Human acetyl-CoA carboxylase 1 / ACACA

evidence_span

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experimental_model

Cryo-EM of endogenous and recombinant human ACC1 filaments

exposure

Inactive substrate-containing and dephosphorylated/citrate-treated states

limitations

Filament presence alone does not mean enzyme activation; the paper resolved both active and inactive arrangements.

nutrient_topic

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

organism

Homo sapiens

plain_language

Biotin is attached at a specific amino-acid site on ACC1.

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 650–661

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-k786 The human ACC1 biotin-carrier domain contains biotin covalently attached to Lys786. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Biotin is attached at a specific amino-acid site on ACC1. 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": 17700, "end_char": 18021, "text_sha256": "577b5c24795f7637a47e725c7e87ae9632c6aa96e74424b66d14ccd76a87e3bb"} [b7-p39383219] Filament structures unveil the dynamic organization of human acetyl-CoA carboxylase. (2024). https://pubmed.ncbi.nlm.nih.gov/39383219/ DOI: 10.1126/sciadv.ado4880

evidence_span

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experimental_model

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

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experimental_model

Cryo-EM of endogenous and recombinant human ACC1 filaments

exposure

Inactive substrate-containing and dephosphorylated/citrate-treated states

limitations

Filament presence alone does not mean enzyme activation; the paper resolved both active and inactive arrangements.

nutrient_topic

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

organism

Homo sapiens

plain_language

ACC1 needs appropriate regulation as well as its vitamin cofactor.

primary_references

[b7-p39383219] Filament structures unveil the dynamic organization of human acetyl-CoA carboxylase. (2024). https://pubmed.ncbi.nlm.nih.gov/39383219/ DOI: 10.1126/sciadv.ado4880

tissue_or_cell_type

Purified human ACC1

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 663–674

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM of endogenous and recombinant human ACC1 filaments · source_derived_draft · unverified_draft

### b7-acc1-active-state Dephosphorylation and citrate treatment produced the activated human ACC1 filament state resolved by cryo-EM. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ACC1 needs appropriate regulation as well as its vitamin cofactor. organism: Homo sapiens tissue_or_cell_type: Purified human ACC1 experimental_model: Cryo-EM of endogenous and recombinant human ACC1 filaments limitations: Filament presence alone does not mean enzyme activation; the paper resolved both active and inactive arrangements. exposure: Inactive substrate-containing and dephosphorylated/citrate-treated states evidence_span: {"source_cache": "artifacts/biotin-research/39383219.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fa420ace21cebdb778923fbf951a99c035c9fae2af8f4876becf672947d9242", "start_char": 0, "end_char": 863, "text_sha256": "7fa420ace21cebdb778923fbf951a99c035c9fae2af8f4876becf672947d9242"} [b7-p39383219] Filament structures unveil the dynamic organization of human acetyl-CoA carboxylase. (2024). https://pubmed.ncbi.nlm.nih.gov/39383219/ DOI: 10.1126/sciadv.ado4880

evidence_span

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experimental_model

Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases

exposure

Stopped-flow and quench-flow transfer kinetics

limitations

Fragment kinetics support differential recognition, not a universal nutrient-deficiency survival order in humans.

nutrient_topic

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

organism

Homo sapiens

plain_language

The two acetyl-CoA carboxylases showed different attachment kinetics from the mitochondrial carboxylase fragments.

primary_references

[b7-p22123817] Selectivity in post-translational biotin addition to five human carboxylases. (2012). https://pubmed.ncbi.nlm.nih.gov/22123817/ DOI: 10.1074/jbc.m111.275982

tissue_or_cell_type

Purified HLCS and acceptor fragments

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 429–440

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases · source_derived_draft · unverified_draft

### b7-hlcs-acaca-acceptor HLCS biotinylation of the human ACACA acceptor fragment was relatively slow and depended hyperbolically on fragment concentration. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two acetyl-CoA carboxylases showed different attachment kinetics from the mitochondrial carboxylase fragments. organism: Homo sapiens tissue_or_cell_type: Purified HLCS and acceptor fragments experimental_model: Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases limitations: Fragment kinetics support differential recognition, not a universal nutrient-deficiency survival order in humans. exposure: Stopped-flow and quench-flow transfer kinetics evidence_span: {"source_cache": "artifacts/biotin-research/22123817.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233", "start_char": 0, "end_char": 1502, "text_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233"} [b7-p22123817] Selectivity in post-translational biotin addition to five human carboxylases. (2012). https://pubmed.ncbi.nlm.nih.gov/22123817/ DOI: 10.1074/jbc.m111.275982

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

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experimental_model

Rat hepatocytes, isolated rat skeletal muscle and metformin-treated rats with an AMPK inhibitor

exposure

Metformin in hepatocytes and in vivo; compound C AMPK inhibition

limitations

The inhibitor experiment supports a requirement for AMPK in these hepatocytes; later work in AMPK-deficient mice reached a different conclusion, recorded separately.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Rat

plain_language

The cell reads the drug as an energy shortage and switches to burning rather than storing.

primary_references

[metformin-p11602624] Role of AMP-activated protein kinase in mechanism of metformin action. (2001). https://pubmed.ncbi.nlm.nih.gov/11602624/ DOI: 10.1172/jci13505

tissue_or_cell_type

Liver and skeletal muscle

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 528–539

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat hepatocytes, isolated rat skeletal muscle and metformin-treated rats with an AMPK inhibitor · source_derived_draft · unverified_draft

