Acetyl-CoA

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

Acetyl-CoA helps put PC into its working shape.

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 559–570

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-acetylcoa Acetyl-CoA stabilized human PC in a catalytically competent conformation in time-resolved structural and biochemical experiments. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Acetyl-CoA helps put PC into its working shape. 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

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

The biotin-carrying enzyme coordinates two reaction stations rather than performing one isolated chemical step.

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 572–583

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-communication Acetyl-CoA-dependent stabilization of human PC triggered ATP hydrolysis and communication between its two reaction centers. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The biotin-carrying enzyme coordinates two reaction stations rather than performing one isolated chemical step. 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

evidence_span

{"source_cache": "artifacts/melatonin-research/10722724.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8", "start_char": 0, "end_char": 1857, "text_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8"}

experimental_model

Purified recombinant enzyme substrate-specificity study

exposure

Serotonin and radiolabeled acetyl-CoA; product HPLC

limitations

Biochemical mechanism, not evidence that dietary B5 or acetyl-CoA availability limits melatonin production in all humans.

nutrient_topic

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

organism

Human AANAT expressed in bacteria

plain_language

This connects melatonin synthesis to the B5-derived coenzyme-A system.

primary_references

[melatonin-p10722724] Substrate specificity and inhibition studies of human serotonin N-acetyltransferase. (2000). https://pubmed.ncbi.nlm.nih.gov/10722724/ DOI: 10.1074/jbc.275.12.8794

tissue_or_cell_type

Serotonin acetylation

Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 188–199

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

### melatonin-aanat-acetyl-coa The human AANAT assay used acetyl-CoA as the acetyl donor in N-acetylserotonin formation. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This connects melatonin synthesis to the B5-derived coenzyme-A system. organism: Human AANAT expressed in bacteria tissue_or_cell_type: Serotonin acetylation experimental_model: Purified recombinant enzyme substrate-specificity study limitations: Biochemical mechanism, not evidence that dietary B5 or acetyl-CoA availability limits melatonin production in all humans. exposure: Serotonin and radiolabeled acetyl-CoA; product HPLC evidence_span: {"source_cache": "artifacts/melatonin-research/10722724.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8", "start_char": 0, "end_char": 1857, "text_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8"} [melatonin-p10722724] Substrate specificity and inhibition studies of human serotonin N-acetyltransferase. (2000). https://pubmed.ncbi.nlm.nih.gov/10722724/ DOI: 10.1074/jbc.275.12.8794

evidence_access

Primary abstract

experimental_model

Human SAT1 initial-velocity, inhibition and pH experiments.

limitations

Mechanism does not quantify whole-body acetyl-CoA competition.

nutrient_topic

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

plain_language

Both the donor and the polyamine must reach the enzyme.

primary_references

Mechanistic and structural analysis of human spermidine/spermine N1-acetyltransferase. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17516632/ · DOI 10.1021/bi700256z

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 86–92

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human SAT1 initial-velocity, inhibition and pH experiments. · source_derived_draft · unverified_draft

## spermidine-sat1-cosubstrate Both the donor and the polyamine must reach the enzyme. Human SAT1 kinetics support a random sequential mechanism involving acetyl donor and polyamine in a ternary complex. Model: Human SAT1 initial-velocity, inhibition and pH experiments. Limitations: Mechanism does not quantify whole-body acetyl-CoA competition. Evidence access: Primary abstract Mechanistic and structural analysis of human spermidine/spermine N1-acetyltransferase. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17516632/ · DOI 10.1021/bi700256z

evidence_span

{"source_cache": "artifacts/citrulline-research/16321554.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ce9d57aba8d7973c01de32ab7d5d0287858119fa75f0a372e3ed99523a861a5", "start_char": 0, "end_char": 1498, "text_sha256": "5ce9d57aba8d7973c01de32ab7d5d0287858119fa75f0a372e3ed99523a861a5"}

experimental_model

Purified recombinant NAGS kinetics

exposure

Glutamate, acetyl-CoA and arginine; mature and conserved-domain constructs

limitations

Construct-specific kinetics; no human B5-deficiency or arginine-repletion trial.

nutrient_topic

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

organism

Human and mouse enzymes; human findings specified

plain_language

This creates a connection to the B5-derived coenzyme-A system.

primary_references

[citrulline-p16321554] Biochemical properties of recombinant human and mouse N-acetylglutamate synthase. (2006). https://pubmed.ncbi.nlm.nih.gov/16321554/ DOI: 10.1016/j.ymgme.2005.10.003

tissue_or_cell_type

N-acetylglutamate formation

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 268–279

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

### citrulline-nags-acetyl-coa Acetyl-CoA is a substrate for human NAGS-mediated N-acetylglutamate synthesis. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This creates a connection to the B5-derived coenzyme-A system. organism: Human and mouse enzymes; human findings specified tissue_or_cell_type: N-acetylglutamate formation experimental_model: Purified recombinant NAGS kinetics limitations: Construct-specific kinetics; no human B5-deficiency or arginine-repletion trial. exposure: Glutamate, acetyl-CoA and arginine; mature and conserved-domain constructs evidence_span: {"source_cache": "artifacts/citrulline-research/16321554.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ce9d57aba8d7973c01de32ab7d5d0287858119fa75f0a372e3ed99523a861a5", "start_char": 0, "end_char": 1498, "text_sha256": "5ce9d57aba8d7973c01de32ab7d5d0287858119fa75f0a372e3ed99523a861a5"} [citrulline-p16321554] Biochemical properties of recombinant human and mouse N-acetylglutamate synthase. (2006). https://pubmed.ncbi.nlm.nih.gov/16321554/ DOI: 10.1016/j.ymgme.2005.10.003

access_level

full_text_and_supplement_review

compartment

In vitro reaction, not an intact-cell compartment

dose

Acetyl-CoA present/absent controls; concentrations and incubation details incompletely specified

duration

Not specified in the reviewed methods

endpoint

hadha-construct-lysine-acetylation

evidence_location

Acetyl-CoA omission control; Figure 6J

experimental_model

Recombinant-protein acetylation assay

exposure

acetyl-coa

limitations

Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. This is an omission-control observation, not a dietary or intracellular acetyl-CoA threshold.

organism

Recombinant mouse Dlat; HADHA construct sequence species unresolved in reviewed methods

plain_language

Omitting acetyl-CoA prevented the Dlat-associated HADHA acetylation signal in the purified-protein assay.

primary_locator

[{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 44, "text_sha256": "e0a92f47bc76c894816706ffb5158242c968928ac61e4561262c370035eda621", "xml_element_id": "Par19"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 46, "text_sha256": "d56a90702bdf004de1efc2e43103b1b771e15b38288dc01f3741676782b1f5ff", "xml_element_id": null}]

primary_references

https://doi.org/10.1038/s41467-026-70703-w

sample_size

4 biological replicates

tissue_or_cell_type

Purified-protein reaction

DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 70–85

AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Recombinant-protein acetylation assay · source_derived_draft · unverified_draft

Omitting acetyl-CoA prevented the Dlat-associated HADHA acetylation signal in the purified-protein assay. organism: Recombinant mouse Dlat; HADHA construct sequence species unresolved in reviewed methods tissue_or_cell_type: Purified-protein reaction experimental_model: Recombinant-protein acetylation assay compartment: In vitro reaction, not an intact-cell compartment dose: Acetyl-CoA present/absent controls; concentrations and incubation details incompletely specified duration: Not specified in the reviewed methods primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: Acetyl-CoA omission control; Figure 6J endpoint: hadha-construct-lysine-acetylation exposure: acetyl-coa limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. This is an omission-control observation, not a dietary or intracellular acetyl-CoA threshold. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 44, "text_sha256": "e0a92f47bc76c894816706ffb5158242c968928ac61e4561262c370035eda621", "xml_element_id": "Par19"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 46, "text_sha256": "d56a90702bdf004de1efc2e43103b1b771e15b38288dc01f3741676782b1f5ff", "xml_element_id": null}] plain_language: Omitting acetyl-CoA prevented the Dlat-associated HADHA acetylation signal in the purified-protein assay. sample_size: 4 biological replicates

evidence_access

Primary abstract

experimental_model

Human HMGCS1/HMGCS2 structures and catalytic reaction description.

limitations

The mitochondrial isoform is distinct from cytosolic HMGCS1 in sterol synthesis.

nutrient_topic

Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake

plain_language

Two carbon-carrying molecules combine on the ketone-production route.

primary_references

Crystal structures of human HMG-CoA synthase isoforms provide insights into inherited ketogenesis disorders and inhibitor design. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20346956/ · DOI 10.1016/j.jmb.2010.03.034

Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 104–110

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human HMGCS1/HMGCS2 structures and catalytic reaction description. · source_derived_draft · unverified_draft

## fast-hmgcs2 Two carbon-carrying molecules combine on the ketone-production route. Mitochondrial HMGCS2 catalyzes condensation of acetyl-CoA and acetoacetyl-CoA to form HMG-CoA. Model: Human HMGCS1/HMGCS2 structures and catalytic reaction description. Limitations: The mitochondrial isoform is distinct from cytosolic HMGCS1 in sterol synthesis. Evidence access: Primary abstract Crystal structures of human HMG-CoA synthase isoforms provide insights into inherited ketogenesis disorders and inhibitor design. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20346956/ · DOI 10.1016/j.jmb.2010.03.034

cross_nutrient

false

experimental_model

Human PANK2 in 293T-cell lysates and purified enzyme assays

exposure

293T-cell-lysate inhibition IC50 was 0.3 micromolar acetyl-CoA; purified-enzyme assays established ATP competition.

limitations

The lysate IC50 is preparation-specific and is not a intracellular or dietary adequacy threshold. Purified-enzyme competition and lysate potency are separately identified.

