Oxoglutarate dehydrogenase

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Overview

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

Units

Much like pyruvate dehydrogenase complex, this enzyme forms a complex composed of three components:

Unit EC number Name Gene Coenzyme
E1 EC 1.2.4.2 oxoglutarate dehydrogenase OGDH thiamine pyrophosphate
E2 EC 2.3.1.61 dihydrolipoyl succinyltransferase DLST lipoic acid
E3 EC 1.8.1.4 dihydrolipoyl dehydrogenase DLD NAD+

In fact, three classes of these multienzyme complexes have been characterized, one specific for pyruvate, a second specific for 2-oxoglutarate and a third specificbranched-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).

Metabolic pathways

This enzyme participates in three different pathways:

Kinetic properties

The following values are from Azotobacter vinelandii (1):

  • KM: 0.14 ± 0.04 mM
  • Vmax : 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+ + CoASuccinyl CoA + CO2 + NADH

This reaction proceeds in three steps:

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.

External links

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  1. Leung PS, Rossaro L, Davis PA; et al. (2007). "Antimitochondrial antibodies in acute liver failure: Implications for primary biliary cirrhosis". doi:10.1002/hep.21828. PMID 17657817.