Component

Human ATP-citrate lyase / ACLY

Human ATP-citrate lyase / ACLY. Identity is distinct from its gene and experimentally modified states; see each claim for organism and scope.

5 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. Hydroxycitrate did not affect the incorporation of acetate or butyrate carbon into lipids even though it inhibited colonic ATP-citrate lyase, suggesting that the short-chain fatty acid carbon used in lipid synthesis by colonocytes is not transported to the cytosol as citrate, and that colonocytes synthesise lipids by a pathway distinct from the liver.

    Human ATP-citrate lyase / ACLY → De novo lipogenesis source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/acetate-research/14608066.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b2c891f60d02b85a8f4e87f26751f1129b0445fe52fb35ca5e5e20a92d4ecc5a", "start_char": 0, "end_char": 1642, "text_sha256": "b2c891f60d02b85a8f4e87f26751f1129b0445fe52fb35ca5e5e20a92d4ecc5a"}
    experimental_model
    Rat colonic epithelial cells with competing labelled substrates and ATP-citrate lyase inhibition
    exposure
    Labelled acetate, propionate, butyrate, 3-hydroxybutyrate, glucose and glutamine, with hydroxycitrate as an ATP-citrate lyase inhibitor
    limitations
    An isolated cell measurement. Its ATP-citrate lyase result anticipates by seventeen years the in vivo finding in this collection that lipogenic acetyl-CoA can arrive without that enzyme.
    nutrient_topic
    Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid
    organism
    Rat
    plain_language
    Blocking the usual enzyme changed nothing, so the carbon was arriving another way.
    primary_references
    [acetate-p14608066] Acetate and butyrate are the major substrates for de novo lipogenesis in rat colonic epithelial cells. (2003). https://pubmed.ncbi.nlm.nih.gov/14608066/ DOI: 10.1093/jn/133.11.3509
    tissue_or_cell_type
    Colonic epithelium

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

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

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

  2. ACLY silencing reduced acetylation of the core histones assayed in HCT116 cells.

    Human ATP-citrate lyase / ACLY → Core histone lysine acetylation source_derived_draftungraded
    Experimental context and source evidence
    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
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Using in vivo isotope tracing, liver-specific deletion of Acly in mice was unable to suppress fructose-induced lipogenesis.

    Liver-specific ATP citrate lyase knockout mouse genotype → 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
    Deleting the enzyme everyone assumed was responsible did not stop the fat being made.
    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 550–561

    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-acly-deletion-insufficient Using in vivo isotope tracing, liver-specific deletion of Acly in mice was unable to suppress fructose-induced lipogenesis. 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: Deleting the enzyme everyone assumed was responsible did not stop the fat being made. 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

  2. When fructose is consumed more gradually to facilitate its absorption in the small intestine, both citrate cleavage in hepatocytes and microorganism-derived acetate contribute to lipogenesis, whereas the lipogenic transcriptional program is activated in response to fructose independently of acetyl-CoA metabolism, revealing a two-pronged mechanism in which fructolysis within hepatocytes provides the signal to express lipogenic genes while microbial acetate feeds the lipogenic acetyl-CoA pools.

    Fructose consumed as a single bolus rather than gradually → De novo lipogenesis source_derived_draftungraded
    Experimental context and source evidence
    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
    How fast the sugar is eaten decides which of the two routes supplies the carbon; the signal that switches the genes on is separate from either.
    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

    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 576–587

    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-intake-rate-decides When fructose is consumed more gradually to facilitate its absorption in the small intestine, both citrate cleavage in hepatocytes and microorganism-derived acetate contribute to lipogenesis, whereas the lipogenic transcriptional program is activated in response to fructose independently of acetyl-CoA metabolism, revealing a two-pronged mechanism in which fructolysis within hepatocytes provides the signal to express lipogenic genes while microbial acetate feeds the lipogenic acetyl-CoA pools. 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: How fast the sugar is eaten decides which of the two routes supplies the carbon; the signal that switches the genes on is separate from either. 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

  3. 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

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards