Dihydrolipoyllysine-residue (2-methylpropanoyl)transferase

Dihydrolipoyllysine-residue (2-methylpropanoyl)transferase, also known as dihydrolipoyl transacylase or dihydrolipoamide acyltransferase, is an enzyme component of the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex. This complex is a multienzyme complex that catalyzes the overall conversion of branched-chain α-keto acids to acyl-CoA derivatives, carbon dioxide, and NADH.

Specifically, dihydrolipoyllysine-residue (2-methylpropanoyl)transferase (EC 2.3.1.168) catalyzes the transfer of the 2-methylpropanoyl (isobutyryl) group from 2-methylpropanoyl-dihydrolipoamide to coenzyme A (CoA). This reaction is a crucial step in the catabolism of branched-chain amino acids such as valine, leucine, and isoleucine.

The enzyme contains a lipoyl domain that is covalently linked to a lysine residue within the protein. This lipoyl domain acts as a swinging arm, shuttling the acyl group between the different active sites of the BCKDH complex. The enzyme's active site binds both the 2-methylpropanoyl-dihydrolipoamide and CoA substrates, facilitating the transfer of the acyl group.

Deficiencies in dihydrolipoyllysine-residue (2-methylpropanoyl)transferase, or other components of the BCKDH complex, can lead to Maple Syrup Urine Disease (MSUD), a metabolic disorder characterized by the accumulation of branched-chain amino acids and their corresponding keto acids in the blood and urine. This condition can cause severe neurological damage and is often fatal if left untreated.