Oxoglutarate dehydrogenase complex

The oxoglutarate dehydrogenase complex (OGDC) or α-ketoglutarate dehydrogenase complex is an enzyme complex, most commonly known for its role in the citric acid cycle.

Units
Much like pyruvate dehydrogenase complex (PDC), this enzyme forms a complex composed of three components:

In fact, three classes of these multienzyme complexes have been characterized, one specific for pyruvate, a second specific for 2-oxoglutarate, and a third specific for branched-chain α-keto acids.

Metabolic pathways
This enzyme participates in three different pathways:
 * Citric acid cycle (KEGG link: MAP00020)
 * Lysine degradation (KEGG link: MAP00310)
 * Tryptophan metabolism (KEGG link: MAP00380)

Kinetic properties
The following values are from Azotobacter vinelandii (1):
 * KM: 0.14 ± 0.04 mM
 * Vmax : 9 ± 3 μmol.min-1.mg-1

Reaction
The reaction catalyzed by this enzyme in the citric acid cycle is:
 * α-ketoglutarate + NAD+ + CoA → Succinyl CoA + CO2 + NADH



This reaction proceeds in three steps:
 * decarboxylation of α-ketoglutarate,
 * reduction of NAD+ to NADH,
 * and subsequent transfer to CoA, which forms the end product, succinyl CoA.

ΔG°' for this reaction is -7.2 kcal mol-1. The energy needed for this oxidation is conserved in the formation of a thioester bond of succinyl CoA.

Regulation
Oxoglutarate dehydrogenase is a key control point in the citric acid cycle. It is inhibited by its products, succinyl CoA and NADH. A high energy charge in the cell will also be inhibitive. ADP and calcium ions are allosteric activators of the enzyme.

Pathology
2-Oxo-glutarate dehydrogrenase is an autoantigen recognized in primary biliary cirrhosis, a form of acute liver failure. These antibodies appear to recognize oxidized protein that has resulted from inflammatory immune responses. Some of these inflammatory responses are explained by gluten sensitivity. Other mitochondrial autoantigens include pyruvate dehydrogenase and branched-chain alpha-keto acid dehydrogenase complex, which are antigens recognized by anti-mitochondrial antibodies. Activity of the 2-oxoglutarate dehydrogenase complex is decreased in many neurodegenerative diseases.