Component

Acetoacetate

Independent small molecule record; interpretation is limited by each linked claim and its study context.

11 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. Mouse hippocampal slices exposed to 10 mM lithium acetoacetate had lower miniature excitatory-current amplitude and frequency than lithium-chloride controls.

    Acetoacetate → Mouse hippocampal miniature excitatory postsynaptic currents source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Mouse acute slices incubated for more than two hours; lithium matched between groups.
    limitations
    High bath exposure and slice conditions are explicit; do not substitute an oral ketone dose or attribute the difference to unmatched lithium.
    nutrient_topic
    L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
    plain_language
    A controlled slice experiment connected the transport finding with synaptic output.
    primary_references
    Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002

    L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 298–304

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse acute slices incubated for more than two hours; lithium matched between groups. · source_derived_draft · unverified_draft

    ## glutamate-ketone-synaptic-response A controlled slice experiment connected the transport finding with synaptic output. Mouse hippocampal slices exposed to 10 mM lithium acetoacetate had lower miniature excitatory-current amplitude and frequency than lithium-chloride controls. Model: Mouse acute slices incubated for more than two hours; lithium matched between groups. Limitations: High bath exposure and slice conditions are explicit; do not substitute an oral ketone dose or attribute the difference to unmatched lithium. Evidence access: Primary full text Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002
    Complete structured claim and evidence

  2. Acetoacetate reversibly inhibited reconstituted rat VGLUT2 uptake with a chloride-dependent shift consistent with competition at allosteric regulation.

    Acetoacetate → Rat vesicular glutamate transporter 2 / Slc17a6 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Purified rat transporter; controlled chloride/acetoacetate concentrations and washout.
    limitations
    This mechanism alone does not establish the effects of fasting or a ketogenic diet in humans.
    nutrient_topic
    L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
    plain_language
    A metabolic fuel-related molecule altered transmitter packaging in a biochemical system.
    primary_references
    Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002

    L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 282–288

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified rat transporter; controlled chloride/acetoacetate concentrations and washout. · source_derived_draft · unverified_draft

    ## glutamate-vglut2-acetoacetate A metabolic fuel-related molecule altered transmitter packaging in a biochemical system. Acetoacetate reversibly inhibited reconstituted rat VGLUT2 uptake with a chloride-dependent shift consistent with competition at allosteric regulation. Model: Purified rat transporter; controlled chloride/acetoacetate concentrations and washout. Limitations: This mechanism alone does not establish the effects of fasting or a ketogenic diet in humans. Evidence access: Primary full text Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002
    Complete structured claim and evidence

  3. OXCT1 transfers CoA from succinyl-CoA to acetoacetate, yielding acetoacetyl-CoA and succinate.

    Acetoacetate → Acetoacetyl-CoA source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract and indexed full-text introduction, PMC3825524
    experimental_model
    Human SCOT structure; described ketolysis reaction.
    limitations
    Production of ketones and ability to use them are different capacities.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    Using ketones requires a separate activation step.
    primary_references
    A structural mapping of mutations causing succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23420214/ · DOI 10.1007/s10545-013-9589-z

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 144–150

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human SCOT structure; described ketolysis reaction. · source_derived_draft · unverified_draft

    ## fast-scot Using ketones requires a separate activation step. OXCT1 transfers CoA from succinyl-CoA to acetoacetate, yielding acetoacetyl-CoA and succinate. Model: Human SCOT structure; described ketolysis reaction. Limitations: Production of ketones and ability to use them are different capacities. Evidence access: Primary abstract and indexed full-text introduction, PMC3825524 A structural mapping of mutations causing succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23420214/ · DOI 10.1007/s10545-013-9589-z
    Complete structured claim and evidence

What acts on it

  1. BDH1 interconverts D-beta-hydroxybutyrate and acetoacetate using the NAD+/NADH redox pair.

    D-(R)-beta-hydroxybutyrate → Acetoacetate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Reactome curated reaction and its primary-study attribution
    experimental_model
    Curated human mitochondrial reaction R-HSA-73920; cites human-heart BDH1 work.
    limitations
    Reversible reaction; redox state and compartment determine net direction.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    Ketone interconversion connects to niacin-derived redox chemistry.
    primary_references
    BDH1: D-beta-hydroxybutyrate + NAD+ ⇌ acetoacetate + NADH + H+ · 2003 · https://reactome.org/content/detail/R-HSA-73920

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 128–134

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Curated human mitochondrial reaction R-HSA-73920; cites human-heart BDH1 work. · source_derived_draft · unverified_draft

    ## fast-bdh-reaction Ketone interconversion connects to niacin-derived redox chemistry. BDH1 interconverts D-beta-hydroxybutyrate and acetoacetate using the NAD+/NADH redox pair. Model: Curated human mitochondrial reaction R-HSA-73920; cites human-heart BDH1 work. Limitations: Reversible reaction; redox state and compartment determine net direction. Evidence access: Reactome curated reaction and its primary-study attribution BDH1: D-beta-hydroxybutyrate + NAD+ ⇌ acetoacetate + NADH + H+ · 2003 · https://reactome.org/content/detail/R-HSA-73920
    Complete structured claim and evidence

  2. Human HMGCL cleaves HMG-CoA to acetoacetate and acetyl-CoA.

    (S)-3-Hydroxy-3-methylglutaryl-CoA → Acetoacetate source_derived_draftungraded
    Experimental context and source evidence
    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
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Serum acetoacetate increased compared with placebo.