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

An existing CoA derivative feeds back to restrain PANK2.

primary_references

[b5-bio-pank2reg] Activation of human mitochondrial pantothenate kinase 2 by palmitoylcarnitine. (2007). https://pubmed.ncbi.nlm.nih.gov/17242360/ DOI: 10.1073/pnas.0607621104

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 600–611

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human PANK2 in 293T-cell lysates and purified enzyme assays · source_derived_draft · unverified_draft

### b5-bio-pank2-acetyl-inhibition Acetyl-CoA inhibited purified human PANK2 competitively with ATP; PANK2 inhibition was submicromolar in the reported preparations. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: An existing CoA derivative feeds back to restrain PANK2. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Human PANK2 in 293T-cell lysates and purified enzyme assays limitations: The lysate IC50 is preparation-specific and is not a intracellular or dietary adequacy threshold. Purified-enzyme competition and lysate potency are separately identified. exposure: 293T-cell-lysate inhibition IC50 was 0.3 micromolar acetyl-CoA; purified-enzyme assays established ATP competition. cross_nutrient: false [b5-bio-pank2reg] Activation of human mitochondrial pantothenate kinase 2 by palmitoylcarnitine. (2007). https://pubmed.ncbi.nlm.nih.gov/17242360/ DOI: 10.1073/pnas.0607621104

cross_nutrient

false

experimental_model

Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments

exposure

In-vitro biochemical exposure; concentrations not extracted.

limitations

Abstract-level structural and biochemical findings; no diet or Mg-repletion experiment. Substrate concentrations not established here.

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

Accumulated acyl-CoA can slow the first step of new CoA production.

primary_references

[b5-bio-pank3allosteric] Allosteric Regulation of Mammalian Pantothenate Kinase. (2016). https://pubmed.ncbi.nlm.nih.gov/27555321/ DOI: 10.1074/jbc.m116.748061

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 509–520

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments · source_derived_draft · unverified_draft

### b5-bio-pank3-feedback Acetyl-CoA stabilizes an inactive human PANK3 dimer conformation, whereas ATP–Mg favors the active state; biochemical analyses showed coordinated switching of its two active sites. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Accumulated acyl-CoA can slow the first step of new CoA production. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments limitations: Abstract-level structural and biochemical findings; no diet or Mg-repletion experiment. Substrate concentrations not established here. exposure: In-vitro biochemical exposure; concentrations not extracted. cross_nutrient: false [b5-bio-pank3allosteric] Allosteric Regulation of Mammalian Pantothenate Kinase. (2016). https://pubmed.ncbi.nlm.nih.gov/27555321/ DOI: 10.1074/jbc.m116.748061

cross_nutrient

true

evidence_location

Full text lines 101, 131; Fig. 4B

experimental_model

Endogenous human ACC1 purified from Expi293F cells and analyzed by cryo-EM

exposure

Substrate preparation contained 10 mM acetyl-CoA, 25 mM bicarbonate, 10 mM MgCl2 and 10 mM ATP; cryo-EM preparation conditions.

limitations

Ligand occupancy in an inactive structure is not an activity or dietary-repletion assay. Biotin density was not resolved in this map. 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

Acetyl-CoA binds the biotin-dependent carboxylase even in a structurally inactive state.

primary_references

[b5-met-acc2024] 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 endogenous Expi293F ACC1

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1033–1045

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Endogenous human ACC1 purified from Expi293F cells and analyzed by cryo-EM · source_derived_draft · unverified_draft

### b5-met-acc-acetylcoa-binding The inactive human ACC1 filament structure resolved acetyl-CoA in a pocket at the carboxyltransferase dimer interface. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Acetyl-CoA binds the biotin-dependent carboxylase even in a structurally inactive state. organism: Homo sapiens tissue_or_cell_type: Purified endogenous Expi293F ACC1 experimental_model: Endogenous human ACC1 purified from Expi293F cells and analyzed by cryo-EM limitations: Ligand occupancy in an inactive structure is not an activity or dietary-repletion assay. Biotin density was not resolved in this map. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Substrate preparation contained 10 mM acetyl-CoA, 25 mM bicarbonate, 10 mM MgCl2 and 10 mM ATP; cryo-EM preparation conditions. cross_nutrient: true evidence_location: Full text lines 101, 131; Fig. 4B [b5-met-acc2024] 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

{"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"}

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

{"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"}

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_access

Primary abstract

experimental_model

Human colonic-cell metabolic experiments.

limitations

This is a multistep metabolic conversion; no single CoA ligase is assigned without direct evidence.

nutrient_topic

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

plain_language

The same carbon source supported both fuel use and adding acetyl marks.

primary_references

The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23063526/ · DOI 10.1016/j.molcel.2012.08.033

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 182–188

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

## butyrate-acetyl-coa The same carbon source supported both fuel use and adding acetyl marks. In the colonic-cell experiments, butyrate metabolism supplied acetyl-CoA for energy metabolism and histone acetyltransferase activity. Model: Human colonic-cell metabolic experiments. Limitations: This is a multistep metabolic conversion; no single CoA ligase is assigned without direct evidence. Evidence access: Primary abstract The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23063526/ · DOI 10.1016/j.molcel.2012.08.033

experimental_model

Purified recombinant human ACAT1/T2 enzyme kinetics and crystal structures

limitations

Thiolase chemistry is reversible and shared with ketone metabolism. These experiments do not measure lysine-specific flux. ACAT1 here denotes acetyl-CoA acetyltransferase, not cholesterol acyltransferase SOAT1.

organism

Homo sapiens

plain_language

The four-carbon intermediate is split into two acetyl-CoA molecules.

primary_references

[haapalainen2007] Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function (2007). https://pubmed.ncbi.nlm.nih.gov/17371050/ DOI: 10.1021/bi6026192

tissue_or_cell_type

Mitochondrial matrix enzyme; recombinant protein study

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 377–385

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human ACAT1/T2 enzyme kinetics and crystal structures · source_derived_draft · unverified_draft

### acat1-acetoacetyl-coa-thiolysis Human mitochondrial acetoacetyl-CoA thiolase ACAT1/T2, a homotetramer, uses coenzyme A to cleave acetoacetyl-CoA into two acetyl-CoA molecules. Plain language: The four-carbon intermediate is split into two acetyl-CoA molecules. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial matrix enzyme; recombinant protein study experimental_model: Purified recombinant human ACAT1/T2 enzyme kinetics and crystal structures limitations: Thiolase chemistry is reversible and shared with ketone metabolism. These experiments do not measure lysine-specific flux. ACAT1 here denotes acetyl-CoA acetyltransferase, not cholesterol acyltransferase SOAT1. [haapalainen2007] Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function (2007). https://pubmed.ncbi.nlm.nih.gov/17371050/ DOI: 10.1021/bi6026192

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Full text lines 107, 123–125; Fig. 4F–G; Extended Data Fig. 5G–H

experimental_model

Matched PA-free/control diets in NOD/Scid mice bearing orthotopic human HCI002 breast-cancer xenografts with carbon-13 glucose tracing

exposure

Diets introduced at 6 weeks of age, progressively over 4 days; typically 5 weeks on the assigned diet before implantation and continued until collection. PA absence verified by LC-MS; control was composition-matched with PA added. Control n=7, PA-free n=8 tumors from independent mice. Carbon-13 glucose tracing followed by LC-MS.

limitations

The same paper found no significant fall in the corresponding CoA/acetyl-CoA pools in WMmix tumors. Tumor concentration and tracer labeling do not establish universal CoA depletion or a human anticancer diet; cellular composition and pool size can affect the measured label. 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

Human HCI002 grafts in Mus musculus hosts

plain_language

B5 restriction also reduced the measured labeled acetyl-CoA formed from glucose in these tumors.

primary_references

[b5-met-myc2024] Vitamin B<sub>5</sub> supports MYC oncogenic metabolism and tumor progression in breast cancer. (2023). https://pubmed.ncbi.nlm.nih.gov/37946084/ DOI: 10.1038/s42255-023-00915-7

tissue_or_cell_type

Orthotopic HCI002 tumor tissue

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1117–1129

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Matched PA-free/control diets in NOD/Scid mice bearing orthotopic human HCI002 breast-cancer xenografts with carbon-13 glucose tracing · source_derived_draft · unverified_draft

### b5-met-diet-hci002-acetylcoa Pantothenate deprivation reduced the amount of glucose-derived carbon-13-labeled acetyl-CoA in HCI002 xenografts. Condition category: nutrient_deficiency nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: B5 restriction also reduced the measured labeled acetyl-CoA formed from glucose in these tumors. organism: Human HCI002 grafts in Mus musculus hosts tissue_or_cell_type: Orthotopic HCI002 tumor tissue experimental_model: Matched PA-free/control diets in NOD/Scid mice bearing orthotopic human HCI002 breast-cancer xenografts with carbon-13 glucose tracing limitations: The same paper found no significant fall in the corresponding CoA/acetyl-CoA pools in WMmix tumors. Tumor concentration and tracer labeling do not establish universal CoA depletion or a human anticancer diet; cellular composition and pool size can affect the measured label. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Diets introduced at 6 weeks of age, progressively over 4 days; typically 5 weeks on the assigned diet before implantation and continued until collection. PA absence verified by LC-MS; control was composition-matched with PA added. Control n=7, PA-free n=8 tumors from independent mice. Carbon-13 glucose tracing followed by LC-MS. cross_nutrient: true evidence_location: Full text lines 107, 123–125; Fig. 4F–G; Extended Data Fig. 5G–H [b5-met-myc2024] Vitamin B<sub>5</sub> supports MYC oncogenic metabolism and tumor progression in breast cancer. (2023). https://pubmed.ncbi.nlm.nih.gov/37946084/ DOI: 10.1038/s42255-023-00915-7

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

evidence_access

Primary abstract

experimental_model

Purified human T2 structural/kinetic study; established product chemistry.

limitations

ACAT1 here is acetyl-CoA acetyltransferase, not the cholesterol-esterifying SOAT1 enzyme sometimes called ACAT.

nutrient_topic

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

plain_language

One carbon skeleton feeds both an acetyl branch and a propionyl branch.

primary_references

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

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 226–232

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human T2 structural/kinetic study; established product chemistry. · source_derived_draft · unverified_draft

## isoleucine-acat1-split One carbon skeleton feeds both an acetyl branch and a propionyl branch. Human mitochondrial ACAT1/T2 degraded 2-methylacetoacetyl-CoA by CoA-dependent thiolysis, yielding the isoleucine-branch acetyl-CoA and propionyl-CoA products. Model: Purified human T2 structural/kinetic study; established product chemistry. Limitations: ACAT1 here is acetyl-CoA acetyltransferase, not the cholesterol-esterifying SOAT1 enzyme sometimes called ACAT. Evidence access: Primary abstract Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17371050/ · DOI 10.1021/bi6026192

evidence_access

Primary preprint full text; not peer reviewed

experimental_model

Mouse KPC2838c3/KPC6419c5 and human MIA-PaCa-2, Panc-1, HPAC and patient-derived cells.

