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

organism

Homo sapiens

plain_language

PC replenishes a key carbon molecule used by several metabolic pathways.

primary_references

[b7-p36283412] Mechanistic insight into allosteric activation of human pyruvate carboxylase by acetyl-CoA. (2022). https://pubmed.ncbi.nlm.nih.gov/36283412/ DOI: 10.1016/j.molcel.2022.09.033

tissue_or_cell_type

Purified human pyruvate carboxylase

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 546–557

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Time-resolved cryo-EM and biochemical analysis of human PC · source_derived_draft · unverified_draft

### b7-pc-reaction Human PC catalyzes two-step pyruvate carboxylation to oxaloacetate. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: PC replenishes a key carbon molecule used by several metabolic pathways. organism: Homo sapiens tissue_or_cell_type: Purified human pyruvate carboxylase experimental_model: Time-resolved cryo-EM and biochemical analysis of human PC limitations: Purified-enzyme regulation is not evidence that consuming B5 or biotin stimulates this pathway in every tissue. exposure: Pyruvate, ATP and acetyl-CoA catalytic conditions evidence_span: {"source_cache": "artifacts/biotin-research/36283412.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2a5fb8ec1c27e243b8c8ba158f2c58ab1592d9895eecf16438175b2a5778de15", "start_char": 0, "end_char": 1060, "text_sha256": "2a5fb8ec1c27e243b8c8ba158f2c58ab1592d9895eecf16438175b2a5778de15"} [b7-p36283412] Mechanistic insight into allosteric activation of human pyruvate carboxylase by acetyl-CoA. (2022). https://pubmed.ncbi.nlm.nih.gov/36283412/ DOI: 10.1016/j.molcel.2022.09.033

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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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

cross_nutrient

Vitamin D regulates osteocalcin expression in specified models; vitamin K-dependent carboxylation modifies its protein product through a distinct enzyme reaction.

evidence_locator

Abstract: reported experimental results

evidence_scope

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

experimental_model

Microsomal vitamin K-dependent carboxylase enriched about 100-fold; bovine osteocalcin substrate and CO2-incorporation assay

exposure

50 mM bicarbonate, excess enriched carboxylase and limiting decarboxylated osteocalcin; vitamin K-dependent reaction conditions.

limitations

In-vitro modification of a defined substrate; no D-plus-K supplementation regimen, K2-specific necessity, improved fracture outcome or obligatory supplement pairing was tested.

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

Bos taurus osteocalcin; liver-derived enzyme preparation

plain_language

Osteocalcin needs a separate vitamin K-dependent protein-modification step; making more osteocalcin is not the same reaction.

primary_references

[vdm-soute1987] Vitamin K-dependent carboxylase: increased efficiency of the carboxylation reaction. (1987). https://pubmed.ncbi.nlm.nih.gov/3495900/ DOI: 10.1055/s-0038-1651066

tissue_or_cell_type

Cell-free enzyme assay

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 889–903

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomal vitamin K-dependent carboxylase enriched about 100-fold; bovine osteocalcin substrate and CO2-incorporation assay · source_derived_draft · unverified_draft

### vdm-vitamin-k-carboxylase-modifies-osteocalcin A concentrated vitamin K-dependent carboxylase preparation converted glutamate residues of decarboxylated bovine osteocalcin into gamma-carboxyglutamate in vitro. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Osteocalcin needs a separate vitamin K-dependent protein-modification step; making more osteocalcin is not the same reaction. organism: Bos taurus osteocalcin; liver-derived enzyme preparation tissue_or_cell_type: Cell-free enzyme assay experimental_model: Microsomal vitamin K-dependent carboxylase enriched about 100-fold; bovine osteocalcin substrate and CO2-incorporation assay limitations: In-vitro modification of a defined substrate; no D-plus-K supplementation regimen, K2-specific necessity, improved fracture outcome or obligatory supplement pairing was tested. exposure: 50 mM bicarbonate, excess enriched carboxylase and limiting decarboxylated osteocalcin; vitamin K-dependent reaction conditions. cross_nutrient: Vitamin D regulates osteocalcin expression in specified models; vitamin K-dependent carboxylation modifies its protein product through a distinct enzyme reaction. 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-soute1987] Vitamin K-dependent carboxylase: increased efficiency of the carboxylation reaction. (1987). https://pubmed.ncbi.nlm.nih.gov/3495900/ DOI: 10.1055/s-0038-1651066

