BCKDH transfers CoA group from CoA-SH to BCAAs

Stable Identifier
Reaction [transition]
Homo sapiens
a-ketoisocaproate, a-keto b-methylvalerate, or a-ketoisovalerate + CoA + NAD+ => isovaleryl-CoA, a-methylbutyryl-CoA, or isobuyryl-CoA + CO2 + NADH + H+, Oxidative decarboxylation of branched-chain alpha-keto acids
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The mitochondrial branched-chain alpha-ketoacid dehydrogenase (BKCDH) complex catalyzes the reactions of alpha-ketoisocaproate, alpha-keto beta-methylvalerate, or alpha-ketoisovalerate with CoA and NAD+ to form isovaleryl-CoA, a-methylbutyryl-CoA, or isobutyryl-CoA, respectively, and CO2 and NADH (Chuang and Shih 2001). While bovine and microbial BCKD complexes have been characterized most extensively (Reed and Hackert 1990), structural studies of individual components and subcomplexes of human BKCD have confirmed their structures and roles in the overall oxidative carboxylation process, and have related these features to the disruptive effects of mutations on branched-chain amino acid metabolism in vivo: E1a and E1b components - AEvarsson et al. 2000; E2 - Chang et al. 2002; E3- Brautigam et al. 2005. In addition, structural studies have confirmed the lipoylation of lysine residue 44 in E2 protein (Chang et al. 2002) and the loss of an aminoterminal mitochondrial transport sequence from mature E3 protein (Bruatigam et al. 2005). Loss of mitochondrial transport sequences from proteins E1a, E1b, and E2 has been domstrated by sequence analysis (Wynn et al. 1999).

Literature References
PubMed ID Title Journal Year
2188967 Structure-function relationships in dihydrolipoamide acyltransferases.

Reed, LJ, Hackert, ML

J Biol Chem 1990
  The Metabolic and Molecular Bases of Inherited Disease, 8th ed

Beaudet, AL, Scriver, CR, Sly, WS, Valle, D

15946682 Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations

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

J Mol Biol 2005
10745006 Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease.

Hol, WG, Turley, S, Chuang, DT, Chuang, JL, Wynn, RM, Aevarsson, A

Structure Fold Des 2000
11839747 Solution structure and dynamics of the lipoic acid-bearing domain of human mitochondrial branched-chain alpha-keto acid dehydrogenase complex

Chuang, DT, Chou, HT, Chuang, JL, Chang, CF, Huang, TH

J Biol Chem 2002
7918575 Differential processing of human and rat E1 alpha precursors of the branched-chain alpha-keto acid dehydrogenase complex caused by an N-terminal proline in the rat sequence

Chuang, DT, Wynn, RM, Kochi, H, Cox, RP

Biochim Biophys Acta 1994
Catalyst Activity

CoA-transferase activity of lipo-BCKDH [mitochondrial matrix]

Orthologous Events
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