acetylCoACoA

Acetyl-CoA is a central metabolic intermediate consisting of an acetyl group linked to coenzyme A by a high-energy thioester bond. It is produced mainly in the mitochondria from pyruvate through the pyruvate dehydrogenase complex during carbohydrate metabolism and also from beta-oxidation of fatty acids; it can also arise from certain ketogenic amino acids.

In the mitochondrion, acetyl-CoA feeds the citric acid cycle by condensing with oxaloacetate to form citrate, a reaction catalyzed by citrate synthase. Through successive steps, the acetyl portion is oxidized to CO2, with generation of NADH and FADH2 that drive oxidative phosphorylation and ATP production.

Acetyl-CoA cannot cross the mitochondrial membrane. Cytosolic acetyl-CoA, needed for fatty acid and cholesterol synthesis, is derived by export of citrate to the cytosol followed by cleavage by ATP-citrate lyase to yield acetyl-CoA and oxaloacetate. This cytosolic pool also provides acetyl groups for protein and histone acetylation, linking metabolism to regulation of gene expression and protein function.

Regulation of acetyl-CoA production and utilization reflects cellular energy status. The pyruvate dehydrogenase complex is inhibited by NADH, acetyl-CoA, and ATP, and activated by pyruvate and ADP, among other signals. In fasting states, excess hepatic acetyl-CoA can be diverted to ketone body synthesis (acetoacetate and beta-hydroxybutyrate).

Coenzyme A, from pantothenic acid (vitamin B5), carries the acetyl group; the acetyl-CoA thioester is a high-energy intermediate that links carbohydrate, lipid, and protein metabolism and influences numerous biosynthetic and energetic pathways.