Citrate

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 needs appropriate regulation as well as its vitamin cofactor.

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 663–674

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-active-state Dephosphorylation and citrate treatment produced the activated human ACC1 filament state resolved by cryo-EM. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ACC1 needs appropriate regulation as well as its vitamin cofactor. 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.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fa420ace21cebdb778923fbf951a99c035c9fae2af8f4876becf672947d9242", "start_char": 0, "end_char": 863, "text_sha256": "7fa420ace21cebdb778923fbf951a99c035c9fae2af8f4876becf672947d9242"} [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

Citrate affects both enzyme speed and effective substrate use.

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 689–700

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-citrate Citrate increased recombinant human ACC2 kcat and kcat/Km for ATP and acetyl-CoA. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Citrate affects both enzyme speed and effective substrate use. 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

compartment_description

Cytosol to extracellular space

experimental_model

Metabolomics and Ank-mutant tissue measurements

limitations

Citrate is a separate substrate; these findings do not prove that citrate alone explains altered bone strength.

nutrient_topic

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

organism

Homo sapiens cells; Mus musculus

plain_language

ANKH affects a mineral-associated organic component as well as PPi supply.

primary_references

[szeri2020] The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP (2020). https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008884 DOI: 10.1371/journal.pgen.1008884

tissue_or_cell_type

Cell medium and bone matrix

Calcium: mechanism-first literature curation (2026-09-17) · lines 1024–1034

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

### ankh-citrate-export ANKH-expressing HEK293 cells released citrate; Ank-mutant mice also had depleted bone-matrix citrate. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: ANKH affects a mineral-associated organic component as well as PPi supply. organism: Homo sapiens cells; Mus musculus tissue_or_cell_type: Cell medium and bone matrix experimental_model: Metabolomics and Ank-mutant tissue measurements limitations: Citrate is a separate substrate; these findings do not prove that citrate alone explains altered bone strength. compartment_description: Cytosol to extracellular space [szeri2020] The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP (2020). https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008884 DOI: 10.1371/journal.pgen.1008884

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

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

endpoint

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

experimental-exposure

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

experimental_model

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

limitations

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

nutrient_topic

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

organism

Rattus norvegicus

plain_language

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

primary_references

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

tissue_or_cell_type

renal proximal-tubule apical membrane

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

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

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

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

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Citrate affects urinary calcium chemistry, but this depletion experiment measured citrate handling rather than stones.

endpoint

The potassium-depleted rats had reduced fractional urinary citrate excretion.

experimental-exposure

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

experimental_model

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

limitations

The transport and excretion measurements were parallel; downstream stone formation was not tested.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Less filtered citrate remained in urine during depletion.

primary_references

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

tissue_or_cell_type

kidney and urine

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1204–1216

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

### k-depletion-lowers-citrate-excretion The potassium-depleted rats had reduced fractional urinary citrate excretion. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less filtered citrate remained in urine during depletion. organism: Rattus norvegicus tissue_or_cell_type: kidney and urine experimental_model: Rats given low-potassium diet for 14 days; urine citrate and renal cortical brush-border membrane vesicle transport kinetics. limitations: The transport and excretion measurements were parallel; downstream stone formation was not tested. cross_nutrient: Citrate affects urinary calcium chemistry, but this depletion experiment measured citrate handling rather than stones. experimental-exposure: Rats given low-potassium diet for 14 days; urine citrate and renal cortical brush-border membrane vesicle transport kinetics. endpoint: The potassium-depleted rats had reduced fractional urinary citrate excretion. [levi-1991-citrate] Chronic K depletion stimulates rat renal brush-border membrane Na-citrate cotransporter (1991). https://pubmed.ncbi.nlm.nih.gov/1683169/ DOI: 10.1152/ajprenal.1991.261.5.F767

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

cross_nutrient

Citrate/alkali coadministration with potassium modifies calcium-stone formation in hypocitraturic stone formers.

endpoint

Potassium citrate reduced new stone formation relative to placebo among participants followed for three years in the hypocitraturic calcium-stone trial.

experimental-exposure

Fifty-seven people with recurrent calcium stones and hypocitraturia randomized to potassium citrate 30-60 mEq/day or placebo; three-year outcomes in 18 and 20 respectively.

experimental_model

Fifty-seven people with recurrent calcium stones and hypocitraturia randomized to potassium citrate 30-60 mEq/day or placebo; three-year outcomes in 18 and 20 respectively.

limitations

57 randomized but 38 contributed the cited three-year comparison; potassium, citrate and alkalinization were cointerventions. Not a potassium-cation-only effect or treatment recommendation.

