IsobutyrylCoA

Isobutyryl-CoA is the coenzyme A thioester of isobutyric acid, also known as 2-methylpropanoic acid. It is an acyl-CoA intermediate generated in cellular metabolism and serves as a carrier for the isobutyryl group in various enzymatic reactions.

Biosynthesis and metabolism: In humans, isobutyryl-CoA is produced during the catabolism of the branched-chain amino acid valine. Valine is transaminated to α-ketoisovalerate and then decarboxylated by the branched-chain α-ketoacid dehydrogenase complex to form isobutyryl-CoA. Through a series of oxidation steps, isobutyryl-CoA is converted by isobutyryl-CoA dehydrogenase and subsequent enzymes into intermediates that feed into the propionyl-CoA and methylmalonyl-CoA pathways, ultimately yielding succinyl-CoA that enters the TCA cycle. This pathway links amino acid degradation to energy production and central carbon metabolism.

Physiological and biochemical role: As a high-energy thioester, isobutyryl-CoA participates in acyl transfer and oxidation reactions. Its metabolism is part of valine catabolism and, more broadly, contributes to the turnover of branched-chain substrates and the maintenance of acetyl- and propionyl-CoA pools that feed into downstream energy and biosynthetic pathways.

Clinical significance: Defects in enzymes that process isobutyryl-CoA, such as isobutyryl-CoA dehydrogenase, can cause metabolic disorders characterized by accumulation of isobutyryl-CoA and related metabolites. Biochemical markers may include elevated isobutyrylcarnitine in blood and increased isobutyrylglycine in urine. Management focuses on metabolic control and avoidance of catabolic stress, with diagnosis aided by acylcarnitine profiling and genetic testing.

See also: valine catabolism, acyl-CoA thioesters, isobutyryl-CoA dehydrogenase deficiency.