dihydrolipoyllysine-residue acetyltransferase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: (R)-N6-dihydrolipoyl-L-lysyl-[protein] + acetyl-CoA = (R)-N6-(S8-acetyldihydrolipoyl)-L-lysyl-[protein] + CoA. [RHEA:17017]

Dihydrolipoyllysine-residue acetyltransferase activity is a crucial enzymatic function involved in the transfer of acetyl groups from acetyl-CoA to the lipoyl moiety of dihydrolipoyllysine residues. This process is essential for the proper functioning of several key metabolic pathways, including the pyruvate dehydrogenase complex (PDC), the α-ketoglutarate dehydrogenase complex (KGDC), and the branched-chain α-ketoacid dehydrogenase complex (BCKDC). These complexes are responsible for the oxidative decarboxylation of pyruvate, α-ketoglutarate, and branched-chain α-ketoacids, respectively.

The catalytic mechanism of dihydrolipoyllysine-residue acetyltransferase involves the following steps:

1. **Binding of acetyl-CoA:** The enzyme binds to acetyl-CoA, which serves as the acetyl group donor.
2. **Formation of an acetyl-enzyme intermediate:** The acetyl group from acetyl-CoA is transferred to a specific lysine residue within the active site of the enzyme, forming an acetyl-enzyme intermediate.
3. **Transfer of the acetyl group to dihydrolipoyllysine:** The acetyl group from the acetyl-enzyme intermediate is then transferred to the lipoyl moiety of dihydrolipoyllysine, which is attached to the E2 subunit of the respective dehydrogenase complex.
4. **Regeneration of the enzyme:** The enzyme is regenerated by the release of CoA and the formation of a free lysine residue in the active site.

The dihydrolipoyllysine-residue acetyltransferase activity plays a crucial role in the regulation of these metabolic pathways. It is often regulated by allosteric mechanisms, where the activity of the enzyme is influenced by the presence of specific metabolites, such as pyruvate, acetyl-CoA, and NADH.

Mutations or deficiencies in the dihydrolipoyllysine-residue acetyltransferase can lead to various metabolic disorders, including pyruvate dehydrogenase complex deficiency (PDCD), α-ketoglutarate dehydrogenase complex deficiency (KGCD), and branched-chain ketoaciduria. These disorders are characterized by the accumulation of specific metabolites and can cause a wide range of symptoms, depending on the severity of the deficiency.'
"

Proteins (2)

Compounds (1)