nutrient_topic

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

organism

Homo sapiens

plain_language

The combined salt changed a stone outcome in a selected clinical group.

primary_references

[barcelo-1993-stones] Randomized double-blind study of potassium citrate in idiopathic hypocitraturic calcium nephrolithiasis (1993). https://www.sciencedirect.com/science/article/pii/S0022534717358883 DOI: 10.1016/S0022-5347(17)35888-3

tissue_or_cell_type

urinary tract

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1438–1450

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fifty-seven people with recurrent calcium stones and hypocitraturia randomized to potassium citrate 30-60 mEq/day or placebo; three-year outcomes in 18 and 20 respectively. · source_derived_draft · unverified_draft

### potassium-citrate-reduces-calcium-stone-formation Potassium citrate reduced new stone formation relative to placebo among participants followed for three years in the hypocitraturic calcium-stone trial. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The combined salt changed a stone outcome in a selected clinical group. organism: Homo sapiens tissue_or_cell_type: urinary tract experimental_model: Fifty-seven people with recurrent calcium stones and hypocitraturia randomized to potassium citrate 30-60 mEq/day or placebo; three-year outcomes in 18 and 20 respectively. limitations: 57 randomized but 38 contributed the cited three-year comparison; potassium, citrate and alkalinization were cointerventions. Not a potassium-cation-only effect or treatment recommendation. cross_nutrient: Citrate/alkali coadministration with potassium modifies calcium-stone formation in hypocitraturic stone formers. experimental-exposure: Fifty-seven people with recurrent calcium stones and hypocitraturia randomized to potassium citrate 30-60 mEq/day or placebo; three-year outcomes in 18 and 20 respectively. endpoint: Potassium citrate reduced new stone formation relative to placebo among participants followed for three years in the hypocitraturic calcium-stone trial. [barcelo-1993-stones] Randomized double-blind study of potassium citrate in idiopathic hypocitraturic calcium nephrolithiasis (1993). https://www.sciencedirect.com/science/article/pii/S0022534717358883 DOI: 10.1016/S0022-5347(17)35888-3

evidence_access

Primary abstract

experimental_model

Spectroscopy, competition assays and structural calculations.

limitations

Fisetin bound iron less strongly than EDTA and citrate under tested conditions; no human iron-depletion outcome measured.

nutrient_topic

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

plain_language

The same molecule binds metal differently as conditions change.

primary_references

Comparative spectroscopic and mechanistic study of chelation properties of fisetin with iron in aqueous buffered solutions. Implications on in vitro antioxidant activity. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21431152/ · DOI 10.1039/c0dt01834a

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 136–142

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Spectroscopy, competition assays and structural calculations. · source_derived_draft · unverified_draft

## fisetin-iron-chelation The same molecule binds metal differently as conditions change. Buffered chemical assays identified 1:1 and 1:2 iron-fisetin complexes with pH-dependent coordination sites. Model: Spectroscopy, competition assays and structural calculations. Limitations: Fisetin bound iron less strongly than EDTA and citrate under tested conditions; no human iron-depletion outcome measured. Evidence access: Primary abstract Comparative spectroscopic and mechanistic study of chelation properties of fisetin with iron in aqueous buffered solutions. Implications on in vitro antioxidant activity. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21431152/ · DOI 10.1039/c0dt01834a

evidence_span

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experimental_model

Eight human subjects infused with sodium acetate at rest and during cycling, with muscle biopsies

exposure

400 mmol sodium acetate infused over 20 min rest, 5 min cycling at 40% and 15 min at 80% of maximal oxygen uptake, against a 400 mmol sodium bicarbonate control two weeks later

limitations

A direct human measurement with a matched sodium control. The effect was present at rest and absent during exercise, so it is not a general property of raised acetate.

nutrient_topic

Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid

organism

Human

plain_language

Raising blood acetate in people switched down the enzyme that commits glucose to being burned.

primary_references

[acetate-p7762627] Skeletal muscle pyruvate dehydrogenase activity during acetate infusion in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/7762627/ DOI: 10.1152/ajpendo.1995.268.5.e1007

tissue_or_cell_type

Skeletal muscle

Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21) · lines 485–496

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Eight human subjects infused with sodium acetate at rest and during cycling, with muscle biopsies · source_derived_draft · unverified_draft