limitations

Primary preprint, not peer reviewed; fractional tracer contribution is not absolute pathway flux.

nutrient_topic

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

plain_language

Cancer-cell carbon allocation favored one branch of the pathway.

primary_references

A nuclear branched-chain amino acid catabolism pathway controls histone propionylation in pancreatic cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40568091/ · DOI 10.1101/2025.04.23.650241

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 474–480

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse KPC2838c3/KPC6419c5 and human MIA-PaCa-2, Panc-1, HPAC and patient-derived cells. · source_derived_draft · unverified_draft

## isoleucine-pancreatic-preprint-flux Cancer-cell carbon allocation favored one branch of the pathway. A pancreatic-cancer preprint traced isoleucine carbon prominently into propionyl-CoA in mouse KPC and human PDA cell lines, with smaller contributions to acetyl-CoA/succinyl-CoA in those assays. Model: Mouse KPC2838c3/KPC6419c5 and human MIA-PaCa-2, Panc-1, HPAC and patient-derived cells. Limitations: Primary preprint, not peer reviewed; fractional tracer contribution is not absolute pathway flux. Evidence access: Primary preprint full text; not peer reviewed A nuclear branched-chain amino acid catabolism pathway controls histone propionylation in pancreatic cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40568091/ · DOI 10.1101/2025.04.23.650241

evidence_access

Primary abstract

experimental_model

Human-fecal bacterial isolates and 13C-acetate tracing.

limitations

This culture fraction is not a universal human conversion percentage.

nutrient_topic

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

plain_language

One bacterium’s fermentation product can become another product’s carbon source.

primary_references

Contribution of acetate to butyrate formation by human faecal bacteria. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15182395/ · DOI 10.1079/BJN20041150

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 54–60

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human-fecal bacterial isolates and 13C-acetate tracing. · source_derived_draft · unverified_draft

## butyrate-acetate-carbon One bacterium’s fermentation product can become another product’s carbon source. Isotope tracing showed external acetate supplied 85–90% of butyrate carbon in the tested F. prausnitzii and Roseburia cultures supplied with 60 mM acetate and 10 mM glucose. Model: Human-fecal bacterial isolates and 13C-acetate tracing. Limitations: This culture fraction is not a universal human conversion percentage. Evidence access: Primary abstract Contribution of acetate to butyrate formation by human faecal bacteria. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15182395/ · DOI 10.1079/BJN20041150

evidence_access

Primary abstract

experimental_model

Anaerobic human-fecal isolates; enzyme assays and gene analysis.

limitations

A defined isolate panel is not a census of every human microbiome.

nutrient_topic

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

plain_language

Many tested gut bacteria used acetate-linked CoA transfer to finish butyrate synthesis.

primary_references

Restricted distribution of the butyrate kinase pathway among butyrate-producing bacteria from the human colon. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15028695/ · DOI 10.1128/JB.186.7.2099-2106.2004

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 38–44

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Anaerobic human-fecal isolates; enzyme assays and gene analysis. · source_derived_draft · unverified_draft

## butyrate-coa-transferase-route Many tested gut bacteria used acetate-linked CoA transfer to finish butyrate synthesis. Butyryl-CoA:acetate CoA-transferase activity was detected in all 38 human-fecal butyrate-producing isolates examined, supporting this terminal route to butyrate. Model: Anaerobic human-fecal isolates; enzyme assays and gene analysis. Limitations: A defined isolate panel is not a census of every human microbiome. Evidence access: Primary abstract Restricted distribution of the butyrate kinase pathway among butyrate-producing bacteria from the human colon. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15028695/ · DOI 10.1128/JB.186.7.2099-2106.2004

evidence_span

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experimental_model

Human CHAT genetics, recombinant expression and enzyme kinetics

exposure

Ten recessive variants in five patients; nine mutant proteins assayed

limitations

Inherited enzyme defects, not a dietary choline-deficiency model. Acetyl-CoA and choline are distinct substrates.

nutrient_topic

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

organism

Human CHAT proteins; COS-cell and bacterial expression systems

plain_language

The neurotransmitter needs both the choline headgroup and an acetyl group supplied by acetyl-CoA.

primary_references

[choline-p11172068] Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11172068/ DOI: 10.1073/pnas.98.4.2017

tissue_or_cell_type

Neuromuscular acetylcholine resynthesis

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 412–423

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CHAT genetics, recombinant expression and enzyme kinetics · source_derived_draft · unverified_draft

### choline-chat-acetylcholine ChAT catalyzes reversible acetylcholine synthesis from choline and acetyl-CoA. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The neurotransmitter needs both the choline headgroup and an acetyl group supplied by acetyl-CoA. organism: Human CHAT proteins; COS-cell and bacterial expression systems tissue_or_cell_type: Neuromuscular acetylcholine resynthesis experimental_model: Human CHAT genetics, recombinant expression and enzyme kinetics limitations: Inherited enzyme defects, not a dietary choline-deficiency model. Acetyl-CoA and choline are distinct substrates. exposure: Ten recessive variants in five patients; nine mutant proteins assayed evidence_span: {"source_cache": "artifacts/choline-research/11172068.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "691b96b9c5c149c554b99d8e1532ffee25084a8970f8deb23f0991dfd6013d39", "start_char": 0, "end_char": 1231, "text_sha256": "691b96b9c5c149c554b99d8e1532ffee25084a8970f8deb23f0991dfd6013d39"} [choline-p11172068] Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11172068/ DOI: 10.1073/pnas.98.4.2017

evidence_span

{"source_cache": "artifacts/melatonin-research/10722724.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8", "start_char": 0, "end_char": 1857, "text_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8"}

experimental_model

Purified recombinant enzyme substrate-specificity study

exposure

Serotonin and radiolabeled acetyl-CoA; product HPLC

limitations

Biochemical mechanism, not evidence that dietary B5 or acetyl-CoA availability limits melatonin production in all humans.

nutrient_topic

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

organism

Human AANAT expressed in bacteria

plain_language

Serotonin is modified before it becomes melatonin.

primary_references

[melatonin-p10722724] Substrate specificity and inhibition studies of human serotonin N-acetyltransferase. (2000). https://pubmed.ncbi.nlm.nih.gov/10722724/ DOI: 10.1074/jbc.275.12.8794

tissue_or_cell_type

Serotonin acetylation

Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 175–186

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

### melatonin-aanat-serotonin Human AANAT transferred an acetyl group from acetyl-CoA to serotonin, producing N-acetylserotonin. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Serotonin is modified before it becomes melatonin. organism: Human AANAT expressed in bacteria tissue_or_cell_type: Serotonin acetylation experimental_model: Purified recombinant enzyme substrate-specificity study limitations: Biochemical mechanism, not evidence that dietary B5 or acetyl-CoA availability limits melatonin production in all humans. exposure: Serotonin and radiolabeled acetyl-CoA; product HPLC evidence_span: {"source_cache": "artifacts/melatonin-research/10722724.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8", "start_char": 0, "end_char": 1857, "text_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8"} [melatonin-p10722724] Substrate specificity and inhibition studies of human serotonin N-acetyltransferase. (2000). https://pubmed.ncbi.nlm.nih.gov/10722724/ DOI: 10.1074/jbc.275.12.8794

cross_nutrient

B1-dependent E1 and B5-derived CoA participate in different sequential steps.

evidence

[{"paper_key": "jiang-2018-pdh-core", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-32"], "locator": "acetyl-accepting CoA", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Human DLAT cryo-EM; bacterial ligand poses used for modeling.

limitations

Ligand positions were modeled, not directly resolved in a human substrate-bound structure; no intake experiment.

nutrient

Thiamine (vitamin B1) · Thiamine (vitamin B1)

nutrient_topic

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

organism

Homo sapiens

plain_language

After B1 acts at E1, the E2 protein transfers the acetyl group onto CoA, a vitamin B5-derived carrier.

primary_references

[jiang-2018-pdh-core] Atomic Structure of the E2 Inner Core of Human Pyruvate Dehydrogenase Complex (2018). https://pubmed.ncbi.nlm.nih.gov/29608861/ DOI: 10.1021/acs.biochem.8b00357

tissue_or_cell_type

Purified catalytic core

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 690–702

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DLAT cryo-EM; bacterial ligand poses used for modeling. · source_derived_draft · unverified_draft

### b1-pdh-dlat-coa-acetylation The human DLAT catalytic core contains a channel for the acetylated lipoyl group and CoA; substrate modeling positions CoA for acetyl-CoA formation. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: After B1 acts at E1, the E2 protein transfers the acetyl group onto CoA, a vitamin B5-derived carrier. organism: Homo sapiens tissue_or_cell_type: Purified catalytic core experimental_model: Human DLAT cryo-EM; bacterial ligand poses used for modeling. limitations: Ligand positions were modeled, not directly resolved in a human substrate-bound structure; no intake experiment. evidence: [{"paper_key": "jiang-2018-pdh-core", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-32"], "locator": "acetyl-accepting CoA", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1-dependent E1 and B5-derived CoA participate in different sequential steps. nutrient: Thiamine (vitamin B1) [jiang-2018-pdh-core] Atomic Structure of the E2 Inner Core of Human Pyruvate Dehydrogenase Complex (2018). https://pubmed.ncbi.nlm.nih.gov/29608861/ DOI: 10.1021/acs.biochem.8b00357

evidence_access

Primary abstract

experimental_model

Human U87MG culture, isotope tracing.

limitations

Does not show that oral acetylcarnitine causes or treats cancer.

nutrient_topic

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

plain_language

The acetylated form can deliver carbon for cellular synthesis.

primary_references

Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 210–216

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human U87MG culture, isotope tracing. · source_derived_draft · unverified_draft

## l-carnitine-acetyl-carbon The acetylated form can deliver carbon for cellular synthesis. Isotope-labeled acetylcarnitine supplied acetyl-CoA and fatty-acid carbon in glucose-limited human U87MG glioma cells. Model: Human U87MG culture, isotope tracing. Limitations: Does not show that oral acetylcarnitine causes or treats cancer. Evidence access: Primary abstract Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848

evidence_access

Primary full-text Figure 3 and enzyme experiments

experimental_model

E. timonensis enzymes; recombinant expression and reconstitution.

limitations

Acetyl-CoA was preferred among tested donors; in vivo donor use can differ.