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Targeted Slc4a2 deletion

exposure

AE2-null versus control mice

limitations

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

nutrient_topic

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

organism

Mouse

plain_language

Stomach acid production requires functioning chloride-handling machinery.

primary_references

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

tissue_or_cell_type

Gastric parietal cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

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

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

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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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

experimental_model

Genetic mapping in 32 Finnish and four Polish patients

exposure

Inherited DRA variants

limitations

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

nutrient_topic

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

organism

Human

plain_language

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

primary_references

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

tissue_or_cell_type

Intestinal epithelium

trigger_kind

machinery_impairment Imported condition classification; unverified.

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

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

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

evidence_span

{"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"}

experimental_model

Expression, duct-cell and pancreatic-tissue experiments

exposure

Low intracellular chloride; WNK1–OSR1/SPAK activation

limitations

Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency.

nutrient_topic

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

organism

Human and guinea pig

plain_language

The channel became better at carrying bicarbonate for alkaline pancreatic fluid.

primary_references

[chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004

tissue_or_cell_type

Pancreatic duct

Chloride: transport, acid-base balance, nutrient interactions and loss states (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 · Expression, duct-cell and pancreatic-tissue experiments · source_derived_draft · unverified_draft

### chloride-pancreatic-bicarbonate WNK1-mediated OSR1/SPAK activation increased CFTR bicarbonate permeability. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The channel became better at carrying bicarbonate for alkaline pancreatic fluid. organism: Human and guinea pig tissue_or_cell_type: Pancreatic duct experimental_model: Expression, duct-cell and pancreatic-tissue experiments limitations: Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency. exposure: Low intracellular chloride; WNK1–OSR1/SPAK activation evidence_span: {"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"} [chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004

evidence_span

{"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"}

experimental_model

Expression, duct-cell and pancreatic-tissue experiments

exposure

Low intracellular chloride; WNK1–OSR1/SPAK activation

limitations

Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency.

nutrient_topic

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

organism

Human and guinea pig

plain_language

The same signaling program reduced an exchange route that could take bicarbonate back from the secretion.

primary_references

[chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004

tissue_or_cell_type

Pancreatic duct

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 289–300

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Expression, duct-cell and pancreatic-tissue experiments · source_derived_draft · unverified_draft

### chloride-pancreatic-exchange OSR1/SPAK activation inhibited CFTR-dependent chloride/bicarbonate exchange in the tested system. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same signaling program reduced an exchange route that could take bicarbonate back from the secretion. organism: Human and guinea pig tissue_or_cell_type: Pancreatic duct experimental_model: Expression, duct-cell and pancreatic-tissue experiments limitations: Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency. exposure: Low intracellular chloride; WNK1–OSR1/SPAK activation evidence_span: {"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"} [chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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

experimental_model

Pendrin knockout and isolated collecting-duct perfusion

exposure

Slc26a4 deletion

limitations

Residual exchange remained; baseline urine chloride excretion was unchanged.

nutrient_topic

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

organism

Mouse

plain_language

The kidney uses chloride exchange to help dispose of bicarbonate.

primary_references

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

tissue_or_cell_type

Non-acid-secreting intercalated cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

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

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

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

evidence_span

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

experimental_model

Primary epithelial cultures and native tissue

exposure

IL-4 induction and pendrin knockdown

limitations

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

nutrient_topic

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

organism

Human nasal and bronchial epithelia

plain_language

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

primary_references

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

tissue_or_cell_type

Ciliated airway surface

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

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

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

evidence_span

{"source_cache": "artifacts/k2-research/41290650.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc", "start_char": 0, "end_char": 1177, "text_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc"}

experimental_model

Cryo-EM, mutagenesis and molecular dynamics

exposure

GGCX complexes with vitamin K, clotting-factor substrates and osteocalcin

limitations

The carbon-capture/proton-transfer sequence is the authors' structural mechanistic model, not a measured human dietary response or an established bicarbonate-supplement interaction.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human GGCX

plain_language

The added chemical group comes from carbon dioxide; vitamin K supports the reaction rather than supplying the carbon.