### acetate-acetate-suppresses-pdh Acetate infusion increased muscle acetyl-CoA, citrate and acetylcarnitine, and resting active-form pyruvate dehydrogenase declined during 20 minutes of acetate infusion from 0.37 to 0.16 mmol per minute per kg wet weight, coinciding with an elevation in the acetyl-CoA to free CoA ratio from 0.28 to 0.73, whereas after the bicarbonate control infusion resting activity was similar to that before acetate. Condition category: normal nutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. plain_language: Raising blood acetate in people switched down the enzyme that commits glucose to being burned. organism: Human tissue_or_cell_type: Skeletal muscle experimental_model: Eight human subjects infused with sodium acetate at rest and during cycling, with muscle biopsies limitations: A direct human measurement with a matched sodium control. The effect was present at rest and absent during exercise, so it is not a general property of raised acetate. exposure: 400 mmol sodium acetate infused over 20 min rest, 5 min cycling at 40% and 15 min at 80% of maximal oxygen uptake, against a 400 mmol sodium bicarbonate control two weeks later evidence_span: {"source_cache": "artifacts/acetate-research/7762627.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "343ba052925b754982d178cee1a1c2e3e0a3d1e940e6dd349989c7d6c2704f76", "start_char": 0, "end_char": 1730, "text_sha256": "343ba052925b754982d178cee1a1c2e3e0a3d1e940e6dd349989c7d6c2704f76"} [acetate-p7762627] Skeletal muscle pyruvate dehydrogenase activity during acetate infusion in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/7762627/ DOI: 10.1152/ajpendo.1995.268.5.e1007

evidence_span

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experimental_model

Rat colonic epithelial cells with competing labelled substrates and ATP-citrate lyase inhibition

exposure

Labelled acetate, propionate, butyrate, 3-hydroxybutyrate, glucose and glutamine, with hydroxycitrate as an ATP-citrate lyase inhibitor

limitations

An isolated cell measurement. Its ATP-citrate lyase result anticipates by seventeen years the in vivo finding in this collection that lipogenic acetyl-CoA can arrive without that enzyme.

nutrient_topic

Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid

organism

Rat

plain_language

Blocking the usual enzyme changed nothing, so the carbon was arriving another way.

primary_references

[acetate-p14608066] Acetate and butyrate are the major substrates for de novo lipogenesis in rat colonic epithelial cells. (2003). https://pubmed.ncbi.nlm.nih.gov/14608066/ DOI: 10.1093/jn/133.11.3509

tissue_or_cell_type

Colonic epithelium

Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21) · lines 537–548

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat colonic epithelial cells with competing labelled substrates and ATP-citrate lyase inhibition · source_derived_draft · unverified_draft

### acetate-citrate-route-not-used Hydroxycitrate did not affect the incorporation of acetate or butyrate carbon into lipids even though it inhibited colonic ATP-citrate lyase, suggesting that the short-chain fatty acid carbon used in lipid synthesis by colonocytes is not transported to the cytosol as citrate, and that colonocytes synthesise lipids by a pathway distinct from the liver. Condition category: normal nutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. plain_language: Blocking the usual enzyme changed nothing, so the carbon was arriving another way. organism: Rat tissue_or_cell_type: Colonic epithelium experimental_model: Rat colonic epithelial cells with competing labelled substrates and ATP-citrate lyase inhibition limitations: An isolated cell measurement. Its ATP-citrate lyase result anticipates by seventeen years the in vivo finding in this collection that lipogenic acetyl-CoA can arrive without that enzyme. exposure: Labelled acetate, propionate, butyrate, 3-hydroxybutyrate, glucose and glutamine, with hydroxycitrate as an ATP-citrate lyase inhibitor evidence_span: {"source_cache": "artifacts/acetate-research/14608066.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b2c891f60d02b85a8f4e87f26751f1129b0445fe52fb35ca5e5e20a92d4ecc5a", "start_char": 0, "end_char": 1642, "text_sha256": "b2c891f60d02b85a8f4e87f26751f1129b0445fe52fb35ca5e5e20a92d4ecc5a"} [acetate-p14608066] Acetate and butyrate are the major substrates for de novo lipogenesis in rat colonic epithelial cells. (2003). https://pubmed.ncbi.nlm.nih.gov/14608066/ DOI: 10.1093/jn/133.11.3509

evidence_access

Primary abstract

experimental_model

Cloned human transporter kinetic analysis.

limitations

Net flux depends on citrate and ion concentrations; not unconditional stimulation at every substrate level.

nutrient_topic

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

plain_language

A stronger apparent response can coexist with a lower maximum rate.