nutrient_topic

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

plain_language

The microbial route first activates its substrate with CoA.

primary_references

Elucidation of an anaerobic pathway for metabolism of l-carnitine-derived γ-butyrobetaine to trimethylamine in human gut bacteria. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34362844/ · DOI 10.1073/pnas.2101498118

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 370–376

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · E. timonensis enzymes; recombinant expression and reconstitution. · source_derived_draft · unverified_draft

## l-carnitine-bbu-coa The microbial route first activates its substrate with CoA. Purified BbuB and BbuC together transferred CoA onto gamma-butyrobetaine; neither component alone reproduced the tested activity. Model: E. timonensis enzymes; recombinant expression and reconstitution. Limitations: Acetyl-CoA was preferred among tested donors; in vivo donor use can differ. Evidence access: Primary full-text Figure 3 and enzyme experiments Elucidation of an anaerobic pathway for metabolism of l-carnitine-derived γ-butyrobetaine to trimethylamine in human gut bacteria. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34362844/ · DOI 10.1073/pnas.2101498118

evidence_access

Primary abstract and full-text Figures 1-4

experimental_model

Muscle-specific mouse knockout, enzyme assays and metabolomics.

limitations

Crat buffer function depends on tissue and substrate conditions.

nutrient_topic

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

plain_language

Carnitine can carry excess acetyl groups as well as long fatty-acid groups.

primary_references

Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 154–160

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Muscle-specific mouse knockout, enzyme assays and metabolomics. · source_derived_draft · unverified_draft

## l-carnitine-crat-buffer Carnitine can carry excess acetyl groups as well as long fatty-acid groups. Muscle Crat deletion reduced short-chain acyltransferase activity and acetylcarnitine pools, supporting transfer of acetyl groups from acetyl-CoA to carnitine. Model: Muscle-specific mouse knockout, enzyme assays and metabolomics. Limitations: Crat buffer function depends on tissue and substrate conditions. Evidence access: Primary abstract and full-text Figures 1-4 Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005

evidence_access

Primary full text and cell-line methods

experimental_model

Mouse HCC cell genetic perturbation and carbon tracing.

limitations

Dependence arises in the specified metabolic background.

nutrient_topic

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

plain_language

The acetyl shuttle can supply lipid synthesis when a usual route is missing.

primary_references

Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37134161/ · DOI 10.1126/sciadv.adf0115

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 242–248

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse HCC cell genetic perturbation and carbon tracing. · source_derived_draft · unverified_draft

## l-carnitine-crat-lipogenesis The acetyl shuttle can supply lipid synthesis when a usual route is missing. Removing Crat impaired glucose-derived lipid synthesis in ACLY-deficient mouse HCC cells. Model: Mouse HCC cell genetic perturbation and carbon tracing. Limitations: Dependence arises in the specified metabolic background. Evidence access: Primary full text and cell-line methods Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37134161/ · DOI 10.1126/sciadv.adf0115

evidence_access

Primary full-text Figure 4

experimental_model

Isolated mouse muscle mitochondria; pyruvate-only respiratory context and direct PDH assay.

limitations

The effect is context-dependent; liver mitochondria also lacked the stimulation.

nutrient_topic

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

plain_language

Carnitine needs the acetyl-transfer enzyme to relieve this brake on glucose oxidation.

primary_references

Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 162–168

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Isolated mouse muscle mitochondria; pyruvate-only respiratory context and direct PDH assay. · source_derived_draft · unverified_draft

## l-carnitine-crat-pdh Carnitine needs the acetyl-transfer enzyme to relieve this brake on glucose oxidation. Adding carnitine stimulated PDH activity 1.8-fold in control muscle mitochondria but did not stimulate it in Crat-null mitochondria. Model: Isolated mouse muscle mitochondria; pyruvate-only respiratory context and direct PDH assay. Limitations: The effect is context-dependent; liver mitochondria also lacked the stimulation. Evidence access: Primary full-text Figure 4 Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005

evidence_access

Primary full-text Figure 6 and cell-line methods

experimental_model

Mouse hepatocellular carcinoma double-knockout cells; supplementation and isotope tracing.

limitations

An engineered cancer-cell bypass is not a general epigenetic benefit.

nutrient_topic

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

plain_language

Acetyl-group transport can connect energy metabolism to chromatin chemistry.

primary_references

Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37134161/ · DOI 10.1126/sciadv.adf0115

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 234–240

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse hepatocellular carcinoma double-knockout cells; supplementation and isotope tracing. · source_derived_draft · unverified_draft

## l-carnitine-histone-carbon Acetyl-group transport can connect energy metabolism to chromatin chemistry. Adding acetylcarnitine increased histone acetylation in lipid-depleted mouse HCC cells lacking both ACLY and ACSS2. Model: Mouse hepatocellular carcinoma double-knockout cells; supplementation and isotope tracing. Limitations: An engineered cancer-cell bypass is not a general epigenetic benefit. Evidence access: Primary full-text Figure 6 and cell-line methods Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37134161/ · DOI 10.1126/sciadv.adf0115

evidence_access

Primary full-text Table 1 and recombinant enzyme methods

experimental_model

Human CRAT expressed in E. coli; steady-state kinetic substrate panel.

limitations

Purified-enzyme capacity does not identify the dominant flux in every compartment.

nutrient_topic

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

plain_language

The human enzyme directly connects carnitine and the CoA pool.

primary_references

Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 498–504

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human CRAT expressed in E. coli; steady-state kinetic substrate panel. · source_derived_draft · unverified_draft

## l-carnitine-human-crat-reaction The human enzyme directly connects carnitine and the CoA pool. Purified recombinant human CRAT transferred short-chain acyl groups including acetyl from acyl-CoA substrates to carnitine in enzyme assays. Model: Human CRAT expressed in E. coli; steady-state kinetic substrate panel. Limitations: Purified-enzyme capacity does not identify the dominant flux in every compartment. Evidence access: Primary full-text Table 1 and recombinant enzyme methods Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848

evidence_access

Primary abstract

experimental_model

AANAT activity screen; substrate-site interaction proposed from docking.

limitations

Binding site and species are not independently established by the accessed abstract.

nutrient_topic

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

plain_language

A step on the serotonin-to-melatonin route can be inhibited.

primary_references

The flavonoid myricetin reduces nocturnal melatonin levels in the blood through the inhibition of serotonin N-acetyltransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24076393/ · DOI 10.1016/j.bbrc.2013.09.076

Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 564–570

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · AANAT activity screen; substrate-site interaction proposed from docking. · source_derived_draft · unverified_draft

## myricetin-aanat A step on the serotonin-to-melatonin route can be inhibited. Myricetin inhibited serotonin N-acetyltransferase activity in the reported enzyme assay. Model: AANAT activity screen; substrate-site interaction proposed from docking. Limitations: Binding site and species are not independently established by the accessed abstract. Evidence access: Primary abstract The flavonoid myricetin reduces nocturnal melatonin levels in the blood through the inhibition of serotonin N-acetyltransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24076393/ · DOI 10.1016/j.bbrc.2013.09.076

evidence_access

Primary abstract

experimental_model

Recombinant human EP300 assay with companion human-cell experiments.

limitations

Biochemical inhibition is not proof of selective target engagement after dietary exposure.

nutrient_topic

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

plain_language

One route changes protein acetylation.

primary_references

Spermidine induces autophagy by inhibiting the acetyltransferase EP300. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25526088/ · DOI 10.1038/cdd.2014.215

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 150–156

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human EP300 assay with companion human-cell experiments. · source_derived_draft · unverified_draft

## spermidine-ep300 One route changes protein acetylation. Spermidine inhibited acetyltransferase activity of recombinant EP300 in vitro. Model: Recombinant human EP300 assay with companion human-cell experiments. Limitations: Biochemical inhibition is not proof of selective target engagement after dietary exposure. Evidence access: Primary abstract Spermidine induces autophagy by inhibiting the acetyltransferase EP300. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25526088/ · DOI 10.1038/cdd.2014.215

evidence_access

Primary abstract

experimental_model

Purified recombinant human SAT1 kinetics and structural analysis.

limitations

Acetyl-CoA dependence connects to CoA metabolism, not demonstrated pantothenate depletion.

nutrient_topic

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

plain_language

A CoA-dependent step changes how spermidine is recycled.

primary_references

Mechanistic and structural analysis of human spermidine/spermine N1-acetyltransferase. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17516632/ · DOI 10.1021/bi700256z

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 78–84

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified recombinant human SAT1 kinetics and structural analysis. · source_derived_draft · unverified_draft

## spermidine-sat1-substrate A CoA-dependent step changes how spermidine is recycled. Human SAT1 catalyzes N1-acetylation of spermidine using acetyl-CoA. Model: Purified recombinant human SAT1 kinetics and structural analysis. Limitations: Acetyl-CoA dependence connects to CoA metabolism, not demonstrated pantothenate depletion. Evidence access: Primary abstract Mechanistic and structural analysis of human spermidine/spermine N1-acetyltransferase. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17516632/ · DOI 10.1021/bi700256z

evidence_access

Primary abstract

experimental_model

Mouse embryonic stem-cell metabolism and amino-acid withdrawal experiments.

limitations

Canonical human TDH is nonfunctional; this route is explicitly mouse-specific.

nutrient_topic

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

plain_language

A specialized mouse cell uses threonine as both carbon and one-carbon support.

primary_references

Dependence of mouse embryonic stem cells on threonine catabolism. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19589965/ · DOI 10.1126/science.1173288

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 322–328

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse embryonic stem-cell metabolism and amino-acid withdrawal experiments. · source_derived_draft · unverified_draft

## l-threonine-mouse-tdh-flux A specialized mouse cell uses threonine as both carbon and one-carbon support. Mouse embryonic stem cells expressed abundant Tdh and used mitochondrial threonine catabolism to support glycine and acetyl-CoA generation. Model: Mouse embryonic stem-cell metabolism and amino-acid withdrawal experiments. Limitations: Canonical human TDH is nonfunctional; this route is explicitly mouse-specific. Evidence access: Primary abstract Dependence of mouse embryonic stem cells on threonine catabolism. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19589965/ · DOI 10.1126/science.1173288

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse stem-cell isotope tracing and culture-medium withdrawal.

