propionylCoAta

Propionyl-CoA (also written propionyl coenzyme A) is a metabolically significant molecule derived from the breakdown of certain amino acids and fatty acids. It is a thioester formed between propionic acid and coenzyme A. The primary metabolic pathways that generate propionyl-CoA include the catabolism of odd-chain fatty acids, the breakdown of the amino acids valine, isoleucine, threonine, and methionine, and the metabolism of cholesterol.

Once formed, propionyl-CoA enters a crucial metabolic pathway known as the propionyl-CoA carboxylase reaction. In this reaction, propionyl-CoA is carboxylated by the enzyme propionyl-CoA carboxylase, which requires biotin as a cofactor. This reaction converts propionyl-CoA into methylmalonyl-CoA. Methylmalonyl-CoA is then isomerized to succinyl-CoA by the enzyme methylmalonyl-CoA mutase.

Succinyl-CoA is an intermediate in the citric acid cycle (also known as the Krebs cycle or TCA cycle), a central pathway in cellular respiration. This conversion allows the carbon atoms derived from propionyl-CoA to enter the citric acid cycle and ultimately be oxidized for energy production. Defects in the enzymes involved in propionyl-CoA metabolism, particularly propionyl-CoA carboxylase or methylmalonyl-CoA mutase, can lead to serious metabolic disorders such as propionic acidemia and methylmalonic acidemia, respectively. These conditions are characterized by the accumulation of toxic metabolites.