Biochemistry · Enzyme
Acetyl-CoA carboxylase (ACC) !
Acetyl-CoA carboxylase decides whether the body makes fat: it turns acetyl-CoA into malonyl-CoA using biotin and ATP.
Updated 2026-11-01
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Key facts
- Rate-limiting step of fatty acid synthesis: acetyl-CoA + HCO₃⁻ + ATP → malonyl-CoA.
- A biotin (B7) enzyme: one domain carboxylates biotin and another hands the carboxyl to acetyl-CoA.
- Citrate activates it by assembling it into filaments; palmitoyl-CoA inhibits it.
- ACC1 is abundant in liver and fat (synthesis); ACC2, in muscle and heart, makes malonyl-CoA that blocks CPT-I.
- Also called
- ACC1 (ACACA, lipogenic), ACC2 (ACACB, mitochondrial)
- EC number
- 6.4.1.2
- Genes
- ACACA
- Structure (PDB)
- 8XL1
Regulation
- Insulin activates it (phosphatase) and raises its synthesis; glucagon and adrenaline switch it off by phosphorylation (PKA).
- AMPK, the low-energy sensor, phosphorylates and inactivates it: exercise favours burning fat.
Inhibitors and toxins
- Avidin (binds biotin)
- Carboxyltransferase-domain inhibitors under study for fatty liver
Clinical notes
- It is a drug target under study for metabolic dysfunction-associated fatty liver disease.
- Biotinidase or holocarboxylase synthetase deficiency lowers the activity of ACC and the other carboxylases.
Pathways
Related conditions
Related
- Malonyl-CoA
- Acetyl-CoA
- Citrate
- Fatty acid synthase (FAS)
- Carnitine palmitoyltransferase I (CPT-I)
- ATP (adenosine triphosphate)
Test yourself
Think of the answer, then tap the question to see it.
Which vitamin cofactor does acetyl-CoA carboxylase need?
Biotin (vitamin B7), which carries the carboxyl group.
What does AMPK do to acetyl-CoA carboxylase?
It phosphorylates and inactivates it: malonyl-CoA falls, CPT-I opens and fatty acids are burned.
Which metabolite activates acetyl-CoA carboxylase?
Citrate, which signals spare acetyl-CoA and energy in the mitochondrion.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: ACACA: Acetyl-CoA carboxylase 1 (human) (UniProt, 2026); Fatty acyl-CoA biosynthesis (Reactome, 2026); 8XL1: Core region of the human acetyl-CoA carboxylase 1 filament in complex with acetyl-CoA (ACC1-inact) (RCSB Protein Data Bank, 2026).
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Representative model, for educational purposes only.