limitations

Do not generalize to all methylation marks, adult human tissues or a threonine treatment for methylation problems.

nutrient_topic

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

plain_language

A nutrient supply change altered a specific epigenetic mark in this cell model.

primary_references

Influence of threonine metabolism on S-adenosylmethionine and histone methylation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23118012/ · DOI 10.1126/science.1226603

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 330–336

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse stem-cell isotope tracing and culture-medium withdrawal. · source_derived_draft · unverified_draft

## l-threonine-mouse-threonine-methylation A nutrient supply change altered a specific epigenetic mark in this cell model. Threonine withdrawal reduced SAM accumulation and H3K4 trimethylation in mouse embryonic stem cells, with slower growth and increased differentiation. Model: Mouse stem-cell isotope tracing and culture-medium withdrawal. Limitations: Do not generalize to all methylation marks, adult human tissues or a threonine treatment for methylation problems. Evidence access: Primary abstract Influence of threonine metabolism on S-adenosylmethionine and histone methylation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23118012/ · DOI 10.1126/science.1226603

evidence_span

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experimental_model

Purified recombinant NAGS kinetics

exposure

Glutamate, acetyl-CoA and arginine; mature and conserved-domain constructs

limitations

Construct-specific kinetics; no human B5-deficiency or arginine-repletion trial.

nutrient_topic

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

organism

Human and mouse enzymes; human findings specified

plain_language

Arginine can feed back on the upstream nitrogen-disposal pathway.

primary_references

[citrulline-p16321554] Biochemical properties of recombinant human and mouse N-acetylglutamate synthase. (2006). https://pubmed.ncbi.nlm.nih.gov/16321554/ DOI: 10.1016/j.ymgme.2005.10.003

tissue_or_cell_type

N-acetylglutamate formation

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 281–292

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

### citrulline-arginine-nags Arginine approximately doubled the activity of both tested human NAGS constructs. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Arginine can feed back on the upstream nitrogen-disposal pathway. organism: Human and mouse enzymes; human findings specified tissue_or_cell_type: N-acetylglutamate formation experimental_model: Purified recombinant NAGS kinetics limitations: Construct-specific kinetics; no human B5-deficiency or arginine-repletion trial. exposure: Glutamate, acetyl-CoA and arginine; mature and conserved-domain constructs evidence_span: {"source_cache": "artifacts/citrulline-research/16321554.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ce9d57aba8d7973c01de32ab7d5d0287858119fa75f0a372e3ed99523a861a5", "start_char": 0, "end_char": 1498, "text_sha256": "5ce9d57aba8d7973c01de32ab7d5d0287858119fa75f0a372e3ed99523a861a5"} [citrulline-p16321554] Biochemical properties of recombinant human and mouse N-acetylglutamate synthase. (2006). https://pubmed.ncbi.nlm.nih.gov/16321554/ DOI: 10.1016/j.ymgme.2005.10.003

evidence_span

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experimental_model

Purified recombinant NAGS kinetics

exposure

Glutamate, acetyl-CoA and arginine; mature and conserved-domain constructs

limitations

Construct-specific kinetics; no human B5-deficiency or arginine-repletion trial.

nutrient_topic

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

organism

Human and mouse enzymes; human findings specified

plain_language

The activator for CPS1 has its own synthesis step.

primary_references

[citrulline-p16321554] Biochemical properties of recombinant human and mouse N-acetylglutamate synthase. (2006). https://pubmed.ncbi.nlm.nih.gov/16321554/ DOI: 10.1016/j.ymgme.2005.10.003

tissue_or_cell_type

N-acetylglutamate formation

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 255–266

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

### citrulline-nags-product Recombinant human NAGS catalyzed N-acetylglutamate formation from glutamate and acetyl-CoA. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The activator for CPS1 has its own synthesis step. organism: Human and mouse enzymes; human findings specified tissue_or_cell_type: N-acetylglutamate formation experimental_model: Purified recombinant NAGS kinetics limitations: Construct-specific kinetics; no human B5-deficiency or arginine-repletion trial. exposure: Glutamate, acetyl-CoA and arginine; mature and conserved-domain constructs evidence_span: {"source_cache": "artifacts/citrulline-research/16321554.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ce9d57aba8d7973c01de32ab7d5d0287858119fa75f0a372e3ed99523a861a5", "start_char": 0, "end_char": 1498, "text_sha256": "5ce9d57aba8d7973c01de32ab7d5d0287858119fa75f0a372e3ed99523a861a5"} [citrulline-p16321554] Biochemical properties of recombinant human and mouse N-acetylglutamate synthase. (2006). https://pubmed.ncbi.nlm.nih.gov/16321554/ DOI: 10.1016/j.ymgme.2005.10.003

evidence_span

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experimental_model

Time-course Western blot analysis of brain and liver histone acetylation in rats after a single oral dose

exposure

A single oral dose of 6 g/kg glyceryl triacetate, an acetate precursor

limitations

A large single dose of a precursor, not dietary acetate. The mechanism is loss of deacetylation rather than added acetylation, and only some marks moved.

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

Three specific marks on brain histones went up for a few hours; the rest, and the liver, did not move.

primary_references

[acetate-p21359531] Acetate supplementation increases brain histone acetylation and inhibits histone deacetylase activity and expression. (2011). https://pubmed.ncbi.nlm.nih.gov/21359531/ DOI: 10.1007/s11010-011-0751-3

tissue_or_cell_type

Brain and liver

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 654–665

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Time-course Western blot analysis of brain and liver histone acetylation in rats after a single oral dose · source_derived_draft · unverified_draft

### acetate-acetate-brain-histones A single oral dose of glyceryl triacetate increased the acetylation state of brain histone H4 at lysine 8 at 2 and 4 hours, histone H4 at lysine 16 at 4 and 24 hours, and histone H3 at lysine 9 at 4 hours, with no changes in other forms of brain or liver H3 and H4 acetylation state at any time measured. 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: Three specific marks on brain histones went up for a few hours; the rest, and the liver, did not move. organism: Rat tissue_or_cell_type: Brain and liver experimental_model: Time-course Western blot analysis of brain and liver histone acetylation in rats after a single oral dose limitations: A large single dose of a precursor, not dietary acetate. The mechanism is loss of deacetylation rather than added acetylation, and only some marks moved. exposure: A single oral dose of 6 g/kg glyceryl triacetate, an acetate precursor evidence_span: {"source_cache": "artifacts/acetate-research/21359531.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a60e30b6fa78f5fc4d9da17279ec1ecc29dd20939df5771ba26996900102014b", "start_char": 0, "end_char": 1456, "text_sha256": "a60e30b6fa78f5fc4d9da17279ec1ecc29dd20939df5771ba26996900102014b"} [acetate-p21359531] Acetate supplementation increases brain histone acetylation and inhibits histone deacetylase activity and expression. (2011). https://pubmed.ncbi.nlm.nih.gov/21359531/ DOI: 10.1007/s11010-011-0751-3

evidence_span

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experimental_model

Drosophila mutagenesis and RNA interference in enteroendocrine cells of the anterior midgut

exposure

Dietary acetate with disruption of a monocarboxylic acid transporter, of histone deacetylation, and of the Tip60 acetyltransferase

limitations

This is a fly study. The mammalian relevance is the authors’ statement that the Tip60-steroid hormone axis is conserved, not a mammalian measurement.

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

Drosophila

plain_language

Acetate has to be carried inside the cell and turned into a chromatin mark; it is not read at the cell surface.

primary_references

[acetate-p34107298] Microbiota-derived acetate activates intestinal innate immunity via the Tip60 histone acetyltransferase complex. (2021). https://pubmed.ncbi.nlm.nih.gov/34107298/ DOI: 10.1016/j.immuni.2021.05.017

tissue_or_cell_type

Anterior midgut

transport_effect

raises The transporter was required for dietary acetate to reach the intracellular acetyl-CoA route.

transport_pool

the intracellular acetate pool The transporter was required for dietary acetate to reach the intracellular acetyl-CoA route.

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 693–704

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Drosophila mutagenesis and RNA interference in enteroendocrine cells of the anterior midgut · source_derived_draft · unverified_draft

### acetate-acetate-must-enter Mutagenesis and RNA interference revealed that the putative monocarboxylic acid transporter Tarag was essential for enhancement of immunodeficiency pathway signalling by dietary acetate, and reduced expression of the histone acetyltransferase Tip60 decreased that signalling and blocked rescue by dietary acetate and by other sources of intracellular acetyl-CoA, while interference with histone deacetylation augmented transcription of ecdysone-regulated genes including pathway targets. 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: Acetate has to be carried inside the cell and turned into a chromatin mark; it is not read at the cell surface. organism: Drosophila tissue_or_cell_type: Anterior midgut experimental_model: Drosophila mutagenesis and RNA interference in enteroendocrine cells of the anterior midgut limitations: This is a fly study. The mammalian relevance is the authors’ statement that the Tip60-steroid hormone axis is conserved, not a mammalian measurement. exposure: Dietary acetate with disruption of a monocarboxylic acid transporter, of histone deacetylation, and of the Tip60 acetyltransferase evidence_span: {"source_cache": "artifacts/acetate-research/34107298.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4e5644412d174b2512ecf9cedea282b022d647b1b8a82f693a8f389da991425a", "start_char": 0, "end_char": 1179, "text_sha256": "4e5644412d174b2512ecf9cedea282b022d647b1b8a82f693a8f389da991425a"} [acetate-p34107298] Microbiota-derived acetate activates intestinal innate immunity via the Tip60 histone acetyltransferase complex. (2021). https://pubmed.ncbi.nlm.nih.gov/34107298/ DOI: 10.1016/j.immuni.2021.05.017

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"}

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

{"source_cache": "artifacts/acetate-research/31645761.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a7a812a410fd8be3bad8512ab46d4b8a7fd3329d1552ee30965b66860eeb2b2f", "start_char": 0, "end_char": 1646, "text_sha256": "a7a812a410fd8be3bad8512ab46d4b8a7fd3329d1552ee30965b66860eeb2b2f"}

experimental_model

In vivo stable-isotope labelling in mice, with primary hippocampal neurons and behavioural testing

exposure

Labelled alcohol or heavy-labelled acetate administered in vivo, with ACSS2 inhibition and deletion

limitations

Isotope labelling traces the actual carbon atoms onto histones, which is stronger than correlating acetylation with exposure. A mouse study; the fetal result is a single reported exposure.