primary_references

[k2-p41290650] Structural insight into bicarbonate-mediated carboxylation by human vitamin K-dependent carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/41290650/ DOI: 10.1038/s41467-025-65488-3

tissue_or_cell_type

Substrate recognition and carbon-dioxide capture

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 422–433

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

### k2-ggcx-carbon-capture Cryo-EM structures and biochemical analyses supported a proposed bicarbonate-mediated carbon-dioxide capture model for GGCX. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The added chemical group comes from carbon dioxide; vitamin K supports the reaction rather than supplying the carbon. organism: Human GGCX tissue_or_cell_type: Substrate recognition and carbon-dioxide capture experimental_model: Cryo-EM, mutagenesis and molecular dynamics limitations: The carbon-capture/proton-transfer sequence is the authors' structural mechanistic model, not a measured human dietary response or an established bicarbonate-supplement interaction. exposure: GGCX complexes with vitamin K, clotting-factor substrates and osteocalcin evidence_span: {"source_cache": "artifacts/k2-research/41290650.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc", "start_char": 0, "end_char": 1177, "text_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc"} [k2-p41290650] Structural insight into bicarbonate-mediated carboxylation by human vitamin K-dependent carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/41290650/ DOI: 10.1038/s41467-025-65488-3

cross_nutrient

Potassium salt/chloride -> acid-base balance.

experimental_model

Same two-week CKD cohort.

limitations

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

nutrient_topic

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

organism

Homo sapiens

plain_language

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

primary_references

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

tissue_or_cell_type

Plasma and urine

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

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

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

availability_state

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-deficient feeding increased urinary ammonium excretion before detectable hypokalemia in the studied rats.

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

The kidney changed nitrogen and acid excretion before blood potassium fell.

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 958–970

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-early-ammonium Potassium-deficient feeding increased urinary ammonium excretion before detectable hypokalemia in the studied rats. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidney changed nitrogen and acid excretion before blood potassium fell. 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-deficient feeding increased urinary ammonium excretion before detectable hypokalemia in the studied rats. [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 changes glutamine nitrogen metabolism and sodium-coupled glutamine transport; these experiments did not manipulate dietary protein adequacy.

endpoint

Potassium deprivation increased renal phosphoenolpyruvate carboxykinase expression in the studied rats.

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

The carbon-processing arm of the ammoniagenic/gluconeogenic pathway adapted alongside the nitrogen-releasing enzymes.

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 1014–1026

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-pck1 Potassium deprivation increased renal phosphoenolpyruvate carboxykinase expression in the studied rats. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The carbon-processing arm of the ammoniagenic/gluconeogenic pathway adapted alongside the nitrogen-releasing enzymes. 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 phosphoenolpyruvate carboxykinase expression in the studied rats. [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

Potassium-salt anion determines effects on urinary citrate, which participates in calcium complexation.

endpoint

Potassium bicarbonate increased urine citrate excretion and clearance in the same comparison.

experimental-exposure

Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day.

experimental_model

Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day.

limitations

Eight patients, short intervention; absence of potassium deficiency limits extrapolation to depletion. Alkali and citrate coeffects cannot be assigned to potassium cation alone.

nutrient_topic

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

organism

Homo sapiens

plain_language

An alkali salt without administered citrate reproduced the citraturic response.

primary_references

[sakhaee-1991-salts] Contrasting effects of various potassium salts on renal citrate excretion (1991). https://pubmed.ncbi.nlm.nih.gov/1899422/ DOI: 10.1210/jcem-72-2-396

tissue_or_cell_type

kidney and urine

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1232–1244

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. · source_derived_draft · unverified_draft

