alpha-ketoadipate + CoASH + NAD+ => glutaryl-CoA + CO2 + NADH + H+

Stable Identifier
R-HSA-71037
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Synonyms
Oxidative decarboxylation of alpha-ketoadipate to glutaryl CoA by alpha-ketoglutarate dehydrogenase
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The mitochondrial alpha-ketoglutarate dehydrogenase complex catalyzes the reaction of alpha-ketoadipate, CoASH, and NAD+ to form glutaryl-CoA, CO2, and NADH. The enzyme complex 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). The reaction starts with the oxidative decarboxylation of alpha-ketoadipate catalyzed by E1alpha and beta (alpha ketoglutarate dehydrogenase). Lipoamide cofactor associated with E1 is reduced at the same time. Next, the glutaryl group derived from alpha ketoglutarate is transferred to coenzyme A in two steps catalyzed 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 with alpha ketoglutarate dehydrogenase complex and subunits purified from bovine tissue (McCartney et al. 1998). While all of the human proteins are known as predicted protein products of cloned genes, direct experimental evidence for their functions is available only for E3 (DLD) (Brautigam et al. 2005).

Literature References
PubMed ID Title Journal Year
15946682 Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations

Brautigam, CA, Chuang, JL, Tomchick, DR, Machius, M, Chuang, DT

J Mol Biol 2005
2188967 Structure-function relationships in dihydrolipoamide acyltransferases.

Reed, LJ, Hackert, ML

J Biol Chem 1990
11752427 The remarkable structural and functional organization of the eukaryotic pyruvate dehydrogenase complexes.

Zhou, ZH, McCarthy, DB, O'Connor, CM, Reed, LJ, Stoops, JK

Proc Natl Acad Sci U S A 2001
9727038 Subunit interactions in the mammalian alpha-ketoglutarate dehydrogenase complex. Evidence for direct association of the alpha-ketoglutarate dehydrogenase and dihydrolipoamide dehydrogenase components.

McCartney, RG, Rice, JE, Sanderson, SJ, Bunik, V, Lindsay, H, Lindsay, JG

J Biol Chem 1998
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
oxoglutarate dehydrogenase (NAD+) activity of lipo-aKGDH [mitochondrial matrix]
Physical Entity
Activity
Orthologous Events
Cross References
Rhea
Authored