Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism.
Acetyl-CoA’s main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production.
Coenzyme A consists of a Beta-mercaptoethylamine group linked to the vitamin pantothenic acid (B5) through an amide linkage and 3′-phosphorylated ADP.
CoA is acetylated to acetyl-CoA by the breakdown of carbohydrates through glycolysis and by the breakdown of fatty acids through beta oxidation.
Acetyl-CoA then enters the citric acid cycle, where the acetyl group is oxidized to carbon dioxide and water: the energy released is captured in the form of 11 ATP and one GTP per acetyl group.
Acetylation of CoA is determined by the carbon sources.
With high glucose levels, glycolysis takes place rapidly, increasing the amount of citrate produced from the tricarboxylic acid cycle.
Citrate is then exported to other organelles outside the mitochondria to be broken into acetyl-CoA and oxaloacetate by the enzyme ATP citrate lyase (ACL).
At low glucose levels: CoA is acetylated using acetate by acetyl-CoA synthetase (ACS), also coupled with ATP hydrolysis.
Ethanol also serves as a carbon source for acetylation of CoA utilizing the enzyme alcohol dehydrogenase.
At high glucose levels, acetyl-CoA is produced through glycolysis.
The oxidative conversion of pyruvate into acetyl-CoA is referred to as the pyruvate dehydrogenase reaction.
Stored energy is released through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins into adenosine triphosphate (ATP) and carbon dioxide.
Acetyl-CoA is produced by the breakdown of both carbohydrates, by glycolysis, and lipids, by β-oxidation.
Acetyl-CoA then enters the citric acid cycle in the mitochondrion by combining with oxaloacetate to form citrate.
Two acetyl-CoA molecules merge to form acetoacetyl-CoA, which gives rise to the formation of acetoacetate and beta-hydroxybutyrate.
Acetoacetate, Beta-hydroxybutyrate, and breakdown product acetone are known as ketone bodies, water-soluble chemical substances.
Ketone bodies are released by the liver into the blood.
Mitochondria in cells can take ketone bodies up from the blood and reconvert them into acetyl-CoA, which can then be used as fuel in their citric acid cycles.
Ketone bodies can cross the blood-brain barrier, making them available as fuel for the cells of the central nervous system, acting as a substitute for glucose, on which these cells normally survive.
High levels of ketone bodies in the blood during: starvation, a low-carbohydrate diet, prolonged heavy exercise, and uncontrolled type-1 diabetes mellitus is known as ketosis.
Ketosis in its extreme form in type-1 diabetes mellitus, as ketoacidosis.
When the insulin concentration in the blood is high, and that of glucagon is low, as after meals, the acetyl-CoA produced by glycolysis condenses as normal with oxaloacetate to form citrate in the mitochondrion.
The citrate is removed from the mitochondrion into the cytoplasm, as it is cleaved by ATP citrate lyase into acetyl-CoA and oxaloacetate.
Cytosolic acetyl-CoA can be used to synthesize fatty acids.
Carboxylation by acetyl-CoA occurs primarily in the liver, adipose tissue and lactating mammary glands, where the fatty acids are combined with glycerol to form triglycerides, the major fuel reservoir.
Fatty acids are also components of the phospholipids that make up the bulk of the lipid bilayers of all cellular membranes.
Acetyl-CoA can also condense with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) which is the rate-limiting step controlling the synthesis of cholesterol.
Cholesterol can be used as a structural component of cellular membranes, or it can be used to synthesize steroid hormones, bile salts, and vitamin D.
Acetyl-CoA is also an important component in the biogenic synthesis of the neurotransmitter acetylcholine.
Choline, in combination with acetyl-CoA, is catalyzed by the enzyme choline acetyltransferase to produce acetylcholine and coenzyme A as a byproduct.
Acetyl-CoA is also the source of the acetyl group incorporated onto certain lysine residues of histone and nonhistone proteins in the posttranslational modification acetylation.
Acetylation affects cell growth, mitosis, and apoptosis.