Dihydrolipoyl transacetylase (DLAT)

Dihydrolipoyl transacetylase (DLAT), also known as the E2 component of the pyruvate dehydrogenase complex (PDC), is a mitochondrial enzyme essential for aerobic metabolism [1]. It catalyzes the conversion of pyruvate into acetyl-CoA by transferring an acetyl group to coenzyme A, a step that links glycolysis to the tricarboxylic acid (TCA) cycle [1, 2]. Structurally, DLAT forms the catalytic core of the PDC, providing the scaffold for the assembly of other subunits [1, 3]. In clinical medicine, DLAT is the primary autoantigen targeted by anti-mitochondrial antibodies in primary biliary cholangitis, an autoimmune liver disease [1]. It is also a target for novel cancer therapies, such as devimistat (CPI-613), which exploits the metabolic vulnerabilities of tumor cells by inhibiting mitochondrial energy production [5, 9, 16]. Genetic mutations in DLAT can result in pyruvate dehydrogenase deficiency, leading to severe metabolic and neurological consequences like lactic acidosis and dystonia [1].

Other names

Dihydrolipoamide S-acetyltransferaseDihydrolipoamide acetyltransferasePDC-E2PDCE2E2 component of pyruvate dehydrogenase complexAcetyl-CoA:dihydrolipoamide S-acetyltransferase

Inhibition of the pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase by mimicking lipoic acid cofactors; disruption of regulatory kinase binding to the E2 core [6, 9, 16].