OGDH complex synthesizes succinyl-CoA from 2-OG

OGDH complex synthesizes succinyl-CoA from 2-OG The mitochondrial alpha-oxoglutarate dehydrogenase complex (αOGDH, αKGDH, OGDHC) catalyzes the reaction of 2-oxoglutarate (2OG), CoASH, and NAD+ to form succinyl-CoA, CO2, and NADH. The enzyme complex ("metabolon") contains multiple copies of three different proteins, E1 (OGDH), E2 (DLST), and E3 (DLD), each with distinct catalytic activities (Reed and Hackert 1990; Zhou et al 2001). Specifically, it is composed of a core of 24 E2 subunits exhibiting octahedral symmetry. To these subunits are bound up to six E1 dimers and to each of these is bound an E3 dimer (Nagy et al., 2021; Skalidis et al., 2023) and to an adaptive MRPS36 unit (Hevler et al., 2023). The reaction starts with the oxidative decarboxylation of 2OG catalyzed by E1alpha and beta (alpha ketoglutarate dehydrogenase). Lipoamide cofactor associated with E2 is reduced at the same time. Next, the succinyl group derived from alpha ketoglutarate is transferred to coenzyme A in two steps catalyzed by E2 (dihydrolipolyl transacetylase). Finally, the oxidized form of lipoamide is regenerated and electrons are transferred to NAD+ in two steps catalyzed by E3 (dihydrolipoyl dehydrogenase). The biochemical details of this reaction have been worked out first with alpha ketoglutarate dehydrogenase complex and subunits purified from bovine tissue (McCartney et al. 1998).

Generation of reactive oxygen species by OGDHC is a major source of mitochondrial oxidative stress under certain pathological conditions.