Dihydrolipoyl transacetylase subunit of pyruvate dehydrogenase complex and 2-oxoglutarate dehydrogenase complex (E2)

The E2 subunit is the central acyltransferase enzyme of large mitochondrial multienzyme complexes—dihydrolipoyl transacetylase for the pyruvate dehydrogenase complex (PDH) and dihydrolipoyl succinyltransferase for the α-ketoglutarate dehydrogenase complex (α-KGDH)[1][2][5]. Both E2 subunits catalyze the transfer of an acyl group from a covalently bound lipoic acid “swinging arm” (attached to a lysine residue) to coenzyme A, producing acetyl-CoA or succinyl-CoA, respectively[5][1]. E2 forms the structural and catalytic core of their respective complexes, recruiting other enzyme subunits (E1 and E3) and mediating substrate channeling to increase catalytic efficiency and limit intermediate diffusion[5][4]. E2 is a large, multidomain protein with several lipoyl domains, a peripheral subunit-binding domain, and a catalytic domain, with roles extending to metabolic homeostasis, cell fate, and disease pathogenesis[2][6]. Mutations or dysfunction in E2 subunits result in severe metabolic impairment, highlighting their essential therapeutic and diagnostic significance. Note: For structured databases or canonical form retrieval, use as separate entries: - "Dihydrolipoyl transacetylase (E2, PDH complex)" [gene: DLAT] - "Dihydrolipoyl succinyltransferase (E2, α-KGDH complex)" [gene: DLST] The submitted label describing both E2 subunits collectively is ambiguous and imprecise for most research or drug discovery purposes.

Other names

dihydrolipoyl transacetylaseLipoamide acetyltransferaseDLATdihydrolipoyl succinyltransferaseLipoamide succinyltransferaseDLST

Covalent modification of lipoic acid arm; Indirect activation/inhibition by regulating upstream PDH kinases/phosphatases