Methylcrotonyl-CoA

Methylcrotonyl-CoA is a key intermediate in the metabolism of leucine, an essential amino acid. It is produced from 3-methylcrotonyl-CoA by the enzyme 3-methylcrotonyl-CoA carboxylase, and is further metabolized to HMG-CoA by the enzyme methylcrotonyl-CoA dehydrogenase.

Metabolism

The metabolism of Methylcrotonyl-CoA is a part of the larger leucine catabolism pathway. The first step in this process is the conversion of leucine to alpha-ketoisocaproate by the enzyme branched-chain amino acid aminotransferase. Alpha-ketoisocaproate is then decarboxylated to isovaleryl-CoA by the enzyme alpha-ketoacid dehydrogenase. Isovaleryl-CoA is subsequently converted to methylcrotonyl-CoA by the enzyme isovaleryl-CoA dehydrogenase.

Methylcrotonyl-CoA is then carboxylated by the enzyme 3-methylcrotonyl-CoA carboxylase to form 3-methylglutaconyl-CoA. This is followed by the hydration of 3-methylglutaconyl-CoA to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) by the enzyme methylglutaconyl-CoA hydratase. HMG-CoA is then cleaved by the enzyme HMG-CoA lyase to form acetoacetate and acetyl-CoA, which can be further metabolized in the citric acid cycle.

Clinical significance

Deficiencies in the enzymes involved in the metabolism of Methylcrotonyl-CoA can lead to various metabolic disorders. For example, a deficiency in 3-methylcrotonyl-CoA carboxylase can lead to 3-Methylcrotonylglycinuria, a rare inherited disorder characterized by an inability to properly process certain proteins.

File:Leucine metabolism.png

Leucine metabolism. Methylcrotonyl-CoA is shown in the middle of the diagram.

See also

• Leucine
• Metabolism
• 3-Methylcrotonylglycinuria