### kbicarbonate-increases-urine-citrate Potassium bicarbonate increased urine citrate excretion and clearance in the same comparison. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: An alkali salt without administered citrate reproduced the citraturic response. organism: Homo sapiens tissue_or_cell_type: kidney and urine experimental_model: Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. limitations: Eight patients, short intervention; absence of potassium deficiency limits extrapolation to depletion. Alkali and citrate coeffects cannot be assigned to potassium cation alone. cross_nutrient: Potassium-salt anion determines effects on urinary citrate, which participates in calcium complexation. experimental-exposure: Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. endpoint: Potassium bicarbonate increased urine citrate excretion and clearance in the same comparison. [sakhaee-1991-salts] Contrasting effects of various potassium salts on renal citrate excretion (1991). https://pubmed.ncbi.nlm.nih.gov/1899422/ DOI: 10.1210/jcem-72-2-396

cross_nutrient

Potassium-salt anion determines effects on urinary citrate, which participates in calcium complexation.

endpoint

Potassium chloride did not significantly raise urinary citrate in these participants without potassium deficiency.

experimental-exposure

Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day.

experimental_model

Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day.

limitations

Eight patients, short intervention; absence of potassium deficiency limits extrapolation to depletion. Alkali and citrate coeffects cannot be assigned to potassium cation alone.

nutrient_topic

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

organism

Homo sapiens

plain_language

Additional potassium without alkali did not reproduce the citrate response in this group.

primary_references

[sakhaee-1991-salts] Contrasting effects of various potassium salts on renal citrate excretion (1991). https://pubmed.ncbi.nlm.nih.gov/1899422/ DOI: 10.1210/jcem-72-2-396

tissue_or_cell_type

kidney and urine

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1246–1258

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. · source_derived_draft · unverified_draft

### kchloride-no-citraturia-nondepleted Potassium chloride did not significantly raise urinary citrate in these participants without potassium deficiency. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Additional potassium without alkali did not reproduce the citrate response in this group. organism: Homo sapiens tissue_or_cell_type: kidney and urine experimental_model: Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. limitations: Eight patients, short intervention; absence of potassium deficiency limits extrapolation to depletion. Alkali and citrate coeffects cannot be assigned to potassium cation alone. cross_nutrient: Potassium-salt anion determines effects on urinary citrate, which participates in calcium complexation. experimental-exposure: Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. endpoint: Potassium chloride did not significantly raise urinary citrate in these participants without potassium deficiency. [sakhaee-1991-salts] Contrasting effects of various potassium salts on renal citrate excretion (1991). https://pubmed.ncbi.nlm.nih.gov/1899422/ DOI: 10.1210/jcem-72-2-396

cross_nutrient

Potassium-salt anion determines effects on urinary citrate, which participates in calcium complexation.

endpoint

Potassium citrate increased urine citrate excretion and clearance in the small stone-patient comparison.

experimental-exposure

Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day.

experimental_model

Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day.

limitations

Eight patients, short intervention; absence of potassium deficiency limits extrapolation to depletion. Alkali and citrate coeffects cannot be assigned to potassium cation alone.

nutrient_topic

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

organism

Homo sapiens

plain_language

This salt raised citrate availability in urine, with accompanying alkali delivery.

primary_references

[sakhaee-1991-salts] Contrasting effects of various potassium salts on renal citrate excretion (1991). https://pubmed.ncbi.nlm.nih.gov/1899422/ DOI: 10.1210/jcem-72-2-396

tissue_or_cell_type

kidney and urine

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1218–1230

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. · source_derived_draft · unverified_draft

### kcitrate-increases-urine-citrate Potassium citrate increased urine citrate excretion and clearance in the small stone-patient comparison. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This salt raised citrate availability in urine, with accompanying alkali delivery. organism: Homo sapiens tissue_or_cell_type: kidney and urine experimental_model: Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. limitations: Eight patients, short intervention; absence of potassium deficiency limits extrapolation to depletion. Alkali and citrate coeffects cannot be assigned to potassium cation alone. cross_nutrient: Potassium-salt anion determines effects on urinary citrate, which participates in calcium complexation. experimental-exposure: Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. endpoint: Potassium citrate increased urine citrate excretion and clearance in the small stone-patient comparison. [sakhaee-1991-salts] Contrasting effects of various potassium salts on renal citrate excretion (1991). https://pubmed.ncbi.nlm.nih.gov/1899422/ DOI: 10.1210/jcem-72-2-396