    Mangiferin → Human serum acetoacetate concentration source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/mangiferin-research/25989216.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f57445ffe1eb20de3c2bf1170d152c358be1d7763cef2a091c0b3052040e539", "start_char": 0, "end_char": 1522, "text_sha256": "2f57445ffe1eb20de3c2bf1170d152c358be1d7763cef2a091c0b3052040e539"}
    experimental_model
    Double-blind randomized placebo-controlled trial
    exposure
    Mangiferin 150 mg/day for 12 weeks
    limitations
    One trial in a selected population; biomarkers do not demonstrate clinical outcomes or directly measure fatty-acid flux.
    nutrient_topic
    Mangiferin research collection; topical membership is not evidence of a direct dietary effect. · Mangiferin
    organism
    Overweight adults with hyperlipidemia; 97 completers
    plain_language
    A second ketone measure increased.
    primary_references
    [mangiferin-p25989216] Mangiferin supplementation improves serum lipid profiles in overweight patients with hyperlipidemia: a double-blind randomized controlled trial. (2015). https://pubmed.ncbi.nlm.nih.gov/25989216/ DOI: 10.1038/srep10344
    tissue_or_cell_type
    Serum metabolic measurements

    Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 1225–1236

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized placebo-controlled trial · source_derived_draft · unverified_draft

    ### mangiferin-trial-acetoacetate Serum acetoacetate increased compared with placebo. Condition category: normal nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second ketone measure increased. organism: Overweight adults with hyperlipidemia; 97 completers tissue_or_cell_type: Serum metabolic measurements experimental_model: Double-blind randomized placebo-controlled trial limitations: One trial in a selected population; biomarkers do not demonstrate clinical outcomes or directly measure fatty-acid flux. exposure: Mangiferin 150 mg/day for 12 weeks evidence_span: {"source_cache": "artifacts/mangiferin-research/25989216.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f57445ffe1eb20de3c2bf1170d152c358be1d7763cef2a091c0b3052040e539", "start_char": 0, "end_char": 1522, "text_sha256": "2f57445ffe1eb20de3c2bf1170d152c358be1d7763cef2a091c0b3052040e539"} [mangiferin-p25989216] Mangiferin supplementation improves serum lipid profiles in overweight patients with hyperlipidemia: a double-blind randomized controlled trial. (2015). https://pubmed.ncbi.nlm.nih.gov/25989216/ DOI: 10.1038/srep10344
    Complete structured claim and evidence

  2. The mouse FAH product complex places acetoacetate at a coordinated calcium ion near a Glu-His catalytic dyad.

    Calcium ion → Mouse fumarylacetoacetate hydrolase / Fah source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Mouse FAH X-ray structure; catalytic roles proposed from structure and mutagenesis.
    limitations
    This is not evidence that calcium supplementation restores FAH disease.
    nutrient_topic
    L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
    plain_language
    A metal participates in the terminal cleavage chemistry.
    primary_references
    Crystal structure and mechanism of a carbon-carbon bond hydrolase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10508789/ · DOI 10.1016/s0969-2126(99)80170-1

    L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 268–274

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse FAH X-ray structure; catalytic roles proposed from structure and mutagenesis. · source_derived_draft · unverified_draft

    ## l-tyrosine-fah-calcium A metal participates in the terminal cleavage chemistry. The mouse FAH product complex places acetoacetate at a coordinated calcium ion near a Glu-His catalytic dyad. Model: Mouse FAH X-ray structure; catalytic roles proposed from structure and mutagenesis. Limitations: This is not evidence that calcium supplementation restores FAH disease. Evidence access: Primary abstract Crystal structure and mechanism of a carbon-carbon bond hydrolase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10508789/ · DOI 10.1016/s0969-2126(99)80170-1
    Complete structured claim and evidence

  3. Mouse FAH structural and biochemical studies support cleavage of fumarylacetoacetate into fumarate and acetoacetate.

    Mouse fumarylacetoacetate hydrolase / Fah → Fumarylacetoacetate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Mouse enzyme structure and physiological-product complexes.
    limitations
    The product-bound structure is mouse evidence; the separate human FAH gene/disease record is retained.
    nutrient_topic
    L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
    plain_language
    The pathway connects the amino-acid carbon skeleton to central metabolism.
    primary_references
    Crystal structure and mechanism of a carbon-carbon bond hydrolase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10508789/ · DOI 10.1016/s0969-2126(99)80170-1

    L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 260–266

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse enzyme structure and physiological-product complexes. · source_derived_draft · unverified_draft

