Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production. Coenzyme A (CoASH or CoA) consists of a β-mercaptoethylamine group linked to pantothenic acid (vitamin B5) through an amide linkage and 3'-phosphorylated ADP. The acetyl group (indicated in blue in the structural diagram on the right) of acetyl-CoA is linked to the sulfhydryl substituent of the β-mercaptoethylamine group. This thioester linkage is a "high energy" bond, which is particularly reactive. Hydrolysis of the thioester bond is exergonic (−31.5 kJ/mol). CoA is acetylated to acetyl-CoA by the breakdown of carbohydrates through glycolysis and by the breakdown of fatty acids through β-oxidation. Acetyl-CoA then enters the citric acid cycle, where the acetyl group is oxidized to carbon dioxide and water, and the energy released is captured in the form of 11 ATP and one GTP per acetyl group. Konrad Bloch and Feodor Lynen were awarded the 1964 Nobel Prize in Physiology or Medicine for their discoveries linking acetyl-CoA and fatty acid metabolism. Fritz Lipmann won the Nobel Prize in 1953 for his discovery of the cofactor coenzyme A.

Role

Acetyl-CoA is a metabolic intermediate that is involved in many metabolic pathways in an organism. It is produced during the breakdown of glucose, fatty acids, and amino acids, and is used in the synthesis of many other biomolecules, including cholesterol, fatty acids, and ketone bodies. Acetyl-CoA is also a key molecule in the citric acid cycle, which is a series of chemical reactions that occur in the mitochondria of cells and is responsible for generating energy in the form of ATP. In addition, acetyl-CoA is a precursor for the biosynthesis of various acetyl-chemicals, acting as an intermediate to transfer an acetyl group during the biosynthesis of those acetyl-chemicals. Acetyl-CoA is also involved in the regulation of various cellular mechanisms by providing acetyl groups to target amino acid residues for post-translational acetylation reactions of proteins.

Biosynthesis

The acetylation of CoA is determined by the carbon sources.

Extramitochondrial

Intramitochondrial

Functions

Intermediates in various pathways

Interactive pathway map

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