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

evidence_access

Primary abstract

experimental_model

Rat perfusion; IMP 0.1 mM.

limitations

T1R involvement was inferred; not proved by receptor deletion.

nutrient_topic

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

plain_language

The two-compound interaction also reached a gut endpoint.

primary_references

Luminal L-glutamate enhances duodenal mucosal defense mechanisms via multiple glutamate receptors in rats. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19643955/ · DOI 10.1152/ajpgi.90605.2008

Monosodium Glutamate (MSG): taste, gut sensing, exposure and cross-nutrient mechanisms (2026-09-20) · lines 202–208

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat perfusion; IMP 0.1 mM. · source_derived_draft · unverified_draft

## monosodium-glutamate-duodenal-imp The two-compound interaction also reached a gut endpoint. Glutamate plus IMP enhanced bicarbonate secretion in rat duodenum. Model: Rat perfusion; IMP 0.1 mM. Limitations: T1R involvement was inferred; not proved by receptor deletion. Evidence access: Primary abstract Luminal L-glutamate enhances duodenal mucosal defense mechanisms via multiple glutamate receptors in rats. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19643955/ · DOI 10.1152/ajpgi.90605.2008

evidence_access

Primary abstract and accessible primary-paper pathway description

experimental_model

Primary paper pathway description supporting human mitochondrial experiments.

limitations

The reaction sequence is described in the primary paper introduction; the 2024 study primarily tests loss of the downstream enzyme.

nutrient_topic

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

plain_language

An activated intermediate links nutrient supply to an RNA modification.

primary_references

Multifaceted roles of t6A biogenesis in efficiency and fidelity of mitochondrial gene expression. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38227555/ · DOI 10.1093/nar/gkae013

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 130–136

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary paper pathway description supporting human mitochondrial experiments. · source_derived_draft · unverified_draft

## l-threonine-trna-intermediate An activated intermediate links nutrient supply to an RNA modification. The t6A pathway first forms threonylcarbamoyladenylate from threonine, bicarbonate and ATP; OSGEPL1 then transfers the threonylcarbamoyl group to mitochondrial tRNA A37. Model: Primary paper pathway description supporting human mitochondrial experiments. Limitations: The reaction sequence is described in the primary paper introduction; the 2024 study primarily tests loss of the downstream enzyme. Evidence access: Primary abstract and accessible primary-paper pathway description Multifaceted roles of t6A biogenesis in efficiency and fidelity of mitochondrial gene expression. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38227555/ · DOI 10.1093/nar/gkae013

evidence_access

Primary abstract

experimental_model

Human mitochondrial tRNA-modification reconstitution and cellular experiments.

limitations

The mark occurs on multiple tRNAs; it is not restricted to the tRNA that carries threonine.

nutrient_topic

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

plain_language

Threonine helps make a decoding mark on tRNA, separate from being loaded for protein synthesis.

primary_references

CO2-sensitive tRNA modification associated with human mitochondrial disease. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29760464/ · DOI 10.1038/s41467-018-04250-4

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 122–128

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human mitochondrial tRNA-modification reconstitution and cellular experiments. · source_derived_draft · unverified_draft

## l-threonine-trna-mark-substrates Threonine helps make a decoding mark on tRNA, separate from being loaded for protein synthesis. Human YRDC and OSGEPL1 supported mitochondrial t6A37 formation using L-threonine, ATP and CO2/bicarbonate as substrates. Model: Human mitochondrial tRNA-modification reconstitution and cellular experiments. Limitations: The mark occurs on multiple tRNAs; it is not restricted to the tRNA that carries threonine. Evidence access: Primary abstract CO2-sensitive tRNA modification associated with human mitochondrial disease. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29760464/ · DOI 10.1038/s41467-018-04250-4