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

Mouse

plain_language

Atoms from the drink end up on the proteins that package DNA in the brain.

primary_references

[acetate-p31645761] Alcohol metabolism contributes to brain histone acetylation. (2019). https://pubmed.ncbi.nlm.nih.gov/31645761/ DOI: 10.1038/s41586-019-1700-7

tissue_or_cell_type

Brain and gestating fetus

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 615–626

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In vivo stable-isotope labelling in mice, with primary hippocampal neurons and behavioural testing · source_derived_draft · unverified_draft

### acetate-alcohol-to-brain-histones Using in vivo stable-isotope labelling in mice, the metabolism of alcohol contributed to rapid acetylation of histones in the brain, in part through direct deposition of acetyl groups derived from alcohol onto histones in an ACSS2-dependent manner, and a similar direct deposition was observed when mice were injected with heavy-labelled acetate in vivo. 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: Atoms from the drink end up on the proteins that package DNA in the brain. organism: Mouse tissue_or_cell_type: Brain and gestating fetus experimental_model: In vivo stable-isotope labelling in mice, with primary hippocampal neurons and behavioural testing limitations: Isotope labelling traces the actual carbon atoms onto histones, which is stronger than correlating acetylation with exposure. A mouse study; the fetal result is a single reported exposure. exposure: Labelled alcohol or heavy-labelled acetate administered in vivo, with ACSS2 inhibition and deletion evidence_span: {"source_cache": "artifacts/acetate-research/31645761.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a7a812a410fd8be3bad8512ab46d4b8a7fd3329d1552ee30965b66860eeb2b2f", "start_char": 0, "end_char": 1646, "text_sha256": "a7a812a410fd8be3bad8512ab46d4b8a7fd3329d1552ee30965b66860eeb2b2f"} [acetate-p31645761] Alcohol metabolism contributes to brain histone acetylation. (2019). https://pubmed.ncbi.nlm.nih.gov/31645761/ DOI: 10.1038/s41586-019-1700-7

evidence_span

{"source_cache": "artifacts/acetate-research/2106256.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fc8e7ceab96e74e4664a17fce6b32ff0b498204a2c2c0df7437a4f6bfe1c5105", "start_char": 0, "end_char": 1005, "text_sha256": "fc8e7ceab96e74e4664a17fce6b32ff0b498204a2c2c0df7437a4f6bfe1c5105"}

experimental_model

Carbon-labelled acetate infusion in four to six human volunteers and in anaesthetised dogs

exposure

Infusion of acetate labelled at carbon 1 or carbon 2, with recovery measured as labelled carbon dioxide

limitations

A methodological result. It applies to every tracer study of substrate oxidation in this collection and elsewhere, and it means such studies underestimate oxidation unless corrected.

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 and dog

plain_language

Where the label sits on the molecule changes how much comes back out as carbon dioxide, so tracer studies of acetate need correcting.

primary_references

[acetate-p2106256] Recovery of labeled CO2 during the infusion of C-1- vs C-2-labeled acetate: implications for tracer studies of substrate oxidation. (1990). https://pubmed.ncbi.nlm.nih.gov/2106256/ DOI: 10.1093/ajcn/51.2.248

tissue_or_cell_type

Whole body

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 511–522

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Carbon-labelled acetate infusion in four to six human volunteers and in anaesthetised dogs · source_derived_draft · unverified_draft

### acetate-label-position-matters In postabsorptive volunteers 81.2% of infused label was recovered as labelled carbon dioxide from carbon-1 labelled acetate against 53.1% from carbon-2 labelled acetate, and in dogs recovery was 75.9% against 40.8%, leading to the conclusion that the position of the label in acetyl-CoA determines the extent to which oxidation of labelled acetyl-CoA is reflected in labelled carbon dioxide excretion. 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: Where the label sits on the molecule changes how much comes back out as carbon dioxide, so tracer studies of acetate need correcting. organism: Human and dog tissue_or_cell_type: Whole body experimental_model: Carbon-labelled acetate infusion in four to six human volunteers and in anaesthetised dogs limitations: A methodological result. It applies to every tracer study of substrate oxidation in this collection and elsewhere, and it means such studies underestimate oxidation unless corrected. exposure: Infusion of acetate labelled at carbon 1 or carbon 2, with recovery measured as labelled carbon dioxide evidence_span: {"source_cache": "artifacts/acetate-research/2106256.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fc8e7ceab96e74e4664a17fce6b32ff0b498204a2c2c0df7437a4f6bfe1c5105", "start_char": 0, "end_char": 1005, "text_sha256": "fc8e7ceab96e74e4664a17fce6b32ff0b498204a2c2c0df7437a4f6bfe1c5105"} [acetate-p2106256] Recovery of labeled CO2 during the infusion of C-1- vs C-2-labeled acetate: implications for tracer studies of substrate oxidation. (1990). https://pubmed.ncbi.nlm.nih.gov/2106256/ DOI: 10.1093/ajcn/51.2.248

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/acetate-research/32214246.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "302837a9fc88030dce2c74e65053f8baae65863245d2d811ccbb3231b95a99e1", "start_char": 0, "end_char": 1782, "text_sha256": "302837a9fc88030dce2c74e65053f8baae65863245d2d811ccbb3231b95a99e1"}

experimental_model

In vivo isotope tracing in mice with liver-specific Acly deletion, microbiota depletion and hepatic ACSS2 silencing

exposure

Bolus or gradual dietary fructose, with genetic, microbial and dose-rate manipulation

limitations

Three independent manipulations converge on the same route. Its dominance depends on how fast the fructose is eaten, and the human contribution is not established here.

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

Mouse

plain_language

The sugar becomes acetate in the gut, and the liver builds fat out of that.

primary_references

[acetate-p32214246] Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. (2020). https://pubmed.ncbi.nlm.nih.gov/32214246/ DOI: 10.1038/s41586-020-2101-7

tissue_or_cell_type

Liver and gut

trigger_kind

machinery_impairment Imported condition classification; unverified.

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 563–574

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In vivo isotope tracing in mice with liver-specific Acly deletion, microbiota depletion and hepatic ACSS2 silencing · source_derived_draft · unverified_draft

### acetate-microbial-acetate-route Dietary fructose is converted to acetate by the gut microbiota and this supplies lipogenic acetyl-CoA independently of ACLY, with depletion of the microbiota or silencing of hepatic ACSS2, which generates acetyl-CoA from acetate, potently suppressing the conversion of bolus fructose into hepatic acetyl-CoA and fatty acids. Condition category: machinery_impairment 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: The sugar becomes acetate in the gut, and the liver builds fat out of that. organism: Mouse tissue_or_cell_type: Liver and gut experimental_model: In vivo isotope tracing in mice with liver-specific Acly deletion, microbiota depletion and hepatic ACSS2 silencing limitations: Three independent manipulations converge on the same route. Its dominance depends on how fast the fructose is eaten, and the human contribution is not established here. exposure: Bolus or gradual dietary fructose, with genetic, microbial and dose-rate manipulation evidence_span: {"source_cache": "artifacts/acetate-research/32214246.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "302837a9fc88030dce2c74e65053f8baae65863245d2d811ccbb3231b95a99e1", "start_char": 0, "end_char": 1782, "text_sha256": "302837a9fc88030dce2c74e65053f8baae65863245d2d811ccbb3231b95a99e1"} [acetate-p32214246] Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. (2020). https://pubmed.ncbi.nlm.nih.gov/32214246/ DOI: 10.1038/s41586-020-2101-7

access_level

full_text_and_supplement_review

compartment

In vitro reaction, not an intact-cell compartment

dose

Acetyl-CoA present/absent controls; concentrations and incubation details incompletely specified

duration

Not specified in the reviewed methods

endpoint

hadha-assay-construct

evidence_location

Recombinant proteins and acetyl-lysine immunoblot; Figure 6J

experimental_model

Recombinant-protein acetylation assay

exposure

mouse-dlat

limitations

Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Reported acetyltransferase interpretation; do not substitute tissue association for this biochemical evidence.

organism

Recombinant mouse Dlat; HADHA construct sequence species unresolved in reviewed methods

plain_language

Purified mouse Dlat increased the acetyl-lysine signal on recombinant HADHA when acetyl-CoA was present.

primary_locator

[{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 44, "text_sha256": "e0a92f47bc76c894816706ffb5158242c968928ac61e4561262c370035eda621", "xml_element_id": "Par19"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 46, "text_sha256": "d56a90702bdf004de1efc2e43103b1b771e15b38288dc01f3741676782b1f5ff", "xml_element_id": null}]

primary_references

https://doi.org/10.1038/s41467-026-70703-w

sample_size

4 biological replicates

tissue_or_cell_type

Purified-protein reaction

DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 52–67

AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Recombinant-protein acetylation assay · source_derived_draft · unverified_draft

Purified mouse Dlat increased the acetyl-lysine signal on recombinant HADHA when acetyl-CoA was present. organism: Recombinant mouse Dlat; HADHA construct sequence species unresolved in reviewed methods tissue_or_cell_type: Purified-protein reaction experimental_model: Recombinant-protein acetylation assay compartment: In vitro reaction, not an intact-cell compartment dose: Acetyl-CoA present/absent controls; concentrations and incubation details incompletely specified duration: Not specified in the reviewed methods primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: Recombinant proteins and acetyl-lysine immunoblot; Figure 6J endpoint: hadha-assay-construct exposure: mouse-dlat limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Reported acetyltransferase interpretation; do not substitute tissue association for this biochemical evidence. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 44, "text_sha256": "e0a92f47bc76c894816706ffb5158242c968928ac61e4561262c370035eda621", "xml_element_id": "Par19"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 46, "text_sha256": "d56a90702bdf004de1efc2e43103b1b771e15b38288dc01f3741676782b1f5ff", "xml_element_id": null}] plain_language: Purified mouse Dlat increased the acetyl-lysine signal on recombinant HADHA when acetyl-CoA was present. sample_size: 4 biological replicates

access_level

full_text_and_supplement_review

compartment

In vitro reaction, not an intact-cell compartment

dose

Acetyl-CoA present/absent controls; concentrations and incubation details incompletely specified

duration

Not specified in the reviewed methods

endpoint

hadha-construct-lysine-acetylation

evidence_location

Figure 7E

experimental_model

Recombinant-protein acetylation assay

exposure

hadha-k728r-construct

limitations

Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. A construct-dependent result, not direct residue-specific occupancy quantification or a mouse-heart mutant experiment.

