Oxidoreductases;
Acting on the aldehyde or oxo group of donors;
With NAD+ or NADP+ as acceptor
BRITE hierarchy

3-methyl-2-oxobutanoate:NAD+ 2-oxidoreductase (CoA-methylpropanoylating)

3-methyl-2-oxobutanoate + CoA + NAD+ = 2-methylpropanoyl-CoA + CO2 + NADH [RN:R01210]

R01210;
(other) R01651 R03171
Reaction

3-methyl-2-oxobutanoate [CPD:C00141];
CoA [CPD:C00010];
NAD+ [CPD:C00003]

This enzyme system catalyses the oxidative decarboxylation of branched-chain alpha-keto acids derived from L-leucine, L-isoleucine, and L-valine to branched-chain acyl-CoAs. It belongs to the 2-oxoacid dehydrogenase system family, which also includes EC 1.2.1.104, pyruvate dehydrogenase system, EC 1.2.1.105, 2-oxoglutarate dehydrogenase system, EC 1.4.1.27, glycine cleavage system, and EC 2.3.1.190, acetoin dehydrogenase system. With the exception of the glycine cleavage system, which contains 4 components, the 2-oxoacid dehydrogenase systems share a common structure, consisting of three main components, namely a 2-oxoacid dehydrogenase (E1), a dihydrolipoamide acyltransferase (E2), and dihydrolipoamide dehydrogenase (E3). The reaction catalysed by this system is the sum of three activities: EC 1.2.4.4, 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring), EC 2.3.1.168, dihydrolipoyllysine-residue (2-methylpropanoyl)transferase, and EC 1.8.1.4, dihydrolipoyl dehydrogenase. The system also acts on (S)-3-methyl-2-oxopentanoate and 4-methyl-2-oxopentanoate.

EC 1.2.1.25 created 1972, modified 2019, modified 2020

1  [PMID:4308861]

Namba Y, Yoshizawa K, Ejima A, Hayashi T, Kaneda T.

Coenzyme A- and nicotinamide adenine dinucleotide-dependent branched chain alpha-keto acid dehydrogenase. I. Purification and properties of the enzyme from Bacillus subtilis.

J Biol Chem 244:4437-47 (1969)

2  [PMID:283398]

Pettit FH, Yeaman SJ, Reed LJ

Purification and characterization of branched chain alpha-keto acid dehydrogenase complex of bovine kidney.

Proc Natl Acad Sci U S A 75:4881-5 (1978)
DOI:10.1073/pnas.75.10.4881

3  [PMID:9381974]

Harris RA, Hawes JW, Popov KM, Zhao Y, Shimomura Y, Sato J, Jaskiewicz J, Hurley TD

Studies on the regulation of the mitochondrial alpha-ketoacid dehydrogenase complexes and their kinases.

Adv Enzyme Regul 37:271-93 (1997)
DOI:10.1016/s0065-2571(96)00009-x

4  [PMID:10745006]

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

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

Structure 8:277-91 (2000)
DOI:10.1016/s0969-2126(00)00105-2

5  [PMID:11477096]

Reed LJ

A trail of research from lipoic acid to alpha-keto acid dehydrogenase complexes.

J Biol Chem 276:38329-36 (2001)
DOI:10.1074/jbc.R100026200