Human acetyl-CoA synthetase 2 / ACSS2

Where it participates (unsigned role)

1. In isolated primary hippocampal neurons ex vivo, extracellular acetate induced transcriptional programs related to learning and memory which were sensitive to ACSS2 inhibition, and alcohol-related associative learning was shown to require ACSS2 in vivo.

   Acetate → Transcriptional programs related to learning and memory in hippocampal neurons source_derived_draftungraded
   Experimental context and source evidence

   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

   Acetate outside the neuron switches on the genes of learning, and blocking the enzyme that uses it blocks the learning too.

   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 641–652

   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-acetate-learning-programs In isolated primary hippocampal neurons ex vivo, extracellular acetate induced transcriptional programs related to learning and memory which were sensitive to ACSS2 inhibition, and alcohol-related associative learning was shown to require ACSS2 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: Acetate outside the neuron switches on the genes of learning, and blocking the enzyme that uses it blocks the learning too. 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

   Complete structured claim and evidence

2. 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.

   Acetate derived from hepatic alcohol metabolism → Histone acetylation in brain neurons source_derived_draftungraded
   Experimental context and source evidence

   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

   Complete structured claim and evidence

3. Exogenous acetate uptake is controlled by expression of both ACSS2 and the mitochondrial ACSS1, and the mitochondrial and lipogenic demand for two-carbon acetyl units considerably exceeds the uptake of exogenous acetate, leaving it to only sparingly contribute to histone acetylation.

   Uptake of acetate from outside the cell → Core histone lysine acetylation source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/acetate-research/28099844.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6df5e8ccde04ad8a222db774f6a8b1e8838ad6a1d918ff84b667d6dde57de188", "start_char": 0, "end_char": 1134, "text_sha256": "6df5e8ccde04ad8a222db774f6a8b1e8838ad6a1d918ff84b667d6dde57de188"}

   experimental_model

   Quantitative analysis of acetate metabolism in cultured cells under oxygen and serum limitation

   exposure

   Exogenous acetate with ACSS2 and ACSS1 manipulation under oxygen and serum limitation

   limitations

   The quantitative accounting here is the important part and it is a limiting result: demand for two-carbon units far exceeds what exogenous acetate supplies. Cultured cells at a given acetate concentration, which is not a fed human.

   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

   Cultured cells

   plain_language

   Acetate taken in from outside is mostly burned or built into fat; very little of it reaches the histones.

   primary_references

   [acetate-p28099844] Acetate Recapturing by Nuclear Acetyl-CoA Synthetase 2 Prevents Loss of Histone Acetylation during Oxygen and Serum Limitation. (2017). https://pubmed.ncbi.nlm.nih.gov/28099844/ DOI: 10.1016/j.celrep.2016.12.055

   tissue_or_cell_type

   Nucleus and cytosol

   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 589–600

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantitative analysis of acetate metabolism in cultured cells under oxygen and serum limitation · source_derived_draft · unverified_draft

   ### acetate-exogenous-acetate-sparing Exogenous acetate uptake is controlled by expression of both ACSS2 and the mitochondrial ACSS1, and the mitochondrial and lipogenic demand for two-carbon acetyl units considerably exceeds the uptake of exogenous acetate, leaving it to only sparingly contribute to histone acetylation. 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 taken in from outside is mostly burned or built into fat; very little of it reaches the histones. organism: Cultured cells tissue_or_cell_type: Nucleus and cytosol experimental_model: Quantitative analysis of acetate metabolism in cultured cells under oxygen and serum limitation limitations: The quantitative accounting here is the important part and it is a limiting result: demand for two-carbon units far exceeds what exogenous acetate supplies. Cultured cells at a given acetate concentration, which is not a fed human. exposure: Exogenous acetate with ACSS2 and ACSS1 manipulation under oxygen and serum limitation evidence_span: {"source_cache": "artifacts/acetate-research/28099844.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6df5e8ccde04ad8a222db774f6a8b1e8838ad6a1d918ff84b667d6dde57de188", "start_char": 0, "end_char": 1134, "text_sha256": "6df5e8ccde04ad8a222db774f6a8b1e8838ad6a1d918ff84b667d6dde57de188"} [acetate-p28099844] Acetate Recapturing by Nuclear Acetyl-CoA Synthetase 2 Prevents Loss of Histone Acetylation during Oxygen and Serum Limitation. (2017). https://pubmed.ncbi.nlm.nih.gov/28099844/ DOI: 10.1016/j.celrep.2016.12.055

   Complete structured claim and evidence

4. In a pregnant mouse, exposure to labelled alcohol resulted in the incorporation of labelled acetyl groups into gestating fetal brains.

