Oxoglutarate dehydrogenase

Oxoglutarate dehydrogenase (aka α-ketoglutarate dehydrogenase) is an enzyme complex most commonly known for its role in the citric acid cycle.

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Much like pyruvate dehydrogenase complex, 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 branched-chain α-keto acids.

Properties

Nomenclature and classification

The official name of this enzyme is oxoglutarate dehydrogenase (OGDC) although it is also commonly known as α-ketoglutarate dehydrogenase (AKGDH).

• CAS: 9031-02-1

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⁾:

• K_M: 0.14 ± 0.04 mM
• V_max : 9 ± 3 μmol.min^-1.mg^-1

Citric acid cycle

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,
• oxidation,
• 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.

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 inflamatory immune responses. Some of these inflamatory responses are explained by gluten sensitivity.^[1] Other mitochondrial autoantigens include pyruvate dehydrogenase and branched-chain alpha-keto acid dehydrogenase complex, which are antigens recognized by anti-mitochondrial antibodies.

References

1. Bunik V, Westphal AH, de Kok A: Kinetic properties of the 2-oxoglutarate dehydrogenase complex from Azotobacter vinelandii evidence for the formation of a precatalytic complex with 2-oxoglutarate. Eur J Biochem 2000; 267(12): 3583-91. PMID 10848975.