organism

Recombinant mouse Dlat; HADHA construct sequence species unresolved in reviewed methods

plain_language

Dlat produced no detectable acetyl-lysine signal on the tested recombinant K728R HADHA construct.

primary_locator

[{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 48, "text_sha256": "134dcda50e7eafd608062a092c3cab71e5febe5935586f7d7d478988d6a3ea8e", "xml_element_id": "Par20"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 50, "text_sha256": "ef3c37a398cc33c2cac08d4fc06ef96648c5fcda5ce3de26387b1afb609af2bf", "xml_element_id": null}]

primary_references

https://doi.org/10.1038/s41467-026-70703-w

sample_size

4 biological replicates

tissue_or_cell_type

Purified-protein reaction

DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 142–157

AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Recombinant-protein acetylation assay · source_derived_draft · unverified_draft

Dlat produced no detectable acetyl-lysine signal on the tested recombinant K728R HADHA construct. organism: Recombinant mouse Dlat; HADHA construct sequence species unresolved in reviewed methods tissue_or_cell_type: Purified-protein reaction experimental_model: Recombinant-protein acetylation assay compartment: In vitro reaction, not an intact-cell compartment dose: Acetyl-CoA present/absent controls; concentrations and incubation details incompletely specified duration: Not specified in the reviewed methods primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: Figure 7E endpoint: hadha-construct-lysine-acetylation exposure: hadha-k728r-construct limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. A construct-dependent result, not direct residue-specific occupancy quantification or a mouse-heart mutant experiment. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 48, "text_sha256": "134dcda50e7eafd608062a092c3cab71e5febe5935586f7d7d478988d6a3ea8e", "xml_element_id": "Par20"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 50, "text_sha256": "ef3c37a398cc33c2cac08d4fc06ef96648c5fcda5ce3de26387b1afb609af2bf", "xml_element_id": null}] plain_language: Dlat produced no detectable acetyl-lysine signal on the tested recombinant K728R HADHA construct. sample_size: 4 biological replicates

access_level

full_text_and_supplement_review

compartment

Mitochondria or cell lysate, depending on assay

dose

Adenovirus MOI 50:1 where applicable; compound concentrations not specified in reviewed methods

duration

Adenovirus incubation 6–8 h; subsequent endpoint timing not consistently specified

endpoint

fatty-acid-oxidation

evidence_location

13C-palmitate tracing; Figure 6L

experimental_model

Adenoviral/cell perturbation study

exposure

rat-dlat-overexpression

limitations

Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Reported metabolite-labeling pattern supports impaired breakdown; it does not itself establish every kinetic step or isolate HADHA from other Dlat effects.

organism

Rattus norvegicus host cells; construct species may be unspecified

plain_language

Dlat-overexpressing rat cardiomyocytes retained more labeled palmitoyl-CoA and showed less label in shorter acyl-CoAs and acetyl-CoA.

primary_locator

[{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 44, "text_sha256": "e0a92f47bc76c894816706ffb5158242c968928ac61e4561262c370035eda621", "xml_element_id": "Par19"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 46, "text_sha256": "d56a90702bdf004de1efc2e43103b1b771e15b38288dc01f3741676782b1f5ff", "xml_element_id": null}]

primary_references

https://doi.org/10.1038/s41467-026-70703-w

sample_size

4 per group

tissue_or_cell_type

Neonatal rat ventricular cardiomyocytes (NRVCMs)

DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 214–229

AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Adenoviral/cell perturbation study · source_derived_draft · unverified_draft

Dlat-overexpressing rat cardiomyocytes retained more labeled palmitoyl-CoA and showed less label in shorter acyl-CoAs and acetyl-CoA. organism: Rattus norvegicus host cells; construct species may be unspecified tissue_or_cell_type: Neonatal rat ventricular cardiomyocytes (NRVCMs) experimental_model: Adenoviral/cell perturbation study compartment: Mitochondria or cell lysate, depending on assay dose: Adenovirus MOI 50:1 where applicable; compound concentrations not specified in reviewed methods duration: Adenovirus incubation 6–8 h; subsequent endpoint timing not consistently specified primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: 13C-palmitate tracing; Figure 6L endpoint: fatty-acid-oxidation exposure: rat-dlat-overexpression limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Reported metabolite-labeling pattern supports impaired breakdown; it does not itself establish every kinetic step or isolate HADHA from other Dlat effects. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 44, "text_sha256": "e0a92f47bc76c894816706ffb5158242c968928ac61e4561262c370035eda621", "xml_element_id": "Par19"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 46, "text_sha256": "d56a90702bdf004de1efc2e43103b1b771e15b38288dc01f3741676782b1f5ff", "xml_element_id": null}] plain_language: Dlat-overexpressing rat cardiomyocytes retained more labeled palmitoyl-CoA and showed less label in shorter acyl-CoAs and acetyl-CoA. sample_size: 4 per group

experimental_model

Human p300 catalytic-domain structure and biochemical assays.

limitations

This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome.

organism

Human

plain_language

Acetyl groups can be written onto lysines already present in proteins.

primary_references

[p300-2008] The structural basis of protein acetylation by the p300/CBP transcriptional coactivator (2008). https://pubmed.ncbi.nlm.nih.gov/18273021/ DOI: 10.1038/nature06546

tissue_or_cell_type

Not specified as a whole tissue; see experimental model.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 527–535

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human p300 catalytic-domain structure and biochemical assays. · source_derived_draft · unverified_draft

### ep300-lysine-acetylation EP300 transfers an acetyl group from acetyl-CoA to a protein lysine side chain. Plain language: Acetyl groups can be written onto lysines already present in proteins. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human p300 catalytic-domain structure and biochemical assays. limitations: This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [p300-2008] The structural basis of protein acetylation by the p300/CBP transcriptional coactivator (2008). https://pubmed.ncbi.nlm.nih.gov/18273021/ DOI: 10.1038/nature06546

availability_state

machinery_impairment Imported condition classification; unverified.

dose

Bolus 2 g/kg labeled fructose plus 2 g/kg glucose; interventions specified by claim

duration

Acute isotope sampling up to 6 h

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Wild-type mice, microbiota depletion and liver Acss2-silencing experiments

exposure_scope

Component mixture

limitations

Carbon tracing supports microbial acetate supply; antibiotic depletion is not a clinical recommendation and microbiota effects are not universal across diets.

nutrient_topic

HFCS chapter: actual formulation studies, component biochemistry and interventions are explicitly distinguished. · High-Fructose Corn Syrup / HFCS

organism

Wild-type mice, microbiota depletion and liver Acss2-silencing experiments

plain_language

Silencing hepatic Acss2 suppressed conversion of bolus fructose carbon into hepatic acetyl-CoA and fatty acids in mice.

primary_references

Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. (2020). https://pubmed.ncbi.nlm.nih.gov/32214246/ DOI: 10.1038/s41586-020-2101-7

route

Oral gavage and experimental microbiota/gene perturbation

tissue

Portal acetate and hepatic fatty-acid labeling

trigger_kind

machinery_impairment Imported condition classification; unverified.

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 221–231

Original AI-assisted curation of twenty primary studies and official FDA composition information, with one reused canonical glucose-transport claim. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Wild-type mice, microbiota depletion and liver Acss2-silencing experiments · source_derived_draft · unverified_draft

## hfcs-acss2-silencing Silencing hepatic Acss2 suppressed conversion of bolus fructose carbon into hepatic acetyl-CoA and fatty acids in mice. Model/species: Wild-type mice, microbiota depletion and liver Acss2-silencing experiments Tissue: Portal acetate and hepatic fatty-acid labeling Exposure: Bolus 2 g/kg labeled fructose plus 2 g/kg glucose; interventions specified by claim Route: Oral gavage and experimental microbiota/gene perturbation Duration: Acute isotope sampling up to 6 h Exposure scope: Component mixture Limits: Carbon tracing supports microbial acetate supply; antibiotic depletion is not a clinical recommendation and microbiota effects are not universal across diets. Reference: Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. (2020). https://pubmed.ncbi.nlm.nih.gov/32214246/ DOI: 10.1038/s41586-020-2101-7 Access: Primary full-text methods/results and metadata inspected.

evidence_access

Primary abstract and indexed full-text introduction, PMC2924059

experimental_model

Human HMGCL structural study; reaction in primary introduction.

limitations

Mitochondrial pathway; net flux is not inferred from structure alone.

nutrient_topic

Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake

plain_language

A second enzyme releases the first ketone body.

primary_references

Functional insights into human HMG-CoA lyase from structures of Acyl-CoA-containing ternary complexes. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20558737/ · DOI 10.1074/jbc.M110.139931

Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 112–118

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human HMGCL structural study; reaction in primary introduction. · source_derived_draft · unverified_draft

## fast-hmgcl A second enzyme releases the first ketone body. Human HMGCL cleaves HMG-CoA to acetoacetate and acetyl-CoA. Model: Human HMGCL structural study; reaction in primary introduction. Limitations: Mitochondrial pathway; net flux is not inferred from structure alone. Evidence access: Primary abstract and indexed full-text introduction, PMC2924059 Functional insights into human HMG-CoA lyase from structures of Acyl-CoA-containing ternary complexes. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20558737/ · DOI 10.1074/jbc.M110.139931

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human patient genetic study with functional expression characterization.

limitations

A single rare disorder is not evidence of dietary aspartate deficiency or that supplying aspartate fixes the defect.

nutrient_topic

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

plain_language

Lack of the derived metabolite can reflect faulty synthesis machinery.

primary_references

Molecular identification of aspartate N-acetyltransferase and its mutation in hypoacetylaspartia. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19807691/ · DOI 10.1042/BJ20091024

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 386–392

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human patient genetic study with functional expression characterization. · source_derived_draft · unverified_draft

## l-aspartate-human-nat8l-loss Lack of the derived metabolite can reflect faulty synthesis machinery. A homozygous 19-base-pair NAT8L deletion in a patient with absent brain NAA produced a frameshift and failure to produce a functional enzyme. Model: Human patient genetic study with functional expression characterization. Limitations: A single rare disorder is not evidence of dietary aspartate deficiency or that supplying aspartate fixes the defect. Evidence access: Primary abstract Molecular identification of aspartate N-acetyltransferase and its mutation in hypoacetylaspartia. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19807691/ · DOI 10.1042/BJ20091024

evidence_access

Primary abstract and primary methods/figure text

experimental_model

Mouse-brain cDNA constructs in hamster/human cell hosts; product identified by HPLC and tandem mass spectrometry.