### metformin-ampk-activation Metformin activated AMPK in hepatocytes, reducing acetyl-CoA carboxylase activity, inducing fatty acid oxidation and suppressing expression of lipogenic enzymes. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The cell reads the drug as an energy shortage and switches to burning rather than storing. organism: Rat tissue_or_cell_type: Liver and skeletal muscle experimental_model: Rat hepatocytes, isolated rat skeletal muscle and metformin-treated rats with an AMPK inhibitor limitations: The inhibitor experiment supports a requirement for AMPK in these hepatocytes; later work in AMPK-deficient mice reached a different conclusion, recorded separately. exposure: Metformin in hepatocytes and in vivo; compound C AMPK inhibition evidence_span: {"source_cache": "artifacts/metformin-research/11602624.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "86e283289def8a6e3e3098d49f321dbcca9a6cd4677ba84f26daf17467179237", "start_char": 0, "end_char": 1390, "text_sha256": "86e283289def8a6e3e3098d49f321dbcca9a6cd4677ba84f26daf17467179237"} [metformin-p11602624] Role of AMP-activated protein kinase in mechanism of metformin action. (2001). https://pubmed.ncbi.nlm.nih.gov/11602624/ DOI: 10.1172/jci13505

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

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experimental_model

Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake

exposure

Metformin and phenformin against thiamine uptake; acute metformin in wild-type mice

limitations

Identifies thiamine as an endogenous OCT1 substrate and shows competitive inhibition by metformin. The steatosis phenotype is a mouse phenotype.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Mouse and human transporter

plain_language

Short vitamin B1 switches on the same energy sensor the drug does.

primary_references

[metformin-p24961373] OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. (2014). https://pubmed.ncbi.nlm.nih.gov/24961373/ DOI: 10.1073/pnas.1314939111

tissue_or_cell_type

Liver and intestine

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 1269–1280

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake · source_derived_draft · unverified_draft

### metformin-oct1-loss-ampk-thiamine Loss of Oct1 raised the AMP to ATP ratio and activated AMPK, and thiamine deficiency itself enhanced phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase. Condition category: nutrient_deficiency nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: Short vitamin B1 switches on the same energy sensor the drug does. organism: Mouse and human transporter tissue_or_cell_type: Liver and intestine experimental_model: Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake limitations: Identifies thiamine as an endogenous OCT1 substrate and shows competitive inhibition by metformin. The steatosis phenotype is a mouse phenotype. exposure: Metformin and phenformin against thiamine uptake; acute metformin in wild-type mice evidence_span: {"source_cache": "artifacts/metformin-research/24961373.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70", "start_char": 0, "end_char": 1270, "text_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70"} [metformin-p24961373] OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. (2014). https://pubmed.ncbi.nlm.nih.gov/24961373/ DOI: 10.1073/pnas.1314939111

evidence_span

{"source_cache": "artifacts/acetate-research/24781306.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4a1cc3cf5135e5856a281cd391c82611caa57afa2f837b0343cf048bb2c11e97", "start_char": 0, "end_char": 1135, "text_sha256": "4a1cc3cf5135e5856a281cd391c82611caa57afa2f837b0343cf048bb2c11e97"}

experimental_model

In vivo carbon-11 acetate PET-CT in rodents with carbon-13 high-resolution magic-angle-spinning spectroscopy

exposure

Colonic and intraperitoneal acetate, and carbon-13 labelled fermentable carbohydrate

limitations

Traces the molecule from colon to brain and then measures what it does there. The appetite endpoint is rodent, and intraperitoneal administration is not a dietary 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

Rodent

plain_language

Once there it changes the hypothalamic circuits that set hunger.

primary_references

[acetate-p24781306] The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. (2014). https://pubmed.ncbi.nlm.nih.gov/24781306/ DOI: 10.1038/ncomms4611

tissue_or_cell_type

Colon, blood-brain barrier and hypothalamus

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 719–730

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In vivo carbon-11 acetate PET-CT in rodents with carbon-13 high-resolution magic-angle-spinning spectroscopy · source_derived_draft · unverified_draft

### acetate-acetate-suppresses-appetite Intraperitoneal acetate resulted in appetite suppression and hypothalamic neuronal activation patterning, was associated with activation of acetyl-CoA carboxylase and changes in the expression profiles of regulatory neuropeptides that favour appetite suppression, and regionally increased the labelling of the glutamate-glutamine and GABA neuroglial cycles, suggesting a direct role for acetate in central appetite regulation. 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: Once there it changes the hypothalamic circuits that set hunger. organism: Rodent tissue_or_cell_type: Colon, blood-brain barrier and hypothalamus experimental_model: In vivo carbon-11 acetate PET-CT in rodents with carbon-13 high-resolution magic-angle-spinning spectroscopy limitations: Traces the molecule from colon to brain and then measures what it does there. The appetite endpoint is rodent, and intraperitoneal administration is not a dietary exposure. exposure: Colonic and intraperitoneal acetate, and carbon-13 labelled fermentable carbohydrate evidence_span: {"source_cache": "artifacts/acetate-research/24781306.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4a1cc3cf5135e5856a281cd391c82611caa57afa2f837b0343cf048bb2c11e97", "start_char": 0, "end_char": 1135, "text_sha256": "4a1cc3cf5135e5856a281cd391c82611caa57afa2f837b0343cf048bb2c11e97"} [acetate-p24781306] The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. (2014). https://pubmed.ncbi.nlm.nih.gov/24781306/ DOI: 10.1038/ncomms4611