primary_references

Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 288–294

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

## lithium-nact-affinity A stronger apparent response can coexist with a lower maximum rate. Lithium shifted human NaCT toward higher substrate affinity and lower transport capacity. Model: Cloned human transporter kinetic analysis. Limitations: Net flux depends on citrate and ion concentrations; not unconditional stimulation at every substrate level. Evidence access: Primary abstract Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523

evidence_access

Primary abstract

experimental_model

Expressed human transporter and human liver-cell experiments.

limitations

Not evidence that trace lithium has the same effect or that citrate salt ingestion determines the response.

nutrient_topic

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

plain_language

A sodium-coupled carrier links lithium to carbon metabolism.

primary_references

Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12826022/ · DOI 10.1042/BJ20030827

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 264–270

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

## lithium-nact-human A sodium-coupled carrier links lithium to carbon metabolism. Lithium stimulated human NaCT-mediated citrate transport at concentrations relevant to prescription exposure. Model: Expressed human transporter and human liver-cell experiments. Limitations: Not evidence that trace lithium has the same effect or that citrate salt ingestion determines the response. Evidence access: Primary abstract Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12826022/ · DOI 10.1042/BJ20030827

evidence_access

Primary abstract

experimental_model

Human liver-cell tracer/transport study.

limitations

Does not establish that this pathway explains clinical weight change.

nutrient_topic

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

plain_language

Transported citrate can enter lipid-building pathways.

primary_references

Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12826022/ · DOI 10.1042/BJ20030827

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 272–278

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human liver-cell tracer/transport study. · source_derived_draft · unverified_draft

## lithium-nact-lipids Transported citrate can enter lipid-building pathways. Lithium increased NaCT-mediated use of extracellular citrate for lipid synthesis in human liver cells. Model: Human liver-cell tracer/transport study. Limitations: Does not establish that this pathway explains clinical weight change. Evidence access: Primary abstract Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12826022/ · DOI 10.1042/BJ20030827

evidence_access

Primary abstract

experimental_model

Transporters cloned from eight species.

limitations

Explicit species difference; no contradiction between correctly scoped records.

nutrient_topic

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

plain_language

The human result cannot be assumed in rodents.

primary_references

Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 280–286

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Transporters cloned from eight species. · source_derived_draft · unverified_draft

## lithium-nact-rat The human result cannot be assumed in rodents. Lithium inhibited rat NaCT while stimulating primate transporters in the same comparative study. Model: Transporters cloned from eight species. Limitations: Explicit species difference; no contradiction between correctly scoped records. Evidence access: Primary abstract Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Site-directed human transporter mutagenesis.

limitations

Engineered variant, not evidence of a common human nutritional phenotype.

nutrient_topic

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

plain_language

A protein variant can change responsiveness independently of intake.

primary_references

Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523

trigger_kind

machinery_impairment Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 296–302

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

## lithium-nact-variant A protein variant can change responsiveness independently of intake. F500W increased baseline transport but nearly eliminated additional lithium stimulation of human NaCT. Model: Site-directed human transporter mutagenesis. Limitations: Engineered variant, not evidence of a common human nutritional phenotype. Evidence access: Primary abstract Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

evidence_location

BioC text lines 11, 17, 51; Fig. 2A,E

experimental_model

ACLY siRNA versus control

exposure

72-hour siRNA treatment.

limitations

Tubulin acetylation was not comparably reduced. This is a source-specific cellular result, not a universal block of protein acetylation. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

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

organism

Homo sapiens

plain_language

Histone acetylation depended partly on this source of acetyl-CoA in colon-cancer cells.

primary_references

[b5-met-chromatin2009] ATP-citrate lyase links cellular metabolism to histone acetylation. (2009). https://pubmed.ncbi.nlm.nih.gov/19461003/ DOI: 10.1126/science.1164097

tissue_or_cell_type

HCT116 cells and acid-extracted histones

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 991–1003

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

### b5-met-acly-hct-histones ACLY silencing reduced acetylation of the core histones assayed in HCT116 cells. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Histone acetylation depended partly on this source of acetyl-CoA in colon-cancer cells. organism: Homo sapiens tissue_or_cell_type: HCT116 cells and acid-extracted histones experimental_model: ACLY siRNA versus control limitations: Tubulin acetylation was not comparably reduced. This is a source-specific cellular result, not a universal block of protein acetylation. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: 72-hour siRNA treatment. cross_nutrient: true evidence_location: BioC text lines 11, 17, 51; Fig. 2A,E [b5-met-chromatin2009] ATP-citrate lyase links cellular metabolism to histone acetylation. (2009). https://pubmed.ncbi.nlm.nih.gov/19461003/ DOI: 10.1126/science.1164097