   Ethanol → Acetyl groups incorporated into gestating fetal brains source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   biomarker_context Imported condition classification; unverified.

   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

   The same atoms cross into the fetus and land on the chromatin of its developing 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

   trigger_kind

   biomarker_context 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 628–639

   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-maternal-alcohol-fetal-brain In a pregnant mouse, exposure to labelled alcohol resulted in the incorporation of labelled acetyl groups into gestating fetal brains. Condition category: biomarker_context 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 same atoms cross into the fetus and land on the chromatin of its developing 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

   Complete structured claim and evidence

5. 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.

   Acetate produced from dietary fructose by the gut microbiota → De novo lipogenesis source_derived_draftungraded
   Experimental context and source evidence

   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

   Complete structured claim and evidence

6. Oxygen and serum limitation increased nuclear localisation of ACSS2, and nuclear ACSS2 recaptures acetate released from histone deacetylation for recycling by histone acetyltransferases, providing evidence for limited equilibration between nuclear and cytosolic acetyl-CoA and demonstrating that ACSS2 retains acetate to maintain histone acetylation.

   Chromatin-bound nuclear acetyl-CoA synthetase 2 → Core histone lysine acetylation source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/acetate-research/28099844.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6df5e8ccde04ad8a222db774f6a8b1e8838ad6a1d918ff84b667d6dde57de188", "start_char": 0, "end_char": 1134, "text_sha256": "6df5e8ccde04ad8a222db774f6a8b1e8838ad6a1d918ff84b667d6dde57de188"}

   experimental_model

   Quantitative analysis of acetate metabolism in cultured cells under oxygen and serum limitation

   exposure

   Exogenous acetate with ACSS2 and ACSS1 manipulation under oxygen and serum limitation

   limitations

   The quantitative accounting here is the important part and it is a limiting result: demand for two-carbon units far exceeds what exogenous acetate supplies. Cultured cells at a given acetate concentration, which is not a fed human.

   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

   Cultured cells

   plain_language

   An enzyme sitting on the chromatin catches the acetate released when marks are removed, and puts it straight back.

   primary_references

   [acetate-p28099844] Acetate Recapturing by Nuclear Acetyl-CoA Synthetase 2 Prevents Loss of Histone Acetylation during Oxygen and Serum Limitation. (2017). https://pubmed.ncbi.nlm.nih.gov/28099844/ DOI: 10.1016/j.celrep.2016.12.055

   tissue_or_cell_type

   Nucleus and cytosol

   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 602–613

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantitative analysis of acetate metabolism in cultured cells under oxygen and serum limitation · source_derived_draft · unverified_draft

   ### acetate-nuclear-acss2-recapture Oxygen and serum limitation increased nuclear localisation of ACSS2, and nuclear ACSS2 recaptures acetate released from histone deacetylation for recycling by histone acetyltransferases, providing evidence for limited equilibration between nuclear and cytosolic acetyl-CoA and demonstrating that ACSS2 retains acetate to maintain histone acetylation. 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: An enzyme sitting on the chromatin catches the acetate released when marks are removed, and puts it straight back. organism: Cultured cells tissue_or_cell_type: Nucleus and cytosol experimental_model: Quantitative analysis of acetate metabolism in cultured cells under oxygen and serum limitation limitations: The quantitative accounting here is the important part and it is a limiting result: demand for two-carbon units far exceeds what exogenous acetate supplies. Cultured cells at a given acetate concentration, which is not a fed human. exposure: Exogenous acetate with ACSS2 and ACSS1 manipulation under oxygen and serum limitation evidence_span: {"source_cache": "artifacts/acetate-research/28099844.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6df5e8ccde04ad8a222db774f6a8b1e8838ad6a1d918ff84b667d6dde57de188", "start_char": 0, "end_char": 1134, "text_sha256": "6df5e8ccde04ad8a222db774f6a8b1e8838ad6a1d918ff84b667d6dde57de188"} [acetate-p28099844] Acetate Recapturing by Nuclear Acetyl-CoA Synthetase 2 Prevents Loss of Histone Acetylation during Oxygen and Serum Limitation. (2017). https://pubmed.ncbi.nlm.nih.gov/28099844/ DOI: 10.1016/j.celrep.2016.12.055

   Complete structured claim and evidence

7. Extracellular acetate restored histone acetylation in ACLY-silenced HCT116 cells in a dose-dependent manner that required AceCS1, now named ACSS2.

   Acetate → Core histone lysine acetylation source_derived_draftungraded
   Experimental context and source evidence

   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

   Complete structured claim and evidence