limitations

Host-cell species is not the enzyme species; no dietary brain-delivery effect was tested.

nutrient_topic

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

plain_language

Aspartate-derived NAA can feed a second, glutamate-containing product.

primary_references

Molecular characterization of N-acetylaspartylglutamate synthetase. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20643647/ · DOI 10.1074/jbc.M110.111765

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 370–376

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse-brain cDNA constructs in hamster/human cell hosts; product identified by HPLC and tandem mass spectrometry. · source_derived_draft · unverified_draft

## l-aspartate-naa-naag-supply Aspartate-derived NAA can feed a second, glutamate-containing product. Coexpressing mouse Nat8l and Rimklb in CHO-K1 or HEK293T cells enabled NAAG production from the NAA-synthesis pathway. Model: Mouse-brain cDNA constructs in hamster/human cell hosts; product identified by HPLC and tandem mass spectrometry. Limitations: Host-cell species is not the enzyme species; no dietary brain-delivery effect was tested. Evidence access: Primary abstract and primary methods/figure text Molecular characterization of N-acetylaspartylglutamate synthetase. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20643647/ · DOI 10.1074/jbc.M110.111765

cross_nutrient

true

experimental_model

Human PANK2 in 293T-cell lysates and purified enzyme assays

exposure

Primary Fig. 4B purified-enzyme assay; carnitine concentration range not extracted.

limitations

The same paper observed free-carnitine activation in lysate preparations at higher concentrations, so the purified-enzyme negative result must not be generalized to every lysate condition. Neither assay tests clinical carnitine 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

The purified enzyme did not respond directly to free carnitine.

primary_references

[b5-bio-pank2reg] Activation of human mitochondrial pantothenate kinase 2 by palmitoylcarnitine. (2007). https://pubmed.ncbi.nlm.nih.gov/17242360/ DOI: 10.1073/pnas.0607621104

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 626–637

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human PANK2 in 293T-cell lysates and purified enzyme assays · source_derived_draft · unverified_draft

### b5-bio-pank2-free-carnitine Free carnitine did not activate purified human PANK2 in the experiment shown in Fig. 4B. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The purified enzyme did not respond directly to free carnitine. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Human PANK2 in 293T-cell lysates and purified enzyme assays limitations: The same paper observed free-carnitine activation in lysate preparations at higher concentrations, so the purified-enzyme negative result must not be generalized to every lysate condition. Neither assay tests clinical carnitine supplementation. exposure: Primary Fig. 4B purified-enzyme assay; carnitine concentration range not extracted. cross_nutrient: true [b5-bio-pank2reg] Activation of human mitochondrial pantothenate kinase 2 by palmitoylcarnitine. (2007). https://pubmed.ncbi.nlm.nih.gov/17242360/ DOI: 10.1073/pnas.0607621104

cross_nutrient

true

experimental_model

Human PANK2 in 293T-cell lysates and purified enzyme assays

exposure

Human PANK2 in 293T lysates and purified-enzyme assays; indexed Fig. 1 used 0.2 micromolar acetyl-CoA.

limitations

Acylcarnitine is a specific molecule; this does not show that free-carnitine supplements activate PANK2 in people. Intact-organism fatty-acid-demand interpretation was proposed.

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

A long-chain acylcarnitine can release the brake on PANK2.

primary_references

[b5-bio-pank2reg] Activation of human mitochondrial pantothenate kinase 2 by palmitoylcarnitine. (2007). https://pubmed.ncbi.nlm.nih.gov/17242360/ DOI: 10.1073/pnas.0607621104

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 613–624

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human PANK2 in 293T-cell lysates and purified enzyme assays · source_derived_draft · unverified_draft

### b5-bio-pank2-palmitoylcarnitine Palmitoylcarnitine antagonized acetyl-CoA inhibition of human PANK2, providing a positive regulatory input in biochemical assays. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A long-chain acylcarnitine can release the brake on PANK2. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Human PANK2 in 293T-cell lysates and purified enzyme assays limitations: Acylcarnitine is a specific molecule; this does not show that free-carnitine supplements activate PANK2 in people. Intact-organism fatty-acid-demand interpretation was proposed. exposure: Human PANK2 in 293T lysates and purified-enzyme assays; indexed Fig. 1 used 0.2 micromolar acetyl-CoA. cross_nutrient: true [b5-bio-pank2reg] Activation of human mitochondrial pantothenate kinase 2 by palmitoylcarnitine. (2007). https://pubmed.ncbi.nlm.nih.gov/17242360/ DOI: 10.1073/pnas.0607621104

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

evidence_location

BioC text lines 11, 51; Fig. 2A–B

experimental_model

ACLY and/or AceCS1 siRNA with acetate supplementation

exposure

0, 1 or 5 mM acetate for 24 hours before lysis after siRNA treatment.

limitations

The authors identify this acetate supply as supraphysiologic; it is not a dietary recommendation and does not show rescue of an absent CoA pool. 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

A second acetyl-CoA-producing route could compensate when enough acetate was supplied.

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

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1005–1017

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ACLY and/or AceCS1 siRNA with acetate supplementation · source_derived_draft · unverified_draft

### b5-met-acetate-acss2-histone-rescue Extracellular acetate restored histone acetylation in ACLY-silenced HCT116 cells in a dose-dependent manner that required AceCS1, now named ACSS2. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second acetyl-CoA-producing route could compensate when enough acetate was supplied. organism: Homo sapiens tissue_or_cell_type: HCT116 cells experimental_model: ACLY and/or AceCS1 siRNA with acetate supplementation limitations: The authors identify this acetate supply as supraphysiologic; it is not a dietary recommendation and does not show rescue of an absent CoA pool. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: 0, 1 or 5 mM acetate for 24 hours before lysis after siRNA treatment. cross_nutrient: false evidence_location: BioC text lines 11, 51; Fig. 2A–B [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

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

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

false

evidence_location

Full text lines 123–125, 173, 229; Fig. 4F; Extended Data Fig. 5G–H

experimental_model

Matched PA-free/control diets in NOD/Scid mice bearing orthotopic human HCI002 breast-cancer xenografts

exposure

Diets introduced at 6 weeks of age, progressively over 4 days; typically 5 weeks on the assigned diet before implantation and continued until collection. PA absence verified by LC-MS; control was composition-matched with PA added. Control n=7, PA-free n=8 tumors from independent mice.

limitations

The same paper found no significant fall in the corresponding CoA/acetyl-CoA pools in WMmix tumors. Tumor concentration and tracer labeling do not establish universal CoA depletion or a human anticancer diet; cellular composition and pool size can affect the measured label. 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

Human HCI002 grafts in Mus musculus hosts

plain_language

Direct B5 restriction lowered the tumor CoA pool in this particular graft model.

primary_references

[b5-met-myc2024] Vitamin B<sub>5</sub> supports MYC oncogenic metabolism and tumor progression in breast cancer. (2023). https://pubmed.ncbi.nlm.nih.gov/37946084/ DOI: 10.1038/s42255-023-00915-7

tissue_or_cell_type

Orthotopic HCI002 tumor tissue

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1103–1115

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Matched PA-free/control diets in NOD/Scid mice bearing orthotopic human HCI002 breast-cancer xenografts · source_derived_draft · unverified_draft

### b5-met-diet-hci002-coa A pantothenate-free diet reduced free CoA measured in human HCI002 breast-cancer xenografts grown in mice. Condition category: nutrient_deficiency nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Direct B5 restriction lowered the tumor CoA pool in this particular graft model. organism: Human HCI002 grafts in Mus musculus hosts tissue_or_cell_type: Orthotopic HCI002 tumor tissue experimental_model: Matched PA-free/control diets in NOD/Scid mice bearing orthotopic human HCI002 breast-cancer xenografts limitations: The same paper found no significant fall in the corresponding CoA/acetyl-CoA pools in WMmix tumors. Tumor concentration and tracer labeling do not establish universal CoA depletion or a human anticancer diet; cellular composition and pool size can affect the measured label. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Diets introduced at 6 weeks of age, progressively over 4 days; typically 5 weeks on the assigned diet before implantation and continued until collection. PA absence verified by LC-MS; control was composition-matched with PA added. Control n=7, PA-free n=8 tumors from independent mice. cross_nutrient: false evidence_location: Full text lines 123–125, 173, 229; Fig. 4F; Extended Data Fig. 5G–H [b5-met-myc2024] Vitamin B<sub>5</sub> supports MYC oncogenic metabolism and tumor progression in breast cancer. (2023). https://pubmed.ncbi.nlm.nih.gov/37946084/ DOI: 10.1038/s42255-023-00915-7

cross_nutrient

true

evidence_location

BioC text line 21; Fig. 3B–C

experimental_model

Serum stimulation with/without glucose and Acly siRNA

exposure

Experimental serum stimulation and glucose withdrawal; no selective pantothenate deprivation.

limitations

Glucose was the experimentally varied fuel. This is not evidence of B5 deficiency; cellular acetyl-CoA sources differ by context. 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

Mus musculus

plain_language

Glucose supply affected histone acetylation through an acetyl-CoA-producing enzyme in this cell model.

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

Immortalized mouse embryonic fibroblasts

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1019–1031

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Serum stimulation with/without glucose and Acly siRNA · source_derived_draft · unverified_draft

### b5-met-glucose-acly-histones Serum-induced histone acetylation in immortalized mouse embryonic fibroblasts depended on glucose availability and was prevented by Acly silencing. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glucose supply affected histone acetylation through an acetyl-CoA-producing enzyme in this cell model. organism: Mus musculus tissue_or_cell_type: Immortalized mouse embryonic fibroblasts experimental_model: Serum stimulation with/without glucose and Acly siRNA limitations: Glucose was the experimentally varied fuel. This is not evidence of B5 deficiency; cellular acetyl-CoA sources differ by context. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Experimental serum stimulation and glucose withdrawal; no selective pantothenate deprivation. cross_nutrient: true evidence_location: BioC text line 21; Fig. 3B–C [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