    ## l-tyrosine-fah-products The pathway connects the amino-acid carbon skeleton to central metabolism. Mouse FAH structural and biochemical studies support cleavage of fumarylacetoacetate into fumarate and acetoacetate. Model: Mouse enzyme structure and physiological-product complexes. Limitations: The product-bound structure is mouse evidence; the separate human FAH gene/disease record is retained. Evidence access: Primary abstract Crystal structure and mechanism of a carbon-carbon bond hydrolase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10508789/ · DOI 10.1016/s0969-2126(99)80170-1
    Complete structured claim and evidence

  4. P6C and acetoacetate form 2-OPP in chemical incubations including plasma.

    Delta1-piperideine-6-carboxylate → 2S,6S-/2S,6R-6-(2-Oxopropyl)piperidine-2-carboxylate source_derived_draftungraded
    Experimental context and source evidence
    affected_machinery
    ALDH7A1
    availability_state
    machinery_impairment Imported condition classification; unverified.
    deficiency_not_equivalent
    Dietary lysine deficiency
    experimental_model
    Chemical incubations in aqueous solutions and human biological matrices
    limitations
    In-vivo formation is inferred; patient flux was not measured.
    organism
    Homo sapiens
    plain_language
    An accumulated intermediate can react with a ketone body.
    primary_references
    [engelke2021] Untargeted metabolomics and infrared ion spectroscopy identify biomarkers for pyridoxine-dependent epilepsy (2021). https://www.jci.org/articles/view/148272 DOI: 10.1172/JCI148272
    tissue_or_cell_type
    Body-fluid reaction model
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Lysine: mechanism-first literature curation (2026-09-17) · lines 302–312

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemical incubations in aqueous solutions and human biological matrices · source_derived_draft · unverified_draft

    ### p6c-acetoacetate-2opp P6C and acetoacetate form 2-OPP in chemical incubations including plasma. Plain language: An accumulated intermediate can react with a ketone body. Condition category: machinery_impairment organism: Homo sapiens tissue_or_cell_type: Body-fluid reaction model experimental_model: Chemical incubations in aqueous solutions and human biological matrices limitations: In-vivo formation is inferred; patient flux was not measured. affected_machinery: ALDH7A1 deficiency_not_equivalent: Dietary lysine deficiency [engelke2021] Untargeted metabolomics and infrared ion spectroscopy identify biomarkers for pyridoxine-dependent epilepsy (2021). https://www.jci.org/articles/view/148272 DOI: 10.1172/JCI148272
    Complete structured claim and evidence

  5. Human-heart mitochondrial BDH1 was described as specifically requiring phosphatidylcholine for enzymic activity.

    Phosphatidylcholine → Human mitochondrial D-beta-hydroxybutyrate dehydrogenase / BDH1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Primary human-heart enzyme cloning and characterization.
    limitations
    Does not establish that supplemental choline increases ketone use.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    A membrane lipid linked to choline supports a ketone enzyme.
    primary_references
    Molecular cloning and characterization of (R)-3-hydroxybutyrate dehydrogenase from human heart. · 1992 · https://pubmed.ncbi.nlm.nih.gov/1639787/

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 136–142

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Primary human-heart enzyme cloning and characterization. · source_derived_draft · unverified_draft

    ## fast-bdh-choline A membrane lipid linked to choline supports a ketone enzyme. Human-heart mitochondrial BDH1 was described as specifically requiring phosphatidylcholine for enzymic activity. Model: Primary human-heart enzyme cloning and characterization. Limitations: Does not establish that supplemental choline increases ketone use. Evidence access: Primary abstract Molecular cloning and characterization of (R)-3-hydroxybutyrate dehydrogenase from human heart. · 1992 · https://pubmed.ncbi.nlm.nih.gov/1639787/
    Complete structured claim and evidence

  6. Beta-hydroxybutyrate and acetoacetate became predominant cerebral fuels after prolonged starvation.

    Fasting / abstention from energy intake → Cerebral ketone-body utilization source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Three obese patients; cerebral catheterization after 5–6 weeks of starvation.
    limitations
    This prolonged, small historical study does not establish a 16-hour switch.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    The brain can use ketones while retaining a glucose requirement.
    primary_references
    Brain metabolism during fasting. · 1967 · https://pubmed.ncbi.nlm.nih.gov/6061736/ · DOI 10.1172/JCI105650

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 88–94

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Three obese patients; cerebral catheterization after 5–6 weeks of starvation. · source_derived_draft · unverified_draft

    ## fast-brain-ketones The brain can use ketones while retaining a glucose requirement. Beta-hydroxybutyrate and acetoacetate became predominant cerebral fuels after prolonged starvation. Model: Three obese patients; cerebral catheterization after 5–6 weeks of starvation. Limitations: This prolonged, small historical study does not establish a 16-hour switch. Evidence access: Primary abstract Brain metabolism during fasting. · 1967 · https://pubmed.ncbi.nlm.nih.gov/6061736/ · DOI 10.1172/JCI105650
    Complete structured claim and evidence

In the sources

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

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