asetyyliKoA

AsetyylikoA, commonly known as acetyl-CoA, is a derivative of coenzyme A that carries an acetyl group in a high-energy thioester bond. It is a central metabolite that links carbohydrate, lipid, and energy metabolism, participating in both energy production and biosynthetic processes. Because acetyl-CoA cannot cross the inner mitochondrial membrane, cells shuttle acetyl groups between compartments primarily in the form of citrate.

Formation and sources: In mitochondria, the pyruvate dehydrogenase complex converts pyruvate into acetyl-CoA, releasing CO2 and producing NADH. Fatty acid beta-oxidation also generates acetyl-CoA. Ketogenic amino acids and, in the liver, ethanol metabolism can supply acetyl-CoA as well. In some conditions, cytosolic acetyl-CoA is produced from acetate via acetyl-CoA synthetase.

Roles in metabolism: Within mitochondria, acetyl-CoA condenses with oxaloacetate to form citrate, which enters the citric acid cycle. Cytosolic acetyl-CoA serves as a key acetyl donor for fatty acid and cholesterol synthesis. Citrate exported to the cytosol is cleaved by ATP citrate lyase to regenerate acetyl-CoA and oxaloacetate. Acetyl-CoA also provides acetyl groups for protein acetylation, including histone acetylation, linking metabolism to gene regulation.

Regulation: Pyruvate dehydrogenase (PDH) activity is controlled by PDH kinases and phosphatases; high NADH and ATP inhibit PDH, while ADP and insulin stimulate it. Cytosolic acetyl-CoA production is influenced by citrate availability and by acetyl-CoA carboxylase, which converts acetyl-CoA into malonyl-CoA, a regulator of fatty acid synthesis and beta-oxidation.

Clinical relevance: PDH deficiency causes lactic acidosis and energy failure. Ethanol metabolism can alter acetyl-CoA pools in the liver. Beyond metabolism, acetyl-CoA is important for epigenetic regulation through histone acetylation.